Immobilized manganese catalyst, its preparation method and application

Abstract

The application discloses a kind of solid supported manganese catalyst and its preparation method and application, the preparation process of the catalyst includes complexing organic ligand with metal manganese salt, forms catalytic active unit, and then polymerizes with comonomer, obtains the solid supported manganese catalyst as shown in formula I or II.The solid supported manganese catalyst belongs to heterogeneous chiral catalyst, with higher catalytic activity and excellent enantioselectivity (ee value is as high as 98.3%), because it is insoluble in reaction solvent, easy to separate and recover with reaction system, with good stability.And it can be combined with continuous flow catalysis, maintain high catalytic activity for a long time, can be applied in the asymmetric epoxidation reaction of alpha, beta-unsaturated carbonyl compound.

Description

Technical Field

[0001] This invention relates to the field of catalytic chemistry, specifically to a supported manganese catalyst, its preparation method, and its application. Background Technology

[0002] Asymmetric epoxidation of olefins is an important class of organic synthesis reactions, and the resulting chiral epoxides are important pharmaceutical intermediates. Therefore, developing highly efficient catalysts for this type of epoxidation reaction is of great significance. Many researchers have developed biomimetic catalysts by mimicking the active sites of metallooxidases P450. Among these catalysts, Salen ligands have attracted considerable attention due to the ease of preparation of their metal-based complexes and their high catalytic activity. Subsequently, scientists discovered that the reaction catalyzed by the manganese complex formed by the non-heme N4 chiral ligand and metallic manganese exhibits higher reaction selectivity and enantioselectivity, proving it to be a highly efficient catalyst for asymmetric epoxidation reactions.

[0003] In 1990, Jacobsen et al. (J. Am. Chem. Soc. 1990, 112, 2801-2803.) reported a reaction system using a chiral Schiff base complex as a catalyst, achieving an epoxide yield of up to 93% and an ee value of 93%. This yielded excellent results in the asymmetric epoxidation of nonfunctionalized olefins. However, this homogeneous catalyst suffered from drawbacks such as difficulty in separation, recovery, and reuse, and a tendency for dimerization and deactivation within the reaction system. To address these issues, in 2000, Kim's research group developed a heterogeneous JandaJel catalyst that could adhere to resins, yielding epoxides with an ee value of up to 97%. However, this complex could only be recycled three times (J. Am. Chem. Soc. 2000, 122, 6929-6934.). In 2008, Bao Hebin's research group achieved the best catalytic effect using the asymmetric epoxidation of styrene as a probe reaction, with Salen-Mn(III) complex as a catalyst, m-chloroperoxybenzoic acid as an oxygen source, and NMO as an axial ligand. The product conversion rate was 85%, the selectivity was 90%, and the ee value reached 60%. They also found that the supported chiral Salen-Mn(III) catalyst was stable and could be recycled up to 6 times (Journal of Chemical Research in Chinese Universities, 2008, 29, 927-931). In 2021, Sun's research group reported the design and synthesis of a non-heme manganese N4 catalyst supported on an organic porous framework. This POP-based manganese catalyst exhibited high reactivity for the asymmetric epoxidation of olefins, with a product ee value as high as 96% and easy recycling. However, it had limited substrate versatility, could only be recycled up to 5 times, and showed a certain scale-up effect in gram-scale reactions (ACS Catal. 2021, 11, 10964-10973). Summary of the Invention

[0004] To address the aforementioned problems in existing technologies, this invention provides a method for preparing a supported manganese catalyst, solving the problem of the inability to recycle and reuse homogeneous catalysts. Furthermore, it is applied to continuous flow catalysis, resolving the issue of decreased yield and enantioselectivity during scale-up reactions. This catalyst exhibits high catalytic activity and excellent enantioselectivity, enabling its application in the asymmetric epoxidation of α,β-unsaturated carbonyl compounds.

[0005] The technical solution adopted in this invention is as follows:

[0006] A supported manganese catalyst having the structure shown in formula (I) or formula (II):

[0007]

[0008] In general formula I, R 1 Selected from hydrogen, C1-C6 straight-chain or branched alkyl groups, C3-C6 cycloalkyl groups, substituted aryl or heterocyclic aryl groups; R 2 Selected from one of the following: hydrogen, C1-C6 straight-chain or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl, halogen;

[0009] In general formulas I and II, n is selected from natural numbers from 1 to 200; X is selected from OTf. -1 OAc -1 ClO4 -1 NO3 -1 One of the halogen anions.

[0010] The supported manganese catalysts of Formula I or II of this invention are polymerized by polymerizing catalytically active units C1 or C2 with divinylbenzene (DVB).

[0011] The preparation method of the supported manganese catalyst includes the following steps:

[0012] (1) The reaction of Boc-L-proline and p-vinylbenzylamine shown in Formula 1 first generates an imine intermediate, which is then reduced by NaBH4 to obtain intermediate 2.

[0013] (2) Intermediate 2 was deprotected by Boc protecting group under the catalysis of trifluoroacetic acid (TFA) to obtain intermediate 3;

[0014] (3) In the presence of K2CO3, 2-chloromethylbenzimidazole or 2-chloromethylpyridine containing substituents are added for nucleophilic substitution to generate organic ligands L1 or L2 with N4 centers.

