A fluorine-containing functionalized macrocyclic supramolecular host molecule cup and a preparation method and application thereof

Abstract

This invention relates to the field of supramolecular chemistry, specifically to a fluorinated functionalized macrocyclic supramolecular host molecular cup, its preparation method, and its applications. It is a 2-difluoromethylbenzimidazole molecular cup host and its metal derivatives. By introducing a difluoromethyl group to moderately increase lipophilicity, the excellent properties of the trifluoromethyl macrocyclic supramolecular host are inherited while increasing water solubility. Furthermore, it can recognize cycloalkanes, alkyl carboxylic acids, especially n-heptanoic acid and n-octanoic acid, thus facilitating a series of molecular recognition studies in aqueous phase. Compared with existing technologies, this invention features a simple process, readily available raw materials, mild reaction conditions, high yield, and good reproducibility. The difluoromethyl-modified macrocyclic molecular cup H1 and the metal molecular cup H formed with palladium in this invention are also described. 1‑Pd It exhibits novel structure and high degree of functionalization, enhancing its molecular recognition ability and selectivity, and can be used in environmental remediation and water pollutant treatment.

Description

Technical Field

[0001] This invention relates to the field of supramolecular chemistry, specifically to a difluoromethyl-modified macrocyclic supramolecular host molecular cup and its synthesis and applications with metal molecular cups. Background Technology

[0002] As a discipline that studies non-covalent interactions between molecules, supramolecular chemistry plays a vital role in scientific research and practical applications. For example, third-generation macrocyclic host calixarnes, due to their excellent host-guest recognition capabilities, show broad application prospects in various fields such as artificial enzyme simulation, asymmetric catalysis, drug delivery, fluorescent probes, and sensors. Among them, cavitary macrocyclic host calixes, with their deepened aromatic walls and large cavity-like structures, exhibit molecularly selective recognition and reaction-selective regulation characteristics of biological receptor enzymes, thus attracting great interest from chemists. However, most biological processes occur in aqueous solutions; therefore, the development of water-soluble functionalized cavitary calixes is of great significance for simulating molecular recognition processes in biological systems.

[0003] Fluorinated organic compounds often exhibit physicochemical properties not found in non-fluorinated organic compounds, making them particularly useful in the pharmaceutical, pesticide, and materials fields. Among these, difluoromethyl (-CF₂H), compared to monofluoromethyl or trifluoromethyl groups, can not only act as a hydrogen bond donor but also modulate the lipophilicity of molecules. Therefore, constructing water-soluble difluoromethyl functionalized deep-cell molecular cups can not only provide new assembly methods for molecular cups but also expand their molecular recognition range, holding particular promise for applications in materials and medicinal chemistry.

[0004] CN202310502333.3 discloses a water-soluble trifluoromethyl macrocyclic supramolecular main molecular cup compound, its preparation method and application. Based on the relisophenol cup [4] aromatic skeleton, the aromatic wall is deepened, and the upper rim 2-trifluoromethyl imidazolium group and the lower rim water-soluble group are introduced in sequence, realizing a novel water-soluble functionalized molecular cup H1, H 1-Pd The method involves the construction of H2. The raw materials are simple and readily available, the reaction conditions are mild, the operation is simple, and the yield is high. It enables the laboratory-scale preparation of molecular cup bodies, providing a prerequisite and foundation for their performance studies. The novel water-soluble functionalized molecular cup body disclosed in this invention possesses a deep hydrophobic cavity that binds to guest molecules and a trifluoromethyl-modified functional group on its upper edge. The introduction of the trifluoromethyl functional group endows the molecular cup body with new and unique recognition properties, which is of great significance for the study of small molecule behavior in confined spaces. However, because trifluoromethyl functionalization significantly increases the lipophilicity of the compound, resulting in poor water solubility, it cannot recognize heptanoic acid, octanoic acid, etc. Furthermore, the disclosed reaction method is time-consuming and requires column chromatography purification. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the existing technology by providing a fluorinated functionalized macrocyclic supramolecular host molecular cup, its preparation method, and its applications. By introducing a difluoromethyl group to moderately increase lipophilicity, the invention inherits the excellent properties of the trifluoromethyl macrocyclic supramolecular host while increasing water solubility. Furthermore, it can recognize cycloalkanes, alkyl carboxylic acids, especially n-heptanoic acid and n-octanoic acid, thus facilitating a series of molecular recognition studies in aqueous phase. Difluoroacetic acid is used simultaneously as both a reactant and a solvent, shortening the reaction time from 72 h to 24 h, and eliminating the need for column chromatography purification to obtain pure compounds.

