A method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst

Abstract

The invention discloses a preparation method of an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst, which belongs to the technical field of chiral catalysts. The method specifically comprises the following steps: using 1,4-dibromobutoxybenzene and 1,4-dimethoxybenzene as raw materials, catalytically synthesizing a mixed column [5] aromatic hydrocarbon intermediate, reacting the intermediate with L- and D-type N-Boc tyrosine methyl esters to obtain tyrosine-based column [5] aromatic hydrocarbons L-3 and D-3, then removing Boc under acidic conditions to prepare compounds L-4 and D-4, and then reacting the products with monomeric quinoline formaldehyde derivatives and metal Cu + The present invention uses self-assembly and chiral induction to synthesize supramolecular polymer chiral catalysts. The catalyst's raw materials are readily available, the preparation method is simple to operate, and the reaction conditions are mild. Controlling the amount of chiral monomers can lead to changes in the polymer and chiral induction effects in different assembly procedures, making it an ideal component for preparing supramolecular chiral catalysts.

Description

Technical Field

[0001] The present invention belongs to the technical field of chiral catalysts, and more particularly relates to a method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst. Background Art

[0002] Supramolecular chiral catalysts are of great significance in the field of chemical asymmetric catalytic synthesis, but there are relatively few studies on them. The synthesis of chiral catalysts containing pillar[5] aromatic groups has broad prospects. Chiral synthesis and asymmetric catalysis are the main methods for synthesizing chiral substances. However, when people carry out chemical synthesis, they often do not obtain a single chiral substance, but rather an equal mixture of a pair of enantiomers. Asymmetric catalysis can achieve chirality amplification and is the most efficient method for obtaining chiral compounds. Metal-organic complex chiral catalysis is currently widely used, but there are many problems that need to be solved in terms of chiral ligands. Therefore, the development of new and efficient chiral catalysts to catalyze asymmetric reactions is the key to research.

[0003] Pillar[5]arene itself has the characteristics of dynamic racemization and is a potential chiral molecular platform. According to previous literature reports, pillar[5]arene is a new type of macrocyclic host with a columnar structure and an electron-rich cavity. The modified functionalized pillar[5]arene has a strong host-guest recognition effect. After interacting with the guest molecule, it can form a stable supramolecular polymer chiral catalyst with metal ions, controlling or affecting the stereoselectivity of asymmetric reactions through its own chiral environment. Pillarene and its derivatives have shown interesting and unique chiral catalytic properties in the past few years, making them ideal components for the preparation of supramolecular chiral catalysts. This study is expected to achieve a variety of asymmetric catalytic reactions.

[0004] Therefore, how to develop a preparation method for amino acid functionalized column[5] aromatic hydrocarbon-based supramolecular chiral catalyst is an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst by chemical synthesis method to solve the shortcomings of the prior art.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst comprises the following steps:

[0008] (1) Synthesis of Compound D-4 or Compound L-4

[0009] ①Synthesis of compound 1

[0010] 1,4-dibromobutane, KI, K2CO3 and acetonitrile were stirred uniformly and then heated to reflux to obtain a mixed solution. An acetonitrile solution of p-diphenol was added dropwise to the mixed solution in an N2 atmosphere. After the addition was complete, the mixture was reacted. After the reaction was completed, the solid was filtered out and washed with deionized water. The mixture was extracted, and the organic phase was collected, dried and concentrated. The crude product was added with anhydrous ethanol and frozen for crystallization. The product was filtered while cold and the solid was collected to obtain compound 1.

[0011] ②Synthesis of compound 2

[0012] Compound 1, 1,4-dimethoxybenzene, paraformaldehyde, and 1,2-dichloroethane were stirred at room temperature, and then boron trifluoride etherate was added to the solution, and then stirred at room temperature. Deionized water was added to quench the reaction. After the reaction was completed, the mixture was concentrated by rotary evaporation, and the organic phase was collected. The organic layer was dried, filtered, and evaporated to obtain a crude product, which was separated by column chromatography to obtain compound 2;

[0013] ③Synthesis of Compound D-3 and Compound L-3

[0014] Compound 2, D- or L-type N-Boc tyrosine methyl ester, K2CO3, KI, and acetonitrile solution were stirred uniformly and heated for reaction. After the reaction, deionized water was added and the mixture was extracted. The organic layer was collected and dried, evaporated and concentrated, and separated by column chromatography to obtain a light yellow oily liquid. After vacuum distillation and cooling, a white solid was obtained, which is compound D-3 or compound L-3;

[0015] ④ Synthesis of Compound D-4 and Compound L-4

[0016] Compound D-3 or compound L-3, trifluoroacetic acid, and dichloromethane are stirred uniformly to react, and then deionized water, NaHCO3, and EDTA are added. After heating to boiling, the mixture is added to a dialysis bag for soaking. Deionized water and EDTA are added and boiled, and the dialysis bag is transferred for soaking. The reaction mixture is then placed in a dialysis bag and soaked with deionized water. The crude product in the dialysis bag is separated and extracted. The organic layer is collected, dichloromethane and petroleum ether are added, and the mixture is concentrated by rotary evaporation to obtain compound D-4 or compound L-4.