[0015] (4) Add manganese salt MnX2 to L1 or L2 to carry out a coordination reaction to obtain catalytic active unit C1 or C2;

[0016] (5) Add divinylbenzene (DVB) and azobisisobutyronitrile (AIBN) to C1 or C2 to carry out copolymerization reaction to obtain supported manganese catalyst I or II.

[0017]

[0018] In step (3), the substituent R of the 2-chloromethylbenzimidazole containing the substituent is... 1 R 2 Similar to Formula I, the negative ion X of the manganese salt MnX2 in step (4) is the same as in Formula I or II.

[0019] In step (1), the molar ratio of Boc-L-proline to p-vinylbenzylamine 1 is 0.8–1.5:1, the reaction is carried out in dichloromethane solution, the reaction temperature is 0–40°C, and the reaction time is 0.5–12 h; the molar ratio of NaBH4 to p-vinylbenzylamine is 2–6:1, the reduction reaction by NaBH4 is carried out in methanol solution, the reaction temperature is -10–40°C, and the reaction time is 0.5–12 h.

[0020] In step (2), the molar ratio of TFA to intermediate 2 is 5 to 50:1, preferably 15 to 25:1. The reaction is carried out in a dichloromethane solution at a temperature of -10 to 40°C for 0.5 to 24 hours.

[0021] In step (3), the molar ratio of 2-chloromethylbenzimidazole or 2-chloromethylpyridine containing substituents to intermediate 3 is 2.0 to 4.0:1, the molar ratio of K2CO3 to intermediate 3 is 1.0 to 4.0:1, the reaction is carried out in acetonitrile solution, the reaction temperature is 20 to 70°C, and the reaction time is 1 to 12 h.

[0022] In step (4), the molar ratio of the manganese salt MnX2 to the organic ligand L1 or L2 is 1.0 to 1.5:1. The reaction is carried out in acetonitrile solution at a temperature of 20 to 70°C for a time of 0.5 to 12 hours.

[0023] In step (5), the molar ratio of DVB to catalytic active unit C1 or C2 is 10-100:1, preferably 20-40:1, and the molar ratio of AIBN to DVB is 0.1%-10%:1, preferably 1%-3%:1. The reaction is carried out in tetrahydrofuran solution at a temperature of 60-120°C for 8-48 hours.

[0024] Furthermore, this invention also provides the application of the supported manganese catalyst prepared using the above-described technical solution in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds:

[0025] The α,β-unsaturated carbonyl compound is dissolved in acetonitrile solution, and supported manganese catalyst I or II is added, along with an acid additive and an oxidant. The reaction temperature is -45 to 30°C. After reaction and purification, a highly enantioselective epoxy compound is prepared. Supported manganese catalyst I or II is recovered by centrifugation. The catalyst can be reused in the next reaction after washing with ethyl acetate. The reaction formula is as follows:

[0026]

[0027] R 3 It is a C1-C6 straight-chain or branched alkyl group, a C3-C6 cycloalkyl group, a substituted aryl group, or a heterocyclic aryl group;

[0028] R 4 It can be a C1-C6 straight-chain or branched alkyl group, a C3-C6 cycloalkyl group, a substituted aryl or heterocyclic aryl group, an alkoxy group, an amino group, or a substituted amino group.

[0029] The oxide is one of hydrogen peroxide, m-chloroperoxybenzoic acid, tert-butyl peroxide, and iodobenzoylbenzene, and its molar ratio with the α,β-unsaturated carbonyl compound is 1.2 to 2:1; the acid added in the reaction is one of acetic acid, 2,2-dimethylbutyric acid, 2-ethylhexanoic acid, butyric acid, 4-methylvaleric acid, 4-phenylbutyric acid, 2-ethylbutyric acid, and 2,2-dimethylpropionic acid, and its molar ratio with the α,β-unsaturated carbonyl compound is 2 to 8:1.

[0030] Furthermore, this invention also provides the application of the supported manganese catalyst prepared using the above-described technical solution in the continuous flow catalysis of the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds:

[0031] The supported manganese catalyst I or II and silica gel are thoroughly ground in a mortar and then packed into a fixed-bed reactor. In one channel, solution A is prepared by dissolving an α,β-unsaturated carbonyl compound and an acid additive in acetonitrile, with concentrations of 0.2–0.4 mol / L for the α,β-unsaturated carbonyl compound and 0.8–2 mol / L for the acid additive. In the other channel, solution B is prepared by dissolving an oxidant in acetonitrile, with an oxidant concentration of 0.5–2 mol / L. The liquid flow rate is controlled by an injection pump, the reaction temperature is -45–30 °C, and the residence time is 10–30 min. After reaction and purification, a highly enantioselective epoxy compound is prepared.

