A primary amine functionalized chiral covalent organic framework and preparation method and application thereof

Abstract

The present application relates to a kind of primary amine functionalized chiral covalent organic framework and its preparation method and application, it is related to the field of catalyst technology.The primary amine functionalized chiral covalent organic framework, high crystallinity, porous and uniform spherical shape can effectively catalyze the asymmetric aldol condensation reaction between cyclohexanone and nitrobenzaldehyde in the presence of water, its reaction yield and ee value are up to 90% and 85% respectively, it is the first chiral COF catalyst that can not use any organic solvent, in aldol condensation reaction in pure water with high reaction activity and enantiomeric selectivity.The primary amine functionalized chiral covalent organic framework not only opens a new way for designing primary amine functionalized chiral COF for asymmetric catalysis, but also lays an important foundation for further exploring green chiral catalysts that can effectively catalyze enantiomeric selective reaction in water.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of catalysts, in particular to a primary amine functionalized chiral covalent organic framework and a preparation method and application thereof. BACKGROUND

[0002] With the continuous deepening of the concept of environmental protection and green chemistry, the exploration of asymmetric catalytic reaction in aqueous phase has important significance because water is an environmentally friendly, non-toxic and resource-rich medium. However, the use of pure water as a solvent in catalytic asymmetric reactions often has a negative impact because water can inhibit catalytic activity or reduce enantioselectivity by interfering with hydrogen bonding and ionic interactions during the formation of transition states. For example, the use of proline as a chiral catalyst for aldol condensation reactions in organic solvents can produce ideal products with high enantioselectivity, while the use of pure water as a solvent produces the corresponding racemate. Therefore, the rational design of new chiral catalysts that can perform asymmetric reactions with excellent yield and enantioselectivity in the presence of water is the current goal of the chemical community.

[0003] In recent years, the synthesis of chiral covalent organic frameworks (COFs) has attracted extensive attention. Due to its wide application prospects in the fields of asymmetric catalysis, chromatographic separation, chemical synthesis, etc., the synthesis of chiral covalent organic frameworks (COFs) has attracted extensive attention in recent years. Asymmetric catalysis, chromatographic separation, chiral recognition, enantioselective adsorption and chiral optical materials have broad application prospects. In particular, chiral COFs have great potential as asymmetric catalysts because their large and straight channels can allow reactants to effectively enter the catalytic sites within the COF framework and promote the transport of reactants and products. Studies have shown that chiral COFs can be excellent catalysts for asymmetric aldol condensation reactions and have good catalytic performance. For example, based on the condensation reaction of chiral pyrrolidine structural units with triformylphloroglucinol and trihydroxytriformylphloroglucinol, respectively, chiral LZU-72 and LZU-76 COFs were directly synthesized. These chiral COFs showed good recyclability and enantioselectivity in asymmetric aldol condensation reactions, with an ee value of up to 88%. Researchers have also prepared a series of binary and ternary chiral COFs, which use a multi-unit strategy to control crystallinity and stability for asymmetric catalytic aldol condensation reactions with an ee value of up to 92%. Researchers have also studied the preparation of chiral COF hybrid materials through in-situ copolymerization, which have high diastereoselectivity and enantioselectivity. Aldol condensation Although the chiral COFs reported for asymmetric aldol condensation reactions have achieved satisfactory results, these catalytic systems are mainly based on organic solvents (DMF, THF) or mixed solvents (DMF / H2O, DMSO / H2O). In contrast, the construction of chiral COFs for asymmetric reactions in pure water systems has largely remained unexplored. In addition, only secondary amine functionalized chiral COFs constructed from proline derivatives have been studied in asymmetric aldol condensation reactions, while the potential of primary amine functionalized chiral COFs constructed from primary amines as catalysts for asymmetric aldol condensation reactions has been largely ignored. Therefore, it is highly desirable to develop primary amine functionalized chiral COF catalysts with high yield and enantioselectivity in water for asymmetric aldol condensation reactions, but it remains a significant challenge. SUMMARY

[0004] To solve the above problems, the application provides a primary amine functionalized chiral covalent organic framework, which has high crystallinity, is porous and has a uniform spherical shape, can effectively catalyze the asymmetric aldol condensation reaction between cyclohexanone and nitrobenzaldehyde in the presence of water, and has a reaction yield and ee value of up to 90% and 85%, respectively, and is the first chiral COF catalyst that has high reaction activity and enantioselectivity when aldol condensation is carried out in pure water without using any organic solvent. The primary amine functionalized chiral covalent organic framework not only opens up a new way for designing primary amine functionalized chiral COFs for asymmetric catalysis, but also lays an important foundation for further exploring green chiral catalysts that can effectively catalyze enantioselective reactions in water.