[0017] (2) Synthesis of monomer 7

[0018] 1) Synthesis of compound 5

[0019] 2-Methyl-8-aminoquinoline and di-tert-butyl dicarbonate were dissolved in 1,4-dioxane, heated for reaction, condensed under reflux, separated by column chromatography, and concentrated by rotary evaporation to obtain a yellow oily liquid. The product was allowed to stand and cool to crystallize, and a white crystalline solid was obtained, which was compound 5.

[0020] 2) Synthesis of Compound 6

[0021] Compound 5 and SeO2 were dissolved in 1,4-dioxane, stirred evenly, heated for reaction, condensed under reflux, extracted, and dried to obtain an orange-yellow liquid, which was separated by column chromatography to obtain a bright yellow solid, namely compound 6;

[0022] 3) Synthesis of monomer 7

[0023] Compound 6, trifluoroacetic acid, and dichloromethane were stirred uniformly at room temperature to obtain a deep red solution. The solution was adjusted to pH = 7 under ice, extracted, and the organic phase was collected, dried, and concentrated by rotary evaporation to obtain orange crystals, which were monomer 7;

[0024] (3)Cu + Synthesis of Metal Complexes:

[0025] Dissolve bistrifluoromethylsulfonyl imide and cuprous oxide in acetonitrile under a nitrogen atmosphere and stir at room temperature. Filter the mixture through SiO2, rinse with dichloromethane, and concentrate by rotary evaporation. Add dichloromethane and allow to stand. Add ether until the upper layer becomes turbid. Allow to stand and form white crystals, which are [Cu(MeCN)4]NTf2. Store in a sealed container.

[0026] (4) Preparation of amino acid functionalized column[5] aromatic-based supramolecular chiral catalyst:

[0027] Compound D-4 or compound L-4, monomer 7 and [Cu(MeCN)4]NTf2 were stirred at room temperature for 48 hours with acetonitrile as solvent under N2 protection, filtered, and distilled under reduced pressure to obtain the above-mentioned amino acid functionalized column [5] aromatic-based supramolecular chiral catalyst.

[0028] Further, in step ①, the mass volume ratio of the 1,4-dibromobutane, KI, K2CO3, acetonitrile and acetonitrile solution of p-diphenol is 13.15mL:13.57g:11.30g:200mL:60mL, and the concentration of the acetonitrile solution of p-diphenol is 4.54×10 -1 mol / L; the above reaction time is 72h.

[0029] Furthermore, in step ①, the volume ratio of the above-mentioned anhydrous ethanol to the acetonitrile solution of diphenol is 100:60.

[0030] Furthermore, in step ①, the mixture is extracted with CH2Cl2.

[0031] Furthermore, in step ②, the mass volume ratio of the above-mentioned compound 1, 1,4-dimethoxybenzene, paraformaldehyde, 1,2-dichloroethane and boron trifluoride etherate is 3.00g:4.36g:1.18g:250mL:7.10mL; the above-mentioned compound 1, 1,4-dimethoxybenzene, paraformaldehyde and 1,2-dichloroethane are stirred at room temperature for 0.5h, and then boron trifluoride etherate is added to the solution, and then stirred at room temperature for 2h.

[0032] Furthermore, in step ②, the volume ratio of deionized water added to quench the reaction to boron trifluoride ether is 200:7.10.

[0033] Furthermore, in step ②, the mixture was extracted with CH2Cl2, the organic layer was dried over Na2SO4, and separated by column chromatography using PE and DCM as eluents, with a volume ratio of PE to DCM of 1:1.

[0034] Furthermore, in step ③, the mass volume ratio of compound 2, D or L-type N-Boc tyrosine methyl ester, K2CO3, KI and acetonitrile is 600 mg:892 mg:835.21 mg:501.60 mg:25 mL, the above heating reaction temperature is 75°C, and the heating reaction time is 12 h.

[0035] Furthermore, in step ③, after the reaction is completed, the volume ratio of the added deionized water to the acetonitrile solution is 100:25.

[0036] Furthermore, in step ③, the mixture was extracted with CH2Cl2, the organic layer was collected and dried over anhydrous Na2SO4, and separated by column chromatography, first eluting with an eluent of PE and EA in a volume ratio of 15:1 for 1 hour, and then performing column chromatography with an eluent of PE and EA in a volume ratio of 5:1.

[0037] Furthermore, in step ④, the mass volume ratio of compound D-3 or compound L-3, trifluoroacetic acid and dichloromethane is 100 mg:3 mg:8 mL; the above reaction temperature is 50° C., and the reaction time is 1 h.