[0032] By employing the above-described technology, the present invention has the following characteristics compared with the prior art:

[0033] This invention provides a method for preparing a supported manganese catalyst. The process includes complexing an organic ligand with a manganese salt to form a catalytically active unit, followed by polymerization with a comonomer to obtain a supported manganese catalyst as shown in Formula I or II. The supported manganese catalyst is a heterogeneous chiral catalyst with high catalytic activity and excellent enantioselectivity (ee value up to 98.3%). Because it is insoluble in the reaction solvent, it is easily separated from the reaction system and recovered, exhibiting good stability. Furthermore, it can be combined with continuous flow catalysis to maintain high catalytic activity for a longer period, and can be applied to the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds. Attached Figure Description

[0034] Figure 1 The results are shown in the scanning electron microscopy (500 nm) characterization of the supported manganese catalyst I-1.

[0035] Figure 2 The results show the transmission electron microscopy (TEM) characterization (10 nm), X-ray energy dispersive spectroscopy (100 nm), and elemental characterization (100 nm) of the supported manganese catalyst I-1.

[0036] Figure 3 The nitrogen adsorption-desorption curves are for the supported manganese catalyst I-1.

[0037] Figure 4 This is a pore size diagram of the supported manganese catalyst I-1.

[0038] Figure 5 The results of thermogravimetric analysis of supported manganese catalyst I-1 are shown. Detailed Implementation

[0039] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0040] Example 1: Preparation of supported manganese catalyst I-1

[0041]

[0042] (1) Add Boc-L-proline (996 mg, 5.0 mmol), vinylbenzylamine 1 (595 mg, 5.0 mmol) and 10 mL of dichloromethane solution to a 100 mL single-necked flask. React at 40 °C for 8 h under a nitrogen atmosphere. The solvent is recovered to obtain a yellow oily liquid. Add 20 mL of methanol solution and add NaBH4 (908 mg, 24.0 mmol) in portions at 0 °C. After reacting for 8 h, the solvent is recovered. Dissolve the solution in 20 mL of water and extract three times with dichloromethane (20 mL × 3). Combine the organic phases and dry to obtain a yellow oily liquid intermediate 2 (1.45 g, 4.6 mmol, yield 92%).

[0043] (2) The intermediate 2 (1.0 g, 3.2 mmol) was dissolved in 20 mL of dichloromethane solution in a 100 mL single-necked flask. TFA (7.21 g, 63.2 mmol) was added at 25 °C and reacted for 12 h. The reaction was quenched with 20 mL of saturated NaHCO3 and extracted twice with dichloromethane (20 mL × 2). The organic phases were combined and dried to obtain yellow oily liquid intermediate 3 (608 mg, 2.8 mmol, yield 88%).

[0044] (3) Add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-methyl-1H-benzimidazole (451 mg, 2.5 mmol), K2CO3 (415 mg, 3.0 mmol), and 20 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C under a nitrogen atmosphere. After 8 h of reaction, recover the solvent, add 20 mL of water to dissolve, and then extract three times with dichloromethane (20 mL × 3). Combine the organic phases, dry them, and purify them by column chromatography to obtain a yellow foamy solid L1-1 (352 mg, 0.7 mmol, yield 70%).

[0045] Structural characterization of L1-1: Yellow solid; 1 H NMR(400MHz,Chloroform-d)δ7.72–7.67(m,2H),7.34(d,J=8.0Hz,2H),7.26–7.20(m,8H),6.68(dd,J=1 7.6,3.2Hz,1H),5.72(dd,J=17.6,1.2Hz,1H),5.23(dd,J=11.2,1.2Hz,1H),4.20(d,J=13.6Hz,1H),3.79 (d,J=13.6Hz,1H),3.71(d,J=13.6Hz,1H),3.67–3.56(m,5H),3.55–3.52(m,1H),3.48(s,3H),2.77–2.64 (m,3H),2.50(dd,J=12.4,7.2Hz,1H),2.28(td,J=9.2,7.2Hz,2H),2.02–1.91(m,1H),1.67–1.46(m,2H); 13C NMR(100MHz,Chloroform-d)δ152.27,151.72,142.17,142.12,137.98,136.80,136.42,136.20,129.77,126.17,122.63,122.38,121.97,12 1.80,119.53,119.46,113.87,109.12,109.10,62.33,59.85,59.38,54.82,52.38,52.10,30.49,30.00,29.72,22.37; HRMS-ESI(m / z):calcd for C 32 H 37 N6[M+H] + :505.3074,found:505.3073.

[0046] (4) Add L1-1 (352 mg, 0.7 mmol), Mn(OTf)2 (270 mg, 0.77 mmol), and 30 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C for 6 h under a nitrogen atmosphere to carry out coordination. After the reaction is completed, the solvent is recovered to obtain a pale yellow solid Cl-1 (458 mg, 0.67 mmol, yield 97%).

[0047] Structural characterization of C1-1: HRMS-ESI(m / z): calcd for C 34 H 36 F6MnN6NaO6S2[M+Na] + :880.1315,found:880.1295.

[0048] (5) Add DVB (780mg, 6.0mmol) and AIBN (15mg), 10mL tetrahydrofuran solution to C1-1 (172mg, 0.2mmol), react at room temperature for 1h, then react at 100℃ for 24h, filter to obtain supported manganese catalyst I-1, yield 75%.

