MOF-cu(II) / CMC composite material, and preparation method therefor and use thereof

Abstract

The present application belongs to the technical field of the synthesis of chiral boron compounds, and in particular relates to an MOF-Cu(II) / CMC composite material, and a preparation method therefor and the use thereof. The preparation method for an MOF-Cu(II) / CMC composite material of the present application comprises: dropwise adding an aqueous solution of sodium carboxymethyl cellulose to an aqueous solution of a bivalent copper salt, performing solid-liquid separation, mixing obtained composite microspheres with an organic solution of trimesic acid, heating the resulting mixture, and subjecting same to solid-liquid separation, so as to obtain an MOF-Cu(II) / CMC composite material. The MOF-Cu(II) / CMC composite material is used in an asymmetric chiral boron addition reaction. The reaction is performed at room temperature, involves mild conditions, is applicable to a wide range of substrates and has a high yield and enantioselectivity. Moreover, the method can achieve the synthesis of a chiral organic boride in a solvent having simple components, providing an efficient new method for the preparation of drug molecules and active intermediates, and also broadening the range of substrates used for the preparation of chiral organic borides.

Description

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

[0001] The present application claims priority to the Chinese patent application No. CN202411139119.7, filed on August 19, 2024, and entitled "MOF-Cu(II) / CMC composite material, preparation method and application thereof", the content of which is incorporated herein by reference in its entirety. TECHNICAL FIELD

[0002] The present application belongs to the technical field of chiral boron compound synthesis, and specifically relates to a MOF-Cu(II) / CMC composite material, a preparation method and application thereof. BACKGROUND

[0003] Chiral characteristics are a key factor for the efficacy and safety of many therapeutic agents. Currently, about 57% of commercially available 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 biotransform synthetic chemicals into drugs with high enantiomeric, chemical and regioselectivity. Biocatalysis is becoming a key component in the chemist's toolbox. In fact, intermediates of many important therapeutic agents, such as sitagliptin, pregabalin, lageritaz, paclitaxel, epothilone, abacavir, atorvastatin, rosuvastatin and omarpatride, have been successfully synthesized by biocatalysis. Chiral boron compounds are important intermediates for the synthesis of chiral drugs, and the chiral C-B bond can undergo a series of transformations through oxidation reaction, Suzuki-Miyaura coupling reaction, Petasis reaction, etc. to obtain chiral C-O bond, chiral C-N bond and chiral C-C bond.

[0004] In the literature (Nanomaterials 2018, 8, 326; doi:10.3390 / nano8050326), copper ions form coordination bonds with amino, hydroxyl and other groups on the polymer chain, and divalent copper (1 mol%, relative to the percentage of the amount of substance of the template reaction substrate) is used for catalysis, realizing the transformation of α, β-unsaturated ketone compounds to β-boronate substituted carbonyl compounds. This work uses chalcone as a template substrate, uses 1.2 equivalents of pinacol diboron reagent, uses a mixture of acetone and water as a solvent, and reacts at room temperature to obtain β-boronate substituted carbonyl compounds. However, the enantioselectivity of the catalyst for chiral boron compounds is low.

[0005] SUMMARY

[0006] Therefore, the present application aims to provide a MOF-Cu(II) / CMC composite material, a preparation method and application thereof.

[0007] To achieve the above-mentioned application purposes, the present application provides the following technical solutions.

[0008] The present application provides a preparation method of a MOF-Cu(II) / CMC composite material, comprising the following steps:

[0009] The aqueous solution of sodium carboxymethyl cellulose is added dropwise into the aqueous solution of divalent copper salt, and solid-liquid separation is performed to obtain composite microbeads;

[0010] The composite microbeads and the organic solution of trimesic acid are mixed, heated, and subjected to solid-liquid separation to obtain the MOF-Cu(II) / CMC composite material.

[0011] Preferably, the concentration of the aqueous solution of sodium carboxymethyl cellulose is 0.015-0.03 g / mL.

