Water-soluble cationic nut [12] arene and synthetic method and application thereof

Abstract

The invention discloses water-soluble cationic nut [12] arene as well as a synthesis method and application thereof. The invention designs and synthesizes a water-soluble cationic nut [12] aromatic hydrocarbon. As a supramolecular macrocyclic host, the substance has the advantages of simple synthesis, considerable yield, low cost and the like, has a large, symmetrical and rigid cavity, and can accommodate various hydrophobic guest molecules.

Description

Technical Field

[0001] The present invention belongs to the fields of organic synthesis and supramolecular host-guest chemistry, and relates to the synthesis of a water-soluble cationic spiro

[12] arene and its application in host-guest chemistry. Background Art

[0002] In supramolecular chemistry, five generations of classic macrocyclic hosts have emerged successively, namely crown ethers, cyclodextrins, calixarenes, cucurbiturils and pillararenes. These macrocycles have been widely used in various fields due to their pre-organized cavity structures and good host-guest properties. In recent years, many new hosts such as carbon nanotubes, crown[n]arenes and spiroaromatics have also emerged, and have shown unique advantages in the fields of catalysis, adsorption separation, molecular recognition and molecular self-assembly.

[0003] Among these new macrocycles, spiroarene has a large, symmetric and rigid cavity, is easily functionalized on the methylene bridge and hydroquinone units, and has a considerable yield, making it an ideal host molecule. However, the reported spiroarenes have poor water solubility and cannot meet the need for host-guest recognition in the aqueous phase. Therefore, it is crucial to design and synthesize a water-soluble spiroarene to achieve host-guest recognition in the aqueous phase.

[0004] At present, water-soluble host molecules play an important role in many fields. For example, in 2021, Huang Jianbin's group published a paper titled "Visual Recognition of Ortho-xylene based on its Host-Guest Crystalline Self-Assembly with α-Cyclodextrin", which used α-cyclodextrin to combine with o-xylene to form a hydrogel, making it easy to distinguish xylene isomers. In 2022, Xing Lingbao's group published a paper titled "Novel Strategy ofConstructing Artificial Light-Harvesting System with Two-Step Sequential Energy Transfer for Efficient Photocatalysis in Water", which used the host-guest interaction between cyano-substituted paraphenylethylene derivatives (PPTA) and water-soluble pillar[5]arene (WP5) to construct a new light energy harvesting system. In 2022, Yao Yong's research group published "A High-Yield Synthesis of [M]biphenyl-Extended Pillar[n]arenes for an Efficient Selective Inclusion of Toluene and M-Xylene in the Solid State", which introduced two hydrophilic polyethylene glycol chains into the biphenyl-extended pillar[6]arenes to prepare the water-soluble macrocyclic AM-[2]BP-ExP6

[71] The macrocycle forms a 2:1 host-guest complex with quaternary ammonium salt-modified TPE (QTPE), effectively restricting the rotation of TPE and enhancing the fluorescence of the guest molecule. The host-guest complex can further self-assemble into fluorescent nanoparticles for application in biological imaging.

[0005] Although there has been a lot of research on water-soluble macrocycles in recent years, there are still problems such as low synthesis yield, high cost, and limited cavity size that cannot meet the needs of binding large-volume guest molecules. Summary of the Invention

[0006] To achieve supramolecular host-guest recognition in aqueous phase, a water-soluble cationic nutraceutical

[12] arene was designed and synthesized. This material has the advantages of simple synthesis, good yield and low cost as a supramolecular macrocyclic host, and has a large, symmetrical and rigid cavity that can accommodate a variety of hydrophobic guest molecules.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] Preparation method of a water-soluble cationic calix

[12] arene

[0009]

[0010] The preparation method of a water-soluble cationic calix

[12] arene described above includes the following steps:

[0011] A synthesis method of a water-soluble cationic calix

[12] arene, characterized in that it includes the following steps:

[0012] (1) Under the protection of inert gas and in an ice-water bath, add compound 1 into a container filled with an organic solvent, add pyridine and trifluoromethanesulfonic anhydride, stir and react. After the reaction is completed, add water to quench the reaction, extract and separate the liquid, collect the organic phase, dry it, concentrate it, and separate and purify it to obtain a white transparent oily product, that is, compound 2;

[0013] The structure of the said compound 1 is as follows: Chemical name: 4,4'-dihydroxydiphenylmethane

[0014] (2) Under the protection of inert gas, add compound 2, 2,5-dimethoxyphenylboronic acid, anhydrous potassium carbonate and tetrakis(triphenylphosphine)palladium into a mixed solution of toluene, ethanol and water (V 甲苯 :V 乙醇 :V 水 =5:4:2), reflux and react at 85-90 °C. After the reaction is completed, cool to room temperature, wash and separate the liquid, collect the organic phase, dry it with anhydrous sodium sulfate, concentrate it to obtain a white product, that is, compound 3.