[0049] In the catalyst I-1 structure, the amount of DVB is 30, as referenced in ACS Catal. 2021, 11, 10964-10973. Since the polymerization reaction is a free radical polymerization, the ratio of DVB to catalyst C1-1 in the supported catalyst is assumed to be the feed ratio for the polymerization reaction, i.e., 30:1.

[0050] Scanning electron microscopy characterization (500 nm) of the supported manganese catalyst I-1 is as follows: Figure 1 As shown in the figure, the supported manganese catalyst I-1 has a large number of mesoporous structures, which is beneficial to the transport of raw materials and products during the catalytic reaction.

[0051] The results of transmission electron microscopy (10 nm), X-ray energy dispersive spectroscopy (100 nm), and elemental characterization (100 nm) of the immobilized manganese catalyst I-1 are summarized in [the table below]. Figure 2 The results indicate that the catalyst monomer C1-1 in the supported catalyst I-1 was successfully immobilized and is uniformly distributed on the porous organic polymer support.

[0052] The nitrogen adsorption-desorption curve of the supported manganese catalyst I-1 is as follows: Figure 3 As shown, this indicates that the supported catalyst has a high specific surface area (98.78 m²). 2 / g).

[0053] Pore ​​size diagram of supported manganese catalyst I-1 is shown below Figure 4 This indicates that the pore size range of this supported catalyst is mainly distributed in the range of 7–20 nm, which belongs to mesoporous supported materials.

[0054] Thermogravimetric analysis results of supported manganese catalyst I-1 are as follows: Figure 5 The figure illustrates that this supported catalyst has good thermodynamic stability.

[0055] Example 2: Preparation of supported manganese catalyst I-2

[0056]

[0057] (1) Add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-ethyl-1H-benzimidazole (487 g, 2.5 mmol), K2CO3 (415 mg, 3.0 mmol), and 20 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C under a nitrogen atmosphere. After 8 h of reaction, recover the solvent, add 20 mL of water to dissolve, and then extract three times with dichloromethane (20 mL × 3). Combine the organic phases, dry them, and purify them by column chromatography to obtain a yellow foamy solid L1-2 (330 mg, 0.62 mmol, yield 62%).

[0058] Structural characterization of L1-2: Yellow solid; 1H NMR(400MHz,Chloroform-d)δδ7.90–7.59(m,2H),7.44–7.28(m,4H),7.26–7.19(m,6H),6.70(dd,J=17.6,10. 8Hz,1H),5.74(d,J=17.6Hz,1H),5.24(d,J=10.8Hz,1H),4.26(d,J=12.8Hz,1H),4.17–3.96(m,2H),3.85–3.7 8(m,2H),3.76–3.72(m,2H),3.65–3.56(m,3H),2.83–2.75(m,1H),2.76–2.60(m,2H),2.58–2.52(m,1H),2.30 –2.21(m,1H),2.00–1.93(m,1H),1.62–1.57(m,1H),1.50–1.36(m,2H),1.28–1.16(m,3H),1.14–1.05(m,3H); 13 C NMR(100MHz,Chloroform-d)δ151.86,150.99,142.42,142.30,137.85,136. 87,136.39,135.13,135.10,129.87,126.17,122.58,122.31,121.88,121.6 8,119.62,119.53,113.90,109.39,109.33,62.18,59.79,59.57,54.77,52. 33,51.83,38.44,38.27,30.56,22.34,14.79,14.72; HRMS-ESI(m / z):calcd forC 34 H 41 N6[M+H] + :533.3387,found:533.3387.

[0059] (2) Add L1-2 (330 mg, 0.62 mmol), Mn(OTf)2 (241 mg, 0.68 mmol), and 30 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C for 6 h under a nitrogen atmosphere to carry out coordination. After the reaction is completed, the solvent is recovered to obtain a pale yellow solid Cl-2 (424 mg, 0.6 mmol, yield 97%).

[0060] Structural characterization of C1-2: HRMS-ESI(m / z): calcd for C 36 H 40 F6MnN6NaO6S2[M+Na] +:908.1628,found:908.1619.

[0061] (3) DVB (780 mg, 6.0 mmol) and AIBN (15 mg), 10 mL of tetrahydrofuran solution were added to C1-2 (177 mg, 0.2 mmol). The reaction was carried out at room temperature for 1 h and then at 100 °C for 24 h. After filtration, the supported manganese catalyst I-2 was obtained with a yield of 72%.

[0062] Example 3: Preparation of supported manganese catalyst I-3

[0063]

[0064] (1) Add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-cyclohexyl-1H-benzimidazole (622 mg, 2.5 mmol), K2CO3 (415 mg, 3.0 mmol), and 20 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C under a nitrogen atmosphere. After 8 h of reaction, recover the solvent, add 20 mL of water to dissolve, and then extract three times with dichloromethane (20 mL × 3). Combine the organic phases, dry them, and purify them by column chromatography to obtain yellow foamy solid L1-3 (340 mg, 0.53 mmol, yield 53%).