[0005] To achieve the above purpose, the application provides a primary amine functionalized chiral covalent organic framework, and the structure of the primary amine functionalized chiral covalent organic framework is shown in Formula I:

[0006]

[0007] The application also provides a preparation method of the primary amine functionalized chiral covalent organic framework, which comprises the following steps:

[0008] Preparation of a chiral precursor: amide reaction of D-alanine-Boc and 2,5-dibromoaniline, and Suzuki coupling reaction to obtain a chiral precursor;

[0009] Preparation of a primary amine functionalized chiral covalent organic framework: Schiff base condensation reaction of the chiral precursor and 1,3,5-tris(4-aminophenyl)benzene to obtain a chiral covalent organic framework with a Boc protecting group, and deprotection treatment of the chiral covalent organic framework with the Boc protecting group to obtain the primary amine functionalized chiral covalent organic framework.

[0010] The above preparation method prepares a chiral D-ADP-TAPB-Boc COF with a tert-butoxycarbonyl (Boc) protecting group through Schiff base reaction of an alanine-derived chiral structural unit (D-ADP-Boc) and 1,3,5-tris(4-aminophenyl)benzene (TAPB), and then successfully constructs a chiral D-ADP-TAPB COF containing a primary amine functional group through deprotection treatment of the D-ADP-TAPB-Boc COF.

[0011] In one of the embodiments, the amide reaction comprises the following steps: mixing D-alanine-Boc, 2,5-dibromoaniline and N,N-dicyclohexyl carbodiimide, stirring, and extracting an organic phase to obtain (R)-(1-((2,5-dibromo phenyl) amino)-1-oxopropan-2-yl) tert-butyl carbamate;

[0012] The Suzuki coupling reaction comprises the following steps: mixing (R)-(1-((2,5-dibromophenyl)amino)-1-oxopropan-2-yl) tert-butyl carbamate, 4-formylphenylboronic acid, potassium carbonate, and triphenylphosphine palladium, heating under a protective atmosphere and in mixed solvents, stirring, extracting the organic phase, and obtaining a chiral precursor.

[0013] In one of the embodiments, in the amidation reaction, the molar ratio of D-alanine-Boc, 2,5-dibromoaniline, and N,N-dicyclohexyl carbodiimide is (1-5):(10-20):(10-20), and the stirring time is 25-35 h.

[0014] In the Suzuki coupling reaction, the molar ratio of (R)-(1-((2,5-dibromophenyl)amino)-1-oxopropan-2-yl) tert-butyl carbamate, 4-formylphenylboronic acid, potassium carbonate, and triphenylphosphine palladium is (1.5-2.5):(4-8):(4-8):(0.15-0.19), the mixed solvents comprise 1,4-dioxane and water, the heating temperature is 100℃, and the stirring time is 20-60 h.

[0015] In one of the embodiments, the Schiff base condensation reaction comprises the following steps: dissolving the chiral precursor and 1,3,5-tris(4-aminophenyl)benzene in a solvent, mixing, adding a catalyst, stirring, performing a condensation reaction, and obtaining a chiral covalent organic framework with a Boc protecting group.

[0016] The deprotection treatment comprises the following steps: deprotecting the chiral covalent organic framework with a Boc protecting group under acidic conditions using 1,4-dioxane to obtain a primary amine functionalized chiral covalent organic framework.

[0017] In one of the embodiments, in the Schiff base condensation reaction, the solvent is acetonitrile, and the catalyst is acetic acid; the molar ratio of the catalyst to the chiral precursor is (10-100):1.

[0018] In one of the embodiments, in the Schiff base condensation reaction, the molar ratio of the chiral precursor and 1,3,5-tris(4-aminophenyl)benzene is (1-1.5):1, the condensation reaction temperature is 20-70℃, and the time is 2-5 days.

[0019] In one of the embodiments, in the deprotection treatment, the acidic conditions are provided by hydrochloric acid.

[0020] The application also provides a use of the primary amine functionalized chiral covalent organic framework or the primary amine functionalized chiral covalent organic framework obtained by the preparation method in the preparation of a drug.