[0015] (3) Under the protection of inert gas, dissolve compound 3 in chloroform solution to obtain a chloroform solution of compound 3. Add boron tribromide under ice-water bath conditions, stir at room temperature for 10-12 h. After the reaction is completed, quickly add 100–120 mL of ice-water mixture to the reaction solution, continue to stir at room temperature for 1-2 h, then quickly filter, collect the filter cake, and wash it with water and chloroform for many times; dry the filter cake to obtain a light brown solid, that is, compound 4;

[0016] (4) Under the protection of inert gas, dissolve anhydrous potassium carbonate and 1,4-dibromobutane in 120-150 mL of acetone solution, dropwise add the acetone solution of compound 4, reflux at 60-65 °C for 20-24 h, and the solution gradually turns reddish-brown; after the reaction is completed, cool the reaction solution to room temperature, wash and separate the liquid, collect the organic phase, dry it with anhydrous sodium sulfate, concentrate it to obtain a crude product, and after separation and purification, obtain a light yellow oily liquid product, that is, compound 5;

[0017] (5) Under the protection of inert gas, dissolve compound 5 in chloroform solution to obtain the chloroform solution of compound 5. Successively add methylal and boron trifluoride diethyl ether, stir at room temperature. After the reaction is completed, add a small amount of water to quench the reaction, wash, separate the liquid, collect the organic phase, dry it with anhydrous sodium sulfate, concentrate, separate and purify to obtain a white oily product, namely compound 6;

[0018] (6) Under the protection of inert gas, add compound 6 and trimethylamine to absolute ethanol, reflux at 80 - 85 °C for 12–18 h. After the reaction is completed, cool it to room temperature, rotary evaporate to remove the solvent to obtain a crude product. First, add a small amount of deionized water to dissolve the crude product, then add an appropriate amount of acetone solution, and a white solid will precipitate. After centrifugation, a white solid is obtained; repeat the reprecipitation treatment 4 - 5 times, and dry it at 65–70 °C to obtain a white solid, namely compound 7.

[0019] (7) Dissolve compound 7 in deionized water solution to obtain a water-soluble cationic spiro

[12] arene solution.

[0020] In the above method, in step (1), the organic solvent is selected from dichloromethane, chloroform or toluene; the specific steps of separation and purification are as follows: pack a chromatography column with silica gel of 200 - 300 mesh, use petroleum ether:dichloromethane = 2:1 as the eluent, and carry out column chromatography separation and purification; the addition amount of pyridine is 20 - z times the equivalent amount of compound 1; the addition amount of trifluoromethanesulfonic anhydride is 3 - 5 times the equivalent amount of compound 1.

[0021] In the above method, in step (2), the organic solvents include toluene and ethanol; the specific separation and purification is as follows: pack a chromatography column with silica gel of 200 - 300 mesh, use a mixed solution of petroleum ether and ethyl acetate as the eluent (V 石油醚 :V 乙酸乙酯 = 20:3), and carry out column chromatography separation and purification; the addition amount of 2,5 - dimethoxyphenylboronic acid is 3 - 5 times the equivalent amount of compound 2; the addition amount of anhydrous potassium carbonate is 15 - 20 times the equivalent amount of compound 2.

[0022] In the above method, in step (3), the base includes Na2CO3, K2CO3, KOH or NaOH, and the addition amount of the base is: 15 - 25 times the molar amount of compound 2; the drying is carried out in a vacuum drying oven at 75 - 80 °C for 12 - 24 h; the addition amount of boron tribromide is 12 - 15 times the equivalent amount of compound 3.

