A functionalized macrocyclic molecule, its preparation method and application

Abstract

The present invention discloses a functionalized macrocyclic molecule, a preparation method thereof and applications. The structure of the functionalized macrocyclic molecule is shown as general formula I or II: #imgabs0# wherein, R1 and R2 are different, and: each occurrence of R1 is independently selected from an alkyl group, a cycloalkyl group, an aromatic hydrocarbon group, wherein the alkyl group is a straight-chain alkyl group having 1 to 16 C atoms or a branched-chain alkyl group having 3 to 16 C atoms; the cycloalkyl group is a cycloalkyl group having 3 to 16 C atoms; each occurrence of R2 is independently selected from a straight-chain alkyl group, H or an inorganic cation, wherein the straight-chain alkyl group is a straight-chain alkyl group having 1 to 16 C atoms. The functionalized macrocyclic molecule in the present invention has fluorescence properties and can detect a substance to be measured according to changes in fluorescence, and has excellent host-guest recognition properties. For example, in a mixed solvent of water and an organic solvent, it can bond polar small molecules such as toluene and p-xylene, and can be used for the detection and removal of environmental pollutants, etc., and has broad application prospects.

Description

Technical Field

[0001] The present invention relates to the fields of organic synthetic chemistry and supramolecular chemistry, and particularly relates to a functionalized macrocyclic molecule, a preparation method thereof, and an application thereof. Background Art

[0002] The development of supramolecular chemistry is inseparable from the discovery and development of supramolecular hosts or receptors. The development from the discovery of crown ethers to the development of hosts such as cyclodextrins, calixarenes, cucurbiturils, and pillararenes has experienced a long process, and researchers have achieved fruitful results in the fields of chemistry, materials science, environmental science, biomedicine, and photochemistry. Macrocyclic compounds are widely used in the fields of supramolecular polymers, supramolecular hydrogels, chromatographic column packings, etc. through functional group modification. For example, cyclodextrin is bonded to the silica surface through an ether bond to form a stable bonded chiral packing for the chiral separation of various difficult-to-separate chiral compounds (J. Chromatogr. 1985, 347, 51); the hydroxyl derivatization of cucurbituril is applied to supramolecular Velcro (J. Am. Chem. Soc. 2003, 125, 10186; Angew. Chem. Int. Ed. 2013, 52, 3140).

[0003] Naphthotubes are a kind of macrocyclic host molecule formed by bridging naphthyl groups through functional groups, and have cavity characteristics similar to those of biological receptors, and have broad application prospects in the fields of detection and removal of environmental pollutants, drug solubilization and targeted delivery, chiral sensing, intelligent materials, etc. For example, naphthotubes are applied to bioorthogonal chemistry through "click reaction", and the aggregation-induced emission star molecule - tetraphenylethylene is connected to naphthotubes to achieve cell targeting and tissue imaging of living animals (CCS Chem. 2022, 4, 1977); naphthotubes are used to prepare cross-linked polymers through "click reaction" for the removal of polar organic pollutants (Angew. Chem. Int. Ed. 2021, 60, 21404). However, at present, the types of functionalized modified molecules based on naphthotubes are still relatively single, which to a certain extent limits the application of functionalized macrocyclic molecules. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. For this purpose, the present invention provides a novel functionalized macrocyclic molecule. The unique molecular structure enables the novel functionalized macrocyclic molecule itself to have fluorescence properties, and the analyte can be detected according to the change of fluorescence during the bonding process with other substances. For example, it has host-guest recognition properties in a water / acetonitrile mixed solvent and can be used for the detection of environmental pollutants, etc., and has good application prospects.

[0005] The present invention also provides a preparation method of the functionalized macrocyclic molecule.

[0006] The present invention also provides a compound.

[0007] The present invention also provides a method for preparing a compound.

[0008] The present invention also provides the applications of the above functionalized macrocyclic molecules and compounds.

[0009] In a first aspect of the present invention, a functionalized macrocyclic molecule is provided, and its structure is shown as general formula I or II:

[0010]

[0011] Wherein, R1 and R2 are different, and:

[0012] Each occurrence of R1 is independently selected from an alkyl group, a cycloalkyl group, and an aromatic hydrocarbon group, wherein the alkyl group is selected from a straight-chain alkyl group having 1 to 16 C atoms or a branched-chain alkyl group having 3 to 16 C atoms; the cycloalkyl group is selected from a cycloalkyl group having 3 to 16 C atoms;

[0013] Each occurrence of R2 is independently selected from a straight-chain alkyl group, H, or an inorganic cation, wherein the straight-chain alkyl group is selected from a straight-chain alkyl group having 1 to 16 C atoms.

[0014] The functionalized macrocyclic molecule according to the embodiment of the present invention has at least the following beneficial effects:

[0015] The functionalized macrocyclic molecule in the present invention is a novel macrocyclic molecule, having a hydrophobic cavity characteristic similar to that of a biological receptor: the hydrogen bond binding site is located in the hydrophobic cavity, and the hydrophobic cavity provides a relatively non-polar environment for hydrogen bond interaction, which can avoid the competition of water molecules. The synergistic effect of the hydrophobic effect and hydrogen bond interaction enhances the interaction between host-guest molecules. The functionalized macrocyclic molecule in the present invention has fluorescence properties due to its unique molecular structure, and can detect the substance to be measured according to the change of fluorescence during the bonding with other substances, and has excellent host-guest recognition properties. Among them, for example, the water-soluble functionalized macrocyclic molecule selectively recognizes neutral molecules, polar small molecules, and drug molecules in water; another example is that the functionalized macrocyclic molecule can bond polar small molecules such as toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene in a mixed solvent of water and an organic solvent (such as a water / acetonitrile mixed solvent), and can be used for the detection and removal of environmental pollutants (such as the detection and removal of organic pollutants), chiral sensing, intelligent materials, etc., and has broad application prospects.

[0016] In some embodiments of the present invention, the functionalized macrocyclic molecule contains a carboxyl group.

[0017] Through the above embodiments, when the functionalized macrocyclic molecule contains a carboxylic acid functional group, it can undergo an amide condensation reaction with an organic amine, featuring functional modification characteristics. For example, the functionalized macrocyclic molecule can react with a polymer containing an NH2 functional group such as polyamide to prepare a high molecular polymer, which is applied in fields such as organic pollutant removal and environmental remediation, showing good application prospects.

[0018] In some embodiments of the present invention, when R1 is a straight-chain alkyl group having 1 to 16 carbon atoms, R1 is selected from at least one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, or hexadecyl;

[0019] When R1 is a branched-chain alkyl group having 3 to 16 carbon atoms, R1 is selected from at least one of isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, tert-pentyl, neohexyl, or isohexyl;

[0020] When R1 is a cycloalkyl group having 3 to 16 carbon atoms, R1 is selected from at least one of cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl;

[0021] When R1 is an aromatic hydrocarbon group, R1 is selected from at least one of phenyl, benzyl, naphthyl, anthryl, phenanthryl, or pyrenyl.

[0022] In some embodiments of the present invention, each occurrence of R1 is independently selected from one of benzyl or methyl.

[0023] In some preferred embodiments of the present invention, the inorganic cation includes Na + , K + or NH4 + and at least one of them.

[0024] In some embodiments of the present invention, each occurrence of R2 is independently selected from one of ethyl, H, Na + , K + or NH4 + and one of them.

[0025] In some embodiments of the present invention, the functionalized macrocyclic molecule includes at least one of the compounds with the following structural formulas:

[0026]

[0027] In the second aspect of the present invention, a preparation method of a functionalized macrocyclic molecule is proposed, including the following steps: S1, taking compound S00 and undergoing an amination reaction to obtain compound S10;

[0028] S2. Take the compound S10 and the compound A, and through amide condensation, obtain the functionalized macrocyclic molecule; wherein, the structural formulas of the compounds S00, S10, and the compound A are as follows:

[0029]

[0030] Each occurrence of the group R3 in the compound A is independently selected from a straight-chain alkyl group having 1 to 16 carbon atoms;

[0031] When one of the R2 in the functionalized macrocyclic molecule is not H and not an inorganic cation, R3 in the compound A is the same as R2 in the functionalized macrocyclic molecule.

[0032] In this article, "≡" means identically equal, that is, it represents the structural formulas of the same compound from different perspectives.

