Nine-membered macrocyclic compound as well as preparation method and application thereof

Abstract

The invention provides a nine-membered macrocyclic compound and belongs to the technical field of macrocyclic compounds, the nine-membered macrocyclic compound is named as benzene-containing cucurbituril [3, 6] and is a gourd-shaped compound formed by bridging 3 benzene ring monomers and 6 glycoluril monomers through 18 methylene-CH2-, the chemical composition general formula of the benzene-containing cucurbituril [3, 6] is C60H54N24O12, the molecular weight of the benzene-containing cucurbituril [3, 6] is 1303.24800, the molecular weight of the benzene-containing cucurbituril [3, 6] is 1303.24800, and the molecular weight of the benzene-containing cucurbituril [3, 6] is 1303.24800. 6) is a white solid and is dissolved in at least one of organic solvents including dimethyl sulfoxide, formic acid, acetic acid and trifluoroacetic acid. The invention also provides a preparation method and application of the nine-membered macrocyclic compound.

Description

Technical Field

[0001] The invention belongs to the technical field of macrocyclic compounds, and particularly relates to a nine-membered macrocyclic compound and a preparation method and application thereof. Background Art

[0002] Supramolecular chemistry is an emerging discipline first proposed by French scientist Jean-Marie Lehn. Unlike molecular chemistry, supramolecular chemistry studies the chemistry of intermolecular bonds. It covers the structure and function of entities formed by the combination of two or more chemical substances, and mainly studies the interactions between non-covalent bonds. Crown ethers, cyclodextrins, calixarene and pillararene are the subjects that are studied more in supramolecular chemistry. Cucurbitacin is a macrocyclic compound studied after them, and is also the subject that has been studied more in supramolecular chemistry in recent years. Supramolecular chemistry studies the science of intermolecular non-covalent bond interactions, and mainly studies molecular recognition, molecular self-assembly, supramolecular reactions and catalysis, molecular transport, carrier design and supramolecular devices. These macrocyclic molecules are hot spots for cross-disciplinary research in chemistry, materials, biology and physics. Summary of the invention

[0003] In order to obtain a new type of macrocyclic compound, the present invention provides a nine-membered macrocyclic compound, which is a white solid, soluble in organic solvents such as dimethyl sulfoxide, formic acid, acetic acid and trifluoroacetic acid, can be used to detect pyridine compounds, and has adsorption properties and can be used for adsorption and impurity removal.

[0004] The invention also provides a preparation method and application of the nine-membered macrocyclic compound.

[0005] The present invention is achieved through the following technical solutions:

[0006] The present invention provides a nine-membered macrocyclic compound, the nine-membered macrocyclic compound is named as containing benzene cucurbital [3,6], and the structural formula of the containing benzene cucurbital [3,6] is shown in Formula 4:

[0007]

[0008] Furthermore, the chemical composition formula of the compound containing benzene cucurbitacin [3,6] is C 60 H 54 N 24 O 12 , molecular weight is 1303.24800;

[0009] The benzene-containing cucurbitacin [3,6] is in the form of a white solid and is soluble in at least one of the organic solvents dimethyl sulfoxide, formic acid, acetic acid and trifluoroacetic acid.

[0010] Based on the same inventive concept, the present invention provides a method for preparing a nine-membered macrocyclic compound, the preparation method comprising:

[0011] Add KCNO to the aqueous solution of compound 1 and react for a period of time to obtain a reaction solution;

[0012] The reaction solution is subjected to solid-liquid separation, and the obtained solid is washed and dried to obtain compound 2;

[0013] The compound 2 is dissolved in formic acid, and then water and glyoxal are added to perform a reflux reaction, followed by solid-liquid separation, liquid spin drying, washing and drying to obtain a compound 3;

[0014] The compound 3 is dissolved in hydrochloric acid, and then a formaldehyde solution is added for reflux reaction to obtain a mixed solution;

[0015] Separating the benzoic acid-containing ring [3,6] from the mixed solution;

[0016] Wherein, the structural formulas of the compound 1, the compound 2 and the compound 3 are shown in Formulas 1 to 3 respectively:

[0017]

[0018] Further, the step of adding KCNO to the aqueous solution of compound 1 and reacting for a period of time to obtain a reaction solution specifically comprises:

[0019] Add KCNO to the aqueous solution of compound 1 and react for 72±2h to obtain a reaction solution;

[0020] In the aqueous solution of the compound 1, the concentration of the compound 1 is 0.1±0.01 mol / L;

[0021] The molar ratio of the compound 1 to the KCNO is 12:105.5.