[0021] This invention also provides the application of the primary amine functionalized chiral covalent organic framework or the primary amine functionalized chiral covalent organic framework obtained by the preparation method in the preparation of β-hydroxy compounds.

[0022] This invention also provides the application of the primary amine functionalized chiral covalent organic framework or the primary amine functionalized chiral covalent organic framework obtained by the preparation method as a catalyst or in the preparation of catalysts.

[0023] In one embodiment, the application includes catalyzing an aldol condensation reaction, wherein the solvent for the aldol condensation reaction includes an organic solvent and / or water.

[0024] In one embodiment, when the solvent for the aldol condensation reaction includes an organic solvent and water, the volume ratio of the organic solvent to water is 10:(1-35).

[0025] In one embodiment, the solvent for the aldol condensation reaction is water.

[0026] In one embodiment, the additive for the aldol condensation reaction is an acidic additive.

[0027] In one embodiment, the acidic additive includes glycolic acid.

[0028] In one embodiment, the reactants of the aldol condensation reaction include cyclohexanone and nitrobenzaldehyde.

[0029] In one embodiment, the nitrobenzaldehyde includes at least one of 4-nitrobenzaldehyde, 3-nitrobenzaldehyde, and 2-nitrobenzaldehyde.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] This invention discloses a primary amine-functionalized chiral covalent organic framework, its preparation method, and its applications. This primary amine-functionalized chiral covalent organic framework, characterized by high crystallinity, porosity, and uniform spherical shape, can effectively catalyze the asymmetric aldol condensation reaction between cyclohexanone and nitrobenzaldehyde in the presence of water, achieving reaction yields and ee values ​​as high as 90% and 85%, respectively. It is the first chiral COF catalyst exhibiting high reactivity and enantioselectivity in aldol condensation reactions conducted in pure water without the use of any organic solvents. This primary amine-functionalized chiral covalent organic framework not only opens a new avenue for designing primary amine-functionalized chiral COFs for asymmetric catalysis but also lays an important foundation for further exploration of green chiral catalysts capable of effectively catalyzing enantioselective reactions in water. Attached Figure Description

[0032] Figure 1X-ray powder diffraction pattern and structure simulation of D-ADP-TAPB-Boc COF and D-ADP-TAPB COF in Example 2: Figure 1 a is the PXRD pattern of D-ADP-TAPB-Boc COF (red curve, i.e. 3rd line from top to bottom) and the PXRD pattern of the structure refinement in AA packing mode (black curve, i.e. 4th line from top to bottom), the difference curve between experimental and refined values (green curve). Figure 1 b is the PXRD pattern of D-ADP-TAPB-Boc COF in AA packing structure. Figure 1 c is the PXRD pattern of D-ADP-TAPB-Boc COF in AB packing structure. Figure 1 d is the PXRD pattern of D-ADP-TAPB COF (blue curve, i.e. 3rd line from top to bottom) and the PXRD pattern of the structure refinement in AA packing mode (red curve, i.e. 4th line from top to bottom), the difference curve between experimental and refined values (green curve, i.e. 5th line from top to bottom). Figure 1 e is the PXRD pattern of D-ADP-TAPB COF in AA packing structure. Figure 1 f is the PXRD pattern of D-ADP-TAPB COF in AB packing structure; orange bars represent Bragg positions.

[0033] Figure 2 Fourier transform infrared spectra of TAPB, D-ADP-Boc, D-ADP-TAPB-Boc COF and D-ADP-TAPB COF.

[0034] Figure 3 Solid state NMR spectra of D-ADP-TAPB-Boc COF and D-ADP-TAPB COF 13 C cross-polarization magic-angle spinning (CP-MAS) nuclear magnetic resonance spectra of D-ADP-TAPB-Boc COF and D-ADP-TAPB COF Figure 3 a) and TGA curve of D-ADP-TAPB-Boc COF Figure 3 b).

[0035] Figure 4 Scanning electron microscopy images of D-ADP-TAPB-Boc COF Figure 4 a) and D-ADP-TAPB COF Figure 4 b). DETAILED DESCRIPTION

[0036] In order to facilitate the understanding of the present application, a more complete description of the application will be provided below with reference to the relevant drawings. The preferred embodiments of the present application are shown in the drawings. However, the present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thorough and comprehensive.