[0006] The objective of this invention can be achieved through the following technical solution: a fluorinated functionalized macrocyclic supramolecular host molecular cup, characterized in that it is a 2-difluoromethylbenzimidazole molecular cup host and its metal derivatives, with the following molecular cup structures H1, H... 1-Pd At least one of the following structures:

[0007]

[0008] Furthermore, the molecular cup H1 has a deep hydrophobic cavity, the main body of which is a benzimidazole group, with four difluoromethyl groups at the upper edge and a 1-methylimidazolium salt-soluble foot at the lower edge. The molecular cup H1 exists in two conformations in water: one with C... 4v The symmetrical "vase" configuration and C 2v The molecular cup exhibits a symmetrical "kite" conformation, with a dynamic equilibrium between the two. A suitable guest molecule induces the molecular cup to form a stable vase conformation, encapsulating the guest molecule within the cavity of the molecular cup.

[0009] Preferably, when the macrocyclic supramolecular host compound derived from the phenolic calix [4] aromatic hydrocarbon in this invention is a molecular calix H 1-Pd In this structure, the molecular cup host H1 can act as a ligand to coordinate with palladium (Pd), forming a metallic molecular cup structure. This metallic molecular cup is characterized by its deep, hydrophobic cavity, primarily composed of benzimidazole groups coordinated and bridged by Pd. The upper edge of the cavity is decorated with four difluoromethyl functional groups, while the lower edge is connected to a 1-methylimidazolium salt, with chloride and nitrate ions as corresponding anions. In the presence of a suitable guest molecule, this metallic molecular cup exists in a "vase" conformation, effectively encapsulating the guest molecule within the cavity.

[0010] This invention also provides a method for preparing a fluorine-functionalized macrocyclic supramolecular host molecular cup, the method comprising the following steps:

[0011] Preparation of molecular cup H1: Water-soluble difluoromethyl molecular cup and its metal derivative were prepared using resorcinol as the starting material. A 1-methylimidazolium salt was introduced into the lower edge of the molecular cup, with chloride as the counter anion, which made the compound water-soluble as a whole. A difluoromethyl group was introduced into the upper edge to obtain the 2-difluoromethylbenzimidazole molecular cup body H1.

[0012] Molecular cup H 1-Pd Preparation: A 1-methylimidazolium salt was introduced into the lower edge of the molecular cup H1, with chloride as the counter anion, making the compound water-soluble. A difluoromethyl group was introduced into the upper edge, and the imidazolium group near the opening coordinated with 4 equivalents of ethylenediamine palladium(II) to obtain the 2-difluoromethylbenzimidazolyl molecular cup metal derivative H. 1-Pd .

[0013] Furthermore, the specific steps of the method are as follows:

[0014] a. Using chloro-8-aminohydrochloride as a molecular cup precursor, excess difluoroacetic acid was added, with difluoroacetic acid used as both reactant and solvent. The reaction was carried out at 110°C for 24 h. After the reaction was complete, the mixture was cooled to room temperature, washed, filtered, and the resulting solid was collected, dried, and purified to finally obtain a white, dense powder product.

[0015] b. Dissolve the product obtained in step a in 1-methylimidazole and stir at 100°C for 24 hours. Then, cool the solution to 0°C in an ice bath, add acetone and sonicate to form a suspension. Then filter under reduced pressure and dry under high vacuum to obtain a white, dense powder of molecular cup H1.

[0016] c. Prepare a heavy aqueous solution of the molecular cup H1 obtained in step b. Then, gradually add the heavy aqueous solution of ethylenediamine nitrate·palladium(II) dihydrate until the spectrum no longer changes except for the free palladium ligand peak, as confirmed by 1H NMR spectroscopy. After ultrasonic treatment, the molecular cup H1 can be obtained. 1-Pd The heavy aqueous solution is light yellow and clear.

