MOF-Cu (II) / CMC composite material and preparation method and application thereof

Abstract

The invention belongs to the technical field of chiral boron compound synthesis, and particularly relates to an MOF-Cu (II) / CMC composite material and a preparation method and application thereof. The preparation method of the MOF-Cu (II) / CMC composite material comprises the following steps: dropwise adding an aqueous solution of sodium carboxymethyl cellulose into an aqueous solution of bivalent copper salt, carrying out solid-liquid separation, mixing obtained composite microspheres and an organic solution of trimesic acid, heating, and carrying out solid-liquid separation to obtain the MOF-Cu (II) / CMC composite material. The composite material is applied to an asymmetric chiral boron addition reaction, the reaction is carried out at room temperature, the conditions are mild, the use range of a substrate is wide, and the yield and enantioselectivity are high. According to the method, the chiral organic boride can be synthesized in a simple component solvent, an efficient new method is provided for preparation of drug molecules and active intermediates, the substrate range of preparation of the chiral organic boride is widened, and the method has important theoretical and practical significance.

Description

Technical Field

[0001] The invention belongs to the technical field of chiral boron compound synthesis, and specifically relates to a MOF-Cu(II) / CMC composite material and a preparation method and application thereof. Background Art

[0002] Chiral characteristics are key factors in the efficacy and safety of many therapeutic agents. Currently, about 57% of marketed drugs are chiral drugs, and about 99% of purified natural products are chiral compounds. Functional microorganisms and biocatalysts derived from them have great potential to bioconvert synthetic chemicals into drugs with high enantio-, chemo-, and regio-selectivity. Biocatalysis is becoming a key component in the toolbox of medicinal chemists. In fact, intermediates of many important therapeutic agents, such as sitagliptin, pregabalin, raglitaza, paclitaxel, epothilone, abacavir, atorvastatin, rosuvastatin, and omapastatin, have been successfully synthesized by biocatalysis. Chiral boron compounds are important intermediates for the synthesis of chiral drugs, and their chiral CB bonds can undergo a series of transformations through oxidation reactions, Suzuki-Miyaura coupling reactions, Petasis reactions, etc. to obtain chiral CO bonds, chiral CN bonds, and chiral CC bonds.

[0003] In the literature (Nanomaterials 2018, 8, 326; doi: 10.3390 / nano8050326), copper ions form coordination bonds with amino groups, hydroxyl groups and other groups on the polymer chain, and the conversion of α, β-unsaturated ketone compounds to β-boronate substituted carbonyl compounds is achieved by using divalent copper (1 mol%, relative to the amount of template reaction substrate) as catalysis. This work uses chalcone as a template substrate, uses 1.2 equivalents of biboronic acid pinacol ester reagent, and uses a mixed solution of acetone and water as a solvent. Under the condition of reacting at room temperature, β-boronate substituted carbonyl compounds are obtained. However, the catalyst has low enantioselectivity for chiral boron compounds. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a MOF-Cu(II) / CMC composite material and a preparation method and application thereof. The MOF-Cu(II) / CMC composite material prepared by the present invention has high enantioselectivity for chiral boron compounds.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a method for preparing a MOF-Cu(II) / CMC composite material, comprising the following steps:

[0007] The aqueous solution of sodium carboxymethyl cellulose is added dropwise to the aqueous solution of divalent copper salt to separate the solid and liquid to obtain composite microbeads;

[0008] The composite microbeads and an organic solution of trimesic acid are mixed, heated, and solid-liquid separated to obtain a MOF-Cu(II) / CMC composite material.

[0009] Preferably, the concentration of the aqueous solution of sodium carboxymethyl cellulose is 1.5 to 3 g / 100 mL.

[0010] Preferably, the divalent copper salt includes one or more of copper acetate, copper chloride, copper bromide and copper sulfate.

[0011] Preferably, the concentration of the aqueous solution of the divalent copper salt is 3-8 wt %.

[0012] Preferably, the volume ratio of the aqueous solution of the divalent copper salt to the aqueous solution of sodium carboxymethyl cellulose is 1:1.