[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0038] Source:

[0039] 1,3,5-tris(4-aminophenyl)benzene (TAPB) was purchased from Shanghai Kaylin Pharmaceutical Co., Ltd. The analytical column TZ1 (250 x 4.6 mm, 5 pm) was kindly provided by Guangdong Langsum Biochemical Technology Co., Ltd. (Guangzhou, China) with amylose tris-(3,5-dimethylphenylcarbamate) coated silica gel packing. Other materials were of reagent grade and obtained from commercial sources without further purification. Powder X-ray diffraction (PXRD) patterns were collected on a Japanese Science Ultima IV X-ray powder diffractometer using Cu Ka radiation (40 kV, 40 mA, l=1.5406 A) at a scan rate of 0.5 ° / min in the 2-Theta range of 5-40°. The sample was prepared by pressing the powder into a thin wafer. Radiation measurements. Ultra-high performance liquid chromatography-Q-TOF-MS / MS analysis was performed using an Agilent ultra-high performance liquid chromatography-Q-TOF-MS / MS system (Agilent Corp, Santa Clara, USA) equipped with an Agilent G6545Q-TOF-MS / MS system. Nuclear magnetic resonance hydrogen and carbon spectra (1H NMR and 1 H NMR and 13 CNMR) were measured at room temperature with tetramethylsilane as an internal standard on a Bruker Avance NEO 600 MHz nuclear magnetic resonance spectrometer. Solid state 13 Cross-polarization magic-angle spinning (CP-MAS) nuclear magnetic resonance was collected on a Bruker AVANCE III 400 WB MHz nuclear magnetic resonance spectrometer with a MAS rate of 10 kHz. Fourier transform infrared spectroscopy (FT-IR) was performed on a Spectrum Two FT-IR spectrometer (PerkinElmer, Germany) using KBr pellets in the 4000-500 cm -1 range. Thermogravimetric analysis (TGA) was determined using a thermogravimetric analyzer (Netzsch TG 209 F3, Germany) under nitrogen atmosphere with a heating rate of 10 °C / min. Scanning electron microscope (SEM) images were taken on a MIRA3 TESCAN field emission scanning electron microscope. Enantiomeric excess (ee) values were determined by high-performance liquid chromatography on a Shimadzu LC-20AD system equipped with a TZ1 analytical column.

[0040] The reagents, materials and equipment used in this example are commercially available unless otherwise specified. The test methods are conventional test methods in the art unless otherwise specified.

[0041] Example 1

[0042] A primary amine functionalized chiral covalent organic framework and a method of preparing the same.

[0043] In this example, a chiral organic building unit, D-ADP-Boc, was synthesized through an amide reaction of commercially available D-alanine-Boc with 2,5-dibromoaniline and a further Suzuki coupling reaction with a high yield. The chiral precursor, D-ADP-Boc, was subjected to a Schiff base condensation reaction with 1,3,5-tris(4-aminophenyl)benzene (TAPB) in a mixture of acetic acid aqueous solution (12 M) / acetonitrile (1:100 v / v) at 45 °C for 3 days to form a chiral D-ADP-TAPB-Boc COF with a Boc protecting group. After treating the D-ADP-TAPB-Boc COF with 4 M HCl / 1,4-dioxane at room temperature for 2 hours, a deprotection treatment was performed to form a chiral D-ADP-TAPB COF containing a naked primary amine functional group. The reaction scheme is shown below.

[0044]

[0045] The preparation method is specifically as follows:

[0046] I. Preparation of a chiral precursor

[0047] The reaction scheme is shown below.

[0048]

[0049] 1. Amide reaction to prepare (R)-(1-((2,5-dibromo-phenyl)amino)-1-oxopropan-2-yl) carbamic acid tert-butyl ester

[0050] 2,5-dibromoaniline (2.50 g, 10 mmol) and N-tert-butoxycarbonyl-D-alanine (referred to as: D-alanine-Boc, 2.27 g, 2 mmol) were dissolved in DCM (100 mL), and then N,N-dicyclohexylcarbodiimide (DCC, 2.27 g, 11 mmol) was added. After the reaction mixture was stirred at room temperature for 28 hours, water was added and extracted with dichloromethane. The combined organic phase was washed with water, dried over Na2SO4, and then concentrated by rotary evaporation. Column chromatography was performed on silica gel with 4:1 EtOAc / hexane as the eluent to obtain compound 1 in the form of white powder (yield 63%). In this example, the molar ratio of D-alanine-Boc, 2,5-dibromoaniline, and N,N-dicyclohexylcarbodiimide was 2:10:11.