[0065] Structural characterization of L1-3: Yellow solid; 1H NMR(400MHz,Chloroform-d)δ7.71–7.67(m,2H),7.59–7.48(m,2H),7.38(d,J=8.4Hz,2H),7.32(d,J=8.0Hz,2H),7.21–7.15(m,4H),6.70(dd,J=17.6,10.8Hz,1H),5.73(d,J=17.6Hz,1H),5.23(d,J=10.8Hz,1H),4.43(tdt,J=12.0,7.6,4.0Hz,2H),4.11(d,J=13.2Hz,1H),3.94(d,J=13.2Hz,1H),3.80(d,J=13.2Hz,1H),3.69(d,J=13.2Hz,1H),3.59(d,J=13.2Hz,1H),3.44(d,J=13.2Hz,1H),2.79–2.67(m,2H),2.67–2.48(m,2H),2.37–2.19(m,2H),2.17–2.00(m,3H),1.98–1.84(m,5H),1.81–1.72(m,3H),1.56–1.47(m,1H),1.36–1.20(m,5H),1.17–1.05(m,2H); 13 C NMR(100MHz,Chloroform-d)δ151.77,150.90,143.08,142.94,138.05,136.86,136.44,134.11,134.09,129.60,126.33,122.04,121.83,121.45,121.27,119.96,119.84,113.80,112.43,112.27,62.22,59.93,59.21,56.16,55.62,54.34,52.85,52.48,31.40,31.34,31.31,31.10,30.76,26.20,25.95,25.83,25.76,25.47,25.40,22.59;HRMS-ESI(m / z):calcd for C 42 H 53 N6[M+H] + :641.4326,found:641.4325.

[0066] (2) Add L1-3 (340 mg, 0.53 mmol), Mn(OTf)2 (206 mg, 0.58 mmol), and 30 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C for 6 h under a nitrogen atmosphere to carry out coordination. After the reaction is completed, the solvent is recovered to obtain a pale yellow solid Cl-3 (510 mg, 0.51 mmol, yield 96%).

[0067] Structural characterization of C1-3: HRMS-ESI(m / z): calcd for C 44 H 52 F6MnN6NaO6S2[M+Na] + :1016.2567,found:1016.2560.

[0068] (3) Add DVB (780mg, 6.0mmol) and AIBN (15mg) and 10mL tetrahydrofuran solution to C1-3 (199mg, 0.2mmol), react at room temperature for 1h and then at 100℃ for 24h. After filtration, the supported manganese catalyst I-3 is obtained with a yield of 70%.

[0069] Example 4: Preparation of supported manganese catalyst I-4

[0070]

[0071] (1) Add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)-1-methyl-4-bromo-1H-benzimidazole (649 mg, 2.5 mmol), K2CO3 (415 mg, 3.0 mmol), and 20 mL of acetonitrile solution to a 100 mL single-necked flask to dissolve the intermediate. React at 60 °C under a nitrogen atmosphere. After reacting for 8 h, the solvent is recovered, and 20 mL of water is added to dissolve the intermediate. The mixture is then extracted three times with dichloromethane (20 mL × 3). The organic phases are combined, dried, and purified by column chromatography to obtain a yellow foamy solid L1-4 (240 mg, 0.36 mmol, yield 36%).

[0072] Structural characterization of L1-4: Yellow solid; 1H NMR(400MHz,Chloroform-d)δ7.82–7.80(m,2H),7.38–7.27(m,4H),7.25–7.18(m,2H),7.12–7. 08(m,1H),7.06–7.02(m,1H),6.68(ddd,J=18.0,11.2,2.8Hz,1H),5.72(d,J=17.6Hz,1H),5.23( d,J=11.2Hz,1H),4.18–4.10(m,1H),3.81–3.72(m,1H),3.71–3.58(m,3H),3.53–3.48(m,7H),2. 70(t,J=8.4Hz,2H),2.63–2.54(m,2H),2.50–2.45(m,1H),2.32–2.22(m,1H),2.11–1.87(m,3H); 13 C NMR(100MHz,Chloroform-d)δ153.35,152.87,143.37,137.72,136.92,136.35,135.14,135.08,129.73,126.18,125.66,125.46,122.31,12 2.23,114.96,114.83,113.96,110.35,110.32,62.33,59.88,59.37,54.83,52.21,51.83,30.43,30.11,29.97,22.43; HRMS-ESI(m / z):calcd forC 32 H 35 Br2N6[M+H] + :661.1284,found:661.1283.

[0073] (2) Add L1-4 (240 mg, 0.36 mmol), Mn(OTf)2 (140 mg, 0.40 mmol), and 30 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C for 6 h under a nitrogen atmosphere to carry out coordination. After the reaction is completed, the solvent is recovered to obtain a pale yellow solid Cl-4 (346 mg, 0.34 mmol, yield 95%).

[0074] Structural characterization of C1-4: HRMS-ESI(m / z): calcd for C 34 H 34 Br2F6MnN6NaO6S2[M+Na] + :1035.9525,found:1035.9523.

[0075] (3) DVB (1.33g, 10.2mmol) and AIBN (15mg), 10mL tetrahydrofuran solution were added to C1-4 (346mg, 0.34mmol), and the reaction was carried out at room temperature for 1h and then at 100℃ for 24h. After filtration, the supported manganese catalyst I-4 was obtained with a yield of 68%.