[0033] Among them, the reaction formula is as follows:

[0034]

[0035] The preparation method of the functionalized macrocyclic molecule according to the embodiment of the present invention has at least the following beneficial effects:

[0036] The preparation method of the functionalized macrocyclic molecule of the present invention has the characteristics of mild reaction conditions, high product yield, and stable intermediate structure. The raw materials are cheap and easy to obtain, and it is suitable for large-scale production. Specifically, in step S1, the dialdehyde compound S00 undergoes an amination reaction to prepare the intermediate compound S10. The synthesis process of the compound S10 is simple and the conditions are mild. The carboxylic acid compound S20 currently has relatively mature synthesis routes and processes. The compound S10 and the compound S20 undergo an amide condensation [1+1] ring-closing reaction to prepare the functionalized macrocyclic molecule; among them, the amide condensation [1+1] ring-closing reaction has a high yield, and the obtained functionalized macrocyclic molecule has good stability.

[0037] In some embodiments of the present invention, in step S2, take a mixed solution containing N,N-dimethylformamide, N,N-diisopropylethylamine, and 1H-benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate, add the compound A and the compound S10, and through amide condensation, obtain the functionalized macrocyclic molecule. Preferably, the reaction temperature is 75-90 °C.

[0038] In some preferred embodiments of the present invention, the molar ratio of the compound A to the compound S10 is (0.8-1.2):(0.8-1.2).

[0039] In some preferred embodiments of the present invention, through amide condensation, under reduced pressure concentration, add a mixed solution of water and methanol, precipitate, filter, dry, and perform column chromatography to obtain the functionalized macrocyclic molecule.

[0040] In some embodiments of the present invention, when R2 is H, step S2 further includes: a step of hydrolysis after amide condensation;

[0041] The reaction formula is as follows:

[0042]

[0043] When R2 is an inorganic cation, step S2 further includes: after amide condensation, a step of first hydrolysis and then reaction with a basic substance. Taking R2 as Na + as an example, the reaction formula is as follows:

[0044]

[0045] In some embodiments of the present invention, R3 is ethyl. The compound A is compound S20, and its structural formula is as follows:

[0046]

[0047] In some embodiments of the present invention, the compound A is compound S20, and the group R2 in the functionalized macrocyclic molecule is at least one of ethyl, H or an inorganic cation.

[0048] In some preferred embodiments of the present invention, the preparation method of the compound S20 includes the following steps: taking compound f, and after oxidation, obtaining the compound S20, wherein the structural formula of compound f is as follows:

[0049]

[0050] In some more preferred embodiments of the present invention, the preparation method of the compound S20 includes the following steps: taking compound f and mixing it with a mixed solvent, adding sulfamic acid and sodium chlorite, stirring, reacting, removing the solvent, adding hydrochloric acid, to obtain the compound S20. Preferably, stir under ice bath conditions, add sulfamic acid and sodium chlorite in sequence, stir at room temperature until the reaction is complete, remove the mixed solvent, add hydrochloric acid to the concentrated solution, precipitate will form after ultrasonic treatment, filter and dry to obtain the compound S20. More preferably, the mixed solvent is a mixture of water, tetrahydrofuran and acetone.

[0051] In some embodiments of the present invention, the compound A is compound S20, and the functionalized macrocyclic molecule is at least one of the compounds of formula Ⅰ-A, Ⅱ-A, Ⅰ-B, Ⅱ-B, Ⅰ-C, Ⅱ-C;

[0052]

[0053]

[0054] Among them, step S2 includes the following operations: taking the compound S10 and the compound S20, and performing amide condensation to obtain the compound of formula I-A and / or formula II-A;

[0055] When the functionalized macrocyclic molecule is the compound of formula I-B, step S2 further includes: obtaining the compound of formula I-A after amide condensation, and hydrolyzing to obtain the compound of formula I-B;

[0056] When the functionalized macrocyclic molecule is the compound of formula II-B, step S2 further includes: obtaining the compound of formula II-A after amide condensation, and hydrolyzing to obtain the compound of formula II-B;

[0057] When the functionalized macrocyclic molecule is the compound of formula I-C, step S2 further includes: obtaining the compound of formula I-B after amide condensation and hydrolysis, and performing an acid-base neutralization reaction with the basic substance III containing sodium to obtain the compound of formula I-C;

[0058] When the functionalized macrocyclic molecule is the compound of formula II-C, step S2 further includes: obtaining the compound of formula II-B after amide condensation and hydrolysis, and performing an acid-base neutralization reaction with the basic substance IV containing sodium to obtain the compound of formula II-C.

[0059] Through the above embodiments, the trifluoroacetamide salt S10 and the carboxylic acid S20 are subjected to an amide condensation [1+1] ring-closing reaction to prepare the functionalized macrocyclic molecule (compounds of formula I-A, II-A, I-B, II-B, I-C, II-C); the amide condensation [1+1] ring-closing reaction has a high yield, and the prepared functionalized macrocyclic molecule has good stability.

[0060] Among them, when the functionalized macrocyclic molecule is at least one of the compounds of formula I-A and II-A, the reaction formula is as follows:

[0061]

[0062] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is the compound of formula I-B, step S2 further includes: obtaining the compound of formula I-A after amide condensation, mixing the compound of formula I-A, the basic substance I and the solvent I, performing a hydrolysis reaction, removing the solvent I, and adding the acidic substance I to obtain the compound of formula I-B.

[0063] In some more preferred embodiments of the present invention, the solvent I is a mixed solution of water, methanol and tetrahydrofuran; preferably, the solvent I is a mixed solvent formed by mixing water, methanol and tetrahydrofuran in a volume ratio of 1:5:5.

[0064] In some more preferred embodiments of the present invention, the reaction temperature is 25-60°C, and the reaction time is 6-24 h.

[0065] In some more preferred embodiments of the present invention, the basic substance I includes at least one of sodium hydroxide or potassium hydroxide.

[0066] In some more preferred embodiments of the present invention, the acidic substance I includes hydrochloric acid.

[0067] In some more preferred embodiments of the present invention, the molar ratio of the compound of formula I-A to the basic substance I is 1:(2 - 20).

[0068] In some more preferred embodiments of the present invention, the molar ratio of the compound of formula I-A to the acidic substance I is 1:(4 - 40).

[0069] In some more preferred embodiments of the present invention, an acidic substance I is added, stirred or sonicated, a precipitate is formed, filtered, and dried to obtain the compound of formula I-B.

[0070] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is the compound of formula II-B, step S2 further includes: obtaining the compound of formula II-A through amide condensation, mixing the compound of formula II-A, a basic substance II, and a solvent II, performing a hydrolysis reaction, removing the solvent II, and adding an acidic substance II to obtain the compound of formula II-B.

[0071] In some more preferred embodiments of the present invention, the solvent II is a mixed solution of water, methanol, and tetrahydrofuran; preferably, the solvent II is a mixed solvent formed by mixing water, methanol, and tetrahydrofuran in a volume ratio of 1:5:5.

[0072] In some more preferred embodiments of the present invention, the reaction temperature is 25 - 60 °C, and the reaction time is 6 - 24 h.

[0073] In some more preferred embodiments of the present invention, the basic substance II includes at least one of sodium hydroxide or potassium hydroxide.

[0074] In some more preferred embodiments of the present invention, the acidic substance II includes hydrochloric acid.

[0075] In some more preferred embodiments of the present invention, the molar ratio of the compound of formula II-A to the basic substance II is 1:(2 - 20).

[0076] In some more preferred embodiments of the present invention, the molar ratio of the compound of formula II-A to the acidic substance II is 1:(4 - 40).

[0077] In some more preferred embodiments of the present invention, an acidic substance II is added, stirred or sonicated, a precipitate is formed, filtered, and dried to obtain the compound of formula II-B.

[0078] The reaction equations for preparing the compounds of formula I-B and II-B from the compounds of formula I-A and II-A are as follows:

[0079]

[0080] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is a compound of formula I-B, step S2 includes: taking the compound S10 and the compound S20, performing amide condensation to obtain a compound of formula I-A, and hydrolyzing to obtain the compound of formula I-B.

[0081] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is a compound of formula II-B, step S2 includes: the compound S10 and the compound S20, performing amide condensation to obtain a compound of formula II-A, and hydrolyzing to obtain the compound of formula II-B.

[0082] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is a compound of formula I-C, step S2 further includes: obtaining a compound of formula I-B through amide condensation and hydrolysis, mixing the compound of formula I-B, the basic substance III and water, performing a neutralization reaction, and drying to obtain the compound of formula I-C.