[0013] Preferably, the concentration of the organic solution of trimesic acid is 0.09-0.11 mmol / mL.

[0014] Preferably, the organic solvent in the organic solution of trimesic acid is N,N-dimethylformamide.

[0015] The present invention also provides a MOF-Cu(II) / CMC composite material obtained by the preparation method described in the above technical solution, wherein the copper content in the MOFS-Cu(II) / CMC composite material is 0.3-1 mmol / g.

[0016] The present invention also provides the use of the MOF-Cu(II) / CMC composite material described in the above technical solution in the catalytic synthesis of asymmetric chiral boron compounds.

[0017] Preferably, the use of the synthesis of non-chiral boron compounds comprises the following steps:

[0018] An α,β-unsaturated ketone compound, biboric acid pinacol ester, a catalytic material, a chiral ligand and a solvent are mixed to perform an asymmetric chiral boron addition reaction to obtain an asymmetric chiral boron compound; the catalytic material is the MOF-Cu(II) / CMC composite material described in the above technical solution; and the solvent is a mixture of toluene and water;

[0019] The structural formula of the α,β-unsaturated ketone compound is shown in Formula 1, and the structural formula of the chiral ligand is shown in Formula 2:

[0020]

[0021] In Formula 1, R1 is phenyl, substituted phenyl or naphthyl, and R2 is phenyl or substituted phenyl.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The invention provides a preparation method of a MOF-Cu(II) / CMC composite material, comprising the following steps: dripping an aqueous solution of sodium carboxymethyl cellulose into an aqueous solution of a divalent copper salt, performing solid-liquid separation, and obtaining composite microbeads; and mixing the composite microbeads and an organic solution of trimesic acid, heating, and performing solid-liquid separation, and obtaining the MOF-Cu(II) / CMC composite material.

[0024] The present invention uses raw material sodium carboxymethyl cellulose to provide a carrier for loading copper, and prepares copper into a metal organic framework (MOF) material. The obtained MOF-Cu(II) / CMC composite material is a nanoporous material, and copper ions are evenly distributed on the biomass-based polymer material, with a size between 10 and 50 nm. It has a good pore structure and a large specific surface area. The average pore diameter of the MOF-Cu(II) / CMC composite material prepared in the embodiment is 22 nm, and the cumulative pore volume is 0.1412 cm 3 / g, specific surface area is 27.53m 2 / g, rigid pores provide space confinement for active metal nanoparticles, which can prevent aggregation and leaching; it has good biocompatibility and high catalytic activity. The (MOFS-Cu(II) / CMC) composite material is used to catalyze the synthesis of chiral boron compounds. No strong base is required in the reaction system. It can react in toluene and mixed solvents. It has high catalytic efficiency and good enantioselectivity. The composite catalytic material is highly stable and recyclable. The synthesis method is green and environmentally friendly, meeting the concept of sustainable industrial production.

[0025] Moreover, the preparation of chiral boron compounds can be carried out at room temperature, the reaction conditions are mild, the operation is simple and easy, and the application is wide. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0027] Figure 1 is the H NMR spectrum of the target product in Application Example 1;

[0028] Figure 2 is the NMR carbon spectrum of the target product in Application Example 1;

[0029] Figure 3 The HPLC spectrum of the racemate of the target product in Application Example 1;

[0030] Figure 4 is the HPLC spectrum of the target product in Application Example 1;

[0031] Figure 5 is the H NMR spectrum of the target product in Application Example 2;

[0032] Figure 6 is the NMR carbon spectrum of the target product in Application Example 2;

[0033] Figure 7 The HPLC spectrum of the racemate of the target product in Application Example 2;

[0034] Figure 8 is the HPLC spectrum of the target product in Application Example 2;

[0035] Fig. 9 is the H NMR spectrum of the target product in Application Example 3;

[0036] Fig.10 is the NMR carbon spectrum of the target product in Application Example 3;

[0037] Fig.11 The HPLC spectrum of the racemate of the target product in Application Example 3;

[0038] Fig.12 The HPLC spectrum of the target product in Application Example 3 is shown in FIG. DETAILED DESCRIPTION

[0039] The present invention provides a method for preparing a MOF-Cu(II) / CMC composite material, comprising the following steps:

[0040] The aqueous solution of sodium carboxymethyl cellulose is added dropwise to the aqueous solution of divalent copper salt to separate the solid and liquid to obtain composite microbeads;

[0041] The composite microbeads and an organic solution of trimesic acid are mixed, heated, and solid-liquid separated to obtain a MOF-Cu(II) / CMC composite material.