[0038] Furthermore, in step ④, after the reaction of every 8 mL of dichloromethane, 500 mL of deionized water, 10 g of NaHCO3, and 0.186 g of EDTA were added, heated to boiling, and then added to a dialysis bag and soaked for 10 minutes. Then, 500 mL of deionized water was added, and 0.186 g of EDTA was added and boiled. The dialysis bag was transferred and soaked for 10 minutes. The reaction mixture was placed in a dialysis bag and soaked with 500 mL of deionized water for 0.5 h, 4 h, and 6 h, respectively. During this period, the reaction progress was tracked by TCL and the water was changed.

[0039] Furthermore, in step 1), the mass volume ratio of the above-mentioned 2-methyl-8-aminoquinoline, di-tert-butyl dicarbonate and 1,4-dioxane is 0.5g:1.72g:20mL; the above-mentioned heating reaction temperature is 85°C, and the heating reaction time is 48h.

[0040] Furthermore, in step 1), the separation is performed by column chromatography, and the eluent is petroleum ether and dichloromethane in a volume ratio of 1:1.

[0041] Furthermore, in step 2), the mass volume ratio of the above-mentioned compound 5, SeO2, and 1,4-dioxane is 0.5g:429.58g:20mL, the above-mentioned heating reaction temperature is 95°C, and the heating reaction time is 18h.

[0042] Furthermore, in step 2), the product is extracted with deionized water and dichloromethane, dried over anhydrous Na2SO4, and separated by column chromatography, with the eluent being petroleum ether and dichloromethane in a volume ratio of 1:1.

[0043] Furthermore, in step 3), the mass volume ratio of the above compound 6, trifluoroacetic acid and dichloromethane is 3.0 g:7.5 mL:22.5 mL; and the above mixture is stirred uniformly at room temperature for 50 min.

[0044] Furthermore, in step 3), the mixture was adjusted with NaHCO 3 solution, extracted with deionized water and dichloromethane, and the organic phase was collected and dried over anhydrous MgSO 4 .

[0045] Furthermore, in step (3), the mass volume ratio of the above-mentioned bistrifluoromethylsulfonyl imide, cuprous oxide and acetonitrile is 1.6 g:0.8 g:10 mL; and the above-mentioned reaction mixture is stirred at room temperature for 15 h.

[0046] Furthermore, in step (3), the above-mentioned step is left to stand for 2 days.

[0047] Furthermore, in step (4), compound D-4 or compound L-4, monomer 7 and [Cu(MeCN)4]NTf2 are subjected to chiral induction self-assembly operation at a molar ratio of 1:16:9, 2:16:9, 3:16:9 or 4:16:9 to obtain the above-mentioned amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst.

[0048] It can be seen from the above technical solution that compared with the prior art, the beneficial effects of the present invention are as follows:

[0049] The present invention provides a method for preparing a chiral catalyst containing a pillar[5]arene supramolecular polymer. The pillar[5]arene supramolecular polymer has good synergistic effect in the host-guest interaction. The preparation method of the chiral catalyst containing a pillar[5]arene group adopts a chemical synthesis method. The present invention uses 1,4-dibromobutoxybenzene and 1,4-dimethoxybenzene as raw materials and synthesizes a mixed pillar[5]arene intermediate under the catalysis of Lewis acid BF3·C2H5OC2H5. The intermediate reacts with L and D type N-Boc tyrosine methyl ester respectively to obtain tyrosine-based pillar[5]arene L-3 and D-3, and then removes Boc under acidic conditions to prepare compounds L-4 and D-4. The products are then reacted with quinoline formaldehyde derivative monomer 7 and metal Cu + Self-assembly and chirality induction are performed to ultimately synthesize a supramolecular polymer chiral catalyst. The catalyst's raw materials are readily available, the method is simple to operate, and the reaction conditions are mild. A pronounced metal-ligand charge transfer (mLCT) phenomenon is observed during the self-assembly process. After self-assembly, the chirality of compounds D-4 and L-4 is successfully transferred to the entire self-assembly, effectively amplifying the chiral signal of the system. Controlling the amount of chiral monomers can lead to changes in the polymer, as well as the chirality induction effects of different assembly procedures, making it an ideal component for preparing supramolecular chiral catalysts.

[0050] The present invention compares different self-assembly procedures, including compound L-4 or compound D-4 and monomer 7 in Cu + The polymers assembled under the complex, the control experimental compound L-4 or compound D-4 and monomer 7, monomer 7 and Cu + Metal complex, compound L-4 or compound D-4 and Cu + Assembly of metal complexes. 1 The data were characterized by HNMR, ultraviolet absorption spectroscopy (UV), and circular dichroism (CD) to obtain characterization data. The research included the formation of supramolecular polymers through self-assembly, the changes in polymers brought about by controlling the amount of chiral monomers, and the chirality-inducing effects of different assembly procedures.