[0083] In some more preferred embodiments of the present invention, the reaction temperature is 25 - 40 °C and the reaction time is 1 - 12 h.

[0084] In some more preferred embodiments of the present invention, the basic substance III includes sodium hydroxide.

[0085] In some more preferred embodiments of the present invention, the molar ratio of the compound of formula I-B to the basic substance III is 1:(1 - 3), preferably about 1:2.

[0086] In some more preferred embodiments of the present invention, the drying method includes freeze-drying.

[0087] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is a compound of formula II-C, step S2 further includes: obtaining a compound of formula II-B through amide condensation and hydrolysis, mixing the compound of formula II-B, the basic substance IV and water, performing a neutralization reaction, and drying to obtain the compound of formula II-C.

[0088] In some more preferred embodiments of the present invention, the reaction temperature is 25 - 40 °C and the reaction time is 1 - 12 h.

[0089] In some more preferred embodiments of the present invention, the basic substance IV includes sodium hydroxide.

[0090] In some more preferred embodiments of the present invention, the molar ratio of the compound of formula II-B to the basic substance IV is 1:(1 - 3), preferably about 1:2.

[0091] In some more preferred embodiments of the present invention, the drying method includes freeze-drying.

[0092] The reaction formulas for preparing the compounds of formula I-C and II-C from the compounds of formula I-B and II-B are as follows:

[0093]

[0094] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is a compound of formula I-C, step S2 includes: taking the compound S10 and the compound S20, performing amide condensation to obtain a compound of formula I-A, hydrolyzing to obtain a compound of formula I-B, and performing an acid-base neutralization reaction with a sodium-containing basic substance III to obtain the compound of formula I-C.

[0095] In some preferred embodiments of the present invention, when the functionalized macrocyclic molecule is a compound of formula II-C, step S2 includes: taking the compound S10 and the compound S20, performing amide condensation to obtain a compound of formula II-A, hydrolyzing to obtain a compound of formula II-B, and performing an acid-base neutralization reaction with a sodium-containing basic substance IV to obtain the compound of formula II-C.

[0096] In some embodiments of the present invention, the preparation method of the compound S00 includes the following steps: taking 2,6-dihydroxynaphthalene and potassium carbonate, mixing, adding methyl iodide, reacting to obtain compound a; taking compound a, adding dichloromethane, adding trifluoroacetic acid, adding 1,1,3,3-tetramethoxypropane, reacting to obtain compound b; taking compound b, adding anhydrous dichloromethane, 1,1-dichloromethyl ether, adding titanium tetrachloride, reacting to obtain the compound S00. The reaction formula is as follows:

[0097]

[0098] In the third aspect of the present invention, a compound is proposed, and its structural formula is as shown in formula I-D and II-D:

[0099]

[0100] Wherein, R4 is selected from a substituted or unsubstituted alkyl group, cycloalkyl group or aromatic hydrocarbon group, wherein, the alkyl group is selected from alkyl groups having 1 to 16 C atoms, the cycloalkyl group is selected from cycloalkyl groups having 1 to 16 C atoms, and the aromatic hydrocarbon group is selected from aromatic hydrocarbon groups having 1 to 16 C atoms.

[0101] In some embodiments of the present invention, the substituent in the substitution is selected from a mercapto group.

[0102] In some embodiments of the present invention, R4 is selected from at least one of mercaptoethyl, mercaptopropyl, mercaptobutyl, or mercaptopentyl.

[0103] In a fourth aspect of the present invention, a method for preparing the above compound is provided, which includes the following steps: an amidation reaction occurs between the functionalized macrocyclic molecule and an organic amine to prepare the compound, wherein the functionalized macrocyclic molecule contains a carboxyl group.

[0104] In some embodiments of the present invention, the organic amine includes at least one of mercaptoethylamine, mercaptopropylamine, mercaptobutylamine, or mercaptopentylamine.

[0105] In some embodiments of the present invention, the functionalized macrocyclic molecule includes at least one of the compounds of formula Ⅰ-B and Ⅱ-B. The reaction formula is as follows:

[0106]

[0107] In some preferred embodiments of the present invention, the method for preparing the compound of formula Ⅰ-D includes the following steps: taking a mixture of the compound of Ⅰ-B, an organic amine, and solvent Ⅲ, adding amide condensing agent Ⅰ, and reacting to obtain the compound of formula Ⅰ-D.

[0108] In some more preferred embodiments of the present invention, the amide condensing agent Ⅰ includes at least one of dicyclohexylcarbodiimide (DCC) or 1H-benzotriazole-1-yloxytris-pyrrolidinophosphonium hexafluorophosphate.

[0109] In some more preferred embodiments of the present invention, the solvent Ⅲ is anhydrous dichloromethane.

[0110] In some more preferred embodiments of the present invention, the reaction temperature is 25 - 60 °C.

[0111] In some more preferred embodiments of the present invention, the reaction time is 12 - 24 h.

[0112] In some preferred embodiments of the present invention, the method for preparing the compound of formula Ⅱ-D includes the following steps: taking a mixture of the compound of Ⅱ-B, an organic amine, and solvent Ⅳ, adding amide condensing agent Ⅱ, and reacting to obtain the compound of formula Ⅱ-D.

[0113] In some more preferred embodiments of the present invention, the amide condensing agent Ⅱ includes at least one of dicyclohexylcarbodiimide (DCC) or 1H-benzotriazole-1-yloxytris-pyrrolidinophosphonium hexafluorophosphate.

[0114] In some more preferred embodiments of the present invention, the solvent IV is anhydrous dichloromethane.

[0115] In some more preferred embodiments of the present invention, the reaction temperature is 25 - 60 °C.

[0116] In some more preferred embodiments of the present invention, the reaction time is 12 - 24 h.

[0117] The fifth aspect of the present invention provides the application of the above functionalized macrocyclic molecule or compound in molecular recognition, removal of organic pollutants or monitoring of environmental pollutants.

[0118] When the above functionalized macrocyclic molecule or compound is used for molecular recognition, the molecular recognition effect is good. By using the above functionalized macrocyclic molecule or compound for the removal of organic pollutants or the monitoring of environmental pollutants, specific pollutants such as polar small molecules like toluene, ethylbenzene, o - xylene, m - xylene, p - xylene, etc., the effect is good. Description of the Drawings

[0119] The following further describes the present invention with reference to the drawings and examples, where:

[0120] Figure 1 is the structural formula of the functionalized macrocyclic molecule of the present invention;

[0121] Figure 2 is of the compound of Formula I - 1 in Example 1 of the present invention 1 HNMR spectrum;

[0122] Figure 3 is of the compound of Formula II - 1 in Example 1 of the present invention 1 HNMR spectrum;

[0123] Figure 4 is of the compound of Formula I - 11 in Example 2 of the present invention 1 HNMR spectrum;

[0124] Figure 5 is of the compound of Formula II - 11 in Example 2 of the present invention 1 HNMR spectrum;

[0125] Figure 6 is of the compound of Formula I - 2 in Example 4 of the present invention 1 HNMR spectrum;

[0126] Figure 7 is of the compound of Formula II - 2 in Example 4 of the present invention 1 HNMR spectrum;

[0127] Figure 8 is of the compound of Formula I - 21 in Example 5 of the present invention 1HNMR spectrum;

[0128] Figure 9 This is the 1 HNMR spectrum of the compound of Formula II-21 in Example 5 of the present invention;

[0129] Figure 10 This is the fluorescence titration spectrum of p-xylene for the pair of I-12 in Example 3 of the present invention;

[0130] Figure 11 This is the fluorescence titration spectrum of p-xylene for the pair of II-12 in Example 3 of the present invention;

[0131] Figure 12 This is the fluorescence titration spectrum of p-xylene for the pair of I-22 in Example 6 of the present invention;

[0132] Figure 13 This is the fluorescence titration spectrum of p-xylene for the pair of II-22 in Example 6 of the present invention. Detailed implementation mode

[0133] The concept of the present invention and the technical effects generated will be clearly and completely described below in conjunction with the embodiments to fully understand the purpose, features, and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative labor belong to the scope of protection of the present invention.

[0134] For the experimental methods without specific conditions noted in the following examples, they are usually carried out according to the conventional conditions in the art or according to the conditions recommended by the manufacturer; the raw materials, reagents, etc. used, unless otherwise specified, are all raw materials and reagents that can be obtained from commercial channels such as the conventional market.