[0042] In the present invention, unless otherwise specified, the materials and equipment used are commercially available products in the art.

[0043] The invention drips the aqueous solution of sodium carboxymethyl cellulose into the aqueous solution of divalent copper salt, separates the solid and the liquid, and obtains the composite microbeads.

[0044] In the present invention, the concentration of the aqueous solution of sodium carboxymethyl cellulose is preferably 1.5-3 g / 100 mL, more preferably 2 g / 100 mL. The aqueous solution of sodium carboxymethyl cellulose is a clear and flowable solution, preferably obtained by stirring sodium carboxymethyl cellulose and water at room temperature, and the stirring time is preferably overnight. The sodium carboxymethyl cellulose provides a carrier for loading copper.

[0045] In the present invention, the divalent copper salt in the aqueous solution of the divalent copper salt preferably includes one or more of copper acetate, copper chloride, copper bromide and copper sulfate, more preferably copper sulfate, and the copper sulfate is preferably anhydrous copper sulfate.

[0046] In the present invention, the concentration of the aqueous solution of the divalent copper salt is preferably 3-8wt%, more preferably 5wt%. The volume ratio of the aqueous solution of the divalent copper salt to the aqueous solution of sodium carboxymethyl cellulose is preferably 1:1. The aqueous solution of the divalent copper salt contains excess copper ions, which are subsequently removed.

[0047] The present invention has no special requirements for the rate of the dripping. Preferably, stirring is further included after the dripping, and the stirring time is preferably 12 hours. The function of the stirring is to prevent the aggregation of the composite microspheres. During the dripping and stirring process, the sodium carboxymethyl cellulose loads Cu ions by chelation, and the divalent copper salt and the sodium carboxymethyl cellulose form a network structure, the copper ions are wrapped inside the molecules, and the polymers are entangled with each other to form composite microspheres with porous interiors and spherical exteriors.

[0048] In the present invention, the solid-liquid separation preferably includes washing, and the washing preferably includes water washing and organic solvent washing. The water washing is used to remove free Cu(II) ions. The organic solvent washing is preferably immersed in methanol (MeOH) and N,N-dimethylformamide (DMF) in sequence. The immersion time is preferably 15 minutes. The organic solvent washing is used to remove moisture inside the composite microbeads.

[0049] After obtaining the composite microbeads, the present invention mixes the composite microbeads with an organic solution of trimesic acid, heats them, and performs solid-liquid separation to obtain a MOF-Cu(II) / CMC composite material.

[0050] In the present invention, the concentration of the organic solution of trimesic acid is preferably 0.09 to 0.11 mmol / mL, more preferably 0.1 mmol / mL.

[0051] In the present invention, the organic solvent in the organic solution of trimesic acid is preferably N,N-dimethylformamide (DMF).

[0052] In the present invention, the composite microbeads and the organic solution of trimesic acid are preferably mixed by stirring, the stirring temperature is preferably 80° C., the time is preferably 1 to 3 hours, and the speed is preferably 100 r / min.

[0053] In the present invention, the heating temperature is preferably 100° C., and the heating time is preferably 12 hours. During the heating process, the metallic copper forms a metal organic framework (MOFs).

[0054] In the present invention, the solid-liquid separation method is preferably filtration. After the solid-liquid separation, it is preferred to further include washing and drying, and the washing includes rinsing and soaking washing. The rinsing preferably includes rinsing with N,N-dimethylformamide (DMF) and ethanol (EtOH) in sequence, and the rinsing is to wash away impurities; the reagent for the soaking wash is preferably dichloromethane, and the soaking wash is preferably replaced with a fresh solvent every 6 hours, and replaced 3 times. The soaking wash reagent of the present invention has good compatibility with other organic solvents, can better remove other organic solvents on the surface, and is highly volatile and easy to remove by itself. The drying temperature is preferably 90°C, and the time is preferably overnight.