[0051] Compound 1: 1 H NMR (600 MHz, DMSO-d6), δ = 9.35 (s, 1H), 8.05 (s, 1H), 7.63 (d, J = 8.6 Hz, 1H), 7.33 (td, J = 10.2, 8.6, 4.7 Hz, 2H), 4.19 (t, J = 7.2 Hz, 1H), 1.41 (s, 9H), 1.30 (d, J = 7.2 Hz, 3H). 13 C NMR (151 MHz, DMSO-d6), δ = 172.07, 155.28, 137.22, 134.15, 134.13, 128.79, 126.56, 120.40, 114.57, 78.41, 28.08, 17.26. HRMS: m / z calcd for C 14 H 18 Br2N2O3[M-H] - : 420.97, found: 420.95.

[0052] 2. Preparation of (R)-(1-((4,4"-dicarboxy-[1,1':4',1"-terphenyl]-2'-yl)amino)-1- oxopropan-2-yl)carbamic acid tert-butyl ester (i.e. chiral pro, D-ADP-Boc) by Suzuki coupling reaction.

[0053] To a double necked flask was added compound 1 (2 eq, 1.79 g), 4-formylphenylboronic acid (6 eq, 2.25 g), K2CO3(6.0 eq, 2.70 g) and Pd(PPh)3(0.17 eq, 0.50 g). To the flask was added a degassed mixture of 1,4-dioxane / H2O = 4 / 1 (v / v) under argon atmosphere. After stirring the reaction mixture at 100 °C for 24 h, water was added and extracted with dichloromethane. The combined organic phase was washed with water, dried over Na2SO4and concentrated in vacuo. Column chromatography on silica gel with 3:1 EtOAc / hexane as eluent gave D-ADP-Boc as a white powder (83% yield). In this example, the Adam's equivalent ratio of (R)-(1-((2,5-dibromophenyl)amino)-1-oxopropan-2-yl)carbamic acid tert-butyl ester, 4-formylphenylboronic acid, potassium carbonate, triphenylphosphine palladium was 2:6:6:0.17.

[0054] D-ADP-Boc: 1 H NMR (600 MHz, DMSO-d6), δ = 10.09 (s, 2H), 9.48 (s, 1H), 8.04

[0055] (s, 2H), 8.00 (s, 3H), 7.94 (s, 2H), 7.74 (s, 1H), 7.69 (s, 2H), 7.55 (s, 1H), 7.02 (s, 1H), 4.04 (s, 1H), 1.36 (s, 9H), 1.17 (s, 3H). 13 C NMR (151 MHz, DMSO-d6) δ = 193.31, 193.19, 172.50, 155.64, 145.27, 144.75, 139.55, 135.86, 135.57, 135.23, 131.56, 130.76, 130.18, 130.03, 127.80, 124.97, 124.81, 78.60, 50.66, 28.61, 18.01. HRMS: m / z calcd for C 28 H 28 N2 O5[M-H] - : 471.20, found: 471.98.

[0056] II. Preparing a primary amine functionalized chiral covalent organic framework.

[0057] 1. Preparing a chiral covalent organic framework with Boc protecting group (D-ADP-TAPB-Boc COF).

[0058] A mixture of 1,3,5-tris(4-aminophenyl)benzene (TAPB, 14.1 mg, 0.04 mmol), D-ADP-Boc (28.4 mg, 0.06 mmol) and acetonitrile (solvent, ACN, 5 mL) was added into a 10 mL reaction vial, sonicated for 5 minutes, and then 100 μΐ^of acetic acid solution (catalyst, 12 M) was added. The reaction mixture was mixed with a vortex mixer for 10 seconds, and then the reaction vial was placed in a 45 °C reactor for 3 days. The precipitate formed was collected by filtration, washed with anhydrous tetrahydrofuran (THF) and MeOH successively, and dried under vacuum to give yellow solid D-ADP-TAPB-Boc COF (32.0 mg, yield 90%). In this example, the molar ratio of chiral precursor, 1,3,5-tris(4-aminophenyl)benzene, was 1.25: 1.

[0059] 2. Preparing a primary amine functionalized chiral covalent organic framework (D-ADP-TAPB COF).

