Deep-hole fluorene [3] arene macrocyclic host compound as well as preparation method and application thereof

Abstract

The invention relates to a deep-hole fluorene [3] arene macrocyclic host compound as well as a preparation method and application thereof. The deep-hole fluorene [3] arene macrocyclic host compound is a water-soluble quinoxalinyl macrocyclic host compound H3. Compared with the prior art, the synthesized water-soluble quinoxaline-based macrocyclic host compound H3 is a deep-hole quinoxaline-based macrocyclic host and is novel in structure, methylene is adopted to replace methylene for bridging, the structural rigidity of macrocyclic molecules can be remarkably improved, then the recognition accuracy of the macrocyclic molecules to guest molecules is enhanced, the depth of the upper edge of the macrocyclic molecules is expanded, and the application range of the macrocyclic molecules is widened. The binding sites between the host and guest molecules are optimized, and the recognition capability of the macrocyclic host to the guest molecules is further enhanced, so that the functional characteristics of the whole molecular system are effectively improved.

Description

Technical Field

[0001] The present invention relates to the technical field of macrocyclic compounds, and in particular to a deep-hole fluorene[3]arene macrocyclic main compound and a preparation method and application thereof. Background Art

[0002] Macrocyclic aromatic hydrocarbons are a class of hydrocarbons consisting of electron-rich aromatic rings connected by sp 3 Hybridized carbon atom-bridged macrocyclic structures. They possess cavities capable of accommodating guests and are widely used in molecular recognition and separation, molecular machines, supramolecular assemblies, drug delivery, and luminescent materials, making them an attractive class of macrocyclic hosts. The advantages of macrocyclic hosts include: 1) ease of synthesis, strong aromaticity, and abundant π electrons; 2) different macrocyclics have varying cavity sizes, translating to a wide range of applications in the recognition of ions, small molecules, and biomacromolecules; 3) the positioning effects of substituents can allow for the macrocyclics to have different connection modes, making them easily adjustable; 4) complexation with substrates can be conveniently detected by nuclear magnetic resonance (NMR); and if the macrocyclic itself possesses a high-performance chromophore, UV and fluorescence spectroscopy can be used to assist in analyzing the binding properties of the macrocyclic host with the substrate; and 5) their structure possesses good chemical stability.

[0003] Fluoren[n]arene is a subclass of macrocyclic molecules, formed by fluorene derivatives bridged by methylene groups at the ortho-alkoxy position. It is mainly divided into two types: fluoren[3]arene and fluoren[5]arene. It is easy to obtain and can be modified to produce products with special structures such as cycloparaphenylene. However, because the bridging part is a methylene group, the structure of this type of macrocycle is relatively flexible and the conformation is easily variable, which is not conducive to the identification of target molecules and the exploration of other functions. Summary of the Invention

[0004] The purpose of the present invention is to overcome the defects of fluorene[n]arene such as structural flexibility and conformational changes that are not conducive to the identification of target molecules, thereby providing a deep-hole fluorene[3]arene macrocyclic main compound and its preparation method and application.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] One of the technical solutions of the present invention is to provide a deep-hole fluorene[3]arene macrocyclic main compound, which is a water-soluble quinoxaline-based macrocyclic main compound H3, and its structural formula is shown below:

[0007]

[0008] Where R is

[0009] The structure of this compound is based on a fluorene[3]arene skeleton. The three aromatic walls are deepened sequentially, with the introduction of quinoxaline groups at the upper edge and water-soluble groups at the lower edge. The main part of the cavity is composed of quinoxaline groups, which deepen the cavity to form a deep, hydrophobic cavity that is richer in electrons. The macrocyclic main body H3 exists alone in water as a dimer in a "kite" conformation. When a suitable guest molecule is present in the aqueous solution, it induces the "kite" conformation and transforms it into a "vase" conformation, encapsulating the guest molecule in the cavity.