[0012] Preferably, the divalent copper salt comprises one or more of copper acetate, copper chloride, copper bromide and copper sulfate.

[0013] Preferably, the concentration of the aqueous solution of divalent copper salt is 3-8 wt%.

[0014] Preferably, the volume ratio of the aqueous solution of divalent copper salt to the aqueous solution of sodium carboxymethyl cellulose is 1:1.

[0015] Preferably, the concentration of the organic solution of trimesic acid is 0.09-0.11 mmol / mL.

[0016] Preferably, the organic solvent in the organic solution of trimesic acid is N,N-dimethylformamide.

[0017] The present application also provides the MOF-Cu(II) / CMC composite material obtained by the preparation method described in the above technical solutions, and the copper content in the MOF-Cu(II) / CMC composite material is 0.3-1 mmol / g.

[0018] The present application also provides the application of the MOF-Cu(II) / CMC composite material described in the above technical solutions in catalytic synthesis of asymmetric chiral boron compounds.

[0019] The present application also provides a method for synthesizing asymmetric chiral boron compounds, comprising the following steps:

[0020] The asymmetric chiral boron addition reaction is carried out by mixing an α,β-unsaturated ketone compound, pinacol diborane, a catalytic material, a chiral ligand and a solvent; 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.

[0021] The α,β-unsaturated ketone compound has a structural formula as shown in Formula 1, and the chiral ligand has a structural formula as shown in Formula 2.

[0022] In Formula 1, R1 is a phenyl group, a substituted phenyl group or a naphthyl group, and R2 is a phenyl group or a substituted phenyl group.

[0023] Compared with the prior art, the present application has the following beneficial effects:

[0024] The present application provides a preparation method of a MOF-Cu(II) / CMC composite material, which comprises the following steps: dropping an aqueous solution of sodium carboxymethyl cellulose into an aqueous solution of a divalent copper salt, performing solid-liquid separation to obtain composite microbeads; mixing the composite microbeads with an organic solution of trimesic acid, heating, and performing solid-liquid separation to obtain the MOF-Cu(II) / CMC composite material.

[0025] The present application uses the raw material sodium carboxymethyl cellulose to provide a carrier for loading copper, and prepares the copper into a metal organic framework (MOF) material. The obtained MOF-Cu(II) / CMC composite material is a nano-porous material, and the copper ions are uniformly distributed on the biomass-based polymer material with a size of 10-50 nm. The MOF-Cu(II) / CMC composite material prepared in the examples has a good pore structure, a large specific surface area, an average pore size of 22 nm, a pore cumulative volume of 0.1412 cm 3 / g, and a specific surface area of 27.53 m 2 / g. The rigid pores provide a spatial restriction for the active metal nanoparticles, which can prevent aggregation and leaching. The MOF-Cu(II) / CMC composite material has good biocompatibility and high catalytic activity. When the composite material is used to catalyze the synthesis of chiral boron compounds, a strong base does not need to be added in the reaction system, and the reaction can be carried out in toluene and a mixed solvent. The MOF-Cu(II) / CMC composite material has high stability and can be recycled. The synthesis method is green and environmentally friendly, and meets the concept of sustainable industrial production.

[0026] Moreover, the preparation of the chiral boron compound can be carried out at room temperature, and the reaction conditions are mild, simple and easy to operate, and have wide applicability. BRIEF DESCRIPTION OF DRAWINGS

[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed in the embodiments. Obviously, the drawings described below only constitute some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without creative labor.