[0055] The present invention also provides a MOF-Cu(II) / CMC composite material obtained by the preparation method described in the above technical solution, wherein the copper content in the MOFS-Cu(II) / CMC composite material is 0.3-1 mmol / g.

[0056] In the present invention, the copper content of the MOFS-Cu(II) / CMC composite material is preferably 0.53 mmol / g. The MOFS-Cu(II) / CMC composite material is a blue spherical particle with a diameter of about 1 mm, and the surface of the bead is evenly covered with a large amount of HKUST-1 with a typical octahedral morphology, and the average particle size is 500nm to 2μm.

[0057] The present invention also provides the use of the MOF-Cu(II) / CMC composite material described in the above technical solution in the catalytic synthesis of asymmetric chiral boron compounds.

[0058] In the present invention, the use of synthesizing non-chiral boron compounds preferably comprises the following steps:

[0059] An α,β-unsaturated ketone compound, biboric acid pinacol ester, a catalytic material, a chiral ligand and a solvent are mixed to perform an asymmetric chiral boron addition reaction to obtain an asymmetric chiral boron compound; the catalytic material is the MOF-Cu(II) / CMC composite material described in the above technical solution; and the solvent is a mixture of toluene and water;

[0060] The structural formula of the α,β-unsaturated ketone compound is shown in Formula 1, and the structural formula of the chiral ligand is shown in Formula 2:

[0061]

[0062] In Formula 1, R1 is phenyl, substituted phenyl or naphthyl, and R2 is phenyl or substituted phenyl.

[0063] In the present invention, the substituted phenyl group in R1 preferably includes: p-methylphenyl, o-methylphenyl, p-chlorophenyl, o-chlorophenyl, m-chlorophenyl or p-bromophenyl, and the substituted phenyl group in R2 preferably includes: p-methoxyphenyl, p-chlorophenyl, o-chlorophenyl, m-chlorophenyl or p-bromophenyl.

[0064] In the present invention, the α,β-unsaturated ketone compound preferably includes chalcone, 3-naphthyl-1-phenylpropyl-2-en-1-one or 4-chlorophenyl-1-phenylpropyl-2-en-1-one.

[0065] In the present invention, MOF-Cu(II) / CMC composite material is Cu 2+ Based on the above, the molar ratio of the α,β-unsaturated ketone compound, the bipyraclostrobin, the catalytic material and the chiral ligand is preferably 1:1.2:0.01-0.05:0.012-0.06, more preferably 1:1.2:0.01:0.012 or 1:1.2:0.015:0.02.

[0066] In the present invention, the volume ratio of toluene to water in the mixed solution of toluene and water is preferably 7 to 11: 1, more preferably 9: 1. The ratio of the α, β-unsaturated ketone compound to the mixed system is preferably 0.2 mmol: 2 mL, and the mixed system is a system obtained by mixing the α, β-unsaturated ketone compound, biboric acid pinacol ester, catalytic material, chiral ligand and solvent.

[0067] In the present invention, the usage ratio of the MOFS-Cu(II) / CMC composite material to the solvent is preferably 8-64 mg:10 mL.

[0068] In the present invention, the temperature of the asymmetric chiral boron addition reaction is preferably room temperature, and the time is preferably 6 to 24 hours, more preferably 10 to 20 hours, and more preferably 12 hours. The asymmetric chiral boron addition reaction is preferably carried out under stirring conditions, and the present invention has no special requirements for the stirring speed. The reaction formula of the asymmetric chiral boron addition reaction is as follows:

[0069]

[0070] In the present invention, the asymmetric chiral boron addition reaction preferably further comprises:

[0071] Solid-liquid separation to obtain solid phase and liquid phase;

[0072] The liquid phase is subjected to a first extraction, the organic phase is dried with a desiccant, and the solvent is removed to obtain a crude product of an asymmetric chiral boron compound; the crude product is subjected to a first column chromatography purification to obtain a chiral organic boron compound; or the crude product, sodium borate tetrahydrate, tetrahydrofuran and water are mixed to undergo an oxidation reaction, followed by a second extraction and a second column chromatography purification to obtain a chiral hydroxy compound;

[0073] The solid phase is washed and dried to obtain a recovered (MOFS-Cu(II) / CMC) composite material.