[0051] The present invention prepares chiral catalysts P-P1 / M-P1 (D-4 / L-4:7:Cu + =1:16:9),P-P2 / M-P2(D-4 / L-4:7:Cu + =2:16:9), P-P3 / M-P3(D-4 / L-4:7:Cu + =3:16:9),P-P4 / M-P4(D-4 / L-4:7:Cu +=4:16:9). The experimental results show that the amount of chiral monomer has different effects on the change of polymer and the chiral induction of the assembly process, and the polymer assembled with monomer 7 and [Cu(MeCN)4]NTf2 does not show chiral signals. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 Compound D-4 and monomer 7 in Example 7 were prepared in the presence of Cu + The following diagram shows the self-assembly process and Example 8 compound L-4 and monomer 7 on Cu + The self-assembly process diagram below;

[0053] Figure 2 Compound D-4 and monomer 7 in Example 7 were prepared in the presence of Cu + Self-assembled 1 HNMR spectrum;

[0054] Figure 3 Compound L-4 and monomer 7 in Example 8 were prepared in the presence of Cu + Self-assembled 1 HNMR spectrum;

[0055] Figure 4 Compound D-4 and monomer 7 in Example 7 were prepared in the presence of Cu + UV spectrum of self-assembly;

[0056] Figure 5 Compound L-4 and monomer 7 in Example 8 were prepared in the presence of Cu + UV spectrum of self-assembly;

[0057] Figure 6 Compound D-4 of Example 7, compound L-4 of Example 8 and monomer 7 in Cu + The CD spectrum of self-assembly is shown below. DETAILED DESCRIPTION

[0058] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0059] Example 1

[0060] The synthesis of compound D-4 specifically includes the following steps:

[0061] ① Synthesis of compound 1: In a 500 mL two-necked flask, 13.15 mL (1 eq) 1,4-dibromobutane, 13.57 g (3 eq) KI, 11.30 g (3 eq) K2CO3 and 200 mL dry acetonitrile were added. After stirring evenly, the temperature was raised to reflux. In a N2 atmosphere, 60 mL of 4.54×10 -1 mol / L acetonitrile solution of p-diphenol was added dropwise and reacted for 72 hours. The reaction progress was monitored by TLC. After the reaction was completed, the solid was filtered out and washed with deionized water. The washing liquid and the filtrate after filtering out the solid and washing again were extracted three times in a dropping funnel (CH2Cl2: 3×20mL). The organic phase was collected, dried and concentrated. The crude product was added with 100mL of anhydrous ethanol for freezing and crystallization. It was filtered while cold and frozen and filtered three times. The solid was collected to obtain a light brown solid, which was compound 1, with a yield of 78%;

[0062] ② Synthesis of Compound 2: In a 500 mL two-necked flask, 3.00 g (1 eq) of Compound 1, 4.36 g (4 eq) of 1,4-dimethoxybenzene, 1.18 g (5 eq) of paraformaldehyde, and 250 mL of 1,2-dichloroethane were added. The mixture was stirred at room temperature for 0.5 h, and 7.10 mL (5 eq) of boron trifluoride etherate was added to the solution. The mixture was stirred at room temperature for another 2 h. The reaction progress was monitored by TLC. 200 mL of deionized water was added to quench the reaction. After the reaction was completed, the mixture was concentrated by rotary evaporation and extracted three times in a separatory funnel (CH2Cl2: 3×20 mL). The organic phase was collected and dried over Na2SO4. The organic layer was filtered and evaporated to obtain the crude product. The crude product was separated by column chromatography using PE / DCM as the eluent (PE / DCM = 1 / 1, v / v) to obtain Compound 2 as a white solid with a yield of 36.7%.

[0063] ③ Synthesis of compound D-3: In a 50 mL single-necked flask, 600 mg (1 eq) of compound 2, 892 mg (3.02 mmol, 5 eq) of D-type N-Boc tyrosine methyl ester, 835.21 mg (6.04 mmol, 10 eq) of K2CO3, 501.60 mg (5 eq) of KI and 25 mL of pure acetonitrile were added, stirred evenly, and reacted at 75 ° C for 12 h. During this period, the reaction progress was tracked by TCL. After the reaction was completed, 100 mL of deionized water was added. The product was transferred to a dropping funnel and extracted three times (CH2Cl2: 3×20mL). The organic layer was collected and dried over anhydrous Na2SO4, evaporated and concentrated, and separated by column chromatography. The eluent was PE / EA = 15:1 (v / v) for 1 hour to completely elute the halogenated hydrocarbons. Then, the eluent was PE / EA = 5:1 (v / v) for column chromatography to obtain a light yellow oily liquid. After vacuum distillation and cooling, a white solid compound D-3 was obtained. The yield was 75%;

[0064] ④ Synthesis of compound D-4: In a 50 mL two-necked flask, 100 mg of compound D-3, 3 mg of trifluoroacetic acid and 8 mL of dichloromethane were added, stirred evenly, and reacted at 50 ° C for 1 h. During this period, TCL was used to track the reaction progress. 500 mL of deionized water, 10 g of NaHCO3, and 0.186 g of EDTA were added. After heating to boiling, a dialysis bag was added and soaked for 10 min. Then 500 mL of deionized water was added, and 0.186 g of EDTA was added and boiled. The dialysis bag was transferred and soaked for 10 min. The reaction mixture was placed in a dialysis bag and soaked with 500 mL of deionized water for 0.5 h, 4 h, and 6 h respectively. During this period, TCL was used to track the reaction progress and the water was changed. The crude product in the dialysis bag was separated and extracted. The organic layer was collected and a mixed solution of (15 mL of dichloromethane + 15 mL of petroleum ether) was added and concentrated by rotary evaporation to obtain a white solid compound D-4.