[0022] Further, the reaction solution is subjected to solid-liquid separation, and the obtained solid is washed and dried to obtain compound 2, which specifically includes:

[0023] The reaction solution was subjected to solid-liquid separation, and the obtained solid was washed with water and acetone in sequence, and dried to obtain compound 2.

[0024] Further, the compound 2 is dissolved in formic acid, and then water and glyoxal are added for reflux reaction, and then solid-liquid separation, liquid spin drying, washing and drying are performed to obtain compound 3, which specifically includes:

[0025] The compound 2 is dissolved in formic acid and then water is added at 98-102° C. for reflux reaction, and then glyoxal is added for reflux reaction for 5±0.5h, and then solid-liquid separation is performed after cooling, and the liquid is spin-dried and washed with water, and dried to obtain compound 3;

[0026] Wherein, the molar ratio of the compound 2 to the glyoxal is 14.6:29.3.

[0027] Furthermore, the compound 3 is dissolved in hydrochloric acid, and then a formaldehyde solution is added for reflux reaction to obtain a mixed solution, which specifically includes:

[0028] The compound 3 is dissolved in 9 mol / L hydrochloric acid, and then a formaldehyde solution is added to react under reflux at 98-102° C. for 9-10 hours to obtain a mixed solution;

[0029] Wherein, the molar ratio of the compound 3 to formaldehyde is 1:2.

[0030] Furthermore, the separation of the benzyl cucurbitacin [3,6] from the mixed solution specifically comprises:

[0031] Add formic acid to the mixed solution to dissolve the solid matter, then add silica gel and spin-dry to obtain a mixture;

[0032] The mixture was loaded into a silica gel column, eluted with a formic acid:acetic acid solution with a volume ratio of 1:1.5, separated and spin-dried to obtain a crude product containing phenylcucurbitacin [3,6];

[0033] The crude product containing phenylcucurbitacin [3,6] was washed with acetone:water solution in a volume ratio of 1:1, and the solid was spin-dried after centrifugation;

[0034] Trifluoroacetic acid was added to the solid after spin drying, followed by centrifugation. The supernatant was spin dried and washed with 1 mol / L NaOH aqueous solution, stirred for 4-5 hours, and then centrifuged, washed and dried to obtain the phenyl cucurbitacin-containing solid [3,6].

[0035] Preferably, the amount of silica gel added is 4-5 times the total mass of the mixed solution after removing the solvent.

[0036] Furthermore, the mass ratio of the silica gel to the compound 3 is 7:1.5008.

[0037] Based on the same inventive concept, the present invention also provides an application of a nine-membered macrocyclic compound as a detection reagent or impurity adsorbent for or in the preparation of pyridine compounds.

[0038] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0039] The present invention discloses a nine-membered macrocyclic compound named as benzene-cucurbit ring [3,6], which is a gourd-shaped compound formed by three benzene ring monomers and six glycoside urea monomers connected by 18 methylene -CH2- bridges, and has a chemical composition formula of C 60 H 54 N 24 O 12 , molecular weight is 1303.24800; the benzene cucurbitacin [3,6]-containing compound is a white solid, soluble in organic solvents such as dimethyl sulfoxide, formic acid, acetic acid and trifluoroacetic acid. The composition of the product is accurately confirmed by mass spectrometry, nuclear magnetic resonance and single crystal structure. The benzene cucurbitacin [3,6]-containing compound can be used to detect pyridine compounds, and the compound has adsorption properties and can be used for adsorption and impurity removal. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0041] Figure 1 For the benzoic acid ring [3,6] in deuterated trifluoroacetic acid 1 H, 13 C NMR spectrum.

[0042] Figure 2 These are the mass spectrometry results for compounds containing benzoic acid rings [3,6].

[0043] Figure 3 This is a single crystal structure diagram of a benzoic acid ring [3,6].

[0044] Figure 4 This is the UV detection diagram of 5,5'-dimethyl-2,2'-bipyridine containing benzoic acid [3,6].

[0045] Figure 5 This is a graph showing the adsorption performance of solid iodine vapor containing benzene cucurbitacin [3,6].

[0046] Figure 6 This is the color change diagram of iodine adsorption in iodocyclohexane solution containing phenylcucurbitacin [3,6].