[0023] In the above method, in step (4), the organic solvent includes acetone; the addition amount of anhydrous potassium carbonate is 15 - 20 times the equivalent amount of compound 4; the addition amount of 1,4 - dibromobutane is 15 - 20 times the equivalent amount of compound 4. It should be noted that there is an error in the original text where "the addition amount of pyridine is 20 - z times the equivalent amount of compound 1", and it should be corrected to a specific numerical value for accurate translation. The above translation is based on the corrected content as much as possible.

[0024] In the above method, in step (5), the specific steps of separation and purification are as follows: packing a chromatographic column with silica gel of 200 - 300 mesh, using a mixed solution of petroleum ether and dichloromethane (Vpetroleum ether: Vdichloromethane = 1:1) as the eluent for column chromatography separation and purification; the addition amount of methylal is 0.1 - 0.2 mL; the addition amount of boron trifluoride diethyl etherate is 0.8 - 1.0 mL.

[0025] In the above method, in step (6), the trimethylamine is an ethanol solution containing 2 mol / L trimethylamine; the addition amount of trimethylamine is 45 - 50 times the equivalent amount of compound 6; the addition amount of absolute ethanol is 40 - 50 mL.

[0026] In the above method, in steps (1) to (6), the inert gas includes nitrogen or argon.

[0027] The water-soluble cationic spiro

[12] arene of the present invention is applied to the study of host-guest binding systems in aqueous phase to reveal the selective binding mechanism of the host structure to guest molecules.

[0028] The reaction route of the present invention is:

[0029]

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

[0031] (1) The water-soluble cationic spiro

[12] arene provided by the present invention is simple to synthesize, has an appreciable yield, and can complex with a variety of guest molecules in aqueous phase, with a binding constant reaching 10 4 -10 6 .

[0032] (2) The water-soluble cationic spiro

[12] arene provided by the present invention is a compound that can emit fluorescence under the excitation of a light source with a specific wavelength. Therefore, the binding constant between the host and the guest can be obtained only through a simple fluorescence test. Description of the Drawings

[0033] Figure 1 are the ultraviolet-visible absorption spectrum (a) and fluorescence emission spectrum (b) of the water-soluble cationic spiro

[12] arene solution prepared in Example 2.

[0034] Figure 2 are the ultraviolet absorption spectrum (a) and fluorescence emission spectrum (b) of the water-soluble cationic spiro

[12] arene solution prepared in Example 2 and sodium copper chlorophyllin.

[0035] Figure 3UV absorption spectra (a) and fluorescence emission spectra (b) of the water-soluble cationic

[12] crownarene solution configured in Example 2 and pyridine dicarboxylic acid.

[0036] Figure 4 Fluorescence emission spectra (a) and binding model fitting curves (b) of the water-soluble cationic

[12] crownarene solution configured in Example 2 and sodium copper chlorophyllin with different equivalent ratios.

[0037] Figure 5 Fluorescence emission spectra (a) and binding model fitting curves (b) of the water-soluble cationic

[12] crownarene solution configured in Example 2 and pyridine dicarboxylic acid with different equivalent ratios.

[0038] Figure 6 1H NMR spectrum of Compound 2;

[0039] Figure 7 1H NMR spectrum of Compound 3;

[0040] Figure 8 1H NMR spectrum of Compound 4;

[0041] Figure 9 1H NMR spectrum of Compound 5;

[0042] Figure 10 1H NMR spectrum of Compound 6;

[0043] Figure 11 1H NMR spectrum of Compound 7. Detailed implementation manners

[0044] The following further illustrates specific examples of the present invention in conjunction with the accompanying drawings and specific embodiments, but the scope claimed by the present invention is not limited to the scope described in the embodiments.

[0045] Example 1

[0046] This example provides a preparation method of a water-soluble cationic

[12] crownarene, and the synthesis route is as follows:

[0047]

[0048] The synthesis steps are as follows:

[0049] (1) Synthesis of Compound 2:

[0050]

[0051] Under nitrogen protection and ice-water bath conditions, 4,4'-dihydroxydiphenylmethane (Compound 1-1, 1.0 g, 5.0 mmol) was added to 200 mL of dry dichloromethane. Subsequently, pyridine (10 g, 125.0 mmol) was added via syringe first, and the reaction was carried out for 15 min. Then, trifluoromethanesulfonic anhydride (7.0 g, 25.0 mmol) was added dropwise via syringe, and the mixture was stirred for 5 h. The reaction progress was monitored by TLC. After the reaction was completed, a small amount of water was slowly added to quench the reaction, and then extracted and separated with 100×3 mL of water. The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated. A chromatography column was packed with silica gel of 200-300 mesh, and petroleum ether:dichloromethane = 2:1 was used as the eluent for column chromatography purification. A white transparent oily product (Compound 2, 2.1 g) was obtained with a yield of 93%.