[0065] Example 2

[0066] The synthesis of compound L-4 specifically includes the following steps:

[0067] ① Synthesis of compound 1: In a 500 mL two-necked flask, 13.15 mL (1 eq) 1,4-dibromobutane, 13.57 g (3 eq) KI, 11.30 g (3 eq) K2CO3 and 200 mL dry acetonitrile were added. After stirring evenly, the temperature was raised to reflux. In a N2 atmosphere, 60 mL of 4.54×10 -1 mol / L acetonitrile solution of p-diphenol was added dropwise and reacted for 72 hours. The reaction progress was monitored by TLC. After the reaction was completed, the solid was filtered out and washed with deionized water. The washing liquid and the filtrate after filtering out the solid and washing again were extracted three times in a dropping funnel (CH2Cl2: 3×20mL). The organic phase was collected, dried and concentrated. The crude product was added with 100mL of anhydrous ethanol for freezing and crystallization. It was filtered while cold and frozen and filtered three times. The solid was collected to obtain a light brown solid, which was compound 1, with a yield of 78%;

[0068] ② Synthesis of Compound 2: In a 500 mL two-necked flask, 3.00 g (1 eq) of Compound 1, 4.36 g (4 eq) of 1,4-dimethoxybenzene, 1.18 g (5 eq) of paraformaldehyde, and 250 mL of 1,2-dichloroethane were added. The mixture was stirred at room temperature for 0.5 h, and 7.10 mL (5 eq) of boron trifluoride etherate was added to the solution. The mixture was stirred at room temperature for another 2 h. The reaction progress was monitored by TLC. 200 mL of deionized water was added to quench the reaction. After the reaction was completed, the mixture was concentrated by rotary evaporation and extracted three times in a separatory funnel (CH2Cl2: 3×20 mL). The organic phase was collected and dried over Na2SO4. The organic layer was filtered and evaporated to obtain the crude product. The crude product was separated by column chromatography using PE / DCM as the eluent (PE / DCM = 1 / 1, v / v) to obtain Compound 2 as a white solid with a yield of 36.7%.

[0069] ③ Synthesis of compound L-3: In a 50 mL single-necked flask, 600 mg (1 eq) of compound 2, 892 mg (3.02 mmol, 5 eq) of L-N-Boc tyrosine methyl ester, 835.21 mg (6.04 mmol, 10 eq) of K2CO3, 501.60 mg (5 eq) of KI and 25 mL of pure acetonitrile solvent were added, stirred evenly, and reacted at 75 ° C for 12 h. During this period, the reaction progress was tracked by TCL. After the reaction was completed, 100 mL of deionized water was added. Deionized water was transferred to a dropping funnel and extracted three times (CH2Cl2: 3×20mL). The organic layer was collected and dried over anhydrous Na2SO4, evaporated and concentrated, and separated by column chromatography. The eluent was first eluted with PE / EA = 15:1 (v / v) for 1 hour to completely elute the halogenated hydrocarbons. Then, the eluent was PE / EA = 5:1 (v / v) for column chromatography to obtain a light yellow oily liquid. After vacuum distillation and cooling, a white solid compound L-3 was obtained with a yield of 75%.

[0070] ④ Synthesis of compound L-4: In a 50mL two-necked flask, 100mg of compound L-3, 3mg of trifluoroacetic acid and 8mL of dichloromethane were added, stirred evenly, and reacted at 50°C for 1h. During this period, TCL was used to track the reaction progress. 500mL of deionized water, 10g of NaHCO3, and 0.186g of EDTA were added. After heating to boiling, a dialysis bag was added and soaked for 10min. Then 500mL of deionized water was added, and 0.186g of EDTA was added and boiled. The dialysis bag was transferred and soaked for 10min. The reaction mixture was placed in a dialysis bag and soaked with 500mL of deionized water for 0.5h, 4h, and 6h respectively. During this period, TCL was used to track the reaction progress and the water was changed. The crude product in the dialysis bag was separated and extracted. The organic layer was collected and a mixed solution of (15mL of dichloromethane + 15mL of petroleum ether) was added and concentrated by rotary evaporation to obtain a white solid compound L-4.