[0074] In the present invention, the solid-liquid separation method is preferably centrifugation and filtration.

[0075] In the present invention, the reagent used in the first extraction is preferably ethyl acetate, the desiccant is preferably Na2SO4, and the method of removing the solvent is preferably rotary evaporation; the eluent for the first column chromatography purification is preferably a mixture of ethyl acetate and petroleum ether, and the volume ratio of ethyl acetate to petroleum ether in the mixture is preferably 1:4 to 9.

[0076] In the present invention, the dosage ratio of the α,β-unsaturated ketone compound, sodium borate tetrahydrate, tetrahydrofuran and water is preferably 0.2mmol:244mg:3mL:2mL. The temperature of the oxidation reaction is preferably room temperature, and the time is preferably 4 to 8h.

[0077] In the present invention, the reagent used in the second extraction is preferably ethyl acetate, and the eluent for the second column chromatography purification is preferably a mixture of ethyl acetate and petroleum ether. The volume ratio of ethyl acetate to petroleum ether in the mixture is preferably 1:4-9.

[0078] The present invention has no special requirements for the solid phase washing and drying methods, and the recovered (MOFS-Cu(II) / CMC) composite material can be recycled. After the (MOFS-Cu(II) / CMC) composite material of the present invention is recycled, the yield and enantioselectivity of the chiral boron-based compound are still relatively high.

[0079] The MOFS-Cu(II) / CMC composite material of the present invention can be applied to a mixed solvent of toluene and water when catalyzing the synthesis of chiral boron compounds, avoiding the use of alkali, being green and environmentally friendly, and having potential industrial application value; having high catalytic efficiency and good enantioselectivity; and being applicable to the chiral boron addition reaction of α,β-unsaturated ketone compounds containing different substituent groups, and having a wide range of substrate applications. Moreover, the preparation of chiral boron compounds can be carried out at room temperature, the reaction conditions are mild, the operation is simple and easy, and the application is wide.

[0080] In order to further illustrate the present invention, the MOF-Cu(II) / CMC composite material provided by the present invention and its preparation method and application are described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0081] Example 1

[0082] The (MOFS-Cu(II) / CMC) catalytic material was prepared by the following method:

[0083] P1. Dissolve 2 g of sodium carboxymethyl cellulose (CMC-Na) in 100 mL of deionized water and stir overnight at room temperature to obtain a clear, flowable solution.

[0084] P2. Use a syringe to drop the above solution into an aqueous solution containing a divalent copper salt (anhydrous copper sulfate, 5wt%, 100mL), and continue to gently stir the mixture at room temperature for 12h to prevent the composite microbeads from aggregating;

[0085] P3, washing the filtered composite microbeads with deionized water to remove free Cu(II) ions, and then immersing the microbeads in MeOH and DMF for 15 minutes each to remove moisture inside the composite microbeads;

[0086] P4, adding the obtained composite microbeads to a pre-prepared 0.1 mmol / mL solution of trimesic acid (solvent: DMF, volume: 30 mL), gently stirring at 80°C for 1 h, and then heating the mixture at 100°C for 12 h;

[0087] P5. Collect the obtained composite microbeads by filtration, and then rinse with DMF and EtOH to remove impurities. Then, soak the composite microbeads in 50 mL of dichloromethane, replace the fresh solvent every 6 hours, and replace it three times. Finally, after vacuum drying at 90°C overnight, blue composite microbeads are obtained, which are (MOFS-Cu(II) / CMC) catalytic materials.

[0088] According to ICP measurement, the copper content in the (MOFS-Cu(II) / CMC) catalytic material is 0.53 mmol / g.