[0010] The second technical solution of the present invention is to provide a method for preparing the deep-hole fluorene[3]arene macrocyclic main compound as described in one of the above technical solutions, comprising the following steps:

[0011] S1. Mix methanol, concentrated hydrochloric acid, and 2,7-dihydroxy-9,9-dimethylfluorene, add 4-chlorobutyraldehyde dimethyl acetal, heat to react, and purify to obtain the main aromatic hydrocarbon of chlorobutyraldehyde[3];

[0012] S2. Add N,N-dimethylformamide to the chlorofluorophene[3]arene main body obtained in step S1 to dissolve it, then add 1,2-difluoro-4,5-dinitrobenzene and triethylamine, heat to react, precipitate solid, and purify to obtain the chlorofluorophene[3]arene main body;

[0013] S3. Add ethanol to the chlorohexanitro main body obtained in step S2 to dissolve it, add stannous dichloride dihydrate and concentrated hydrochloric acid, heat to react, precipitate a solid, and obtain the chlorohexanitro main body;

[0014] S4. Add water / ethanol solvent to the chloro-hexamethylenediamine main body obtained in step S3 to dissolve it, add potassium carbonate and glyoxal, and react at room temperature to obtain a chloro-quinoxaline main body;

[0015] S5. Add pyridine to the chloroquinoxaline main body obtained in step S4, heat to react, precipitate a solid, and obtain a water-soluble quinoxaline-based macrocyclic main compound H3.

[0016] In some specific embodiments, in step S1, the molar ratio of 2,7-dihydroxy-9,9-dimethylfluorene to 4-chlorobutyraldehyde dimethyl acetal is 1:3.1.

[0017] In some embodiments, in step S1, the heating reaction is carried out under stirring in an oil bath at 55°C for 4-6 days. Excessively high reaction temperatures or prolonged reaction times can result in the conversion of more products into long-chain polymers, making the reaction solution viscous.

[0018] More preferably, in step S1, the heating reaction is carried out under the conditions of stirring in an oil bath at 55°C for 4 days.

[0019] More preferably, in step S1, methanol and concentrated hydrochloric acid are mixed in an ice-water bath, 2,7-dihydroxy-9,9-dimethylfluorene is added to the mixed solution, and the mixture is stirred at room temperature. After complete dissolution, 4-chlorobutyraldehyde dimethyl acetal is added dropwise to the mixed solution, and the mixture is transferred to a 55°C oil bath and stirred for 4 days. After the reaction is completed, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation, the solid is collected, and the chloro-foot-containing fluorene[3] aromatic hydrocarbon body is obtained after purification by column chromatography. Post-treatment requires pouring a certain concentration of sodium hydroxide solution into the receiving bottle before rotary evaporation.

[0020] In some specific embodiments, in step S2, the molar ratio of chlorofluorene[3]arene, 1,2-difluoro-4,5-dinitrobenzene, and triethylamine is 1:(2-4):(9-11).

[0021] More preferably, in step S2, the molar ratio of chlorofluorene[3]arene, 1,2-difluoro-4,5-dinitrobenzene and triethylamine is 1:3:10.

[0022] In some embodiments, in step S2, the heating reaction is carried out in an oil bath at 55-60° C. for 6-7 hours. Longer reaction times will reduce the yield.

[0023] More preferably, in step S2, the heating reaction condition is: reacting in an oil bath at 60°C for 7 hours.

[0024] As a more preferred embodiment, in step S2, the chlorohexanitro main body obtained in step S1 is dissolved with N,N-dimethylformamide, and then 1,2-difluoro-4,5-dinitrobenzene is added thereto, and triethylamine is added dropwise, and stirred in a 60°C oil bath for 7 hours; after the reaction, most of the triethylamine and N,N-dimethylformamide are removed by rotary evaporation, and 1N hydrochloric acid is added dropwise to the residue until most of the solid is precipitated. After ultrasonication for 2 hours, the residue is filtered under reduced pressure, and the filter residue is rinsed with 1N hydrochloric acid and dissolved with dichloromethane. The filtrate is collected and the solvent is removed, and the chlorohexanitro main body is purified by column chromatography. Post-treatment requires treatment with 1N hydrochloric acid to neutralize the triethylamine and to remove N,N-dimethylformamide from the chlorohexanitro main body.

[0025] In some specific embodiments, in step S3, the molar ratio of the hexanitrochlorobenzene to stannous dichloride dihydrate is not less than 1:120, and the volume ratio of concentrated hydrochloric acid to ethanol is 1:2.6.

[0026] In some specific embodiments, in step S3, the heating reaction conditions are: (105-115) °C in an oil bath for (1.5-2) hours.

[0027] More preferably, in step S3, the heating reaction condition is: oil bath at 110° C. for 1.5 hours.