[0028] Figure 1 is the nuclear magnetic hydrogen spectrum of the target product in application example 1;

[0029] Figure 2 is the nuclear magnetic carbon spectrum of the target product in application example 1;

[0030] Figure 3 is the HPLC spectrum of the racemate of the target product in application example 1;

[0031] Figure 4 is the HPLC spectrum of the target product in application example 1;

[0032] Figure 5 is the nuclear magnetic hydrogen spectrum of the target product in application example 2;

[0033] Figure 6 is the nuclear magnetic carbon spectrum of the target product in application example 2;

[0034] Figure 7 is the HPLC spectrum of the racemate of the target product in application example 2;

[0035] Figure 8 is the HPLC spectrum of the target product in application example 2;

[0036] Figure 9 is the nuclear magnetic hydrogen spectrum of the target product in application example 3;

[0037] Figure 10 is the nuclear magnetic carbon spectrum of the target product in application example 3;

[0038] Figure 11 is the HPLC spectrum of the racemate of the target product in application example 3;

[0039] Figure 12 is the HPLC spectrum of the target product in application example 3. DETAILED DESCRIPTION

[0040] The present application provides a preparation method of MOF-Cu(II) / CMC composite material, comprising the following steps:

[0041] The aqueous solution of carboxymethyl cellulose sodium is added dropwise into the aqueous solution of divalent copper salt, and solid-liquid separation is performed to obtain composite microbeads;

[0042] The composite microbeads and the organic solution of trimesic acid are mixed, heated, and subjected to solid-liquid separation to obtain the MOF-Cu(II) / CMC composite material.

[0043] In the present application, unless otherwise specified, the materials and equipment used are commercially available in the art.

[0044] The aqueous solution of sodium carboxymethyl cellulose is added dropwise into the aqueous solution of divalent copper salt, and solid-liquid separation is performed to obtain the composite microbeads.

[0045] In the present application, the concentration of the aqueous solution of sodium carboxymethyl cellulose is preferably 1.5-3 g / 100 mL, and more preferably 2 g / 100 mL. The aqueous solution of sodium carboxymethyl cellulose is a clear and flowable solution, which is 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 copper-loaded carrier.

[0046] In the present application, the divalent copper salt in the aqueous solution of divalent copper salt preferably includes one or more of copper acetate, copper chloride, copper bromide and copper sulfate, and more preferably is copper sulfate, which is preferably anhydrous copper sulfate.

[0047] In the present application, the concentration of the aqueous solution of divalent copper salt is preferably 3-8 wt%, and more preferably 5 wt%. The volume ratio of the aqueous solution of divalent copper salt to the aqueous solution of sodium carboxymethyl cellulose is preferably 1:1. The aqueous solution of divalent copper salt is excessive in copper ions, and the excess copper ions are subsequently removed.

[0048] In the present application, the mass ratio of the divalent copper salt to sodium carboxymethyl cellulose is preferably 3-8:2, and more preferably 5:2.

[0049] The present application does not have special requirements for the rate of the dropwise addition. The dropwise addition is preferably followed by stirring, and the stirring time is preferably 12 h. The stirring prevents the aggregation of the composite microbeads. During the dropwise addition and stirring, the sodium carboxymethyl cellulose loads Cu ions by chelation, the divalent copper salt forms a network structure with the sodium carboxymethyl cellulose, the copper ions are wrapped inside the molecules, the high molecules are intertwined with each other, and the composite microbeads with internal porosity and external spherical shape are formed.

[0050] In the present application, the solid-liquid separation is preferably followed by washing, which preferably includes water washing and organic solvent washing. The water washing removes free Cu(II) ions, and the organic solvent washing preferably includes immersion in methanol (MeOH) and N,N-dimethylformamide (DMF) in sequence, and the immersion time is preferably 15 min for each. The organic solvent washing removes the water in the interior of the composite microbeads.

[0051] After obtaining the composite microbeads, the present application mixes the composite microbeads and an organic solution of trimesic acid, heats, and performs solid-liquid separation to obtain a MOF-Cu(II) / CMC composite material.

[0052] In the present application, the concentration of the organic solution of trimesic acid is preferably 0.09-0.11 mmol / mL, and more preferably 0.1 mmol / mL.

[0053] In the present application, the organic solvent in the organic solution of trimesic acid is preferably N,N-dimethylformamide (DMF).