[0047] Figure 7 This is a color comparison chart of the benzyl alcohol ring [3,6] before and after iodine adsorption. DETAILED DESCRIPTION

[0048] The present invention will be described in detail below in conjunction with specific implementations and examples, and the advantages and various effects of the present invention will be more clearly presented. It should be understood by those skilled in the art that these specific implementations and examples are used to illustrate the present invention, rather than to limit the present invention.

[0049] Throughout the specification, unless otherwise specifically stated, the terms used herein should be understood as meanings commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. In the event of a conflict, the present specification takes precedence.

[0050] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0051] The overall idea of ​​the present invention is as follows:

[0052] The present invention discloses a method for preparing a compound containing benzene cucurbitacin rings, the method comprising:

[0053] S1. adding KCNO to an aqueous solution of compound 1 and reacting for a period of time to obtain a reaction solution;

[0054] S2. The reaction solution is subjected to solid-liquid separation, and the obtained solid is washed and dried to obtain compound 2;

[0055] S3. The compound 2 is dissolved in formic acid, and then water and glyoxal are added to reflux the reaction, followed by solid-liquid separation, liquid spin drying, washing and drying to obtain compound 3;

[0056] S4. dissolving the compound 3 in hydrochloric acid, and then adding formaldehyde solution to reflux reaction to obtain a mixed solution;

[0057] S5. Separate the benzoic acid-containing ring [3,6] from the mixed solution.

[0058] In the benzene-containing cucurbitacin [3,6] of the present invention, the first number in the square brackets represents the number of benzenes in the macrocycle, and the second number represents the number of glycoside urea in the macrocycle.

[0059] Step S1 specifically includes:

[0060] Add KCNO to the aqueous solution of compound 1 and react for 72±2h to obtain a reaction solution;

[0061] In the aqueous solution of the compound 1, the concentration of the compound 1 is 0.1±0.01 mol / L;

[0062] The molar ratio of the compound 1 to the KCNO is 12:105.5.

[0063] In the present invention, the purpose of adding KCNO to the aqueous solution of compound 1 for reaction is to react compound 1 to generate compound 2. The advantage of the molar ratio of compound 1 to KCNO being 12:105.5 is to ensure that compound 1 reacts as completely as possible.

[0064] Step S2 specifically includes:

[0065] The reaction solution was subjected to solid-liquid separation, and the obtained solid was washed with water and acetone in sequence, and dried to obtain compound 2.

[0066] In the present invention, the purpose of washing the obtained solid with water and acetone in sequence is to wash away the excess KCNO in the reaction.

[0067] Step S3 specifically includes:

[0068] The compound 2 is dissolved in formic acid and then water is added at 98-102° C. for reflux reaction, and then glyoxal is added for reflux reaction for 5±0.5h, and then solid-liquid separation is performed after cooling, and the liquid is spin-dried and washed with water, and dried to obtain compound 3;

[0069] Wherein, the molar ratio of the compound 2 to the glyoxal is 14.6:29.3.

[0070] In the present invention, the molar ratio of compound 2 to glyoxal is 14.6:29.3, which has the advantage that compound 2 can react completely to generate compound 3.

[0071] Step S4 specifically includes:

[0072] The compound 3 is dissolved in 9 mol / L hydrochloric acid, and then a formaldehyde solution is added to react under reflux at 98-102° C. for 9-10 hours to obtain a mixed solution;

[0073] Wherein, the molar ratio of the compound 3 to formaldehyde is 1:2.

[0074] In the present invention, the molar ratio of compound 3 to formaldehyde is 1:2, which has the advantage that compound 3 can react completely to generate compound 4.

[0075] Step S5 specifically includes:

[0076] Add formic acid to the mixed solution to dissolve the solid matter, then add silica gel and spin-dry to obtain a mixture;

[0077] The mixture was loaded into a silica gel column, eluted with a formic acid:acetic acid solution with a volume ratio of 1:1.5, separated and spin-dried to obtain a crude product containing phenylcucurbitacin [3,6];

[0078] The crude product containing phenylcucurbitacin [3,6] was washed with acetone:water solution in a volume ratio of 1:1, and the solid was spin-dried after centrifugation;

[0079] Trifluoroacetic acid was added to the solid after spin drying, followed by centrifugation. The liquid was spin dried and washed with 1 mol / L NaOH aqueous solution and stirred for 4-5 hours. After centrifugation, washing and drying, the benzyl cucurbitacin was obtained [3,6].