[0089] Application Example 1

[0090] The (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 is applied to synthesize chiral boron-based compounds using benzylideneacetophenone as a substrate, comprising the following steps:

[0091] Step (1): adding chalcone, bipyraclostrobin, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand into a mixed solvent of toluene / distilled water = 9:1 (v / v), and mixing and stirring at room temperature for 12 hours, wherein the molar ratio of chalcone, bipyraclostrobin, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand is 1:1.2:1.5%:2%, wherein the (MOFS-Cu(II) / CMC) catalytic material (Cu 2+ As a benchmark), the percentage of Bolm ligand is calculated based on the amount of chalcone; chalcone is calculated as 0.2mmol, and each substance is mixed in proportion and fixed to 2mL with a mixed solvent; the chemical reaction equation is as follows:

[0092]

[0093] In the reaction equation, B2pin2 is biboric acid pinacol ester, and its structural formula is Chiral Ligand is a chiral ligand (Bolm ligand), with the structural formula

[0094] Step (2): After the reaction is completed, the obtained mixed system is centrifuged and filtered, and the obtained liquid phase is extracted with ethyl acetate, dried with anhydrous Na2SO4 and rotary evaporated to obtain a crude boride product. The crude boride product (0.2mmol α, β-unsaturated ketone compound) is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244mg), tetrahydrofuran (3mL), and deionized water (2mL) are added in sequence to react at room temperature for 4h, followed by extraction with ethyl acetate (adding a small amount of saturated brine), drying with anhydrous sodium sulfate, and thin layer chromatography to obtain a chiral hydroxy compound. The chemical reaction equation is as follows:

[0095]

[0096] The filtered precipitate is washed and dried to obtain the recovered (MOFS-Cu(II) / CMC) catalytic material for the next recycling.

[0097] Step (1) The (MOFS-Cu(II) / CMC) catalytic material is applied to the chiral boron addition reaction of chalcone, and the yield and enantioselectivity of the target product (chiral boron-based compound) are 96% and 95%, respectively.

[0098] The target product has a hydrogen NMR spectrum, a carbon NMR spectrum and a HPLC spectrum. Figures 1 to 4 As shown, Figure 3 is the HPLC spectrum of the target product racemate, Figure 4 The HPLC spectrum of the synthesized target product is as follows:

[0099] 1 H NMR(400MHz,Chloroform-d)δ8.01-7.89(m,2H),7.59(t,J=7.4Hz,1H),7.46(dd,J=13.0,7.4Hz ,4H),7.39(t,J=7.5Hz,2H),7.31(t,J=7.3Hz,1H),5.36(t,J=6.1Hz,1H),3.38(d,J=6.0Hz,2H).

[0100] 13 C NMR (101MHz, CDCl3) δ200.36,143.01,136.62,133.82,128.85,128.72,128.29,127.83,125.88,70.15,47.52.

[0101] HPLC (Dialcel Chiralcel OD-H, n hexane / i PrOH=90 / 10, flow rate 1.0mL / min);

[0102] t R =12.1min(S,minor),t R =13.1min(R,major).

[0103] The (MOFS-Cu(II) / CMC) catalytic material was recycled 4 times and applied to the chiral boron addition reaction of chalcone for the 5th time. The yield and enantioselectivity of the target product (chiral boron-based compound) were 93% and 94%, respectively.

[0104] Application Example 2

[0105] The (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 is applied to synthesize chiral boron-based compounds using 3-naphthyl-1-phenylpropyl-2-ene-1-one as a substrate, comprising the following steps:

[0106] Step (1): 3-naphthyl-1-phenylpropyl-2-en-1-one, bipyraclostrobin, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand are added to a mixed solvent of toluene / distilled water = 9:1 (v / v), and mixed and stirred at room temperature for 12 hours, wherein the molar ratio of the four substances of 3-naphthyl-1-phenylpropyl-2-en-1-one, bipyraclostrobin, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand is 1:1.2:1.5%:2%; the chemical reaction equation is as follows:

[0107]

[0108] Step (2): After the reaction is completed, the obtained mixed system is centrifuged and filtered, and the obtained liquid phase is extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain a crude boride product. The crude boride product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), tetrahydrofuran (3 mL), and deionized water (2 mL) are added in sequence to react at room temperature for 4 hours, and then extracted, dried, and thin-layer chromatography to obtain a chiral hydroxy compound. The chemical reaction equation is as follows:

[0109]

[0110] The filtered precipitate is washed and dried to obtain the recovered (MOFS-Cu(II) / CMC) catalytic material for the next recycling.