[0135] Among them, the mass fraction of HCl in the hydrochloric acid used is about 36%;

[0136] Boron tribromide / dichloromethane solution: The concentration of boron tribromide is about 1 mol / L.

[0137] Example 1

[0138] This example discloses a functionalized macrocyclic molecule, and the functionalized macrocyclic molecule has any of the following structures:

[0139]

[0140] The preparation process of the functionalized macrocyclic molecule includes:

[0141] At 85 °C, N,N-diisopropylethylamine (4.0 mL, 22.7 mmol) and 1H-benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (5.0 g, 9.7 mmol) were added to 500 mL of anhydrous N,N-dimethylformamide solvent. Under stirring, solutions of ester-based diacid S20 (2.0 g, 2.8 mmol) and methyl trifluoroacetate ammonium salt S10 (2.0 g, 2.98 mmol) in N,N-dimethylformamide were added respectively at a constant rate (125 μL / s) using a syringe pump. After the reaction was completed, it was concentrated under reduced pressure, and a mixture of water and methanol (500 mL of water and 500 mL of methanol) was added. A precipitate formed, which was filtered and dried in vacuo. The crude product was separated by column chromatography on a silica gel column (eluent: DCM:MeOH = 1000:1 - 1000:15, 200 - 300 mesh) to obtain compound of formula I-1 (310 mg, yield 11%) and compound of formula II-1 (600 mg, yield 21%).

[0142] The reaction equation is as follows:

[0143]

[0144] The prepared compound of formula I-1 and compound of formula II-1 were tested, and it was proved that the compound of formula I-1 and compound of formula II-1 were successfully prepared. Specifically:

[0145] The structural analysis of the compound of formula I-1 is as follows:

[0146] 1 The HNMR spectrum is as Figure 2 shown, m.p. > 300 °C. 1 H NMR (400 MHz, CD2Cl 2, 298 K) δ [ppm]: 8.40 (d, J = 9.3 Hz, 2H), 8.27 (d, J = 9.4 Hz, 2H), 7.76 (d, J = 9.2 Hz, 2H), 7.63 (d, J = 9.2 Hz, 2H), 7.24 (d, J = 9.4 Hz, 2H), 7.07 (dd, J = 14.8, 9.2 Hz, 4H), 6.98 (d, J = 9.4 Hz, 2H), 6.27–6.19 (m, 2H), 5.63 (d, J = 7.3 Hz, 2H), 5.27 (d, J = 19.5 Hz, 1H), 5.12 (dd, J = 13.6, 7.9 Hz, 2H), 4.83 (dd, J = 13.7, 1.9 Hz, 2H), 4.73–4.55 (m, 4H), 4.05 (qq, J = 10.7, 7.1 Hz, 4H), 3.87 (s, 6H), 2.60 (dt, J = 32.5, 2.7 Hz, 4H), 1.11 (t, J = 7.1 Hz, 6H). 1313C NMR(126MHz,CD2Cl 2, 298K)δ[ppm]168.91,165.72,153.52,149.92,149.76,149.03,128.38,127.26,126.51,126.19,125.69,124.54,124.11,122.93,122.51,119.97,119.72,119.11,119.00,113.68,113.10,91.37,91.17,66.77,61.25,56.70,33.63,25.79,25.55,22.55,22.43,13.66.

[0147] ESI-HRMS:m / z calcd for[M+H] + C 60 H 51 N2O 14 + ,1023.3340;found 1023.3311(error=-2.8ppm).

[0148] The structural analysis of the compound of Formula II-1 is as follows:

[0149] 1 The 1H NMR spectrum is as Figure 3 shown, m.p.>300℃. 1 1H NMR(400MHz,CD2Cl 2, 298K)δ[ppm]8.40(d,J=9.4Hz,2H),8.28(d,J=9.4Hz,2H),7.69(d,J=9.2Hz,2H),7.54(d,J=9.2Hz,2H),7.21(d,J=9.4Hz,2H),7.10–6.92(m,6H),6.27–6.17(m,2H),5.31–5.16(m,2H),4.78–4.49(m,6H),4.00(dq,J=10.8,7.2Hz,2H),3.87(s,6H),3.79(dq,J=10.8,7.2Hz,2H),2.60(dt,J=19.5,2.6Hz,4H),0.95(t,J=7.1Hz,6H). 13 13C NMR(126MHz,CD2Cl 2,At 298 K) δ [ppm] 168.48, 165.97, 153.18, 149.58, 149.50, 148.77, 128.46, 127.03, 126.12, 126.07, 125.35, 124.55, 124.06, 122.77, 119.77, 119.41, 119.39, 119.06, 118.61, 113.48, 113.20, 91.49, 91.38, 66.49, 61.21, 56.52, 34.11, 25.99, 25.59, 22.56, 13.70, -17.98.

[0150] ESI-HRMS: m / z calcd for [M+H] + C 60 H 51 N2O 14 + , 1023.3340; found 1023.3308 (error = -3.1 ppm).

[0151] Among them, the ester-based diacid S20 (Compound S20) can be obtained by the following method: Using the ester-based dialdehyde f (Compound f) as a raw material, the ester-based diacid S20 is prepared, and the reaction formula is as follows:

[0152]

[0153] Among them, the synthesis of the ester-based dialdehyde f refers to the literature (J. Am. Chem. Soc., 2004, 126, 12732, Nat. Chem., 2019, 11, 470).

[0154] The preparation process of the ester-based diacid S20 includes:

[0155] Add the ester-based dialdehyde f (8.0 g, 13.7 mmol), 200 mL of water, 200 mL of tetrahydrofuran, and 300 mL of acetone to a 1000 mL two-necked flask. Stir under ice bath conditions (0 °C), and sequentially add sulfamic acid (10.0 g, 103.0 mmol) and sodium chlorite (10.0 g, 108.2 mmol). Stir at room temperature for 12 hours. After the reaction is completed, rotate and evaporate to remove the solvent, add 2 mL of hydrochloric acid to the concentrated solution, precipitate appears after ultrasonic treatment, filter and dry to obtain 8.3 g of a grayish-white solid compound S20, and the yield is 98%.

[0156] In addition, the methyl trifluoroacetate ammonium salt S10 (Compound S10) is obtained by the following method: Using the methyl dialdehyde c (Compound c) as a raw material, the methyl trifluoroacetate ammonium salt S10 is prepared, and the reaction formula is as follows:

[0157]

[0158] The synthesis of methyl trifluoroacetate ammonium salt S10 was carried out with reference to the literature (Org. Biomol. Chem., 2020, 18, 1900). The preparation process of methyl trifluoroacetate ammonium salt S10 includes:

[0159] Add methyl dialdehyde c (10.0 g, 22.7 mmol), tert-butyl carbamate (13.3 g, 113.5 mmol), 100 mL of acetonitrile, and 350 mL of dichloromethane into a 1000 mL two-necked flask. Then, successively add triethylsilane (18.0 mL, 113.5 mmol) and 8 mL of trifluoroacetic acid, and stir at room temperature for 6 hours. Rotate and evaporate to remove dichloromethane, add 200 mL of acetonitrile, and precipitate will form upon ultrasonic treatment. Filter, and the filter cake is dried under vacuum to obtain a white solid. Add 250 mL of dichloromethane and 25 mL of trifluoroacetic acid to the above white solid successively, and stir at room temperature for 6 hours. After the reaction is completed, rotate and evaporate to remove dichloromethane, add 100 mL of anhydrous ether to the concentrated solution, and precipitate will form upon ultrasonic treatment. Filter and dry to obtain 12 g of white solid compound S10 with a yield of 80%.

[0160] Methyl dialdehyde c (compound c) used in the preparation of methyl trifluoroacetate ammonium salt S10 can be obtained by any one or both of the following two methods:

[0161] Method 1: The reaction formula is as follows:

[0162]

[0163] (Ⅰ) Synthesis of compound a (methyl monosubstituted)

[0164] Add 2,6-dihydroxynaphthalene (50.0 g, 312.2 mmol) and potassium carbonate (47.5 g, 343.4 mmol) into a 1 L two-necked flask, add 500 mL of DMF, stir to dissolve, and add methyl iodide (21.4 mL, 343.4 mmol) dropwise using a constant pressure dropping funnel. React at 85 °C for 12 h. After the reaction is completed, rotate and evaporate to concentrate, pour the reaction solution into 2 L of ice water, adjust the pH of the solution to about 6, filter, wash the filter cake with water 3 times, and dry under vacuum to obtain the crude product. Wash the crude product with methanol 2 - 3 times, collect the filtrate, dry it with anhydrous sodium sulfate, and concentrate under reduced pressure. Purify through a silica gel column chromatography to obtain 19 g of white solid compound a with a yield of 35%.