[0052] 1H NMR data of Compound 2: 1 H NMR(400MHz,Chloroform-d)δ7.30–7.12(m,8H),4.01(s,2H).(As Figure 6 shown).

[0053] (2) Synthesis of Compound 3:

[0054]

[0055] Under nitrogen protection, Compound 2 (1.0 g, 2.3 mmol), 2,5-dimethoxyphenylboronic acid (1.8 g, 9.2 mmol), anhydrous potassium carbonate (3.4 g, 23.0 mmol) and a catalytic amount of tetrakis(triphenylphosphine)palladium (100 mg, 0.1 mmol) were added to a mixed solution of toluene, ethanol and water (V 甲苯 :V 乙醇 :V 水 = 5:4:2), and refluxed at 90 °C for 12 h. The reaction progress was monitored by TLC. After the reaction was completed, the temperature was lowered to room temperature, and 100×3 mL of water was added for washing and liquid separation. The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated. A chromatography column was packed with silica gel of 200-300 mesh, and a mixed solution of petroleum ether and ethyl acetate was used as the eluent (V 石油醚 :V 乙酸乙酯 = 20:3) for column chromatography purification. A white product (Compound 3, 0.86 g) was obtained with a yield of 90%.

[0056] 1H NMR data of Compound 3: 11H NMR (400 MHz, Chloroform-d) δ 7.51–7.43 (m, 4H), 7.32–7.26 (m, 4H), 6.94–6.88 (m, 4H), 6.84 (dd, J = 9.0, 3.0 Hz, 2H), 4.06 (s, 2H), 3.80 (s, 6H), 3.76 (s, 6H). (As Figure 7 shown).

[0057] (3) Synthesis of Compound 4:

[0058]

[0059] Under nitrogen protection, dissolve Compound 3 (400 mg, 1.0 mmol) in 100 mL of chloroform solution. Slowly add boron tribromide (1.5 mL, 16.0 mmol) dropwise with a syringe under an ice-water bath, and stir at room temperature for 12 h. After the reaction is completed, quickly add 100 mL of ice-water mixture to the reaction solution, and continue to stir at room temperature for 1-2 h. At this time, white solid can be observed. Then quickly filter by suction, collect the filter cake, and wash it with water and chloroform for several times. Place the filter cake in a vacuum drying oven and dry it at 75 °C for 24 h to obtain a light brown solid (Compound 4, 327.2 mg), with a yield of 95%.

[0060] 1H NMR data of Compound 4: 1 1H NMR (400 MHz, DMSO-d6) δ 8.73 (s, 4H), 7.49–7.39 (m, 4H), 7.27 (d, J = 8.0 Hz, 4H), 6.72 (d, J = 8.6 Hz, 2H), 6.64 (d, J = 2.9 Hz, 2H), 6.55 (dd, J = 8.5, 2.9 Hz, 2H), 3.96 (s, 2H). (As Figure 8 shown).

[0061] (4) Synthesis of Compound 5:

[0062]

[0063] Under nitrogen protection, anhydrous potassium carbonate (2.7 g, 20.0 mmol) and 1,4-dibromobutane (2.4 mL, 20.0 mmol) were dissolved in 150 mL of acetone solution. The acetone solution of compound 4 (dissolving 350 mg, 1.0 mmol of compound 1-4 in 50 mL of acetone solution) was slowly added dropwise within 1 h, and the mixture was refluxed at 60 °C for 24 h, and the solution turned reddish-brown. The reaction process was monitored by TLC. After the reaction was completed, the reaction solution was cooled to room temperature, washed with 100×3 mL of water and separated by liquid separation. The organic phase was collected, dried over anhydrous sodium sulfate, concentrated to obtain a crude product. A chromatography column was packed with silica gel of 200-300 mesh, and a mixed solution of petroleum ether and dichloromethane (V 石油醚 :V 二氯甲烷 = 1:1) was used as the eluent for column chromatography separation and purification. A light yellow oily liquid product (compound 5, 454 mg) was obtained with a yield of 54%.