[0028] More preferably, in step S3, the chlorohexanitro-substrate obtained in step S2 is dissolved in ethanol, stannous chloride dihydrate and concentrated hydrochloric acid are added under ice bath, and the mixture is in an oil bath at 110°C for 1.5 hours. After the reaction is completed, the mixture is cooled to room temperature, 3N hydrochloric acid is added under ice bath, and the solid is filtered to obtain a solid. The solid is then washed with 3N hydrochloric acid and acetonitrile at 0°C, respectively, and the solid is collected and dried under vacuum to obtain the chlorohexanitro-substrate. To prevent oxidation of the product, the product that is not placed in an ice bath should be avoided from being exposed to air for a long time. The concentration of hydrochloric acid used to wash the solid should be no less than 3 mol / L.

[0029] In some specific embodiments, in step S4, the molar ratio of the hexamethylenediamine monomer, potassium carbonate and glyoxal is 1:(7-9):(7-9); the reaction is carried out at room temperature for (16-20) hours.

[0030] More preferably, in step S4, the molar ratio of the hexamethylenediamine, potassium carbonate and glyoxal is 1:8:8; and the reaction is carried out at room temperature for 18 hours.

[0031] More preferably, in step S4, the product prepared in step c is added to a round-bottom flask, the hexachloroquinoline hexaamino body obtained in step S3 is dissolved in a 30% water / ethanol solvent, 8 equivalents of potassium carbonate solid is added, and after stirring at room temperature for 10 minutes, 8 equivalents of 40% glyoxal solution is added, and the reaction is carried out at room temperature for 18 hours; after the reaction is completed, the solid is filtered, washed with water, and dried under vacuum to obtain a relatively pure chloroquinoline body. Post-treatment is performed by washing with deionized water to remove excess potassium carbonate and glyoxal.

[0032] In some specific embodiments, in step S5, the heating reaction conditions are: (105-115) °C in an oil bath for (20-25) hours.

[0033] More preferably, in step S5, the heating reaction is carried out in an oil bath at 110° C. for 24 hours.

[0034] More preferably, in step S5, the product prepared in step d is added to a round-bottom flask, and the chloroquinoxaline wall body obtained in step S4 is stirred with an appropriate amount of pyridine at room temperature until the solid is evenly dispersed, and vigorously stirred in an oil bath at 110°C for 24 hours. After the reaction, the reaction solution is cooled to room temperature, acetone is added to precipitate a white solid, and a crude product is obtained by centrifugation. The solid is refluxed in acetone for 24 hours, cooled to room temperature, and centrifuged. The solid is washed with acetone at least 3 times, the solid is collected, and vacuum dried to obtain a water-soluble quinoxaline macrocyclic main compound H3.

[0035] The third technical solution of the present invention is to provide an application of a deep-hole fluorene[3]arene macrocyclic main compound as described in one of the above technical solutions, wherein the deep-hole fluorene[3]arene macrocyclic main compound is used to identify amphiphilic molecules having adamantane structure.

[0036] The water-soluble quinoxaline-based macrocyclic main body H3 has a large hydrophobic cavity, which can rely on hydrophobic interactions and other non-covalent bond interactions to synergistically recognize amphiphilic molecules with adamantane structure.

[0037] In some specific embodiments, the adamantane-structured amphiphilic molecule is selected from any one of 1-adamantaneacetic acid and 1-adamantanecarboxylic acid.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] (1) The synthesis route of the water-soluble quinoxaline-based macrocyclic compound H3 provided by the present invention is simple, the raw materials are readily available, the reaction conditions are mild, and the reproducibility is good;

[0040] (2) The water-soluble quinoxaline-based macrocyclic host compound H3 synthesized in the present invention is a deep-cavity quinoxaline-based macrocyclic host with a novel structure. The use of methine groups instead of methylene groups for bridging can significantly improve the structural rigidity of the macrocyclic molecule, thereby enhancing its recognition accuracy of guest molecules, and expanding the depth of the upper edge of the macrocyclic ring, optimizing the binding site between the host and guest molecules, further strengthening the recognition ability of the macrocyclic host for guest molecules, thereby effectively improving the functional properties of the entire molecular system. The host has a deeper hydrophobic cavity and more controllable conformation than the methylene-bridged fluorene[3]arene, which enhances the potential application of the macrocyclic host in the fields of supramolecular catalysis, biomimetic recognition, and molecular reaction vessels. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is the H NMR spectrum (600 MHz, DMSO-d6, 298 K) of the macrocyclic host H1 in Example 1 of the present invention.