[0080] In the present invention, the advantage of using a formic acid:acetic acid solution with a volume ratio of 1:1.5 for elution is that the phenyl cucurbitacin [3,6] is fully dissolved and separated cleanly on the silica gel column.

[0081] In the present invention, the benzene-containing ring [3,6] is far away from other points and is easy to be separated by column, and the column chromatography stationary phase is silica gel.

[0082] The following is a detailed description of a nine-membered macrocyclic compound of the present application, its preparation method and application, in combination with examples and experimental data.

[0083] Example 1

[0084] The present embodiment provides a method for preparing a nine-membered macrocyclic compound, comprising the following steps:

[0085] 1. As shown in Formula 5, compound 1 (6.2169 g, 12.0 mmol) was weighed into a 250 mL round-bottom flask, 120 mL of H2O was added thereto, and the mixture was stirred at room temperature to completely dissolve compound 1, and KCNO (8.5572 g, 105.5 mmol) was added, and the resulting mixture was stirred at room temperature for 72 h. Centrifugation was performed, and the solid was washed with H2O (3×40 mL) and acetone (3×40 mL), and dried to obtain compound 2: 4.1844 g, with a yield of 95.15%. mp.341-342°C (dec); 1 H NMR (400MHz, CF3CO2D) δ7.41 (s, 2H), 4.59 (s, 8H); 13 C NMR(100MHz,CF3CO2D)δ163.25,137.01,132.58,43.95; HRMS Ca lcdfor C 14 H 22 N8O4(M+Na):389.1662; found:389.1668.

[0086]

[0087] 2. As in Formula 6, weigh compound 2 (5.3637 g, 14.6 mmol) in a 1000 mL round-bottom flask, add HCOOH (250 mL), stir at 98-102°C to completely dissolve compound 2, quickly add H2O (324 mL), reflux and stir until the temperature of the reaction system rises to 98-102°C, then add 40 wt% glyoxal aqueous solution (3.36 mL, 29.3 mmol), reflux for 5 h. Cool, place in the refrigerator overnight, centrifuge, spin dry the liquid, wash with H2O (3×40 mL), and dry to obtain compound 3: 2.0342 g, with a yield of 33.86%. mp.353-354°C (dec); 1 H NMR (400MHz, CF3CO2D) δ7.35 (s, 2H), 5.78 (d, J = 8.0Hz, 2H), 5.66 (d, J = 8.0Hz, 2H), 4.83 (d, J = 16.0Hz, 4H), 4.52 (d, J = 16.0Hz, 4H); 13 C NMR (100MHz, CF3CO2D) δ163.68,138.59,133.16,77.26,64.73,47.29; HRMS Ca lcd forC 18 H 18 N8O4(M+H):411.1529; found:411.1526.

[0088]

[0089] 3. As shown in formula 7, compound 3 (1.5008 g, 3.65 mmol) was weighed into a 50 mL round-bottom flask, 9 mol / L HCl (8.130 mL) was added, and the mixture was stirred at 98-102°C to completely dissolve compound 3. Then, 37-40% HCHO aqueous solution (480 uL) was added, and the mixture was refluxed and stirred for 10 h. After the reaction was completed, 20 mL HCOOH was added to the reaction solution to completely dissolve the reaction mixture, 7 g silica gel was added and the mixture was spin-dried, and the mixture was rinsed with a formic acid:acetic acid solution with a volume ratio of 1:1.5, and the mixture was separated and spin-dried to obtain a crude product containing benzene cucurbitacin [3,6]. The crude product containing benzene cucurbitacin [3,6] was washed with an acetone:water solution with a volume ratio of 1:1 (3×40 mL), and the solid was spin-dried after centrifugation. Trifluoroacetic acid (4 mL) was added to the solid, and the mixture was centrifuged. After the liquid was spin-dried, it was washed with a 1 mol / L NaOH aqueous solution (30 mL) and stirred for 5 h. After centrifugation, the solid was washed with CH3OH (3×10 mL), centrifuged, and the solid was dried to obtain product 4: 0.0682 g, with a yield of 4.30%. mp.341-342℃(dec); 1H NMR (400MHz, CF3CO2D) δ7.32 (s, 6H), 6.07 (d, J = 16.0Hz, 6H), 5.63 (s, 12H), 4.77 (d, J = 16.0Hz, 12H), 4.56 (d, J = 16.0Hz, 12H), 4.46 (d, J = 16.0Hz, 6H); 13 CNMR(100MHz,CF3CO2D)δ159.91,137.63,133.40,72.87,72.09,53.89,47.80; HRMS Ca lcdfor C 60 H 54 N 24 O 12 (M+Na):1325.4251; found:1325.4242.