[0017] Furthermore, the amount of difluoroacetic acid added in step a is excessive;

[0018] Furthermore, in step a, the washing is performed multiple times with deionized water until the filtrate no longer exhibits an acidic reaction; only thorough washing of the product is required, without further purification.

[0019] Furthermore, in step b, the drying temperature under high vacuum is no higher than 50°C, and the vacuum degree is 0.09–0.1 MPa.

[0020] Furthermore, in step C, the concentration of the heavy aqueous solution prepared by molecular cup H1 is 1 mmol / L.

[0021] The concentration of the heavy aqueous solution of ethylenediamine nitrate·palladium(II) dihydrate is 100 mmol / L.

[0022] The present invention also provides an application of a fluorinated functionalized macrocyclic supramolecular host molecular cup, wherein the fluorinated functionalized macrocyclic supramolecular host molecular cup is used to identify at least one of cycloalkanes and alkyl carboxylic acids.

[0023] The fluorine-functionalized macrocyclic supramolecular host molecular cup forms a 1:1 host-guest complex with the guest molecules in the aqueous phase.

[0024] Preferably, when the macrocyclic supramolecular host compound derived from the phenolic calix[4]arene of the present invention has the structure of molecular calix H1, the molecular calix H1 can realize aqueous phase recognition of cycloalkanes and straight-chain carboxylic acids.

[0025] Preferably, when the macrocyclic supramolecular host compound derived from the phenolic calix [4] aromatic hydrocarbon of the present invention has a molecular calix H 1-Pd When considering the structure, it can selectively identify cis-1,2-dichloroethylene in a mixture of cis-trans isomers of 1,2-dichloroethylene.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1. The synthetic route of the present invention is simple, the raw materials are readily available, the reaction conditions are mild, the yield is high, and the reproducibility is good. Compared with CN202310502333.3, it takes less time, has a higher yield, and can obtain pure compounds without column chromatography purification.

[0028] 2. The novel water-soluble functionalized 2-difluoromethylbenzimidazole molecular cup matrix H1, H1 of this invention 1-Pd The novel structure and the introduction of the difluoromethyl group give the molecular calix a wider range of guest recognition. The difluoromethyl group allows the molecular calix to recognize heptanoic acid and octanoic acid, which are not recognized in CN202310502333.3.

[0029] 3. The novel water-soluble functionalized 2-difluoromethylbenzimidazole metal molecular cup host of the present invention H 1-Pd Capable of selectively identifying water pollutants, molecular cup H 1-Pd It can adsorb organic pollutants in water, specifically cis / trans-1,2-dichloroethylene, and can selectively complex the cis isomers in cis / trans isomer mixtures of 1,2-dichloroethylene. Attached Figure Description

[0030] Figure 1The above is the 1H NMR spectrum of molecular cup H1 in Example 1 of the present invention (600MHz, Deuterium Oxide:DMSO-d6=100:1, v / v mL, 298K).

[0031] Figure 2 The NMR fluorine spectrum of molecular cup H1 in Example 1 of this invention is shown as follows (565MHz, Deuterium Oxide:DMSO-d6=100:1, v / v mL, 298K).

[0032] Figure 3 The image shows the carbon NMR spectrum (151 MHz, DMSO-d6, 298 K) of molecular cup H1 in Example 1 of this invention.

[0033] Figure 4 This is a high-resolution mass spectrum of molecular cup H1 in Example 1 of the present invention.

[0034] Figure 5 The molecular cup H in Example 1 of this invention 1-Pd The proton NMR spectrum (600 MHz, Deuterium Oxide:Cyclopentane = 500:1, v / v mL, 298 K).

[0035] Figure 6 The NMR titration is obtained by adding ethylenediamine nitrate·palladium(II) dihydrate heavy aqueous solution to H1 heavy aqueous solution with 2 μL cyclohexane as the guest by equivalent amount.

[0036] Figure 7 The following are the 1H NMR spectra (600MHz, Deuterium Oxide, 298K) of molecular cup H1 (1mmol / L, 500μL) for the recognition of cycloalkanes (2μL). Inset a) shows the recognition of cyclopentane; inset b) shows the recognition of cyclohexane; inset c) shows the recognition of cycloheptane; inset d) shows the recognition of cyclooctane; inset e) shows the recognition of cyclodecane; and inset f) shows the recognition of cyclododecane.