[0165] (Ⅱ) Synthesis of compound b (methyl dimer)

[0166] Add compound a (25.0 g, 43.5 mmol), 300 mL of dichloromethane to a 500 mL two-necked flask, stir and dissolve it under an ice-water bath, add 150 mL of trifluoroacetic acid, add 11.8 mL of 1,1,3,3-tetramethoxypropane through a constant-pressure dropping funnel, and react at room temperature for 12 h. After the reaction, pour the reaction solution into 1 L of ice water, adjust the pH of the solution to about 8, extract and separate the layers. The organic layer is dried with saturated brine, washed with water and anhydrous sodium sulfate, concentrated under reduced pressure, add 300 mL of methanol to the concentrated solution and precipitate by ultrasonic treatment, filter and dry in vacuo to obtain 18 g of a grayish-white solid compound b, with a yield of 68%.

[0167] (Ⅲ) Synthesis of compound c (methyl dialdehyde S00)

[0168] Add compound b (25.0 g, 65.0 mmol), 300 mL of anhydrous dichloromethane, 23.5 mL of 1,1-dichloroether to a 500 mL two-necked flask in sequence, stir and dissolve it under an ice-water bath, add 28.5 mL of titanium tetrachloride through a constant-pressure dropping funnel, and react at room temperature for 12 h. After the reaction, pour the reaction solution into 1000 mL of ice water, adjust the pH of the solution to about 8, extract and separate the layers. The organic layer is dried with saturated brine, washed with water and anhydrous sodium sulfate, concentrated under reduced pressure, add 100 mL of acetone to the concentrated solution and precipitate by ultrasonic treatment, filter and dry in vacuo to obtain 18 g of a yellow solid compound c, with a yield of 63%.

[0169] Method 2: Refer to the literature (Org. Biomol. Chem., 2020, 18, 1900), and the reaction formula is as follows:

[0170]

[0171] (Ⅰ) Synthesis of compound e (bromo dimer)

[0172] Add 6-bromo-2-naphthol (25.0 g, 43.5 mmol), 300 mL of dichloromethane to a 500 mL two-necked flask, stir and dissolve it under an ice-water bath, add 150 mL of trifluoroacetic acid, add 11.1 mL of 1,1,3,3-tetramethoxypropane through a constant-pressure dropping funnel, and react at room temperature for 12 h. After the reaction, pour the reaction solution into 1 L of ice water, adjust the pH of the solution to about 8, extract and separate the layers. The organic layer is dried with saturated brine, washed with water and anhydrous sodium sulfate, concentrated under reduced pressure, add methanol to the concentrated solution and precipitate by ultrasonic treatment, filter and dry in vacuo to obtain 22 g of a grayish-white solid compound e, with a yield of 83%.

[0173] (Ⅱ) Synthesis of compound b (methyl dimer)

[0174] Sodium methoxide (21.6 g, 399.9 mmol) and 50 mL of methanol were added to a 500 mL two-necked flask and stirred at room temperature for 5 minutes. Compound e (10.0 g, 20.8 mmol) and 150 mL of N,N-dimethylformamide were added successively, and the mixture was deoxygenated; cuprous iodide (1.5 g, 8.0 mmol) was added and the reaction was carried out at 130 °C for 6 h. After the reaction was completed, the reaction solution was poured into 1 L of ice water, saturated ammonium chloride aqueous solution was added, and the mixture was filtered and dried to obtain a filter cake, which was purified by column chromatography on a silica gel column to obtain 6.1 g of white solid compound b with a yield of 76%.

[0175] (Ⅲ) The synthesis of compound c (methyl dialdehyde S00) was the same as that in Method 1.

[0176] Example 2

[0177] This example discloses a functionalized macrocyclic molecule having any one of the following structures:

[0178]

[0179] The preparation process of the compound of formula I-11 includes:

[0180] Compound of formula I-1 (860 mg, 0.84 mmol) and sodium hydroxide (336.0 mg, 8.4 mmol) were successively added to a mixed solvent (100 mL of methanol + 20 mL of water + 100 mL of tetrahydrofuran), and the mixture was stirred and reacted at 50 °C under heating for 12 h. After the reaction was completed, it was concentrated under reduced pressure, 2 mL of hydrochloric acid was added, sonicated for precipitation, centrifuged and washed with a large amount of water, and dried to obtain a solid (750 mg, yield 93%).

[0181] Among them, the reaction formula is shown as follows, and the compound of formula I-1 is the compound of formula I-1 prepared in Example 1:

[0182]

[0183] The prepared compound of formula I-11 was tested, and it was proved that the compound of formula I-11 was successfully prepared. Specifically, the structural analysis of the compound of formula I-11 is as follows:

[0184] 1 The HNMR spectrum is as Figure 4 shown, m.p. > 300 °C. 11H NMR(500 MHz, DMSO-d6, 298 K) δ [ppm] 13.16 (s, 2H), 8.63 (d, J = 9.6 Hz, 2H), 8.54 (d, J = 9.6 Hz, 2H), 7.72 (d, J = 9.2 Hz, 2H), 7.50 (d, J = 9.1 Hz, 4H), 7.28 (d, J = 9.5 Hz, 2H), 7.18 (dd, J = 9.4, 4.3 Hz, 4H), 7.12 (d, J = 9.1 Hz, 2H), 6.34 (q, J = 1.9 Hz, 1H), 6.29 (q, J = 2.0 Hz, 1H), 5.60 (s, 2H), 4.98 (dd, J = 13.8, 8.4 Hz, 2H), 4.82 (d, J = 16.9 Hz, 2H), 4.63 (d, J = 16.9 Hz, 2H), 4.56–4.48 (m, 2H), 3.79 (s, 6H), 2.56 (d, J = 2.7 Hz, 2H), 2.45 (d, J = 2.8 Hz, 2H). 13 13C NMR(126 MHz, DMSO-d6, 298 K) δ [ppm] 171.81, 165.78, 153.98, 150.65, 149.24, 148.77, 128.52, 127.11, 126.89, 126.65, 126.47, 125.75, 124.63, 123.57, 122.71, 120.37, 120.13, 119.62, 119.59, 119.32, 115.02, 114.34, 91.07, 90.86, 66.39, 57.51, 33.27, 25.69, 25.46, 21.72, 21.59.

[0185] ESI-HRMS: m / z calcd for [M+H] + C 56 H 43 N2O 14 + , 967.2714; found 967.2714 (error = -3.1 ppm).

[0186] The preparation process of the compound of formula II-11 includes:

[0187] To the mixed solvent (100 mL of methanol + 20 mL of water + 100 mL of tetrahydrofuran) was successively added the compound of formula II-1 (1.0 g, 0.98 mmol) and sodium hydroxide (392.0 mg, 9.8 mmol), and the mixture was stirred and reacted at 50 °C for 12 h. After the reaction was completed, it was concentrated under reduced pressure, 2 mL of hydrochloric acid was added, sonicated for precipitation, centrifuged and washed with a large amount of water, and dried to obtain a solid (850 mg, yield 89%).

[0188] Among them, the reaction formula is as follows, and the compound of formula II-1 is the compound of formula II-1 prepared in Example 1:

[0189]

[0190] The prepared compound of formula II-11 was tested, and it was proved that the compound of formula II-11 was successfully prepared. Specifically, the structural analysis of the compound of formula II-11 is as follows:

[0191] 1 The HNMR spectrum is as Figure 5 shown, m.p. > 300 °C. 1 H NMR (500 MHz, DMSO-d 6, 298K) δ 13.22 (s, 2H), 8.56 (dd, J = 28.4, 9.6 Hz, 4H), 7.62 (d, J = 9.4 Hz, 2H), 7.46 (d, J = 9.1 Hz, 2H), 7.24 (d, J = 9.5 Hz, 2H), 7.16 (dd, J = 12.8, 8.3 Hz, 4H), 7.05 (dd, J = 20.3, 9.2 Hz, 4H), 6.31 (q, J = 1.7 Hz, 2H), 5.59 (d, J = 4.2 Hz, 2H), 5.20 (dd, J = 13.6, 7.2 Hz, 2H), 4.76 (d, J = 16.6 Hz, 2H), 4.63 (d, J = 16.7 Hz, 2H), 4.33 (dd, J = 13.3, 2.1 Hz, 2H), 3.81 (s, 6H), 2.53 (s, 2H), 2.46 (s, 2H). 13 C NMR (126 MHz, DMSO-d 6, 298K) δ [ppm] 171.47, 165.90, 153.25, 150.32, 149.22, 148.51, 129.25, 127.10, 126.68, 126.64, 126.06, 125.44, 124.51, 123.43, 123.40, 120.00, 119.89, 119.36, 119.32, 119.19, 115.26, 113.44, 91.19, 91.15, 66.60, 56.82, 33.50, 26.17, 25.67, 21.78, 21.73.