[0071] Synthesis route of tyrosine-containing column [5] aromatic hydrocarbon derivative compound D-4 or compound L-4:

[0072]

[0073] Example 3

[0074] The synthesis of monomer 7 specifically includes the following steps:

[0075] 1) Synthesis of Compound 5: In a 50 mL two-necked flask, 0.5 g of 2-methyl-8-aminoquinoline (1 eq) and 1.72 g of di-tert-butyl dicarbonate (1.82 mL, 2.5 eq) were dissolved in 20 mL of 1,4-dioxane. The mixture was reacted at 85° C. for 48 h, refluxed under condensation, and separated by column chromatography using a PE:DCM = 1:1 (v:v) eluent. The mixture was concentrated by rotary evaporation to obtain a yellow oily liquid, which was allowed to cool and crystallize to obtain a white crystalline solid, namely Compound 5, with a yield of 70%;

[0076] 2) Synthesis of Compound 6: In a 50 mL single-necked flask, 0.5 g of compound 5 (1 eq) and 429.58 mg of SeO2 (2 eq) were dissolved in 20 mL of 1,4-dioxane, stirred evenly, and reacted at 95°C for 18 h. The mixture was condensed and refluxed, extracted three times with deionized water and dichloromethane, and dried over anhydrous Na2SO4 to obtain an orange-yellow liquid. The mixture was separated by column chromatography using a 1:1 volume ratio of petroleum ether and dichloromethane as the eluent to obtain a bright yellow solid, namely compound 6, with a yield of 75%;

[0077] 3) Synthesis of Monomer 7: In a 50 mL single-necked flask, 0.3 g of compound 6, 7.5 mL of trifluoroacetic acid (1 eq), and 22.5 mL of dichloromethane (3 eq) were added. The mixture was stirred uniformly at room temperature for 50 min to obtain a deep red solution. The solution was adjusted to pH 7 with NaHCO3 solution in an ice-water bath. The solution was extracted three times with deionized water and dichloromethane. The organic phase was collected, dried over anhydrous MgSO4, and concentrated by rotary evaporation to obtain orange crystals, namely monomer 7, with a yield of 75%.

[0078] Synthesis route of monomer 7:

[0079]

[0080] Example 4

[0081] Cu + The synthesis of the metal complex specifically comprises the following steps:

[0082] In a N2 glove box, 1.6 g of bistrifluoromethylsulfonyl imide (2 eq) and 0.8 g of cuprous oxide (1 eq) were dissolved in 10 mL of acetonitrile and stirred at room temperature for 15 h. The mixture was filtered through SiO2, rinsed with dichloromethane, and concentrated by rotary evaporation. 3 mL of dichloromethane was added and the mixture was allowed to stand in a vial. Ether was added until the upper liquid became turbid. After standing for 2 days, white crystals [Cu(MeCN)4]NTf2 appeared. The mixture was sealed well to prevent water absorption and oxidation.

[0083] Cu + Synthesis route of metal complexes:

[0084]

[0085] Example 5

[0086] The preparation of amino acid functionalized column [5] aromatic-based supramolecular chiral catalyst P-P1 specifically includes the following steps:

[0087] Using the raw materials prepared in Example 1-4, D-4 (4.88 mg, 0.0019 mmol, 1 eq), monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 1:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst P-P1. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0088] Example 6

[0089] The preparation of amino acid functionalized column [5] aromatic-based supramolecular chiral catalyst M-P1 specifically includes the following steps:

[0090] Using the raw materials prepared in Example 1-4, L-4 (4.88 mg, 0.0019 mmol, 1 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 1:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst M-P1. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0091] Example 7

[0092] The preparation of amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst P-P2 specifically includes the following steps:

[0093] Using the raw materials prepared in Example 1-4, D-4 (9.76 mg, 0.0038 mmol, 2 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 2:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst P-P2. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0094] Example 8

[0095] The preparation of amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst M-P2 specifically includes the following steps:

[0096] Using the raw materials prepared in Example 1-4, L-4 (9.76 mg, 0.0038 mmol, 2 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 2:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst M-P2. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0097] Example 9

[0098] The preparation of amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst P-P3 specifically includes the following steps:

[0099] Using the raw materials prepared in Example 1-4, D-4 (14.64 mg, 0.0057 mmol, 3 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 3:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst P-P3. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0100] Example 10

[0101] The preparation of amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst M-P3 specifically includes the following steps:

[0102] Using the raw materials prepared in Example 1-4, L-4 (14.64 mg, 0.0057 mmol, 3 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 3:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst M-P3. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0103] Example 11

[0104] The preparation of amino acid functionalized column [5] aromatic-based supramolecular chiral catalyst P-P4 specifically includes the following steps:

[0105] Using the raw materials prepared in Example 1-4, D-4 (19.52 mg, 0.0076 mmol, 4 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 4:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst P-P4. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0106] Example 12

[0107] The preparation of amino acid functionalized column [5] aromatic-based supramolecular chiral catalyst M-P4 specifically includes the following steps:

[0108] Using the raw materials prepared in Example 1-4, L-4 (19.52 mg, 0.0076 mmol, 4 eq) monomer 7 (5 mg, 0.030 mmol, 16 eq) and [Cu(MeCN)4]NTf2 (9.68 mg, 0.017 mmol, 9 eq) were dissolved in dry, degassed MeCN (0.5 mL) at a molar ratio of 4:16:9 under N2 atmosphere to obtain a brown solution. The solution was stirred at room temperature for 48 hours, filtered, and distilled under reduced pressure. The solvent was evaporated to obtain a dark brown solid, namely, the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst M-P4. The sample was stored under N2 atmosphere until further experiments / analysis were required.