[0054] In the present application, the mixing method of the composite microbeads and the organic solution of trimesic acid is preferably stirring, the temperature of the stirring is preferably 80℃, the time is preferably 1-3h, and the rate is preferably 100r / min.

[0055] In the present application, the temperature of the heating is preferably 100℃, and the time is preferably 12h. During the heating, the copper forms metal organic frameworks (MOFs).

[0056] In the present application, the method of the solid-liquid separation is preferably filtration. After the solid-liquid separation, preferably, washing and drying are further included. The washing includes rinsing and soaking washing. The rinsing preferably includes rinsing with N,N-dimethylformamide (DMF) and ethanol (EtOH) in sequence, which is to wash away impurities. The reagent of the soaking washing is preferably dichloromethane. The soaking washing preferably uses fresh solvent to replace every 6h, and the replacement is performed 3 times. The reagent of the soaking washing in the present application has good compatibility with other organic solvents, can better remove other organic solvents on the surface, and has strong volatility and is easy to remove itself. The temperature of the drying is preferably 90℃, and the time is preferably overnight.

[0057] The present application also provides the MOF-Cu(II) / CMC composite material prepared by the preparation method.

[0058] In the present application, the copper content in the MOF-Cu(II) / CMC composite material is preferably 0.53mmol / g. The MOF-Cu(II) / CMC composite material is a blue spherical particle with a diameter of about 1mm. The surface of the bead body is uniformly covered with a large number of HKUST-1 with typical octahedral morphology, and the average particle size is 500nm-2μm.

[0059] The present application also provides the application of the MOF-Cu(II) / CMC composite material in catalytic synthesis of asymmetric chiral boron compounds.

[0060] The present application also provides a method for synthesizing asymmetric chiral boron compounds, including the following steps:

[0061] The asymmetric chiral boron addition reaction is carried out by mixing an α,β-unsaturated ketone compound, pinacol diborane, a catalytic material, a chiral ligand and a solvent, wherein the catalytic material is the MOF-Cu(II) / CMC composite material, and the solvent is a mixture of toluene and water.

[0062] The α,β-unsaturated ketone compound has a structure as shown in Formula 1, and the chiral ligand has a structure as shown in Formula 2.

[0063] In Formula 1, R1 is a phenyl group, a substituted phenyl group or a naphthyl group, and R2 is a phenyl group or a substituted phenyl group.

[0064] In the present application, the substituted phenyl group in R1 preferably includes a p-methylphenyl group, an o-methylphenyl group, a p-chlorophenyl group, an o-chlorophenyl group, a m-chlorophenyl group or a p-bromophenyl group, and the substituted phenyl group in R2 preferably includes a p-methoxyphenyl group, a p-chlorophenyl group, an o-chlorophenyl group, a m-chlorophenyl group or a p-bromophenyl group.

[0065] In the present application, the α,β-unsaturated ketone compound preferably includes a chalcone, 3-naphthyl-1-phenylpropyl-2-en-1-one or 4-chlorophenyl 1-phenylpropyl-2-en-1-one.

[0066] In the present application, the amount of Cu(II) in the MOF-Cu(II) / CMC composite material is calculated. 2+ The amount-of-substance ratio of the α,β-unsaturated ketone compound, pinacol diborane, catalytic material and 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.

[0067] In the present application, the volume ratio of toluene to water in the mixture of toluene and water is preferably 7-11:1, more preferably 9:1. The ratio of the α,β-unsaturated ketone compound to the mixed system is preferably 0.2 mmol:2 mL, wherein the mixed system is a system obtained by mixing the α,β-unsaturated ketone compound, pinacol diborane, catalytic material, chiral ligand and solvent.

[0068] In the present application, the amount ratio of the MOF-Cu(II) / CMC composite material to solvent is preferably 8-64 mg:10 mL.