[0064] 1H NMR data of compound 5: 1 H NMR (400 MHz, Chloroform-d) δ 7.46 (d, J = 7.8 Hz, 4H), 7.27 (d, J = 7.9 Hz, 4H), 6.89 (dd, J = 6.1, 2.9 Hz, 4H), 6.80 (dd, J = 8.9, 3.0 Hz, 2H), 4.07 (s, 2H), 3.98 (t, J = 6.0 Hz, 4H), 3.88 (t, J = 5.9 Hz, 4H), 3.49 (t, J = 6.6 Hz, 4H), 3.32 (t, J = 6.5 Hz, 4H), 2.12–2.01 (m, 4H), 1.97–1.85 (m, 8H), 1.85–1.76 (m, 4H). (As Figure 9 shown).

[0065] (5) Synthesis of compound 6:

[0066]

[0067] Under nitrogen protection, compound 5 (300 mg, 1.0 mmol) was dissolved in 200 mL of chloroform solution. Subsequently, 0.2 mL of methylal and 1.0 mL of boron trifluoride diethyl ether were successively added with a syringe, and the mixture was stirred at room temperature for 30 min. The reaction process was monitored by TLC. After the reaction was completed, a small amount of water was added to quench the reaction, and then washed with 100×3 mL of water and separated by liquid separation. The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated. A chromatography column was packed with silica gel of 200-300 mesh, and a mixed solution of petroleum ether and dichloromethane (V 石油醚 :V 二氯甲烷 = 1:1) was used as the eluent for column chromatography separation and purification. A white oily product (compound 6, 98 mg) was obtained with a yield of 20%.

[0068] 1H NMR data of Compound 6: 1 H NMR(400MHz,Chloroform-d)δ7.48(d,J=7.9Hz,12H),7.28(d,J=8.1Hz,12H),6.87(s,6H),6.78(s,6H),4.09(s,6H),4.06–3.97(m,18H),3.80(t,J=5.9Hz,12H),3.47(t,J=6.4Hz,12H),3.27(t,J=6.5Hz,12H),2.07–1.99(m,12H),1.96(dt,J=9.4,5.9Hz,12H),1.88–1.81(m,12H),1.75(dt,J=9.6,6.6,6.0Hz,12H).(As Figure 10 shown).

[0069] (6)Synthesis of Compound 7:

[0070]

[0071] Under nitrogen protection,Compound 6(500mg,0.595mmol)and trimethylamine(2mol / L ethanol solution,3.2mL,23.8mmol)were added to 50mL of anhydrous ethanol,and the mixture was refluxed overnight at 80℃.After the reaction was completed,it was cooled to room temperature.Then the solvent was removed by rotary evaporation to obtain a crude product.First,a small amount of deionized water was added to dissolve the crude product,and then an appropriate amount of acetone solution was added to precipitate a white solid.After centrifugation,a white solid was obtained.The re-precipitation treatment was repeated 4-5 times,and the product was dried at 65℃ to obtain Compound 7 with higher purity(white solid,410mg,88%).

[0072] 1H NMR data of Compound 7: 1 H NMR(400MHz,Methanol-d4)δ7.69(d,J=7.9Hz,12H),7.49(d,J=8.0Hz,12H),7.09(s,6H),6.92(s,6H),4.22(t,J=5.9Hz,13H),4.15(d,J=11.5Hz,13H),4.03(t,J=5.5Hz,12H),3.60(t,J=8.4Hz,12H),3.40(s,7H),3.37(d,J=4.7Hz,7H),3.24(s,54H),3.01(s,53H),2.07–1.95(m,25H),1.82(q,J=9.6,6.1Hz,24H).(As Figure 11 shown).

[0073] Example 2

[0074] In this example, the spectral and fluorescence emission spectra of the water-soluble cationic

[12] arene solution (WHN

[12] ) were tested.

[0075] The water-soluble cationic

[12] arene prepared in Example 1 was formulated into a solution with a concentration of 5×10 -6 mol / L with distilled water. Ultraviolet-visible absorption spectroscopy and fluorescence emission spectroscopy were performed. The measured ultraviolet-visible absorption spectrum and fluorescence emission spectrum are respectively shown in Figure 1 (a) and (b) below. The ultraviolet-visible absorption wavelengths are 260 nm and 305 nm, and the strongest emission wavelength of the fluorescence emission spectrum is 370 nm.