[0109] Performance testing:

[0110] Figure 2 Compound D-4 and monomer 7 in Example 7 were prepared in the presence of Cu + Self-assembled 1 HNMR spectrum;

[0111] Depend on Figure 2 As you can see, we use 1 HNMR spectra of D-4 and monomer 7 in Cu + The self-assembly was characterized. Compared with D-4 and monomer 7, the proton signal of the system became significantly broadened and split into multiple peaks after self-assembly, indicating the formation of supramolecular polymers.

[0112] Figure 3 Compound L-4 and monomer 7 in Example 8 were prepared in the presence of Cu + Self-assembled 1 HNMR spectrum;

[0113] Depend on Figure 3 As you can see, we use 1 HNMR spectra of L-4 and monomer 7 in Cu + The self-assembly was characterized. Compared with L-4 and monomer 7, the proton signal of the system became significantly broadened and split into multiple peaks after self-assembly, indicating the formation of supramolecular polymers.

[0114] Figure 4 Compound D-4 and monomer 7 in Example 7 were prepared in the presence of Cu + UV spectrum of self-assembly;

[0115] Depend on Figure 4 It can be seen that at a concentration of 1×10 -5mol / L, we observed that D-4 and monomer 7 + Compared with the monomer 7 before self-assembly reaction, the absorption peak is obviously broader in the range of 250-500 nm, and the metal ligand charge transfer (MLCT) phenomenon occurs, forming a supramolecular polymer.

[0116] Figure 5 Compound L-4 and monomer 7 in Example 8 were prepared in the presence of Cu + UV spectrum of self-assembly;

[0117] Depend on Figure 5 It can be seen that at a concentration of 1×10 -5 mol / L, we observed that L-4 and monomer 7 + Compared with the monomer 7 before self-assembly reaction, the absorption peak is obviously broader in the range of 250-500 nm, and the metal ligand charge transfer (MLCT) phenomenon occurs, forming a supramolecular polymer.

[0118] Figure 6 Compound D-4 of Example 7, compound L-4 of Example 8 and monomer 7 in Cu + The CD spectrum of self-assembly is shown below.

[0119] Depend on Figure 6 It can be seen that compounds D-4, L-4 and monomer 7 have + By comparing the self-assembled polymers under Cu, it was found that they showed strong CD signals at 300-600nm, indicating that polymers with chiral induction ability have been formed. + Self-assembled polymers L-4 and monomer 7 on Cu + The CD signals of the self-assembled polymers are mirror images of each other. The polymer assembled with D-4 exhibits a positive Cotton effect at 325-375nm and a negative Cotton effect at 375nm-600nm. Conversely, the polymer assembled with L-4 exhibits a negative Cotton effect at 325-375nm and a positive Cotton effect at 375nm-600nm. This indicates that different configurations affect the choice of chiral induction. We can use compounds D-4 and L-4 with different configurations to control the chiral properties of supramolecular systems.