[0060] Into a 10 mL volumetric flask was added 30.0 mg of D-ADP-TAPB-Boc COF and 1.0 mL of 4 M HC1 / 1,4-dioxane. The mixture was filtered and washed sequentially with THF (1 x 6 mL), MeOH (with 2% Et3N) (2 x 6 mL), H2O (1 x 6 mL), THF (1 x 6 mL), and Et2O (1 x 6 mL). The resulting product was further purified by Soxhlet extraction using anhydrous THF for 24 h and then dried under vacuum at 60 °C to give D-ADP-TAPB COF as a light yellow powder (25.6 mg, 80% yield).

[0061] Example 2

[0062] The primary amine-functionalized chiral covalent organic frameworks prepared in Example 1 were tested.

[0063] I. The crystal structures of chiral D-ADP-TAPB-Boc and D-ADP-TAPB COFs were characterized by powder X-ray diffraction (PXRD) analysis using Cu Ka radiation.

[0064] As shown in Figure 1 a (red curve), D-ADP-TAPB-Boc COF exhibited a distinct diffraction peak at 2.05°, which corresponds to the (100) plane. Similarly, after removal of the Boc protecting group, a strong diffraction peak at 2.05° was also observed for D-ADP-TAPB COF Figure 1 d (red curve), indicating that D-ADP-TAPB-Boc COF and D-ADP-TAPB COF have similar crystal structures. The simulated PXRD patterns of D-ADP-TAPB-Boc COF Figure 1 b-1c) and D-ADP-TAPB COF Figure 1 e-1f) modeled two possible structures with different packing modes, i.e., AA and AB packing modes. As shown in Figure 1 a and Figure 1 d, the experimental PXRD patterns of D-ADP-TAPB-Boc and D-ADP-TAPB COF both matched well with the corresponding calculated PXRD patterns generated from the AA packing model.

[0065] II. Chiral D-ADP-TAPB-Boc COF and D-ADP-TAPB COF were further verified by Fourier transform infrared spectroscopy (FT-IR).

[0066] The Fourier transform infrared spectra of these chiral COFs showed amino vibrations (3200-3500 cm -1 ) and aldehyde group vibrations (1700 cm -1) and at ~1624 cm -1 The presence of a characteristic C=N stretch vibration indicates the successful construction of the imine bond Figure 2 Further comparison of the Fourier transform infrared spectra of D-ADP-TAPB-Boc COF and D-ADP-TAPB COF shows that the spectra of the two are essentially the same, indicating that the main framework of D-ADP-TAPB COF is not damaged after removing the Boc group. 13 Cross-polarization magic-angle spinning (CP / MAS) nuclear magnetic resonance analysis provides more detailed information Figure 3 a). 13 The C CP / MAS NMR spectrum shows that both chiral D-ADP-TAPB-Boc and D-ADP-TAPB COF have a signal peak of imine carbon at ~160 ppm, again proving the formation of the C=N bond. The peaks at 171, 155, 80, 51, 28, and 18 ppm are likely to be carbon atoms of the chiral D-alanine-Boc molecule. In addition, D-ADP-TAPB COF has no chemical shift at 28, 80, and 155 ppm, indicating that the Boc protecting group has been successfully removed. Thermogravimetric analysis (TGA) shows that the two chiral COFs obtained have high thermal stability, up to 375°C Figure 3 b) under nitrogen environment

[0067] III. Scanning electron microscope (SEM) images show that D-ADP-TAPB-Boc COF is uniformly spherical with an average diameter of about 2.2 μm, as shown in Figure 4 a. After deprotection of the Boc group, the morphology of the generated D-ADP-TAPB COF remains unchanged Figure 4 b).

[0068] Example 3

[0069] Asymmetric catalysis of the primary amine functionalized chiral covalent organic frameworks prepared in Example 1.

[0070] The aldol condensation reaction is one of the important asymmetric catalytic reactions, which can generate β-hydroxy compounds, which are widely used for the synthesis of natural products and pharmaceuticals. In this regard, the catalytic performance of primary amine functionalized chiral D-ADP-TAPB COF in the direct aldol condensation reaction of cyclohexanone and nitrobenzaldehyde was studied (as shown in Table 1). The present application first studied the catalytic activity of D-ADP-TAPB COF in the aldol condensation reaction of cyclohexanone and p-nitrobenzaldehyde in different solvents.