[0111] Step (1) The (MOFS-Cu(II) / CMC) catalytic material is applied to the chiral boron addition reaction of 3-naphthyl-1-phenylpropyl-2-ene-1-one, and the yield and enantioselectivity of the target product (chiral boron-based compound) are 99% and 97%, respectively.

[0112] The target product has a hydrogen NMR spectrum, a carbon NMR spectrum and a HPLC spectrum. Figures 5 to 8 As shown, Figure 7 is the HPLC spectrum of the target product racemate, Figure 8 The HPLC spectrum of the synthesized target product is as follows:

[0113] 1 H NMR(400MHz,Chloroform-d)δ8.09-8.01(m,1H),7.99-7.94(m,2H),7.93-7.87(m,1H) ,7.85-7.75(m,2H),7.63-7.41(m,6H),6.16(dd,J=9.3,2.5Hz,1H),3.88-3.20(m,2H).

[0114] 13 C NMR (101MHz, CDCl3) δ200.49,138.56,136.62,133.91,133.85,130.02,129.20, 128.85,128.33,128.21,126.39,125.78,125.70,123.29,122.92,66.93,46.93.

[0115] HPLC (Dialcel Chiralcel OD-H, n hexane / i PrOH=95 / 5, flow rate 1.0mL / min);

[0116] t R =23.5min(S,minor),t R =31.2min(R,major).

[0117] Application Example 3

[0118] The (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 is applied to synthesize chiral boron-based compounds using 4-chlorophenyl-1-phenylpropyl-2-ene-1-one as a substrate, comprising the following steps:

[0119] Step (1): Add 4-chlorophenyl 1-phenylpropyl-2-ene-1-one, bipyraclostrobin, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand into a mixed solvent of toluene / distilled water = 9:1 (v / v), and mix and stir for 12 hours at room temperature, wherein the molar ratio of 4-chlorophenyl 1-phenylpropyl-2-ene-1-one, bipyraclostrobin, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand is 1:1.2:1.5%:2%; the chemical reaction equation is as follows:

[0120]

[0121] Step (2): After the reaction is completed, the obtained mixed system is centrifuged and filtered. The obtained liquid phase is then extracted with ethyl acetate solution, dried with anhydrous Na2SO4 and rotary evaporated to obtain a crude boride product. The crude boride product is transferred to a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), tetrahydrofuran (3 mL), and deionized water (2 mL) are added in sequence to react at room temperature for 4 hours, followed by extraction, drying, and thin layer chromatography to obtain a chiral hydroxy compound. The chemical reaction equation is as follows:

[0122]

[0123] The filtered precipitate is washed and dried to obtain the recovered (MOFS-Cu(II) / CMC) catalytic material for the next recycling.

[0124] Step (1) The (MOFS-Cu(II) / CMC) catalytic material is applied to the chiral boron addition reaction of 4-chlorophenyl-1-phenylpropyl-2-ene-1-one, and the yield and enantioselectivity of the target product (chiral boron-based compound) are 92% and 95%, respectively.

[0125] The target product has a hydrogen NMR spectrum, a carbon NMR spectrum and a HPLC spectrum. Figures 9 to 12 As shown, Fig.11 is the HPLC spectrum of the target product racemate, Fig.12 The HPLC spectrum of the synthesized target product is as follows:

[0126] 1 H NMR(400MHz,Chloroform-d)δ7.98-7.91(m,2H),7.60(t,J=7.4Hz,1H),7.47(t,J=7.6H z,2H),7.42-7.29(m,4H),5.32(dd,J=7.2,4.9Hz,1H),3.69(s,1H),3.43-3.25(m,2H).