[0037] Figure 8 The 1H NMR spectra (600MHz, Deuterium Oxide, 298K) of molecular cup H1 (1mmol / L, 500μL) for the recognition of straight-chain carboxylic acids (2μL) are shown. Inset a) shows the recognition of heptanoic acid; inset b) shows the recognition of octanoic acid; inset c) shows the recognition of nonanoic acid; inset d) shows the recognition of decanoic acid; inset e) shows the recognition of undecanoic acid; inset f) shows the recognition of dodecaenoic acid; and inset g) shows the recognition of tridecaenoic acid.

[0038] Figure 9 For molecular cup H 1-Pd(1 mmol / L, 500 μL) Selective identification of 1,2-dichloroethylene 1H NMR spectrum (600 MHz, Deuterium Oxide, 298 K). Inset a) shows the identification of cis-1,2-dichloroethylene; inset b) shows the identification of trans-1,2-dichloroethylene; inset c) shows the selective identification of cis-1,2-dichloroethylene in a 1:1 mixture of cis / trans-1,2-dichloroethylene 1H NMR spectrum. Detailed Implementation

[0039] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0040] The present invention will be further described in detail below with reference to specific embodiments. It should be noted that the specific embodiments are illustrative of the invention and not limiting. Preferred embodiments of the present invention are described in detail below:

[0041] Example 1:

[0042] In this embodiment, a novel water-soluble functionalized 2-difluoromethylbenzimidazole molecular cup was successfully synthesized by introducing a 2-difluoromethylimidazolium group at the upper edge of the molecular cup and a water-soluble 1-methylimidazolium salt at the lower edge. The introduction of the difluoromethyl group and the water-soluble group (such as 1-methylimidazolium salt) enhances the molecular cup's recognition ability for guest molecules and gives it good solubility in aqueous solution, which is particularly important for molecular recognition in aqueous phases and potential biomedical applications. Molecular cups H1 and H 1-Pd The structural formula is as follows:

[0043]

[0044] The preparation method of the macrocyclic supramolecular host compound H1 derived from the phenol calix [4] aromatic hydrocarbon in this embodiment includes the following steps:

[0045] Using chloro-8-amino hydrochloride molecular calix S1 as the starting material, the water-soluble 2-difluoromethylimidazolium molecular calix H1 was synthesized through a series of acid-amine cyclization condensations with difluoroacetic acid and the introduction of the lower water-soluble 1-methylimidazolium salt. The specific synthetic route and steps are as follows:

[0046]

[0047] The specific synthetic route and steps of the molecular cup body H1 are as follows:

[0048] a. In a 25 mL round-bottom flask cooled in an ice bath, chloro-8-amino hydrochloride molecular cup S1 (200.0 mg, 0.133 mmol, 1 eq.) was dispersed in 10 mL difluoroacetic acid; the mixture was stirred in an ice bath for 30 minutes. After the mixture returned to room temperature, a condenser was installed, and the mixture was heated to 110 °C and stirred for 24 hours under nitrogen protection; after the reaction was completed, the mixture was cooled to room temperature and poured into deionized water, and filtered under reduced pressure; the mixture was washed thoroughly with deionized water in small amounts several times until the filtrate was no longer acidic and dried under high vacuum to obtain compound S2, which was a white, dense powder solid, 171.68 mg, with a yield of 89.2%;

[0049] b. In a 25 mL round-bottom flask, the product S2 (100 mg, 0.069 mmol) prepared in step a was dissolved in 4 mL of 1-methylimidazole. The mixture was heated to 90 °C under nitrogen protection and reacted for 24 hours. After the reaction was complete, the flask was placed in an ice-water bath to cool. After cooling, the reaction solution was added dropwise to 20 mL of acetone, resulting in the precipitation of a grayish-white solid. This solid was obtained by centrifugation. The crude product was then refluxed in 20 mL of acetone overnight, cooled to room temperature, filtered, and the filter cake was washed three times with 20 mL of acetone. The solid was collected and dried under vacuum to obtain 92 mg of a water-soluble molecular cup H1, a pale yellow powder, with a yield of 75.4%.