[0071] As shown in Table 1, when using pure organic solvents such as DCM, PhMe (toluene), DOX, DMF, MTBE (methyl tert-butyl ether), etc., the aldol condensation reaction hardly proceeds (entries 1-7 in Table 1). In sharp contrast, after adding a small amount of water to the above-mentioned organic solvents, both the catalytic activity (yield of 30%-87%) and the enantioselectivity (ee value of 60%-69%) are greatly improved. Next, the effect of acidic and basic additives on the asymmetric aldol condensation reaction was studied. It was found that using glycolic acid as an additive is more effective for catalyzing the asymmetric aldol condensation reaction. Therefore, considering the reaction yield and enantioselectivity, glycolic acid and DMF / H2O were used as the additive and the reaction solvent, respectively. To further demonstrate the importance of water, the effect of the amount of water was also evaluated, and the results are summarized in Table 1. Notably, as the amount of water in the solvent mixture increases, the enantioselectivity and diastereoselectivity increase from 62% to 84% and 1:2.7 to 1:4.9, respectively (entries 8-11 in Table 1). Interestingly, when pure water is used as the solvent (entry 12 in Table 1), the reaction yield and enantiomeric excess (ee) value are as high as 90% and 85%, respectively.

[0072] These results indicate that water is indispensable for high reactivity and high enantioselectivity. The present inventors compared the asymmetric catalytic performance of the primary amine functionalized chiral D-ADP-TAPB COF with other chiral COFs and metal-organic frameworks (MOFs) catalysts previously reported for the aldol condensation reaction. The asymmetric catalytic efficiency of chiral D-ADP-TAPB COF for the aldol condensation reaction of 4-nitrobenzaldehyde and cyclohexanone in water is superior to most of the reported chiral COFs, including DMTA-TPB1 / 2', DMTA-TPB1 / 3' and L-HPP-TZ-NH, and chiral MOFs, such as CMIL-1, Zn-MOF1, Ap@3, RR-DUT-136-amine and DUT-32-NHPro, making it a promising chiral catalyst for the efficient asymmetric catalysis of aldol condensation reactions.

[0073] More importantly, the reported chiral COFs for asymmetric reactions are mainly based on organic solvents (such as DMF, THF, etc.) or mixed solvents (DMF / H2O, DMSO / H2O). However, the construction of chiral COF for asymmetric aldol condensation reaction in pure water system has not been reported yet. The prepared primary amine functionalized chiral D-ADP-TAPB COF is the first chiral COF catalyst for aldol condensation reaction in pure water without using any organic solvent, which has very high reaction activity and enantioselectivity. After the optimal reaction conditions, cyclohexanone was reacted with 3-nitrobenzaldehyde and 2-nitrobenzaldehyde, respectively, to expand the reaction range of aldol condensation reaction, and the results are shown in Table 1 (entries 13-14). Under the catalysis of chiral D-ADP-TAPB COF, aldol condensation reaction of cyclohexanone with 3-nitrobenzaldehyde occurred to obtain the desired aldol condensation product with a yield of 62% and an ee value of 89% (entry 13 in Table 1).

[0074] In addition, when the substrate is replaced by 2-nitrobenzaldehyde, the chiral D-ADP-TAPB COF catalyst can generate the target aldol condensation product with an ee value and a dr value as high as 90% and 1:15.0 (entry 14 in Table 1), respectively, while the reaction yield is only 25%, which may be related to the steric hindrance of the ortho-nitro group.

[0075] As a heterogeneous catalyst, the recyclability of chiral D-ADP-TAPB COF was also investigated by the inventors. After each reaction, the COF solid catalyst was easily recovered by centrifugation and washed with MeOH and dichloromethane, and then dried under vacuum at 60°C for the next catalytic run under the same reaction conditions. Even after 3 catalytic cycles, the reaction yield and ee value were as high as 80% and 85%, respectively. The relatively small decrease in conversion and ee value after 3 catalytic cycles indicates that the chiral COF catalyst has a significant effect on recycling.

[0076] Table 1 Asymmetric aldol condensation reaction catalyzed by primary amine functionalized chiral D-ADP-TAPB-COF

[0077]

[0078]

[0079] Note: in Table 1 a Reaction conditions: aldehyde (0.10 mmol), ketone (0.3 mL), D-ADP-TAPB COF (0.03 mmol), glycolic acid (0.03 mmol) and solvent (1 mL), reaction at room temperature for 3 days. b Isolated yield. c Determined by chiral HPLC. d1 HNMR spectrum was determined. e DMF / H2O (1 mL / 0.1 mL). f DMF / H2O (1 mL / 0.3 mL). g DMF / H2O (0.5 mL / 1 mL). h DMF / H2O (0.3 mL / 1 mL).