[0076] Example 5: Preparation of Supported Manganese Catalyst II

[0077]

[0078] (1) Add intermediate 3 (216 mg, 1.0 mmol), 2-(chloromethyl)pyridine (319 mg, 2.5 mmol), K2CO3 (415 mg, 3.0 mmol), and 20 mL of acetonitrile solution to a 100 mL single-necked flask and dissolve. React at 60 °C under a nitrogen atmosphere. After 8 h of reaction, recover the solvent, add 20 mL of water to dissolve, and then extract three times with dichloromethane (20 mL × 3). Combine the organic phases, dry them, and purify them by column chromatography to obtain a yellow foamy solid L2 (279 mg, 0.7 mmol, yield 70%).

[0079] Structural characterization of L2: Yellow solid; 1 H NMR(400MHz,Chloroform-d)δ8.52–8.48(m,2H),7.64–7.56(m,2H),7.55–7.49(m,1 H),7.39–7.24(m,5H),7.16–7.06(m,2H),6.68(dd,J=17.6,10.8Hz,1H),5.71(d,J=1 7.6Hz,1H),5.20(d,J=11.2Hz,1H),4.37–4.10(m,1H),3.82–3.68(m,2H),3.68–3.39 (m,3H),2.82–2.37(m,3H),2.25–2.14(m,1H),2.10–1.83(m,2H),1.76–1.50(m,3H); 13 C NMR(100MHz,Chloroform-d)δ160.22,148.92,148.78,139.04,136.66,136.37,136.35,136.32,129.19,126.09,123 .07,123.00,121.89,121.79,113.35,62.35,61.30,61.16,59.44,59.02,54.87,30.11,22.57; HRMS-ESI(m / z):calcd forC 26 H 31N4[M+H] + :399.2543,found:399.2540.

[0080] (5) Add L2 (279 mg, 0.7 mmol), Mn(OTf)2 (270 mg, 0.77 mmol), and 30 mL of acetonitrile solution to a 100 mL single-necked flask. React at 60 °C for 6 h under a nitrogen atmosphere to carry out coordination. After the reaction is completed, the solvent is recovered to obtain a pale yellow solid C2 (499 mg, 0.67 mmol, yield 96%).

[0081] Structural characterization of C2: HRMS-ESI(m / z): calcd for C 28 H 30 F6MnN4NaO6S2[M+Na] + :774.0784,found:774.0777.

[0082] (3) Add DVB (780mg, 6.0mmol) and AIBN (15mg), 10mL tetrahydrofuran solution to C2 (150mg, 0.2mmol), react at room temperature for 1h, then react at 100℃ for 24h, filter to obtain supported manganese catalyst II, yield 80%.

[0083] Example 6: Preparation of supported manganese catalyst I-5

[0084]

[0085] DVB (261 mg, 2 mmol) and AIBN (5 mg), 10 mL of tetrahydrofuran solution were added to C1-1 (172 mg, 0.2 mmol), and the mixture was reacted at room temperature for 1 h and then at 100 °C for 24 h. After filtration, the supported manganese catalyst I-5 was obtained.

[0086] Example 7: Preparation of supported manganese catalyst I-6

[0087]

[0088] DVB (1.57 g, 12 mmol) and AIBN (30 mg), 10 mL of tetrahydrofuran solution were added to C1-1 (172 mg, 0.2 mmol). The mixture was reacted at room temperature for 1 h and then at 100 °C for 24 h. After filtration, the supported manganese catalyst I-6 was obtained.

[0089] Example 8: Application of supported manganese catalyst I-1 in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0090]

[0091] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst I-1 (11.9 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst I-1 was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (53.2 mg, 0.237 mmol, yield 95%, ee value 95.7%).

[0092] Example 9: Application of supported manganese catalyst I-2 in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0093]

[0094] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst I-2 (12.0 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst I-2 was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (52.7 mg, 0.235 mmol, yield 94%, ee value 94.5%).

[0095] Example 10: Application of supported manganese catalyst I-3 in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0096]

[0097] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst I-3 (12.2 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst I-3 was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (52.1 mg, 0.232 mmol, yield 93%, ee value 94.6%).

[0098] Example 11: Application of supported manganese catalyst I-4 in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0099]

[0100] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst I-4 (12.3 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst I-4 was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (37.5 mg, 0.167 mmol, yield 67%, ee value 91.3%).

[0101] Example 12: Application of supported manganese catalyst II in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0102]

[0103] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst II (11.6 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst II was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (51.6 mg, 0.230 mmol, yield 92%, ee value 89.5%).

[0104] Example 13: Application of supported manganese catalyst I-5 in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0105]

[0106] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst I-5 (5.4 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst I-5 was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (52.1 mg, 0.232 mmol, yield 93%, ee value 95.4%).