[0050] In this embodiment, the intermediate product S2 was characterized by NMR and mass spectrometry. 1 H NMR(600MHz,Chloroform-d:MeOH=9:1,v / v mL)δ7.65(s,8H),7.47(s,4H),7.22(s,4H),6.59(t,J=54.0Hz,4H),5.75(t,J =8.3Hz,4H),3.70(t,J=6.2Hz,12H),2.43(q,J=8.1Hz,8H),1.91–1.83(m,8H). 19 F NMR (565MHz, Chloroform-d:MeOH=9:1, v / v mL) δ-116.95 (d, J=55.1Hz 8F). 13 C NMR(151MHz,DMSO-d6)δ155.69,149.36,147.12,135.18,124.89,116.92,111.53 ,109.96,108.40,56.50,45.41,33.19,31.39,29.03,19.02.ESI-HRMS:Calcd.for chemicalformula C 72 H 52 C l4F8N8O8:1451.0400.found1451.2600.

[0051] In this embodiment, see Figure 1-4 The molecular cup H1 was characterized by NMR and mass spectrometry. Figure 1 The above is the 1H NMR spectrum of molecular cup H1 in Example 1 of the present invention (600MHz, Deuterium Oxide:DMSO-d6=100:1, v / v mL, 298K). Figure 2 The NMR fluorine spectrum of molecular cup H1 in Example 1 of this invention is shown as follows (565MHz, Deuterium Oxide:DMSO-d6=100:1, v / v mL, 298K). Figure 3 The image shows the carbon NMR spectrum (151 MHz, DMSO-d6, 298 K) of molecular cup H1 in Example 1 of this invention. Figure 4 This is a high-resolution mass spectrum of the molecular cup H1 in Example 1 of the present invention. As can be seen from the figure:

[0052] 1 H NMR(600MHz,Deuterium Oxide:DMSO-d6=100:1,v / v mL)δ7.87(s,8H),7.71(s,4H),7.57(s,4H),7.36(d,J=15.2Hz,8H),6.78(t,J=53.9Hz,4H),5.45( t,J=8.5Hz,4H),4.25(t,J=6.9Hz,8H),3.77(s,12H),2.47(d,J=9.7Hz,8H),1.88(d,J=7.5Hz,8H). 19 F NMR (565MHz, Deuterium Oxide: DMSO-d6=100:1, v / v mL) δ-116.95 (d, J=55.1Hz8F). 13 C NMR(151MHz,DMSO-d6)δ157.69(d,J=61.0Hz),152.59,150.90,149.23,141.87,139.44,137.62,133.56,1 28.23,126.17,125.27,119.10,117.27,112.18,110.02,51.94,38.53,36.16,30.72.ESI-HRMS:Calcd.for chemical formula C 88 H 76 Cl4F8N 16 O8:1779.47.found 557.5258.([M-3Cl- ] 3+ )

[0053] In this embodiment, the macrocyclic supramolecular host compound H, derived from relaseol calix [4] aromatic hydrocarbons, is... 1-Pd The preparation method uses molecular cup H1 as the starting material to prepare the metal coordination molecular cup host H. 1-Pd The synthesis steps are as follows:

[0054]

[0055] In this embodiment, the macrocyclic supramolecular host compound H, derived from relaseol calix [4] aromatic hydrocarbons, is... 1-Pd The preparation method includes the following synthesis steps:

[0056] To a heavy aqueous solution of molecular cup H1, add four equivalents of a heavy aqueous solution of ethylenediamine nitrate·palladium(II) dihydrate, and sonicate for four hours to obtain molecular cup H. 1-Pd The heavy aqueous solution of [a substance] is a yellow-green transparent solution. For example... Figure 6 As shown.