[0069] In the present application, the temperature of the asymmetric chiral boron addition reaction is preferably room temperature, and the time is preferably 6-24 h, more preferably 10-20 h, and even more preferably 12 h. The asymmetric chiral boron addition reaction is preferably carried out under stirring, and the present application does not have a special requirement for the stirring speed. The reaction formula of the asymmetric chiral boron addition reaction is as follows:

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

[0071] The obtained reaction solution is subjected to solid-liquid separation to obtain a solid phase and a liquid phase;

[0072] The liquid phase is subjected to first extraction, the obtained organic phase is dried using a drying agent, and the organic solvent is removed to obtain a crude product of the asymmetric chiral boron compound; the crude product is subjected to first column chromatography purification to obtain the asymmetric chiral boron compound; or the crude product, sodium borate tetrahydrate, tetrahydrofuran and water are mixed to perform an oxidation reaction, second extraction, and second column chromatography purification to obtain an asymmetric chiral hydroxyl compound;

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

[0074] In the present application, the solid-liquid separation is preferably carried out by centrifugation and filtration.

[0075] In the present application, the reagent used in the first extraction is preferably ethyl acetate, the drying agent is preferably Na2SO4, and the removal of the solvent is preferably carried out by rotary evaporation; the eluent used in 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 1:4-9.

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

[0077] In the present application, the reagent used in the second extraction is preferably ethyl acetate, and the eluent used in the second 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 1:4-9.

[0078] The present application does not have a special requirement for the method of washing and drying the solid phase, and the recycled (MOFS-Cu(II) / CMC) composite material can be recycled. After the (MOFS-Cu(II) / CMC) composite material of the present application is recycled, the yield and enantioselectivity value of the chiral boron-based compound are still relatively high.

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

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

[0081] Example 1

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

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

[0084] P2, the above solution is dropped into an aqueous solution containing a divalent copper salt (copper sulfate anhydrous, 5 wt%, 100 mL) by a syringe, and the mixture is continuously stirred at room temperature for 12 h to prevent the aggregation of the composite microbeads;

[0085] P3, the obtained composite microbeads are washed with deionized water to remove free Cu(II) ions, and then the microbeads are sequentially immersed in MeOH and DMF for 15 minutes to remove the water in the interior of the composite microbeads;

[0086] P4, the obtained composite microbeads are added into a prepared 0.1 mmol / mL solution of trimesic acid (solvent: DMF, volume: 30 mL), and the mixture is stirred at 80°C for 1 h, and then the mixture is heated at 100°C for 12 h;

[0087] P5, the obtained composite microbeads are collected by filtration, and then washed with DMF and EtOH to remove impurities. Then, the composite microbeads are soaked in 50 mL of dichloromethane, and the fresh solvent is replaced every 6 h for three times. Finally, after drying at 90°C under vacuum overnight, blue composite microbeads are obtained, which are the (MOFS-Cu(II) / CMC) catalytic material.

[0088] The copper content in the (MOFS-Cu(II) / CMC) catalytic material is 0.53 mmol / g as determined by ICP.

[0089] Example 1

[0090] The (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 was applied to the synthesis of chiral boron-based compounds with benzalmalononitrile as the substrate, including the following steps:

[0091] Step (1): Chalcone, pinacol diborane, (MOFS-Cu(II) / CMC) catalytic material, Bolm ligand were added to a mixture of toluene / distilled water = 9:1 (v / v) mixed solvent, and mixed and stirred at room temperature for 12 h, wherein the molar ratio of chalcone, pinacol diborane, (MOFS-Cu(II) / CMC) catalytic material, and Bolm ligand was 1:1.2:1.5%:2%, wherein the percentage of (MOFS-Cu(II) / CMC) catalytic material (based on Cu 2+ ) and Bolm ligand was based on the amount of chalcone, 0.2 mmol; after mixing the substances in proportion, the mixed solvent was added to 2 mL; the chemical reaction equation is as follows:

[0092] In the reaction equation, B2pin2 is pinacol diborane, and the structural formula is Chiral Ligand is a chiral ligand (Bolm ligand), and the structural formula is

[0093] Step (2): After the reaction was completed, the obtained mixed system was centrifuged and filtered, the obtained liquid phase was extracted with ethyl acetate, dried with anhydrous Na2SO4, and rotary evaporated to obtain boride crude product. The boride crude product (0.2 mmol of α, β-unsaturated ketone compound) was transferred to a reaction bottle, a magnetic stirrer, sodium borate tetrahydrate (244 mg), tetrahydrofuran (3 mL), and deionized water (2 mL) were sequentially added, and the mixture was reacted at room temperature for 4 h, and then extracted with ethyl acetate (a small amount of saturated brine was added), dried with anhydrous sodium sulfate, and thin layer chromatography to obtain a chiral hydroxyl compound. The chemical reaction equation is as follows:

[0094] After the precipitate obtained by filtration was washed and dried, the recovered (MOFS-Cu(II) / CMC) catalytic material was obtained for the next cycle.

[0095] Step (1): The (MOFS-Cu(II) / CMC) catalytic material was applied to the chiral boron addition reaction of chalcone, and the yield and enantioselectivity values of the target product (chiral boron-based compound) were 96% and 95%, respectively.

[0096] The H NMR and C NMR spectra and HPLC spectrum of the target product are shown in Figures 1-4, wherein Figure 3 is the HPLC spectrum of the racemate of the target product, and Figure 4 is the HPLC spectrum of the synthesized target product, and the results of the integration of the chromatographic peaks of the racemate and the synthesized target product are shown in Table 1:

[0097] Table 1: Results of the integration of the chromatographic peaks of the racemate and the synthesized target product of Example 1

[0098] The NMR data are as follows:

[0099] 1 H NMR (400 MHz, Chloroform-d) δ 8.01-7.89 (m, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (dd, J = 13.0, 7.4 Hz, 4H), 7.39 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 7.3 Hz, 1H), 5.36 (t, J = 6.1 Hz, 1H), 3.38 (d, J = 6.0 Hz, 2H).

[0100] 13 C NMR (101 MHz, CDCl3) δ 200.36, 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 1.0 mL / min);

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

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

[0104] Example 2

[0105] The (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 was applied in the synthesis of chiral boron-based compounds with 3-naphthyl-1-phenylpropyl-2-en-1-one as the substrate, including the following steps:

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

[0107] Step (2): after the reaction was completed, the obtained mixed system was centrifuged and filtered, the obtained liquid phase was extracted by an ethyl acetate solution, dried by anhydrous Na2SO4 and rotary evaporated to obtain a boron compound crude product. The boron compound crude product was transferred into a reaction bottle, a magnetic stirring bar, sodium borate tetrahydrate (244 mg), tetrahydrofuran (3 mL) and deionized water (2 mL) were sequentially added and reacted at room temperature for 4 h, and then extracted, dried and subjected to thin layer chromatography to obtain a chiral hydroxyl compound. The chemical reaction equation is as follows:

[0108] After the precipitate obtained by filtration was washed and dried, the recovered (MOFS-Cu(II) / CMC) catalytic material was obtained and used for the next cycle.

[0109] Step (1): (MOFS-Cu(II) / CMC) catalytic material was applied to the chiral boron addition reaction of 3-naphthyl-1-phenylpropyl-2-en-1-one, and the yield and enantioselectivity values of the target product (chiral boron-based compound) were 99% and 97%, respectively.

[0110] The nuclear magnetic hydrogen spectrum and carbon spectrum and HPLC spectrum of the target product are shown in Figures 5 to 8, wherein Figure 7 is the HPLC spectrum of the racemate of the target product, and Figure 8 is the HPLC spectrum of the synthesized target product, and the chromatographic peak integration results of the racemate and the synthesized target product are shown in Table 2:

[0111] Table 2 Chromatographic peak integration results of the racemate and the synthesized target product of Example 2

[0112] The nuclear magnetic data are as follows:

[0113] 1H NMR (400 MHz, Chloroform-d) δ 8.09 - 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, 2.5 Hz, 1H), 3.88 - 3.20 (m, 2H).