[0042] Figure 2 This is the H NMR spectrum (600 MHz, DMSO-d6, 298 K) of the macrocyclic host H2 in Example 1 of the present invention.

[0043] Figure 3 This is the H NMR spectrum (600 MHz, DMSO-d6, 298 K) of the macrocyclic host H3 in Example 1 of the present invention.

[0044] Figure 4 This is the C NMR spectrum (151 MHz, DMSO-d6, 298 K) of the macrocyclic host H3 in Example 1 of the present invention.

[0045] Figure 5This is a high-resolution mass spectrum of the macrocyclic host H3 in Example 1 of the present invention.

[0046] Figure 6 This is the H NMR spectrum (600 MHz, D2O, 298 K) of the macrocyclic host H3 in Example 1 of the present invention.

[0047] Figure 7 This is the H NMR spectrum (600 MHz, D2O, 298 K) of the host-guest complex identified by the macrocyclic host H3 (1 mmol / L, 500 μL, D2O) with 1-adamantaneacetic acid (50 mmol / L in CD3OD, 10 μL) in Example 1 of the present invention.

[0048] Figure 8 This is the H NMR spectrum (600 MHz, D2O, 298 K) of the host-guest complex identified by the macrocyclic host H3 (1 mmol / L, 500 μL, D2O) with 1-adamantanecarboxylic acid (50 mmol / L in CD3OD, 10 μL) in Example 1 of the present invention.

[0049] Figure 9 This is a flow chart for the preparation of the macrocyclic host H3 in Example 1 of the present invention. DETAILED DESCRIPTION

[0050] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0051] In the following examples and comparative examples, unless otherwise specified, raw materials or processing techniques are conventional commercially available raw materials or conventional processing techniques in the art.

[0052] Example 1

[0053] In this embodiment, the novel functionalized deep-hole fluorene[3]arene macrocyclic main body (i.e., water-soluble quinoxaline-based macrocyclic main body compound H3) was synthesized by deepening the three aromatic walls, introducing quinoxaline groups at the upper edge, and introducing water-soluble groups at the lower edge with fluorene[3]arene as the skeleton. 2,7-dihydroxy-9,9-dimethylfluorene S1 was used as the starting reaction raw material. A quinoxaline structure was introduced at the upper edge by condensation of glyoxal and o-phenylenediamine, and a pyridinium salt was introduced at the lower edge to give the main body water solubility. The synthesis steps are as follows: Figure 9 As shown, it specifically includes the following synthesis steps:

[0054] (1) In an ice-water bath, 100 mL of methanol and 25 mL of concentrated hydrochloric acid were added to a 250 mL round-bottom flask. 2,7-dihydroxy-9,9-dimethylfluorene S1 (5 g, 22.12 mmol, 1 eq) was added to the solution and stirred at room temperature for 5 minutes. After complete dissolution, 4-chlorobutyraldehyde dimethyl acetal (10 mL, 68.14 mmol, 3.1 eq) was added dropwise to the solution. The solution was transferred to a 55°C oil bath and stirred for 4 days. After the reaction was completed, the solution was cooled to room temperature, the solvent was removed by rotary evaporation, and the solid was collected. After purification by column chromatography, 1815 mg of chlorobutyraldehyde[3]arene H1 was obtained as a dark green solid with a yield of 11.7%.

[0055] (2) The chlorohexanilide [3]arene H1 (300 mg, 0.32 mmol, 1 eq) prepared in step (1) was added to a 50 mL round-bottom flask and dissolved with 20 mL N, N-dimethylformamide. 1,2-difluoro-4,5-dinitrobenzene (200 mg, 0.98 mmol, 3 eq) was then added thereto, and triethylamine (440 μL, 3.18 mmol, 10 eq) was added dropwise. The mixture was stirred in an oil bath at 60°C for 7 hours. After the reaction was completed, most of the triethylamine and N, N-dimethylformamide were removed by rotary evaporation. 1N hydrochloric acid was added dropwise to the residue until most of the solid precipitated. After ultrasonication for 2 hours, the mixture was filtered under reduced pressure. The filter residue was rinsed with 1N hydrochloric acid and dissolved with dichloromethane. The filtrate was collected and the solvent was removed. The mixture was purified by column chromatography to obtain 215 mg of the chlorohexanilide H2 with a yield of 47.1%.