[0127] 13 C NMR (101MHz, CDCl3) δ200.10,141.54,136.50,133.94,133.45,128.89,128.82,128.27,127.29,69.53,47.36.

[0128] HPLC (Dialcel Chiralcel OD-H, n hexane / i PrOH=90 / 10, flow rate 1.0mL / min);

[0129] t R =12.7min(S,minor),t R =14.5min(R,major).

[0130] The present invention applies the composite material to an asymmetric chiral boron addition reaction, and after the reaction is completed, the catalyst can be recovered. The results of Application Example 1 show that the (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 has high conversion rate and enantioselectivity of chalcone in the boron addition reaction, and the yield and enantioselectivity of the target product (chiral boron-based compound) reach 96% and 95%, respectively. The catalytic material can be recycled and reused. After being recycled for 4 times, it is applied to the chiral boron addition reaction of chalcone for the fifth time, and the yield and enantioselectivity of the target product (chiral boron-based compound) reach 93% and 94%, respectively.

[0131] The asymmetric chiral boron addition reaction of the present invention is carried out at room temperature, under mild conditions, with a wide range of substrates, high yield and enantioselectivity, and simple reaction components. In addition, the method can synthesize chiral organic boron compounds in simple component solvents, providing a new and efficient method for the preparation of drug molecules and active intermediates, broadening the range of substrates for preparing chiral organic boron compounds, and having important theoretical and practical significance.

[0132] Although the above-mentioned embodiments have made a detailed description of the present invention, they are only some embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments based on the embodiments of the present invention without creative work, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a MOF-Cu(II) / CMC composite material, characterized in that: The following steps are involved: The aqueous solution of sodium carboxymethyl cellulose is added dropwise to the aqueous solution of divalent copper salt to separate the solid and liquid to obtain composite microbeads; The composite microbeads and an organic solution of trimesic acid are mixed, heated, and solid-liquid separated to obtain a MOF-Cu(II) / CMC composite material.

2. The preparation method according to claim 1, characterized in that: The concentration of the aqueous solution of sodium carboxymethyl cellulose is 1.5-3 g / 100 mL.

3. The preparation method according to claim 1, characterized in that: The divalent copper salt includes one or more of copper acetate, copper chloride, copper bromide and copper sulfate.

4. The preparation method according to claim 1 or 3, characterized in that: The concentration of the aqueous solution of the divalent copper salt is 3-8 wt %.

5. The preparation method according to claim 2 or 3, characterized in that: The volume ratio of the aqueous solution of the divalent copper salt to the aqueous solution of sodium carboxymethyl cellulose is 1:

1.

6. The preparation method according to claim 1, characterized in that: The concentration of the organic solution of trimesic acid is 0.09-0.11 mmol / mL.

7. The preparation method according to claim 1 or 6, characterized in that: The organic solvent in the organic solution of trimesic acid is N,N-dimethylformamide.

8. The MOF-Cu(II) / CMC composite material obtained by the preparation method according to any one of claims 1 to 7, characterized in that: The copper content in the MOFS-Cu(II) / CMC composite material is 0.3-1 mmol / g.

9. Use of the MOF-Cu(II) / CMC composite material according to claim 8 in the catalytic synthesis of asymmetric chiral boron compounds.

10. The use according to claim 9, characterized in that: The application of synthesizing non-chiral boron compounds comprises the following steps: An α,β-unsaturated ketone compound, biboric acid pinacol ester, a catalytic material, a chiral ligand and a solvent are mixed to perform an asymmetric chiral boron addition reaction to obtain an asymmetric chiral boron compound; the catalytic material is the MOF-Cu(II) / CMC composite material according to claim 8; and the solvent is a mixture of toluene and water; The structural formula of the α,β-unsaturated ketone compound is shown in Formula 1, and the structural formula of the chiral ligand is shown in Formula 2: In Formula 1, R1 is phenyl, substituted phenyl or naphthyl, and R2 is phenyl or substituted phenyl.

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