[0114] 13 C NMR (101 MHz, CDCI3) δ 200.49, 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 1.0 mL / min);

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

[0117] Application Example 3

[0118] The (MOFS-Cu(II) / CMC) catalytic material prepared in Example 1 was applied to the synthesis of chiral boron-based compounds with 4-chlorophenyl 1-phenylpropyl-2- en-1-one as the substrate, including the following steps:

[0119] Step (1): 4-chlorophenyl 1-phenylpropyl-2-en-1-one, pinacol diboronic acid, (MOFS-Cu(II) / CMC) catalytic material, Bolm ligand were added into a mixed solvent of toluene / distilled water = 9:1 (v / v), and mixed and stirred at room temperature for 12 h, wherein the molar ratio of 4-chlorophenyl 1-phenylpropyl-2-en-1-one, pinacol diboronic acid, (MOFS-Cu(II) / CMC) catalytic material, Bolm ligand was 1:1.2:1.5%:2%; the chemical reaction equation is as follows:

[0120] Step (2): After the reaction was completed, the obtained mixture was centrifuged and filtered. The obtained liquid phase was extracted with ethyl acetate solution, dried with anhydrous Na2SO4, and rotary evaporated to obtain the boron compound crude product. The boron compound crude product was transferred into a reaction bottle, and a magnetic stirrer, sodium borate tetrahydrate (244 mg), tetrahydrofuran (3 mL), and deionized water (2 mL) were sequentially added. The reaction was carried out at room temperature for 4 h, followed by extraction, drying, and thin layer chromatography to obtain the chiral hydroxyl compound. The chemical reaction equation is as follows:

[0121] After the obtained precipitate was washed and dried, the recovered (MOFS-Cu(II) / CMC) catalytic material was obtained, which was used for the next cycle.

[0122] Step (1): The (MOFS-Cu(II) / CMC) catalytic material was applied to the chiral boron addition reaction of 4-chlorophenyl 1-phenylpropyl-2-en-1-one. The yield and enantioselectivity of the target product (chiral boron-based compound) were 92% and 95%, respectively.

[0123] The nuclear magnetic hydrogen spectrum and carbon spectrum and HPLC spectrum of the target product are shown in FIGS. 9-12. FIG. 11 is the HPLC spectrum of the racemate of the target product, and FIG. 12 is the HPLC spectrum of the synthesized target product. The chromatographic peak integration results of the racemate and the synthesized target product are shown in Table 3:

[0124] Table 3 Chromatographic peak integration results of the racemate and the synthesized target product of Example 3

[0125] The nuclear magnetic data are as follows:

[0126] 1 H NMR (400 MHz, Chloroform-d) δ 7.98-7.91 (m, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.42-7.29 (m, 4H), 5.32 (dd, J = 7.2, 4.9 Hz, 1H), 3.69 (s, 1H), 3.43-3.25 (m, 2H).

[0127] 13 C NMR (101 MHz, CDCl3) δ 200.10, 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 1.0 mL / min);

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

[0130] The application applies the composite material to the asymmetric chiral boron addition reaction, and the catalyst can be recovered after the reaction. The results of application example 1 show that the conversion rate and enantioselectivity of chalcone in the boron addition reaction participated by the (MOFS-Cu(II) / CMC) catalytic material prepared in example 1 are high, and the yield and enantioselectivity values of the target product (chiral boron-based compound) reach 96% and 95% respectively. The catalytic material can be recycled and used for 4 times, and when it is applied to the chiral boron addition reaction of chalcone for the fifth time, the yield and enantioselectivity values of the target product (chiral boron-based compound) reach 93% and 94% respectively.