[0192] ESI-HRMS: m / z calcd for [M+H] + C 56 H 43 N2O 14 +,967.2714; found 967.2689 (error = -2.6 ppm).

[0193] Example 3

[0194] This example discloses a functionalized macrocyclic molecule, which has any of the following structures:

[0195]

[0196] The preparation process of the compound of formula Ⅰ-12 includes:

[0197] Add ultrapure water to the compound of formula Ⅰ-11 (105.0 mg, 0.109 mmol), add sodium hydroxide (10.9 mg, 0.273 mmol), stir and react for 1 h (the reaction temperature can be 25 - 40 °C), filter, and the filtrate is freeze-dried to obtain 101 mg of a white powder solid of the compound of formula Ⅰ-12, with a yield of 95%.

[0198] Among them, the reaction formula is as shown below, and the compound of formula Ⅰ-11 is the compound of formula Ⅰ-11 prepared in Example 2:

[0199]

[0200] The preparation process of the compound of formula Ⅱ-12 includes:

[0201] Add ultrapure water to the compound of formula Ⅱ-11 (113.0 mg, 0.117 mmol), add sodium hydroxide (11.7 mg, 0.293 mmol), stir and react for 1 h (the reaction temperature can be 25 - 40 °C), filter, and the filtrate is freeze-dried to obtain 101 mg of a white powder solid, thereby obtaining the compound of formula Ⅱ-12, with a yield of 86%.

[0202] Among them, the reaction formula is as shown below, and the compound of formula Ⅱ-11 is the compound of formula Ⅱ-11 prepared in Example 2:

[0203]

[0204] Example 4

[0205] This example discloses a functionalized macrocyclic molecule, which has any of the following structures:

[0206]

[0207] The preparation process of the functionalized macrocyclic molecule includes:

[0208] At 85 °C, N,N-diisopropylethylamine (3.2 mL, 18.6 mmol) and 1H-benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (4.1 g, 7.9 mmol) were added to 500 mL of anhydrous N,N-dimethylformamide solvent. Under stirring, the N,N-dimethylformamide solutions of ester group diacid S20 (1.60 g, 2.3 mmol) and benzyl trifluoroacetate ammonium salt S30 (2.0 g, 2.43 mmol) were added respectively at a constant rate (125 μL / s) using a syringe pump. After the reaction was completed, it was concentrated under reduced pressure, and a mixture of water and methanol (500 mL of water, 500 mL of methanol) was added to precipitate. It was filtered and dried in vacuo. The crude product was separated by a silica gel column for column chromatography (eluent: DCM:MeOH = 1000:1 - 1000:15, 200 - 300 mesh) to obtain compound of formula I-2 (285 mg, yield 10%) and compound of formula II-2 (629 mg, yield 23%).

[0209] The reaction formula is as follows:

[0210]

[0211] The prepared compound of formula I-2 and compound of formula II-2 were tested, and it was proved that the compound of formula I-2 and compound of formula II-2 were successfully prepared. Specifically:

[0212] The structural analysis of the compound of formula I-2 is as follows:

[0213] 1 The HNMR spectrum is as Figure 6 shown, m.p. > 300 °C. 1 H NMR (500 MHz, CD2Cl 2,298K) δ [ppm] 8.39 (d, J = 9.4 Hz, 2H), 8.29 (d, J = 9.4 Hz, 2H), 7.78 (d, J = 9.2 Hz, 2H), 7.68 (d, J = 9.2 Hz, 2H), 7.47 (d, J = 7.2 Hz, 4H), 7.44–7.38 (m, 4H), 7.38–7.32 (m, 2H), 7.27 (d, J = 9.4 Hz, 2H), 7.10 (dd, J = 13.7, 9.2 Hz, 4H), 6.97 (d, J = 9.4 Hz, 2H), 6.25 (dq, J = 12.8, 1.9 Hz, 2H), 5.73 (dd, J = 7.9, 1.8 Hz, 2H), 5.28 (dt, J = 20.2, 3.2 Hz, 2H), 5.23–5.08 (m, 6H), 4.97 (dd, J = 13.8, 1.8 Hz, 2H), 4.63 (d, J = 16.5 Hz, 2H), 4.53 (d, J = 16.5 Hz, 2H), 4.11 (q, J = 7.1 Hz, 1H), 3.93 (q, J = 7.1 Hz, 4H), 2.66 (t, J = 2.6 Hz, 2H), 2.57 (t, J = 2.6 Hz, 2H), 1.02 (t, J = 7.1 Hz, 6H). 13 13C NMR (126 MHz, CD2Cl 2, 298K) δ [ppm] 168.81, 165.72, 152.55, 149.89, 149.74, 149.21, 137.23, 128.49, 128.40, 127.87, 127.28, 127.11, 126.50, 126.43, 125.63, 124.52, 124.07, 123.05, 122.40, 120.12, 120.00, 119.72, 119.16, 118.99, 114.71, 113.40, 91.37, 91.18, 71.49, 66.47, 61.21, 33.84, 25.76, 25.54, 22.57, 22.45, 13.70.

[0214] ESI-HRMS: m / z calcd for [M + H] + C 72 H 59 N2O 14 + , 1175.3966; found 1175.3973 (error = 0.6 ppm).

[0215] The structural analysis of the compound of Formula II-2 is as follows:

[0216] 1The HNMR spectrum is as follows Figure 7 shown, m.p. > 300 °C. 1 H NMR (500 MHz, CD2Cl 2, 298 K) δ [ppm] 8.40 (d, J = 9.4 Hz, 2H), 8.30 (d, J = 9.4 Hz, 2H), 7.73 (d, J = 9.2 Hz, 2H), 7.54–7.48 (m, 4H), 7.45 (d, J = 9.1 Hz, 2H), 7.41–7.36 (m, 4H), 7.35–7.30 (m, 2H), 7.26 (d, J = 9.4 Hz, 2H), 7.09 (d, J = 9.2 Hz, 2H), 7.00 (d, J = 9.4 Hz, 2H), 6.83 (d, J = 9.1 Hz, 2H), 6.28–6.17 (m, 2H), 5.44 (dd, J = 13.5, 5.8 Hz, 2H), 5.29–5.15 (m, 5H), 5.09 (d, J = 11.9 Hz, 2H), 4.76–4.59 (m, 6H), 4.01 (dq, J = 10.7, 7.1 Hz, 2H), 3.78 (dq, J = 10.8, 7.1 Hz, 2H), 2.61 (dt, J = 12.1, 2.7 Hz, 4H), 0.92 (t, J = 7.1 Hz, 6H). 13 C NMR (126 MHz, CD2Cl 2, 298 K) δ [ppm] 168.41, 165.95, 152.20, 149.65, 149.49, 148.98, 137.03, 128.51, 128.49, 127.92, 127.18, 127.01, 126.36, 126.00, 125.44, 124.62, 123.99, 122.90, 122.62, 119.75, 119.49, 119.43, 119.30, 119.09, 114.62, 113.41, 91.44, 91.39, 71.15, 66.50, 61.18, 34.34, 25.88, 25.47, 22.55, 22.53, 13.67.

[0217] ESI-HRMS: m / z calcd for [M+H] + C 72 H 59 N2O 14 + , 1175.3966; found 1175.3976 (error = 0.9 ppm).