[0057] Figure 6 To obtain the NMR titration chromatogram of ethylenediamine nitrate·palladium dihydrate (II) heavy aqueous solution added dropwise to a heavy aqueous solution of H1 with 2 μL cyclohexane as a guest molecule, molecular cuvette H1 was accurately weighed and prepared into a 1 mmol heavy aqueous solution. Ethylenediamine nitrate·palladium dihydrate (II) was accurately weighed and prepared into a 100 mmol heavy aqueous solution. 0.5 mL of the prepared molecular cuvette heavy aqueous solution was added to the sample vial, followed by 2 μL (excess) cyclopentane as a guest molecule. After thorough mixing in an ultrasonic cell for one hour, the heavy aqueous solution of ethylenediamine nitrate·palladium dihydrate (II) was added dropwise in equal parts until six equivalents were added. After each addition, the sample was sonicated for one hour, and the 1H NMR spectrum at 298 K was measured. The NMR spectrum was analyzed... 1¹H NMR data revealed a clear trend in the characteristic peaks of the system as ethylenediamine nitrate·palladium(II) dihydrate was gradually added: In the aromatic region of molecular calix H1, the signal peaks transitioned from ordered to disordered and then back to ordered states as the equivalent of ethylenediamine nitrate·palladium(II) dihydrate increased. Furthermore, the characteristic peak of the methine group in molecular calix H1 at 5.4 ppm showed a gradual shift towards higher fields. Simultaneously, the signal peak of ethylenediamine nitrate·palladium(II) dihydrate coordinated with molecular calix H1 gradually strengthened and eventually stabilized, reflecting that the coordination between ethylenediamine nitrate·palladium(II) dihydrate and the molecular calix reached saturation. After adding four equivalents, free ethylenediamine nitrate·palladium(II) dihydrate that had not coordinated with the molecular calix began to appear and gradually increased. In addition, the guest signal peaks in the high-field region gradually split into multiple peaks and subsequently stabilized at lower chemical shifts. Based on these observations, the presence of ethylenediamine nitrate·palladium(II) dihydrate in the metal molecular calix H1 was confirmed. 1-4Pd The successful construction and further confirmation of the metal molecular cup H 1-4Pd The coordination ratio of H1 to ethylenediamine dihydrate palladium(II) is 1:4.

[0058] In this embodiment, see Figure 5 For metal molecular cup H 1-Pd Perform NMR characterization. 1 H NMR(600MHz,Deuterium Oxide:Cyclopentane=500:1,v / v mL)δ8.70(s,4H),8.48(d,J=2.1Hz,8H),8.20(s,4H),7.85–7.60(m,4H),7.37(dd,J=4.0,2.1Hz,10H),5.32(t,J=8.4H z,4H),4.21(t,J=6.8Hz,8H),3.82(d,J=2.1Hz,12H),2.79–2.67(m,16H),2.30(d,J=8.4Hz,8H),1.79(d,J=7.8Hz,8H).

[0059] Experimental test analysis:

[0060] An excess or equivalent amount of guest molecules was added to the molecular cuvette H1 solution (500 μL, 1 mM in Deuterium Oxide). After mixing, the solution was sonicated for 1 hour, and the 1H NMR spectrum at 298 K was measured using a Bruker AVANCE III HD 600M instrument. The spectral width was set to 25 ppm, the center width to 5 ppm, and the number of scans was 64. The 1H NMR spectrum was analyzed to confirm whether self-assembly behavior exists in the molecular cuvette H1.

[0061] Figure 7The 1H NMR spectrum (600MHz, Deuterium Oxide, 298K) of molecular cuvette H1 (1mmol / L, 500μL) for the recognition of cycloalkanes (2μL) is shown. Inset a) shows the recognition of cyclopentane; inset b) shows the recognition of cyclohexane; inset c) shows the recognition of cycloheptane; inset d) shows the recognition of cyclooctane; inset e) shows the recognition of cyclodecane; and inset f) shows the recognition of cyclododecane. Molecular cuvette H1 was accurately weighed and prepared into a 1mmol heavy aqueous solution. 0.5mL of the prepared molecular cuvette heavy aqueous solution was added to the sample vial, followed by 2μL (excess) of cycloalkanes as guest molecules. The mixture was thoroughly mixed in an ultrasonic cell for one hour, and the 1H NMR spectrum at 298K was measured. Analysis of the 1H NMR spectrum... 1 ¹H NMR data revealed that all cycloalkanes exhibited a single peak for their complexation signal. This is because cycloalkanes freely tumble and rotate within the cavity during the NMR time, ensuring all protons on the ring are in the same chemical environment. Cyclopentane, due to its smaller volume compared to the cavity size of molecular cup H1, exhibits a broader peak due to faster exchange processes. As the volume of cycloalkanes increases, their signal peaks gradually shift towards the lower field region, and the Δδ value gradually decreases. This indicates that as the guest molecule size increases, its complexation position in molecular cup H1 becomes shallower, further away from the bottom of the cavity where the shielding effect is strongest. Smaller guest molecules occupy deeper positions, with cyclopentane reaching a Δδ value of -4.62 ppm.