[0131] The asymmetric chiral boron addition reaction of the application is carried out at room temperature, has mild conditions, a wide range of substrates, high yield and enantioselectivity, and simple reaction components. The method can be used to synthesize chiral organoborides in a simple component solvent, provides an efficient new method for the preparation of drug molecules and active intermediates, widens the substrate range for the preparation of chiral organoborides, and has important theoretical and practical significance.

[0132] Although the above examples make a detailed description of the application, it is only a part of the examples of the application, not all the examples, and people can also obtain other examples according to the examples of the application without creative labor, which all belong to the protection scope of the application.

Claims

1. A method for preparing a MOF-Cu(II) / CMC composite material, characterized in that, The method comprises the following steps: adding an aqueous solution of sodium carboxymethyl cellulose into an aqueous solution of a divalent copper salt, and separating the solid and liquid to obtain the composite microbeads; mixing the composite microbeads with an organic solution of trimesic acid, heating, and separating the solid and liquid to obtain the MOF-Cu(II) / CMC composite material.

2. The production method according to claim 1, characterized by, The concentration of the aqueous solution of sodium carboxymethyl cellulose is 0.015-0.03 g / mL.

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

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

5. The production method according to claim 2 or 3, characterized by, 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 method of claim 1, wherein, The concentration of the organic solution of trimesic acid is 0.09-0.11 mmol / mL.

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

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

9. The MOF-Cu(II) / CMC composite material of claim 8 is used in catalytic synthesis of asymmetric chiral boron compounds.

10. A method of synthesizing asymmetric chiral boron compounds, characterized by, The method comprises the following steps: mixing an α,β-unsaturated ketone compound, pinacol diboronic acid, a catalytic material, a chiral ligand and a solvent 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 of claim 8; and the solvent is a mixture of toluene and water. The α,β-unsaturated ketone compound has a structural formula as shown in Formula 1, and the chiral ligand has a structural formula as shown in Formula 2: In formula 1, R1 is a phenyl group, a substituted phenyl group or a naphthyl group, and R2 is a phenyl group or a substituted phenyl group.

11. The method of synthesizing an asymmetric chiral boron compound according to claim 10, wherein, The α,β-unsaturated ketone compound comprises a chalcone, 3-naphthyl-1-phenylpropyl-2-en-1-ketone or 4-chlorophenyl 1-phenylpropyl-2-en-1-ketone.

12. The method of synthesizing an asymmetric chiral boron compound according to claim 10, wherein, The amount of Cu in the MOF-Cu(II) / CMC composite is calculated as Cu 2+ The molar ratio of the α,β-unsaturated ketone compound, pinacol diboronic acid ester, catalytic material and chiral ligand is 1 : 1.2: 0.01-0.05: 0.012-0.

06.

13. The method of synthesizing an asymmetric chiral boron compound according to claim 10 or 12, wherein, The temperature of the asymmetric chiral boron addition reaction is room temperature, and the time is 6-24 h.

14. The method of synthesizing an asymmetric chiral boron compound according to claim 10, wherein, After the asymmetric chiral boron addition reaction, the method further comprises: separating the obtained reaction liquid into a solid phase and a liquid phase; drying the obtained organic phase using a drying agent to remove the organic solvent, and obtaining a crude product of the asymmetric chiral boron compound; purifying the crude product through first column chromatography to obtain the asymmetric chiral boron compound, or mixing the crude product, sodium borate tetrahydrate, tetrahydrofuran and water to perform an oxidation reaction, second extraction and second column chromatography purification to obtain an asymmetric chiral hydroxyl compound.

15. The method of synthesizing an asymmetric chiral boron compound according to claim 14, wherein, After obtaining the solid phase, the method further comprises: washing and drying the solid phase to obtain the recovered MOF-Cu(II) / CMC composite material.

16. The method of synthesizing an asymmetric chiral boron compound according to claim 14, wherein, The temperature of the oxidation reaction is room temperature, and the time is 4-8 h.

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