[0107] Example 14: Application of supported manganese catalyst I-6 in the asymmetric epoxidation reaction of α,β-unsaturated carbonyl compounds

[0108]

[0109] Chalcone 4 (52 mg, 0.25 mmol) was dissolved in 1 mL of acetonitrile solution, and supported manganese catalyst I-6 (21.7 mg) and 2,2-dimethylbutyric acid (145 mg, 1.25 mmol) were added. The mixture was cooled to -40 °C, and 50% hydrogen peroxide (26 mg, 0.375 mmol) was diluted with acetonitrile to 0.5 mL. After the addition was completed over 2 h, the mixture was kept at this temperature for 2 h. After the reaction was completed, catalyst I-6 was recovered by centrifugation and filtration. The filtrate was concentrated to dryness under reduced pressure, and the residue was separated by column chromatography (ethyl acetate: n-hexane = 1:20, v / v) to give a yellow solid (44.8 mg, 0.200 mmol, yield 80%, ee value 95.5%).

[0110] Example 15: Recovery and recycling experiment of supported manganese catalyst I-1

[0111] Following the experimental procedure described in Example 8, catalyst I-1 was washed with 1 mL of ethyl acetate after centrifugation, dried, and then added to the reaction. This experimental procedure was repeated. A significant decrease in yield was observed after the fifth cycle, indicating metal loss. Therefore, before the sixth cycle, the recovered I-1 was placed in 1 mL of acetonitrile, and Mn(OTf)₂ (0.4 mg) was added. The mixture was reacted at 60°C for 6 hours under a nitrogen atmosphere to re-coordinate, centrifuged, dried, and then added back to the reaction. The yields and ee values ​​of the recovery cycle experiments are shown in Table 1.

[0112] Table 1. Recovery and recycling experiments of supported manganese catalyst I-1

[0113] Loop count Yield (%) ee(%) 1 94 95.7 2 93 95.5 3 91 95.6 4 90 95.6 5 82 95.5 6 93 95.5

[0114] Example 16: Application of supported manganese catalyst I-1 in continuous flow catalysis

[0115] I-1 (238 mg) and silica gel (2.0 g) were thoroughly ground in a mortar and packed into the tubing of a fixed-bed reactor. Chalcone 4 (2.08 g, 10 mmol) and 2,2-dimethylbutyric acid (5.8 g, 50 mmol) were dissolved in acetonitrile and diluted to 36 mL. The solution was injected into the fixed-bed reactor using syringe pump 1 (flow rate 40 μL / min). Simultaneously, 50% hydrogen peroxide (816 mg, 12 mmol) was diluted to 18 mL with acetonitrile and injected into the fixed-bed reactor using syringe pump 2 (flow rate 20 μL / min). The reaction temperature was controlled at -40 °C, and the residence time of the reaction solution in the fixed bed was 20 min. The reactor was continuously run for 90–900 min. The yield and ee value are shown in Table 2.

[0116] Table 2 Application of supported manganese catalyst I-1 in continuous flow catalysis

[0117] Serial Number Running time (min) Yield (%) ee(%) 1 90 93 95.5 2 180 93 95.5 3 270 93 95.5 4 360 93 95.5 5 450 93 95.5 6 540 93 95.5 7 630 93 95.5 8 720 92 95.5 9 810 90 95.3 10 900 87 95.0

[0118] Table 2 shows the yield and ee value of the catalyst under continuous operation time in continuous flow catalysis. The reaction results show that the reaction yield can still reach 87% when the catalyst is continuously running for 900 min, indicating that the catalyst has high stability.

[0119] The operation steps described in Examples 17-44 are repeated in Example 8, except that the structure of the α,β-unsaturated carbonyl compound derivatives of the reaction raw materials is changed. The yield, purity and ee value of the corresponding epoxidation products are shown in Table 3 below.

[0120] Table 3 Examples 17-44

[0121]

[0122]

[0123]

[0124]

[0125] (Examples 17-44 are all known materials)

[0126] The contents described in this specification are merely an enumeration of the implementation forms of the inventive concept, and the scope of protection of this invention should not be regarded as limited to the specific forms described in the embodiments.

Claims

1. A supported manganese catalyst in α,β Its application in the asymmetric epoxidation reaction of unsaturated carbonyl compounds, characterized by, The supported manganese catalyst has a structure as shown in Formula I or Formula II: ； In general formula I, R 1 Selected from hydrogen, C1-C6 straight-chain or branched alkyl groups, C3-C6 cycloalkyl groups, substituted aryl or heterocyclic aryl groups; R 2 Selected from one of the following: hydrogen, C1-C6 straight-chain or branched alkyl, C3-C6 cycloalkyl, substituted aryl or heterocyclic aryl, halogen; In general formulas I and II, n is selected from one of the natural numbers from 1 to 200; X is selected from... - OTf, - OAc, ClO4 -1 NO3 -1 One of the halogen anions.

2. The application as described in claim 1, characterized in that, The method for preparing a supported manganese catalyst includes the following steps: (1) Boc-L-proline and p-vinylbenzylamine as shown in Formula 1 are reacted to generate an imine intermediate, which is then reduced by NaBH4 to obtain intermediate 2; (2) Intermediate 2 undergoes a reaction to remove the Boc protecting group under the catalysis of trifluoroacetic acid to obtain intermediate 3; (3) In the presence of K2CO3, intermediate 3 undergoes a nucleophilic substitution reaction with 2-chloromethylbenzimidazole or 2-chloromethylpyridine containing substituents to generate organic ligands L1 or L2 with N4 centers; (4) Organic ligands L1 or L2 undergo coordination reactions with manganese salt MnX2 to obtain catalytically active units C1 or C2; (5) Catalytic active unit C1 or C2 undergoes copolymerization with divinylbenzene (DVB) in the presence of azobisisobutyronitrile (AIBN) to obtain a supported manganese catalyst as shown in Formula I or Formula II, with the following reaction formula: ； In step (3), the substituent R of the 2-chloromethylbenzimidazole containing the substituent is... 1 R 2 Similar to Formula I, the negative ion X of the manganese salt MnX2 in step (4) is the same as in Formula I or II.