[0090]

[0091] Figure 1 : containing phenyl cucurbitacin [3,6] in deuterated trifluoroacetic acid 1 H, 13 C NMR spectrum: 1 H NMR (400MHz, CF3CO2D) δ7.32 (s, 6H), 6.07 (d, J = 16.0Hz, 6H), 5.63 (s, 12H), 4.77 (d, J = 16.0Hz, 12H), 4.56 (d, J = 16.0Hz, 12H), 4.46 (d, J = 16.0Hz, 6H); 13 C NMR (100MHz, CF3CO2D) δ159.91,137.63,133.40,72.87,72.09,53.89,47.80.

[0092] Figure 2 : Mass spectrometry results of benzocucurbitacin [3,6]: HRMS Ca lcd for C 60 H 54 N 24 O 12 (M+Na):1325.4251; found:1325.4242.

[0093] Figure 3 :Single crystal structure of benzocuculline [3,6]: CCDC 2380524, color: C, gray; H, green; N, blue; O, red.

[0094] Example 2

[0095] The ultraviolet detection of 5,5'-dimethyl-2,2'-bipyridine by a nine-membered macrocyclic compound in this embodiment is as follows:

[0096] 1. Use an analytical balance to weigh 0.0018 g of 5,5'-dimethyl-2,2'-bipyridine and place it in a 5 mL centrifuge tube. Add 1 mL of HCOOH:H2O=1:1 mixed solution to dissolve it. Transfer it to a 10 mL volumetric flask and add HCOOH:H2O=1:1 mixed solution to make up the volume. You can get 1×10 -3 mol / L 5,5'-dimethyl-2,2'-bipyridine stock solution; use a pipette to accurately measure 0.5 mL (1×10 -3 mol / L) of 5,5'-dimethyl-2,2'-bipyridine stock solution was transferred to a 5 mL volumetric flask and fixed to volume with HCOOH:H2O=1:1 mixture to obtain 1×10 -4 mol / L 5,5'-dimethyl-2,2'-bipyridine stock solution; then use a pipette to accurately measure 2.5 mL (1×10 -4 mol / L) of 5,5'-dimethyl-2,2'-bipyridine stock solution was transferred to a 5 mL volumetric flask and fixed to volume with a mixture of HCOOH:H2O=1:1 to obtain 5×10 -5 mol / L stock solution of 5,5'-dimethyl-2,2'-bipyridine to be tested under UV.

[0097] 2. Use an analytical balance to weigh 0.0013 g of benzoic acid [3,6] and place it in a 1.5 mL centrifuge tube. Use a pipette to accurately measure 0.10 mL of HCOOH:H2O = 1:1 mixed solution to dissolve it, and obtain 1×10 -2 mol / L main solution containing benzyl cucurbitacin [3,6].

[0098] 3. Use a pipette to accurately measure 3.0 mL of 5×10 -5 mol / L 5,5'-dimethyl-2,2'-bipyridine stock solution was placed in a cuvette and UV measurement was performed in the form of a main (6uL / time) droplet. Figure 4 It can be seen that with the addition of benzocucurbitacin [3,6], the UV absorption of 5,5'-dimethyl-2,2'-bipyridine is enhanced, indicating that they undergo host-guest interaction.

[0099] Attached Figure 4 : UV detection diagram of 5,5'-dimethyl-2,2'-bipyridine by benzocucurbitacin [3,6]: Among them, the UV absorption of 5,5'-dimethyl-2,2'-bipyridine is the weakest, and the absorption is enhanced after adding benzocucurbitacin [3,6].