[0062] Figure 8 The 1H NMR spectra (600MHz, Deuterium Oxide, 298K) of molecular cuvette H1 (1mmol / L, 500μL) for the recognition of straight-chain carboxylic acids (2μL) are shown. Inset a) shows the recognition of heptanoic acid; inset b) shows the recognition of octanoic acid; inset c) shows the recognition of nonanoic acid; inset d) shows the recognition of decanoic acid; inset e) shows the recognition of undecanoic acid; inset f) shows the recognition of dodecaic acid; and inset g) shows the recognition of tridecanoic acid. Molecular cuvette H1 was accurately weighed and prepared into a 1mmol / L heavy aqueous solution. 0.5mL of the prepared molecular cuvette heavy aqueous solution was added to the sample vial, followed by 2μL (excess) of a straight-chain carboxylic acid as the guest molecule. The mixture was thoroughly mixed in an ultrasonic cell for one hour, and then the 298K 1H NMR spectrum was measured. Analysis of the 1H NMR spectrum... 1According to H NMR data, the methyl group is located at the deepest part of the cavity with a Δδ value of -5.30 ppm. The methylene groups near the methyl end are arranged one by one until the upper edge of the molecular cup, and their Δδ value does not change with the length of the carbon chain. The carboxyl or hydroxyl groups at the hydrophilic end are fixed at the upper edge of the molecular cup H1 cavity due to solvation. However, the signal peaks of the methylene group near the hydrophilic end gradually become denser with the increase of the carbon chain length, and the chemical shift value is close to that of the free guest. This indicates that the depth of the main cavity is insufficient to accommodate all the carbon chains of the through-hole conformation. The part of the carbon chain near the hydrophilic end that exceeds the depth that the molecular cup H1 can accommodate is located at the opening of the upper edge of the molecular cup in a coiled and folded conformation.

[0063] Figure 9 For molecular cup H 1-Pd (1 mmol / L, 500 μL) Selective recognition of 1,2-dichloroethylene 1H NMR spectrum (600 MHz, Deuterium Oxide, 298 K). Inset a) shows recognition of cis-1,2-dichloroethylene; inset b) shows recognition of trans-1,2-dichloroethylene; inset c) shows selective recognition of cis-1,2-dichloroethylene in a 1:1 cis / trans-1,2-dichloroethylene mixture. Molecular cup H1 was accurately weighed and prepared as a 1 mmol / L heavy aqueous solution. 0.5 mL of the prepared molecular cup heavy aqueous solution was added to the sample vial, followed by 2 μL (excess) of a 1:1 cis / trans-1,2-dichloroethylene mixture as the guest molecule. The mixture was thoroughly mixed in an ultrasonic cell for one hour, and then the 298 K 1H NMR spectrum was measured. Analysis of the 1H NMR spectrum... 1 ¹H NMR data showed that only cis-1,2-dichloroethylene characteristic peaks existed in the high-field region, indicating that the ¹H NMR of the metal molecular cup... 1-4Pd In the presence of both cis- and trans-1,2-dichloroethylene, selective recognition of cis-1,2-dichloroethylene is achieved. However, since dichloroethylene also has some solubility in heavy water, cis- and trans-1,2-dichloroethylene are also dissolved in heavy water, making it impossible to remove the metal molecular cup H from the heavy water solution by extraction. 1-4Pd The isolated cis-1,2-dichloroethylene resulted in the inability to accurately quantify the H+ in the metal molecular cup. 1-4Pd The selective recognition efficiency for cis-1,2-dichloroethylene was determined by proton NMR spectroscopy. 1-4Pd The cis conformation can be selectively identified from cis / trans-1,2-dichloroethylene.

[0064] In summary, the above embodiments describe the preparation method and application of the novel water-soluble 2-difluoromethylbenzimidazole molecular cup. The upper edge introduces the 2-difluoromethylimidazolium group through amidation, nucleophilic addition cyclization, and dehydration aromatization of difluoroacetic acid and o-phenylenediamine. The lower edge introduces the water-soluble 1-methylimidazolium salt through oxidation and nucleophilic substitution reactions, thus completing the novel molecular cup H1,H. 1-Pd The construction.