3. The application as described in claim 2, characterized in that, In step (1), the molar ratio of Boc-L-proline to p-vinylbenzylamine is 0.8–1.5:1, the reaction is carried out in dichloromethane solution, the reaction temperature is 0–40 °C, and the reaction time is 0.5–12 h; the molar ratio of NaBH4 to p-vinylbenzylamine is 2–6:1, the reduction reaction by NaBH4 is carried out in methanol solution, the reaction temperature is -10–40 °C, and the reaction time is 0.5–12 h.

4. The application as described in claim 2, characterized in that, In step (2), the molar ratio of TFA to intermediate 2 is 5-50:

1. The reaction is carried out in dichloromethane solution at a temperature of -10 to 40 °C for 0.5 to 24 h.

5. The application as described in claim 4, characterized in that, In step (2), the molar ratio of TFA to intermediate 2 is 15-25:

1.

6. The application as described in claim 2, characterized in that, In step (3), the molar ratio of 2-chloromethylbenzimidazole or 2-chloromethylpyridine containing substituents to intermediate 3 is 2.0–4.0:1, the molar ratio of K2CO3 to intermediate 3 is 1.0–4.0:1, the reaction is carried out in acetonitrile solution, the reaction temperature is 20–70 °C, and the reaction time is 1–12 h.

7. The application as described in claim 2, characterized in that, In step (4), the molar ratio of the manganese salt MnX2 to the organic ligand L1 or L2 is 1.0 to 1.5:

1. The reaction is carried out in acetonitrile solution at a temperature of 20 to 70 °C for a time of 0.5 to 12 h.

8. The application as described in claim 2, characterized in that, In step (5), the molar ratio of DVB to catalytic active unit C1 or C2 is 10-100:1, the molar ratio of AIBN to DVB is 0.1%-10%:1, the reaction is carried out in tetrahydrofuran solution, the reaction temperature is 60-120 °C, and the reaction time is 8-48 h.

9. The application as described in claim 8, characterized in that, In step (5), the molar ratio of DVB to catalytic active unit C1 or C2 is 20~40:1, and the molar ratio of AIBN to DVB is 1%~3%:

1.

10. The application as described in claim 1, characterized in that... The α,β Unsaturated carbonyl compounds are dissolved in an organic solvent, and supported manganese catalyst I or II is added, along with an acid additive and an oxidant. The reaction temperature is -45 to 30°C. After reaction and purification, highly enantioselective epoxy compounds are prepared. Supported manganese catalyst I or II is recovered by centrifugation. The reaction formula is as follows: ； The above reaction formula α,β In the structure of -unsaturated carbonyl compounds, R 3 It is a C1-C6 straight-chain or branched alkyl group, a C3-C6 cycloalkyl group, a substituted aryl group, or a heterocyclic aryl group; R 4 It is a C1-C6 straight-chain or branched alkyl group, a C3-C6 cycloalkyl group, a substituted aryl or heterocyclic aryl group, an alkoxy group, an amino group, or a substituted amino group.

11. The application as described in claim 10, characterized in that... The oxidant is one of hydrogen peroxide, m-chloroperoxybenzoic acid, tert-butyl peroxide, and iodobenzoylbenzene, which, together with... α,β The molar ratio of the unsaturated carbonyl compound is 1.2 to 2:1; the acid added in the reaction is one of acetic acid, 2,2-dimethylbutyric acid, 2-ethylhexanoic acid, butyric acid, 4-methylvaleric acid, 4-phenylbutyric acid, 2-ethylbutyric acid, or 2,2-dimethylpropionic acid, and its reaction with... α,β The molar ratio of the unsaturated carbonyl compounds is 2 to 8:1; the organic solvent is acetonitrile.

12. The application as described in claim 10, characterized in that... The application method is as follows: Supported manganese catalyst I or II and silica gel are thoroughly ground in a mortar and then packed into a fixed-bed reactor; in one channel... α,β Solution A is prepared by dissolving an unsaturated carbonyl compound and an acid additive in an organic solvent. In solution A... α,β The concentrations of the unsaturated carbonyl compound and the acid additive are 0.2–0.4 mol / L and 0.8–2 mol / L, respectively. In another channel, solution B is prepared by dissolving the oxidant in an organic solvent. The concentration of the oxidant in solution B is 0.5–2 mol / L. The liquid flow rate is controlled by a syringe pump. The reaction temperature is -45–30 °C and the residence time of the reaction system is 10–30 min. After reaction and purification, a highly enantioselective epoxy compound is prepared.

Images