[0218] Among them, benzyldiamine S30 (Compound S30) can be obtained by the following method:

[0219] Using benzyl dialdehyde h (Compound h) as a raw material, benzyl diamine S30 was prepared, and the reaction formula is as follows:

[0220]

[0221] The preparation process of benzyl diamine S30 includes:

[0222] Add benzyl dialdehyde h (6.0 g, 10.1 mmol), tert-butyl carbamate (5.9 g, 50.5 mmol), 100 mL of acetonitrile, and 300 mL of dichloromethane to a 1000 mL two-necked flask. Then, successively add triethylsilane (8.0 mL, 50.5 mmol) and 8 mL of trifluoroacetic acid, and stir at room temperature for 6 hours. Rotary evaporate to remove dichloromethane, add 150 mL of acetonitrile, ultrasonic to precipitate, filter, and the filter cake is dried in vacuo to obtain a white solid. Add 250 mL of dichloromethane and 20 mL of trifluoroacetic acid to the above white solid in sequence, and stir at room temperature for 6 hours. After the reaction is completed, rotary evaporate to remove dichloromethane, add 100 mL of anhydrous ether to the concentrated solution, ultrasonic to precipitate, filter and dry to obtain 7 g of white solid compound S30, and the yield is 84%.

[0223] Regarding benzyl dialdehyde h, it can be obtained by any one or both of the following two methods:

[0224] Method 1: The reaction formula is as follows:

[0225]

[0226] Specifically, it includes the following steps: Add compound c (10.0 g, 22.7 mmol) to a 1000 mL two-necked flask, add 300 mL of anhydrous dichloromethane, stir and dissolve under ice bath conditions (0 °C), dropwise add boron tribromide / dichloromethane solution (136.0 mL, 136.0 mmol), protect with argon, and react for 12 h. After the reaction is completed, add 10 mL of methanol under ice bath conditions (0 °C) to quench the reaction, rotary evaporate to remove the solvent to obtain a solid, wash the solid with 100 mL of anhydrous ethanol, filter to obtain a filter cake, and dry in vacuo to obtain 9.3 g of hydroxy dialdehyde. Add 9.3 g of hydroxy dialdehyde, cesium carbonate (18.5 g, 56.8 mmol) to a 250 mL two-necked flask, add 10 mL of DMF, stir and dissolve, then add benzyl bromide (15.5 g, 90.8 mmol), and react at 80 °C for 12 h. After the reaction is completed, pour the reaction solution into 100 mL of ice water, filter, and the filter cake is washed with water and dried in vacuo to obtain 5.5 g of yellow solid benzyl dialdehyde S00, and the yield is 41%.

[0227] Method 2: Refer to the literature (CN 113845527 A), and the reaction formula is as follows:

[0228]

[0229] Example 5

[0230] This example discloses a functionalized macrocyclic molecule, and the functionalized macrocyclic molecule has any one of the following structures:

[0231]

[0232] The preparation process of the compound of formula I-21 includes:

[0233] To the mixed solvent (100 mL of methanol + 20 mL of water + 100 mL of tetrahydrofuran), the compound of formula I-2 (400 mg, 0.34 mmol) and sodium hydroxide (272.0 mg, 6.8 mmol) were added successively, and the reaction was stirred at 50 °C for 12 h under heating conditions. After the reaction was completed, it was concentrated under reduced pressure, 2 mL of hydrochloric acid was added, sonicated for precipitation, centrifuged and washed with a large amount of water, and after drying, a solid (330 mg, yield 87%) was obtained.

[0234] Among them, the reaction formula is as shown below, and the compound of formula I-2 is the compound of formula I-2 prepared in Example 4:

[0235]

[0236] The prepared compound of formula I-21 was tested, and it was proved that the compound of formula I-21 was successfully prepared. Specifically, the structural analysis is as follows:

[0237] 1 The HNMR spectrum is as Figure 8 shown, m.p. > 300 °C. 1 H NMR (500 MHz, DMSO-d6, 298 K) δ [ppm] 13.14 (s, 2H), 8.59 (dd, J = 31.3, 9.6 Hz, 4H), 7.72 (d, J = 9.3 Hz, 2H), 7.53 (dd, J = 14.8, 8.8 Hz, 4H), 7.47–7.37 (m, 8H), 7.33 (dd, J = 8.2, 6.4 Hz, 3H), 7.19 (dd, J = 9.3, 5.8 Hz, 3H), 7.13 (d, J = 9.1 Hz, 2H), 6.32 (d, J = 28.4 Hz, 2H), 5.60 (dt, J = 6.2, 3.4 Hz, 2H), 5.17 (d, J = 11.8 Hz, 2H), 5.09–4.95 (m, 4H), 4.81 (d, J = 17.0 Hz, 2H), 4.61 (dd, J = 15.4, 4.0 Hz, 4H), 2.62–2.55 (m, 1H), 2.45 (d, J = 3.3 Hz, 1H). 1313C NMR(126MHz, DMSO, 298K) δ [ppm] 171.77, 165.83, 153.00, 150.67, 149.25, 148.95, 137.62, 128.94, 128.51, 128.29, 128.04, 127.13, 127.10, 126.64, 126.49, 125.71, 124.60, 123.66, 122.65, 120.48, 120.46, 120.15, 119.64, 119.36, 115.84, 114.99, 91.08, 90.87, 71.70, 66.35, 33.45, 25.62, 25.45, 21.73, 21.58.

[0238] ESI-HRMS: m / z calcd for [M+H] + C 68 H 51 N2O 14 + , 1119.3340; found 1119.3345 (error = 0.4 ppm).

[0239] The preparation process of the compound of formula II-21 includes:

[0240] To the mixed solvent (250 mL of methanol + 50 mL of water + 250 mL of tetrahydrofuran), the compound of formula II-2 (2.0 g, 1.70 mmol) and sodium hydroxide (1.36 g, 34.0 mmol) were added successively, and the mixture was stirred and reacted at 50 °C for 12 h. After the reaction was completed, it was concentrated under reduced pressure, 5 mL of hydrochloric acid was added, sonicated for precipitation, centrifuged and washed with a large amount of water, and dried to obtain a solid (1.8 g, yield 95%).

[0241] Among them, the reaction formula is as shown below, and the compound of formula II-2 is the compound of formula II-2 prepared in Example 4:

[0242]

[0243] The prepared compound of formula II-21 was tested, and it was proved that the compound of formula II-21 was successfully prepared. Specifically, the structure analysis is as follows:

[0244] 1 The 1H NMR spectrum is as Figure 9 shown, m.p. > 300 °C. 1 1H NMR (500 MHz, DMSO-d 6,298K) δ [ppm] 13.19 (s, 2H), 8.54 (dd, J = 25.6, 9.6 Hz, 4H), 7.61 (d, J = 9.4 Hz, 2H), 7.58–7.51 (m, 4H), 7.44–7.30 (m, 9H), 7.27 (d, J = 9.5 Hz, 2H), 7.13 (d, J = 9.4 Hz, 3H), 7.02 (d, J = 9.2 Hz, 2H), 6.69 (d, J = 9.1 Hz, 2H), 6.29 (dq, J = 28.7, 1.8 Hz, 2H), 5.57 (dd, J = 8.3, 4.3 Hz, 2H), 5.33 (dd, J = 13.5, 7.0 Hz, 2H), 5.22 (d, J = 12.3 Hz, 2H), 5.09 (d, J = 12.3 Hz, 2H), 4.73 (d, J = 16.6 Hz, 2H), 4.64 (d, J = 16.6 Hz, 2H), 4.36 (dd, J = 13.3, 2.1 Hz, 2H), 2.47 (d, J = 2.9 Hz, 2H). 13 C NMR (126 MHz, DMSO , 298K) δ [ppm] 171.34, 165.96, 152.16, 150.47, 149.08, 148.68, 137.80, 129.27, 128.80, 128.11, 127.64, 127.11, 126.78, 126.59, 126.11, 125.46, 124.43, 123.55, 123.10, 120.02, 119.97, 119.60, 119.33, 118.96, 115.21, 114.80, 91.16, 70.45, 66.61, 33.75, 26.04, 25.63, 21.76, 21.70.

[0245] ESI-HRMS: m / z calcd for [M+H] + C 68 H 51 N2O 14 + , 1119.3340; found 1119.3340 (error = 0 ppm).

[0246] Example 6

[0247] This example discloses a functionalized macrocyclic molecule, and the functionalized macrocyclic molecule has any of the following structures:

[0248]

[0249] The preparation process of the compound of formula I-22 includes:

[0250] To the compound of Formula I-21 (87.0 mg, 0.078 mmol), ultrapure water was added, and sodium hydroxide (7.8 mg, 0.198 mmol) was added. The mixture was stirred for 1 h, filtered, and the filtrate was lyophilized to obtain 83 mg of the white powder solid of the compound of Formula I-22, with a yield of 92%.