[0056] (3) The chlorohexanitro-host H2 (100 mg, 0.07 mmol, 1 eq) prepared in step (2) was added to a 25 mL round-bottom flask, dissolved in 6 mL of ethanol solvent, and stannous chloride dihydrate (1.88 g, 10.99 mmol, 120 eq) and 2.28 mL of concentrated hydrochloric acid were added under ice bath, and the mixture was in an oil bath at 110 ° C for 1.5 hours; after the reaction was completed, it was cooled to room temperature, 30 mL of 3N hydrochloric acid was added under ice bath, and the solid was filtered to obtain the solid, which was washed with 3N hydrochloric acid and acetonitrile at 0 ° C, respectively. The solid was collected and dried under vacuum to obtain 61 mg of chlorohexanitro-host S2 with a yield of 69.7%.

[0057] (4) The chlorohexamethylenediamine main body S2 (60 mg, 0.05 mmol, 1 eq) prepared in step (3) was added to a 25 mL round-bottom flask, dissolved in 30% water / ethanol solvent, and potassium carbonate solid (55 mg, 0.40 mmol, 8 eq) was added. After stirring at room temperature for 10 minutes, 40% glyoxal solution (50 μL, 0.40 mmol, 8 eq) was added and reacted at room temperature for 18 hours. After the reaction was completed, the solid was filtered, washed with water and dried in vacuum to obtain 38 mg of relatively pure chloroquinoxaline main body S3 with a yield of 60.8%.

[0058] (5) The chloroquinoxaline-based main body S3 (38 mg, 0.03 mmol, 1 eq) prepared in step (4) was added to a 25 mL round-bottom flask, and 8 mL of pyridine was added and stirred at room temperature until the solid was evenly dispersed. The mixture was vigorously stirred in an oil bath at 110°C and reacted for 24 hours. After the reaction, the reaction solution was cooled to room temperature and acetone was added to precipitate a white solid. The crude product was obtained by centrifugation. The solid was refluxed in acetone for 24 hours, cooled to room temperature, centrifuged, and washed with acetone at least 3 times. The solid was collected and dried in vacuo to obtain 22 mg of a water-soluble quinoxaline-based macrocyclic main compound H3 with a yield of 52.6%.

[0059] In this embodiment, the intermediate product chlorofluorene[3]arene H1 was characterized by nuclear magnetic resonance and mass spectrometry, such as Figure 1 As shown, 1 H NMR (600MHz, DMSO-d6, 298K, δppm) δ9.42(s,6H),7.91(s,6H),6.81(s,6H),4.75(t,J=8.1Hz,3H ),3.74(t,J=6.6Hz,6H),2.45(q,J=8.1Hz,6H),1.77(p,J=6.8Hz,6H),1.31(s,9H),1.14(s,9H). 13 C NMR(151MHz,DMSO DMSO-d6,298K,δppm)δ152.37,151.80,131.62,130.18,117.17,110.15,45.54,45.27,32.86,31.53,31.06,27.59,26.76.HRMS(ESI):Calcd.for chemical formula C 57 H 57 Cl3O6:[M+Na] + 965.3118,found:965.3118[M+Na] + .

[0060] In this embodiment, the intermediate product chlorohexanitrohexanitrile H2 was characterized by nuclear magnetic resonance and mass spectrometry, such as Figure 2 As shown, 1 HNMR(600MHz,DMSO-d6,298K,δppm)δ8.95(s,6H),8.12(s,6H),8.02(s,6H),5.95(t,J=8.3Hz,3H ),3.81(t,J=6.6Hz,6H),2.63(q,J=7.5Hz,6H),1.91(p,J=6.8Hz,6H),1.49(s,9H),1.13(s,9H). 13C NMR(151MHz,DMSO DMSO-d6,298K,δppm)δ155.82,154.57,153.93,139.72,136.93,136.01,122.99,117.98 ,116.96,54.91,46.80,45.10,33.51,30.97,29.30,26.46,26.16.HRMS(ESI):Calcd.for chemical formula C 75 H 57 Cl3N6O 18 :[M+H] + 1435.2873,found:1435.2926[M+H] + .