[0076] Example 3

[0077] Host-guest tests of the water-soluble cationic

[12] arene solution (WHN

[12] ) with sodium copper chlorophyllin (G1) and pyridine dicarboxylic acid (G2).

[0078] Prepare a 5×10 -4 mol / L water-soluble cationic

[12] arene solution (the preparation method is as in Example 2). Prepare a 5×10 -4 mol / L aqueous solution of sodium copper chlorophyllin with distilled water, and prepare a 5×10 -4 mol / L methanol solution of pyridine dicarboxylic acid with methanol. Then, for 1 equivalent of the

[12] arene solution and 3 equivalents of the guest solution, measure the ultraviolet absorption spectra and fluorescence emission spectra before and after mixing, as shown in Figure 2 (a) and (b) below and Figure 3 (a) and (b) below.

[0079] Example 4

[0080] Fluorescence titration tests of the water-soluble cationic

[12] arene solution (WHN

[12] ) with the sodium copper chlorophyllin solution and the pyridine dicarboxylic acid solution.

[0081] Prepare a 5×10 -6 mol / L water-soluble cationic

[12] arene solution (the preparation method is as in Example 3). Prepare 5×10 -4 mol / L mother liquors of sodium copper chlorophyllin and pyridine dicarboxylic acid (the preparation method is as in Example 3). Then, gradually add 0 - 5.5 equivalents of the guest mother liquor solution to the

[12] arene solution, and perform fluorescence emission spectroscopy tests at an excitation wavelength of 305 nm in sequence.

[0082] From Figure 4 andFigure 5 It can be found that as the concentration of the guest in the test system increases, the fluorescence emission intensity of the host gradually decreases accordingly, which is manifested as fluorescence quenching. Then, by fitting the data with scientist software, the binding constant between the host and the guest can be obtained.

[0083] The present invention is not limited to the above optional embodiments, and anyone can obtain other various forms of products under the inspiration of the present invention. However, no matter what changes are made in its shape or structure, as long as the technical solutions fall within the scope defined by the claims of the present invention, they are all within the protection scope of the present invention.

Claims

1. A method for synthesizing a water-soluble cationic calix[12]arene, characterized in that, It includes the following steps: (1) Under the protection of inert gas and in an ice-water bath, add Compound 1 into a container filled with an organic solvent, add pyridine and trifluoromethanesulfonic anhydride, stir and react. After the reaction is completed, add water to quench the reaction, extract and separate the layers, collect the organic phase, dry it, concentrate it, and separate and purify it to obtain a white transparent oily product, namely Compound 2; Compound 1 is 4,4'-dihydroxydiphenylmethane; (2) Under the protection of inert gas, add Compound 2, 2,5-dimethoxyphenylboronic acid, anhydrous potassium carbonate, and tetrakis(triphenylphosphine)palladium into a mixed solution of toluene, ethanol, and water, and reflux the reaction at 85 - 90 °C. After the reaction is completed, cool it to room temperature, wash and separate the layers, collect the organic phase, dry it with anhydrous sodium sulfate, concentrate it, and obtain a white product, namely Compound 3; (3) Under the protection of inert gas, dissolve Compound 3 in a chloroform solution to obtain a chloroform solution of Compound 3. Add boron tribromide in an ice-water bath, stir at room temperature. After the reaction is completed, add an ice-water mixture to the reaction solution, continue to stir at room temperature, then quickly filter, collect the filter cake, and wash it with water and chloroform multiple times; dry the filter cake to obtain a light brown solid, namely Compound 4; (4) Under the protection of inert gas, dissolve anhydrous potassium carbonate and 1,4-dibromobutane in an acetone solution, dropwise add an acetone solution of Compound 4, and reflux. The solution gradually turns reddish-brown; after the reaction is completed, cool the reaction solution to room temperature, wash and separate the layers, collect the organic phase, dry it with anhydrous sodium sulfate, concentrate it to obtain a crude product, and after separation and purification, obtain a light yellow oily liquid product, namely Compound 5; (5) Under the protection of inert gas, dissolve Compound 5 in a chloroform solution to obtain a chloroform solution of Compound 5. Successively add methylal and boron trifluoride diethyl ether, stir at room temperature. After the reaction is completed, add a small amount of water to quench the reaction, wash and separate the layers, collect the organic phase, dry it with anhydrous sodium sulfate, concentrate it, separate and purify it to obtain a white oily product, namely Compound 6; (6) Under the protection of inert gas, add Compound 6 and trimethylamine into absolute ethanol, reflux. After the reaction is completed, cool it to room temperature, rotary evaporate to remove the solvent to obtain a crude product. First, add a small amount of deionized water to dissolve the crude product, then add an acetone solution, and a white solid precipitates. After centrifugation, a white solid is obtained; repeatedly perform reprecipitation treatment, dry it to obtain a white solid, namely Compound 7; (7) Dissolve Compound 7 in a deionized water solution to obtain a water-soluble cationic spiro[12]arene solution.