[0251] Among them, the reaction formula is as shown below, and the compound of Formula I-21 is the compound of Formula I-21 prepared in Example 5:

[0252]

[0253] The preparation process of the compound of Formula II-22 includes:

[0254] To the compound of Formula II-21 (100.0 mg, 0.089 mmol), ultrapure water was added, and sodium hydroxide (8.9 mg, 0.223 mmol) was added. The mixture was stirred for 1 h, filtered, and the filtrate was lyophilized to obtain 53 mg of the white powder solid of the compound of Formula II-22, with a yield of 51%.

[0255] Among them, the reaction formula is as shown below, and the compound of Formula II-21 is the compound of Formula II-21 prepared in Example 5:

[0256]

[0257] Example 7

[0258] This example discloses a macrocyclic molecule, which is a functionalized macrocyclic molecule, and its structural formula is as shown below:

[0259]

[0260] Its preparation process includes:

[0261] At 55 °C, to the compound of Formula II-11 (50 mg, 0.052 mmol), 5 mL of anhydrous dichloromethane was added and stirred to obtain a turbid solution; to the above turbid solution, N,N-diisopropylethylamine (36 μL, 0.21 mmol), 1H-benzotriazole-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (109 mg, 0.21 mmol), and 2-mercaptoethylamine (16 mg, 0.21 mmol) were successively added, and the reaction solution changed from turbid to clear; after the reaction was completed, it was concentrated under reduced pressure, and the crude product was separated by column chromatography on a silica gel column to obtain the compound of Formula II-13 (42 mg, yield 75%).

[0262] Among them, the reaction formula is as shown below, and the compound of Formula II-11 is the compound of Formula II-11 prepared in Example 2:

[0263]

[0264] Test Example

[0265] In this test example, the performance of the functionalized macrocyclic molecules obtained in the examples was tested, specifically including host-guest performance testing:

[0266] (1) The water-soluble functionalized macrocyclic molecules of formula Ⅰ-12 and formula Ⅱ-12 prepared in Example 3 were used for the recognition of aromatic compounds. By fluorescence titration method, the binding constants of the compounds of formula Ⅰ-12 and formula Ⅱ-12 in a water / acetonitrile (3:1, v / v) mixed solvent were determined. The test data are shown in Table 1, and the fluorescence titration spectra of the compounds of formula Ⅰ-12 and Ⅱ-12 for p-xylene are shown respectively as Figure 10 、 11 shown.

[0267]

[0268] Fluorescence titration experimental conditions: The fluorescence spectrometer model is Shimadzu RF-6000, the solvent is a water / acetonitrile (3:1, v / v) mixed solvent, the temperature is 25 °C, the host concentration is 0.01 mmol / L, the concentration of benzene is 40.0 mmol / L, and the concentrations of other guests except benzene are all 10.0 mmol / L. Measure 3 times in parallel.

[0269] Table 1

[0270] <![CDATA[Binding constant (Ka / M -1 )]]> Compound of Formula Ⅰ-12 Compound of Formula Ⅱ-12 Benzene 17±1 53±11 Toluene 181±17 291±23 Ethylbenzene 87±12 246±8 o-Xylene 77±6 71±12 m-Xylene 217±24 174±21 p-Xylene 403±56 1092±104

[0271] From the data in Table 1, it can be seen that the binding abilities of the compounds of formula Ⅰ-12 and formula Ⅱ-12 to aromatic ring compounds in a water / acetonitrile (3:1, v / v) mixed solvent are different, showing obvious selectivity. Among them, the binding constant of the compound of formula Ⅱ-12 to p-xylene is (1092 ± 104) M -1 .

[0272] (2) The water-soluble functionalized macrocyclic molecules of formula Ⅰ-22 and formula Ⅱ-22 prepared in Example 6 were used for the recognition of the following aromatic compounds:

[0273]

[0274] By fluorescence titration method, the binding constants of the compounds of formula Ⅰ-22 and formula Ⅱ-22 in a water / acetonitrile (3:1, v / v) mixed solvent were determined. The test data are shown in Table 1, and the fluorescence titration spectra of the compounds of formula Ⅰ-22 and Ⅱ-22 for p-xylene are shown respectively as Figure 12 、 13As shown in the figure. Fluorescence titration experimental conditions: The model of the fluorescence spectrometer is Shimadzu RF-6000, the solvent is a mixed solvent of water / acetonitrile (3:1, volume ratio), the temperature is 25 °C, the concentration of the host is 0.01 mmol / L, and the concentration of the guest is 5.0 mmol / L.

[0275] Table 2

[0276] <![CDATA[Binding constant (Ka / M -1 )]]> Compound of Formula Ⅰ-22 Compound of Formula Ⅱ-22 Benzene Not detected 315 Toluene 359 801 Ethylbenzene 117 704 o-Xylene Not detected 48 m-Xylene 426 62 p-Xylene 487 1756

[0277] From the data in Table 2, it can be seen that the compounds of Formula I-22 and Formula II-22 have different binding abilities to aromatic ring compounds in a mixed solvent of water / acetonitrile (3:1, volume ratio), showing obvious selectivity. Among them, the binding constant of the compound of Formula II-22 to p-xylene is 1756 M -1 .

[0278] The functionalized macrocyclic molecules (Formula I, Formula II) and compounds (Formula I-D, II-D) in the present invention are applied to the detection, monitoring and removal of polar small molecules such as toluene, ethylbenzene, o-xylene, m-xylene, p-xylene, etc., and the effect is good. Among them, especially for the detection and monitoring of p-xylene, the effect is excellent.

[0279] In summary, a functionalized macrocyclic molecule provided by the present invention, as shown in Formula I or II, has cavity characteristics similar to those of biological receptors: the hydrogen bond binding sites are located in the hydrophobic cavity, and the hydrophobic cavity provides a relatively non-polar environment for hydrogen bond interactions, which can avoid the competition of water molecules. The synergistic effect of the hydrophobic effect and hydrogen bond interaction enhances the interaction between the host and guest molecules. The functionalized macrocyclic molecules in the present invention have fluorescence properties due to their unique molecular structures, and the analytes can be detected according to the changes in fluorescence during the binding process with other substances. Among them, water-soluble functionalized macrocyclic molecules selectively recognize neutral molecules, polar small molecules and drug molecules in water; for another example, functionalized macrocyclic molecules can bind polar small molecules such as toluene, ethylbenzene, o-xylene, m-xylene, p-xylene, etc. in a mixed solvent of water and organic solvents (such as water / acetonitrile mixed solvent), and the host-guest recognition properties are excellent, and can be used for the detection and removal of environmental pollutants (such as the detection and removal of organic pollutants), chiral sensing, intelligent materials, etc., and have broad application prospects. In addition, when the functionalized macrocyclic molecule contains a carboxylic acid functional group, it can undergo an amide condensation reaction with an organic amine, and has the characteristics of functional modification, and can be used in molecular recognition or amide functionalization. For example, the functionalized macrocyclic molecule can undergo an amidation reaction with a polymer containing an NH2 functional group such as polyamide to prepare a high molecular polymer, which is applied to the fields of organic pollutant removal and environmental remediation, and has good application prospects.

[0280] The preparation method of the functionalized macrocyclic molecule provided by the present invention has the characteristics of mild reaction conditions, high product yield, and stable intermediate structure. The raw materials are cheap and easily available, and it is suitable for large-scale production. Preferably, the ring closure yield is increased by changing the reaction temperature parameter. The functionalized macrocyclic molecule in the present invention contains 2 carboxylic acid groups and can undergo an amidation reaction with an organic amine, having the characteristics of functional modification.

[0281] It should be noted that "room temperature" in this article is about 25 °C without special instructions; the meaning of "about" related to numerical values in this article is an error of ±5%.

[0282] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the scope of knowledge possessed by those of ordinary skill in the art. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. Use of a functionalized macrocyclic molecule in detecting a substance to be measured in a mixed solvent of water and an organic solvent or in preparing a product for detecting a substance to be measured in a mixed solvent of water and an organic solvent, characterized in that, The structure of the functionalized macrocyclic molecule is shown in General Formula II: wherein, R1 and R2 are different, and: R1 is benzyl; R2 is an inorganic cation selected from Na + , K + or NH4 + ; The substance to be detected is p-xylene.

2. The application according to claim 1, wherein The functionalized macrocyclic molecule includes a compound with the following structural formula:

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