[0061] In this example, the intermediate product, chlorohexamethylenediamine S2, was characterized by nuclear magnetic resonance. 1 H NMR (600MHz, DMSO-d6, 298K, δppm) δ8.31(s,6H),7.52(s,6H),7.43(s,6H),5.95(t,J=8.3Hz,3H ),3.79(t,J=6.6Hz,6H),2.62(q,J=7.3Hz,6H),1.87(p,J=6.8Hz,6H),1.44(s,9H),1.12(s,9H). 13 C NMR(151MHz,DMSO DMSO-d6,298K, δppm) δ155.67,152.80,137.26,135.73,135.38,118.94,116.19,56.06,46.33,45.13,33.40,31.16,29.45,27.08,26.58.

[0062] In this embodiment, the intermediate product chloroquinoxaline-based main body S3 was characterized by nuclear magnetic resonance and mass spectrometry. 1 HNMR (600MHz, DMSO-d6, 298K, δppm) δ8.87(s,6H),8.72(s,6H),8.09(s,6H),8.03(s,6H),6.09(t,J=8. 1Hz, 3H), 3.86 (t, J = 6.6Hz, 6H), 2.67 (q, J = 7.8Hz, 6H), 1.96 (p, J = 6.8Hz, 6H), 1.54 (s, 9H), 1.02 (s, 9H). 13C NMR(151MHz,DMSO DMSO-d6,298K,δppm)δ155.16,154.76,153.64,145.57,141.00,137.07,135.56,123.82,117.45 ,116.96,54.92,46.66,45.31,45.21,33.63,31.09,29.13,26.61,26.03.HRMS(ESI):Calcd.for chemical formulaC 81 H 63 Cl3N6O6:[M+H] + 1321.3953,found:1321.3970[M+H] + .

[0063] In this embodiment, the water-soluble quinoxaline-based macrocyclic compound H3 was characterized by nuclear magnetic resonance and mass spectrometry, such as Figures 3-5 As shown, 1 H NMR (600MHz, DMSO-d6, 298K, δppm) δ9.38(d,J=6.2Hz,6H),8.86(s,6H),8.81(s,6H),8.67(s,6H),8.62(t,J=7.8Hz,3H),8.22(t,J=6.9H z,6H),7.93(s,6H),5.93(t,J=8.1Hz,3H),4.91(t,J=7.2Hz,6H),2.83(q,J=8.2Hz,6H),2.20(p,J=7.5Hz,6H),1.52(s,9H),0.98(s,9H). 13 C NMR(151MHz,DMSO DMSO-d6,298K,δppm)δ154.89,153.17,145.51,145.39,145.05,140.97,137.05,136.06,128.22,123.75 ,119.84,116.25,61.05,54.93,46.71,34.71,30.71,29.98,28.72,26.84,25.93.HRMS(ESI):Calcd.for chemicalformula C 96 H 78 N9O6:[M+3H] 3+ 485.2103,found:485.2065[M+3H] 3+ .

[0064] Host-guest NMR data analysis:

[0065] The water-soluble quinoxaline-based macrocyclic compound H3 (14.4 mg, 10.00 μmol) was added to a 25 mL sample bottle, 10 mL of heavy water was added, and the solution was completely dissolved by ultrasonication to obtain a clear and transparent light yellow solution (1 mmol / L in D2O).

[0066] 500 μL of the above-mentioned water-soluble quinoxaline-based macrocyclic main compound H3 solution was added to an NMR tube, and then 10 μL of 1-adamantaneacetic acid (50 mmol / L in CD3OD) or 1-adamantanecarboxylic acid (50 mmol / L in CD3OD) was added to the NMR tube. The mixture was ultrasonicated at room temperature for 2 h. After mixing, the 298K nuclear magnetic resonance hydrogen spectrum was measured on a Bruker AVANCEⅢHD 600M machine. The scan width was set to 25, the center was 5, and the number of scans was 64.

[0067] The H NMR spectrum analysis of the host-guest complex of the water-soluble quinoxaline-based macrocyclic compound H3 with 1-adamantaneacetic acid and 1-adamantanecarboxylic acid, such as Figures 6-8 As shown, the changes in the red and blue peaks indicate that the water-soluble quinoxaline-based macrocyclic compound H3 can recognize 1-adamantanacetic acid and 1-adamantancarboxylic acid, respectively. The water-soluble quinoxaline-based macrocyclic compound H3 has a large hydrophobic cavity. The adamantane end of the adamantane acid enters the cavity, leaving the carboxyl group in contact with water. Therefore, it can recognize the hydrophilic groups of 1-adamantanacetic acid and 1-adamantancarboxylic acid.