2. The synthesis method of the water-soluble cationic [12]crownarene according to claim 1, wherein In step (1), the organic solvent is selected from dichloromethane, chloroform, or toluene; the specific steps of the separation and purification are: pack a chromatography column with silica gel of 200 - 300 mesh, use petroleum ether: dichloromethane = 2:1 as the eluent, and perform column chromatography separation and purification; the addition amount of pyridine is 20 - 25 times the equivalent of Compound 1; the addition amount of trifluoromethanesulfonic anhydride is 3 - 5 times the equivalent of Compound 1.

3. The synthesis method of the water-soluble cationic [12]crownarene according to claim 1, characterized in that, In step (2), the organic solvents include toluene and ethanol; the separation and purification specifically are: packing a chromatography column with silica gel of 200-300 mesh, using a mixed solution of petroleum ether and ethyl acetate as an eluent (V 石油醚 :V 乙酸乙酯 = 20:3), and performing column chromatography separation and purification; the addition amount of 2,5-dimethoxyphenylboronic acid is 3-5 times the equivalent amount of compound 2; the addition amount of anhydrous potassium carbonate is 15-20 times the equivalent amount of compound 2.

4. The synthesis method of the water-soluble cationic calix[12]arene according to claim 1, characterized in that, In step (3), the base includes Na2CO3, K2CO3, KOH or NaOH, and the addition amount of the base is: 15 - 25 times the molar amount of compound 2; the drying is carried out in a vacuum drying oven at 75 - 80 °C for 12 - 24 h; the addition amount of boron tribromide is 12 - 15 times the equivalent amount of compound 3.

5. The synthesis method of the water-soluble cationic calix[12]arene according to claim 1, wherein, In step (4), the organic solvent includes acetone; the addition amount of anhydrous potassium carbonate is 15 - 20 times the equivalent amount of compound 4; the addition amount of 1,4 - dibromobutane is 15 - 20 times the equivalent amount of compound 4; the reflux time is 20 - 24 h; the reflux temperature is 60 - 65 °C.

6. The synthetic method of the water-soluble cationic [12]crownarene according to claim 1, characterized in that, In step (5), the specific steps of separation and purification are: packing a chromatography column with silica gel of 200 - 300 mesh, using a mixed solution of petroleum ether and dichloromethane (Vpetroleum ether:Vdichloromethane = 1:1) as the eluent for column chromatography separation and purification; the addition amount of methylal is 0.1 - 0.2 mL; the addition amount of boron trifluoride diethyl etherate is 0.8 - 1.0 mL.

7. The synthesis method of the water-soluble cationic calix[12]arene according to claim 1, wherein, In step (6), the trimethylamine is an ethanol solution containing 2 mol / L trimethylamine; the addition amount of trimethylamine is 45 - 50 times the equivalent amount of compound 6; the addition amount of absolute ethanol is 40 - 50 mL; the reflux temperature is 80 - 85 °C, and the reflux time is 12 - 18 h; the number of times of re - precipitation treatment is 4 - 5 times; the drying temperature is 65 - 70 °C.

8. The synthesis method of the water-soluble cationic calix[12]arene according to claim 1, characterized in that, In steps (1) to (6), the inert gas includes nitrogen or argon.

9. The water-soluble cationic spiro[12]arene synthesized by the synthesis method according to any one of claims 1 to 8, characterized in that, The structure is as follows:

10. The water - soluble cationic spiro[12]arene described in claim 9 is applied to the study of the host - guest binding system in the aqueous phase to reveal the selective binding mechanism of the host structure to guest molecules.

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