[0120] The disclosed embodiments are described to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is to be construed in the widest possible manner consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst, characterized in that: The specific steps include: (1) Synthesis of Compound D-4 or Compound L-4 ①Synthesis of compound 1 1,4-dibromobutane, KI, K2CO3 and acetonitrile were stirred uniformly and then heated to reflux to obtain a mixed solution. An acetonitrile solution of p-diphenol was added dropwise to the mixed solution in an N2 atmosphere. After the addition was complete, the mixture was reacted. After the reaction was completed, the solid was filtered out and washed with deionized water. The mixture was extracted, and the organic phase was collected, dried and concentrated. The crude product was added with anhydrous ethanol and frozen for crystallization. The product was filtered while cold and the solid was collected to obtain compound 1. ②Synthesis of compound 2 Compound 1, 1,4-dimethoxybenzene, paraformaldehyde, and 1,2-dichloroethane were stirred at room temperature, and then boron trifluoride etherate was added to the solution, and then stirred at room temperature. Deionized water was added to quench the reaction. After the reaction was completed, the mixture was concentrated by rotary evaporation, and the organic phase was collected. The organic layer was dried, filtered, and evaporated to obtain a crude product, which was separated by column chromatography to obtain compound 2; ③Synthesis of Compound D-3 and Compound L-3 Compound 2, D- or L-type N-Boc tyrosine methyl ester, K2CO3, KI, and acetonitrile solution were stirred uniformly and heated for reaction. After the reaction, deionized water was added and the mixture was extracted. The organic layer was collected and dried, evaporated and concentrated, and separated by column chromatography to obtain a light yellow oily liquid. After vacuum distillation and cooling, a white solid was obtained, which is compound D-3 or compound L-3; ④ Synthesis of Compound D-4 and Compound L-4 Compound D-3 or compound L-3, trifluoroacetic acid, and dichloromethane are stirred uniformly to react, and then deionized water, NaHCO3, and EDTA are added. After heating to boiling, a dialysis bag is added for soaking, and deionized water and EDTA are added. The dialysis bag is transferred for soaking, and then the reaction mixture is placed in a dialysis bag and soaked with deionized water. The crude product in the dialysis bag is separated and extracted. The organic layer is collected, dichloromethane and petroleum ether are added, and the mixture is concentrated by rotary evaporation to obtain compound D-4 or compound L-4; (2) Synthesis of monomer 7 1) Synthesis of compound 5 2-Methyl-8-aminoquinoline and di-tert-butyl dicarbonate were dissolved in 1,4-dioxane, heated for reaction, condensed under reflux, separated by column chromatography, and concentrated by rotary evaporation to obtain a yellow oily liquid. The product was allowed to stand and cool to crystallize, and a white crystalline solid was obtained, which was compound 5. 2) Synthesis of Compound 6 Compound 5 and SeO2 were dissolved in 1,4-dioxane, stirred evenly, heated for reaction, condensed under reflux, extracted, and dried to obtain an orange-yellow liquid, which was separated by column chromatography to obtain a bright yellow solid, namely compound 6; 3) Synthesis of monomer 7 Compound 6, trifluoroacetic acid, and dichloromethane were stirred uniformly at room temperature to obtain a deep red solution. The solution was adjusted to pH = 7 under ice, extracted, and the organic phase was collected, dried, and concentrated by rotary evaporation to obtain orange crystals, which were monomer 7; (3)Cu + Synthesis of Metal Complexes: Dissolve bistrifluoromethylsulfonyl imide and cuprous oxide in acetonitrile under a nitrogen atmosphere and stir at room temperature. Filter the mixture through SiO2, rinse with dichloromethane, and concentrate by rotary evaporation. Add dichloromethane and allow to stand. Add ether until the upper layer becomes turbid. Allow to stand and form white crystals, which are [Cu(MeCN)4]NTf2. Store in a sealed container. (4) Preparation of amino acid functionalized column[5] aromatic-based supramolecular chiral catalyst: Compound D-4 or compound L-4, monomer 7 and [Cu(MeCN)4]NTf2 were stirred at room temperature for 48 hours with acetonitrile as solvent under N2 protection, filtered, and distilled under reduced pressure to obtain the amino acid functionalized column [5] aromatic-based supramolecular chiral catalyst.

2. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step ①, the mass volume ratio of the 1,4-dibromobutane, KI, K2CO3, acetonitrile and acetonitrile solution of p-diphenol is 13.15mL:13.57g:11.30g:200mL:60mL, and the concentration of the acetonitrile solution of p-diphenol is 4.54×10 -1 mol / L; the reaction time is 72h.

3. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step ②, the mass volume ratio of the compound 1, 1,4-dimethoxybenzene, paraformaldehyde, 1,2-dichloroethane and boron trifluoride etherate is 3.00 g:4.36 g:1.18 g:250 mL:7.10 mL; the compound 1, 1,4-dimethoxybenzene, paraformaldehyde and 1,2-dichloroethane are stirred at room temperature for 0.5 h, and then boron trifluoride etherate is added to the solution, and then stirred at room temperature for 2 h.

4. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step ③, the mass volume ratio of compound 2, D or L-type N-Boc tyrosine methyl ester, K2CO3, KI and acetonitrile is 600 mg:892 mg:835.21 mg:501.60 mg:25 mL; the heating reaction temperature is 75°C, and the heating reaction time is 12 h.

5. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step ④, the mass volume ratio of compound D-3 or compound L-3, trifluoroacetic acid and dichloromethane is 100 mg:3 mg:8 mL; the reaction temperature is 50° C., and the reaction time is 1 h.

6. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step 1), the mass volume ratio of the 2-methyl-8-aminoquinoline, di-tert-butyl dicarbonate and 1,4-dioxane is 0.5 g:1.72 g:20 mL; the heating reaction temperature is 85° C., and the heating reaction time is 48 h.

7. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step 2), the mass volume ratio of the compound 5, SeO2, and 1,4-dioxane is 0.5 g:429.58 g:20 mL; the heating reaction temperature is 95° C., and the heating reaction time is 18 h.

8. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step 3), the mass volume ratio of the compound 6, trifluoroacetic acid and dichloromethane is 3.0 g:7.5 mL:22.5 mL; and the mixture is stirred uniformly at room temperature for 50 min.

9. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step (3), the mass volume ratio of the bistrifluoromethylsulfonyl imide, cuprous oxide and acetonitrile is 1.6 g:0.8 g:10 mL; and the mixture is stirred at room temperature for 15 h.

10. The method for preparing an amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst according to claim 1, characterized in that: In step (4), the compound D-4 or compound L-4, monomer 7 and [Cu(MeCN)4]NTf2 are self-assembled in a molar ratio of 1:16:9, 2:16:9, 3:16:9 or 4:16:9 to obtain the amino acid functionalized column [5] aromatic hydrocarbon-based supramolecular chiral catalyst.

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