[0080] In summary, the present inventors developed a primary amine functionalized chiral COF catalyst for asymmetric aldol condensation reaction, which exhibits excellent reaction yield and enantioselectivity in water without adding any organic solvent. It should be pointed out that this is the first chiral COF catalyst with high reaction activity and enantiomeric selectivity when performing aldol condensation reaction in water. The research results of the present application not only open up a new way for designing primary amine functionalized chiral COF for asymmetric catalysis, but also lay an important foundation for developing green chiral catalysts that can effectively catalyze enantioselective reactions in water.

[0081] Each of the technical features of the above-described embodiments can be combined arbitrarily, and in order to make the description simple, each of the technical features in the above-described embodiments is not described in all possible combinations, however, as long as the combination of the technical features does not exist contradictory, it should be considered as the scope of the present disclosure.

[0082] The above-described embodiments only express several embodiments of the present application, and the description is more specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be pointed out that for ordinary skilled in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which are all within the scope of the present application. Therefore, the scope of protection of the present application should be subject to the appended claims.

Claims

1. A primary amine functionalized chiral covalent organic framework, characterized in that, The structure of the primary amine functionalized chiral functional organic framework is shown as formula I:

2. The method of claim 1, wherein the preparation of the primary amine functionalized chiral covalent organic frameworks is characterized by, The method comprises the following steps: Preparation of a chiral precursor: D-alanine-Boc is subjected to an amidation reaction with 2,5-dibromoaniline, and a Suzuki coupling reaction to obtain a chiral precursor; Preparation of a primary amine functionalized chiral covalent organic framework: the chiral precursor is subjected to a Schiff base condensation reaction with 1,3,5-tris(4-aminophenyl)benzene to obtain a chiral covalent organic framework with a Boc protecting group, and the chiral covalent organic framework with the Boc protecting group is subjected to a deprotection treatment to obtain the primary amine functionalized chiral covalent organic framework.

3. The production method according to claim 2, characterized by, The amidation reaction comprises the following steps: D-alanine-Boc, 2,5-dibromoaniline and N,N-dicyclohexylcarbodiimide are mixed, stirred, and the organic phase is extracted to obtain (R)-(1-((2,5-dibromophenyl)amino)-1-oxopropan-2-yl)carbamic acid tert-butyl ester; The Suzuki coupling reaction comprises the following steps: (R)-(1-((2,5-dibromophenyl)amino)-1-oxopropan-2-yl)carbamic acid tert-butyl ester, 4-formylphenylboronic acid, potassium carbonate and triphenylphosphine palladium are mixed, heated under a protective atmosphere and mixed solvents, stirred, the organic phase is extracted to obtain the chiral precursor.

4. The preparation method according to claim 2, characterized in that, The Schiff base condensation reaction comprises the following steps: the chiral precursor and 1,3,5-tris(4-aminophenyl)benzene are dissolved in a solvent, mixed, a catalyst is added, stirred, and a condensation reaction is performed, and the precipitate is obtained to obtain the chiral covalent organic framework with the Boc protecting group; The deprotection treatment comprises the following steps: the chiral covalent organic framework with the Boc protecting group is subjected to deprotection under acidic conditions using 1,4-dioxane to obtain the primary amine functionalized chiral covalent organic framework.

5. Use of the primary amine functionalized chiral covalent organic framework of claim 1 or the primary amine functionalized chiral covalent organic framework obtained by the preparation method of any one of claims 2-4 in preparation of a beta-hydroxyl compound.

6. Use of the primary amine functionalized chiral covalent organic framework of claim 1 or the primary amine functionalized chiral covalent organic framework obtained by the preparation method of any one of claims 2-4 as a catalyst or in preparation of a catalyst.

7. Use according to claim 6, characterized in that, The application comprises catalyzing an aldol condensation reaction, and a solvent of the aldol condensation reaction comprises an organic solvent and / or water.

8. Use according to claim 7, characterized in that, An additive of the aldol condensation reaction is an acidic additive.

9. Use according to any one of claims 7-8, characterized in that, Reactants of the aldol condensation reaction comprise cyclohexanone and nitrobenzaldehyde.

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