[0065] The resulting novel water-soluble functionalized 2-difluoromethylbenzimidazole molecular cup host H1, H1-Pd The structure is novel, and the introduction of difluoromethyl groups enables the molecular cup to recognize n-heptanoic acid and n-octanoic acid, which cannot be recognized in CN202310502333.3.

[0066] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0067] The above embodiments merely illustrate preferred implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the appended claims.

Claims

1. A fluorine-functionalized macrocyclic supramolecular host molecular cup, characterized in that, It is a 2-difluoromethyl benzimidazolyl molecular cup host and its metal derivative, the structure is as follows Molecular cup H1, H 1-Pd At least one structure in the following formula: 。 2. A method for preparing the fluorine-functionalized macrocyclic supramolecular host molecular cup as described in claim 1, characterized in that, The method includes the following steps: Preparation of molecular cup H1: Water-soluble difluoromethyl molecular cup and its metal derivative were prepared using resorcinol as the starting material. A 1-methylimidazolium salt was introduced into the lower edge of the molecular cup, with chloride as the counter anion, which made the compound water-soluble as a whole. A difluoromethyl group was introduced into the upper edge to obtain the 2-difluoromethylbenzimidazole molecular cup body H1. Molecular cup H 1-Pd Preparation: A 1-methylimidazolium salt was introduced into the lower edge of the molecular cup H1, with chloride as the counter anion, making the compound water-soluble. A difluoromethyl group was introduced into the upper edge, and the imidazolium group near the opening coordinated with 4 equivalents of ethylenediamine palladium(II) to obtain the 2-difluoromethylbenzimidazolyl molecular cup metal derivative H. 1-Pd ; The specific steps of the method are as follows: a. Using chloro-8-amino hydrochloride as a molecular cup precursor, excess difluoroacetic acid was added as a reactant and solvent. After the reaction was completed, the mixture was cooled to room temperature, washed, filtered, and the resulting solid was collected, dried, purified, and finally a white, dense powder product was obtained. The structural formula of chloro-8-aminohydrochloride is as follows: b. Dissolve the product obtained in step a in 1-methylimidazole and stir at 100°C for 24 hours. Then, cool the solution to 0°C in an ice bath, add acetone and sonicate to form a suspension. Then filter under reduced pressure and dry under high vacuum to obtain a white, dense powder of molecular cup H1. c. Prepare a heavy aqueous solution of the molecular cup H1 obtained in step b. Then, add equimolar amounts of ethylenediamine nitrate·palladium(II) dihydrate heavy aqueous solution until the spectrum no longer changes except for the free palladium ligand peak, as confirmed by 1H NMR spectroscopy. After sonication, the molecular cup H1 can be obtained. 1-Pd The heavy aqueous solution is light yellow and clear.

3. The method for preparing the fluorine-functionalized macrocyclic supramolecular host molecular cup according to claim 2, characterized in that, The amount of difluoroacetic acid added in step a is excessive.

4. The method for preparing the fluorine-functionalized macrocyclic supramolecular host molecular cup according to claim 2, characterized in that, In step a, the washing is performed multiple times with deionized water until the filtrate no longer shows an acidic reaction; and column chromatography purification is not required.

5. The method for preparing the fluorine-functionalized macrocyclic supramolecular host molecular cup according to claim 2, characterized in that, The drying temperature in step b under high vacuum shall not exceed 50℃, and the vacuum degree shall be 0.09~0.1 MPa.

6. The method for preparing the fluorine-functionalized macrocyclic supramolecular host molecular cup according to claim 2, characterized in that, In step C, the concentration of the heavy aqueous solution prepared by molecular cup H1 is 1 mmol / L, and the concentration of the heavy aqueous solution of ethylenediamine nitrate·palladium(II) dihydrate is 100 mmol / L.

7. An application of the fluorine-functionalized macrocyclic supramolecular host molecular cup as described in claim 1, characterized in that, The fluorinated functionalized macrocyclic supramolecular host molecular cup is used to recognize at least one of cycloalkanes and alkylcarboxylic acids.

8. The application of the fluorine-functionalized macrocyclic supramolecular host molecular cup according to claim 7, characterized in that, The fluorine-functionalized macrocyclic supramolecular host molecular cup forms a 1:1 host-guest complex with the guest molecules in the aqueous phase.

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