[0068] In summary, the present invention synthesized a water-soluble supramolecular macrocyclic host compound derived from fluorene[3]arene, namely a water-soluble quinoxaline-based macrocyclic host compound H3. Using fluorene[3]arene as the skeleton, the novel functionalized deep-cavity fluorene[3]arene macrocyclic host H3 was synthesized by successively deepening the three aromatic walls and introducing quinoxaline groups on the upper edge and water-soluble groups on the lower edge. Compared with traditional fluorene[3]arene, this molecule has a deeper hydrophobic cavity and a controllable conformation. It has an electron-rich hydrophobic cavity and can recognize 1-adamantaneacetic acid and 1-adamantanecarboxylic acid in the aqueous phase. The above experimental results show that the macrocyclic host H3 has excellent host-guest recognition.

[0069] The above description of the embodiments is intended to facilitate understanding and use of the invention by those skilled in the art. It will be apparent that those skilled in the art can readily make various modifications to these embodiments and apply the general principles described herein to other embodiments without requiring inventive effort. Therefore, the present invention is not limited to the above-described embodiments. Improvements and modifications made by those skilled in the art based on the disclosure of the present invention, without departing from the scope of the present invention, should be within the scope of protection of the present invention.

Claims

1. A deep-hole fluorene[3]arene macrocyclic main compound, characterized in that: It is a water-soluble quinoxaline-based macrocyclic main compound H3, and its structural formula is shown below: Where R is 2. A method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 1, characterized in that: The steps include: S1. Mix methanol, concentrated hydrochloric acid, and 2,7-dihydroxy-9,9-dimethylfluorene, add 4-chlorobutyraldehyde dimethyl acetal, heat to react, and purify to obtain the main aromatic hydrocarbon of chlorobutyraldehyde[3]; S2. Add N,N-dimethylformamide to the chlorofluorophene[3]arene main body obtained in step S1 to dissolve it, then add 1,2-difluoro-4,5-dinitrobenzene and triethylamine, heat to react, precipitate solid, and purify to obtain the chlorofluorophene[3]arene main body; S3. Add ethanol to the chlorohexanitro main body obtained in step S2 to dissolve it, add stannous dichloride dihydrate and concentrated hydrochloric acid, heat to react, precipitate a solid, and obtain the chlorohexanitro main body; S4. Add water / ethanol solvent to the chloro-hexamethylenediamine main body obtained in step S3 to dissolve it, add potassium carbonate and glyoxal, and react at room temperature to obtain a chloro-quinoxaline main body; S5. Add pyridine to the chloroquinoxaline-based main body obtained in step S4, heat the reaction, precipitate a solid, and obtain a water-soluble quinoxaline-based macrocyclic main compound H3.

3. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S1, the molar ratio of 2,7-dihydroxy-9,9-dimethylfluorene to 4-chlorobutyraldehyde dimethyl acetal is 1:3.

1.

4. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S1, the heating reaction conditions are: stirring in a 55°C oil bath for (4-6) days.

5. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S2, the molar ratio of chlorofluorene[3]arene, 1,2-difluoro-4,5-dinitrobenzene, and triethylamine is 1:(2-4):(9-11).

6. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S2, the heating reaction conditions are: reacting in an oil bath at (55-60)°C for (6-7) hours.

7. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S3, the molar ratio of the hexanitrochlorobenzene to stannous dichloride dihydrate is not less than 1:120, and the volume ratio of concentrated hydrochloric acid to ethanol is 1:2.

6.

8. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S3, the heating reaction conditions are: (105-115) °C in an oil bath for (1.5-2) hours.

9. The method for preparing the deep-hole fluorene[3]arene macrocyclic main compound according to claim 2, characterized in that: In step S4, the molar ratio of the hexamethylenediamine monomer, potassium carbonate, and glyoxal is 1:(7-9):(7-9); the reaction is carried out at room temperature for (16-20) hours; In step S5, the heating reaction conditions are: (105-115)°C in an oil bath for (20-25) hours.

10. A use of the deep-hole fluorene[3]arene macrocyclic main compound as claimed in claim 1, characterized in that: The deep-hole fluorene[3]arene macrocyclic main compound is used to identify amphiphilic molecules with adamantane structure.

Images