[0100] Example 3

[0101] The adsorption performance of a nine-membered macrocyclic compound of this embodiment on solid iodine vapor is as follows:

[0102] Weigh 20 mg of benzoic acid [3,6] with an analytical balance and place it in an open glass bottle, then weigh and record the weight. Place it and 100 mg of solid iodine in a glass bottle with a cap, tighten the cap, and place the glass bottle in a 70°C oven for adsorption. Take out the glass bottle at regular intervals, let it cool to room temperature, take out the open glass bottle, weigh and record the weight until the mass no longer changes. Plot the graph with time as the horizontal axis and adsorption capacity as the vertical axis. Figure 5 ,Depend on Figure 5 It can be seen that in the first 10.0h of adsorption, the adsorption rate of iodine vapor by benzyl cucurbitacin [3,6] increased rapidly; the adsorption rate increased slowly from 10.0h to 20.0h; after 20.0h, the adsorption of iodine vapor by benzyl cucurbitacin [3,6] did not change significantly, indicating that the adsorption of iodine vapor by the adsorbent benzyl cucurbitacin [3,6] reached equilibrium at around 20.0h and could maintain relative adsorption stability for 40h.

[0103] The adsorption formula of solid iodine vapor by benzene-containing rings [3,6] is:

[0104]

[0105] Where: q s is the mass of iodine captured by phenylcucurbitacin [3,6] (g·g -1 ); m0 is the mass of the benzene-containing ring [3,6] at the initial moment (g); m n is the mass (g) of the benzoic acid ring [3,6] at a certain moment.

[0106] Color comparison of benzoic acid ring [3,6] before and after adsorption Figure 7 As shown (the left picture is before adsorption, and the right picture is after adsorption).

[0107] Attached Figure 5 : The adsorption performance diagram of solid iodine vapor containing benzene cucurbitacin [3,6] is plotted with time as the horizontal axis and adsorption capacity as the vertical axis to obtain the adsorption performance diagram of solid iodine vapor containing benzene cucurbitacin [3,6].

[0108] Example 4

[0109] The adsorption performance of a nine-membered macrocyclic compound of this embodiment on iodine in iodocyclohexane solution is as follows:

[0110] At a mass concentration of 30 mg·L -1 In the iodine cyclohexane solution (where the elemental iodine impurity concentration is 25-35 mg·L -1), add 4 mg of benzene cucurbitacin [3,6] as adsorbent, and observe the color change trend of iodocyclohexane solution as the adsorption time increases ( Figure 6 ).Depend on Figure 6 It can be seen that the color of the iodocyclohexane solution was pink at first. As the adsorption time increased, the color of the solution gradually became lighter. When the adsorption time reached 4.0 h, the color basically disappeared. This result shows that the adsorption of iodine in the cyclohexane solution by the benzene ring [3,6] was basically complete at 4 h.

[0111] Attached Figure 6 : Color change diagram of iodine adsorption in iodocyclohexane solution containing phenylcucurbitacin [3,6]: the color gradually becomes lighter from left to right.

[0112] Finally, it should be noted that the terms "comprises," "includes," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements that are inherent to such process, method, article, or apparatus.

[0113] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0114] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A nine-membered macrocyclic compound, characterized in that: The nine-membered macrocyclic compound is named as benzocucurbitacin [3,6], and the structural formula of the benzocucurbitacin [3,6] is shown in Formula 4:

2. A nine-membered macrocyclic compound according to claim 1, characterized in that: The chemical composition formula of the benzene cucurbit ring [3,6] is C 60 H 54 N 24 O 12 , molecular weight is 1303.24800; The benzene-containing cucurbitacin [3,6] is in the form of a white solid and is soluble in at least one of the organic solvents dimethyl sulfoxide, formic acid, acetic acid and trifluoroacetic acid.

3. A method for preparing a nine-membered macrocyclic compound according to claim 1 or 2, characterized in that: The preparation method comprises: Add KCNO to the aqueous solution of compound 1 and react for a period of time to obtain a reaction solution; The reaction solution is subjected to solid-liquid separation, and the obtained solid is washed and dried to obtain compound 2; The compound 2 is dissolved in formic acid, and then water and glyoxal are added to perform a reflux reaction, followed by solid-liquid separation, liquid spin drying, washing and drying to obtain a compound 3; The compound 3 is dissolved in hydrochloric acid, and then a formaldehyde solution is added for reflux reaction to obtain a mixed solution; Separating the benzoic acid-containing ring [3,6] from the mixed solution; Wherein, the structural formulas of the compound 1, the compound 2 and the compound 3 are shown in Formulas 1 to 3 respectively:

4. The method for preparing a nine-membered macrocyclic compound according to claim 3, characterized in that: The step of adding KCNO to the aqueous solution of compound 1 and reacting for a period of time to obtain a reaction solution specifically comprises: Add KCNO to the aqueous solution of compound 1 and react for 72±2h to obtain a reaction solution; In the aqueous solution of the compound 1, the concentration of the compound 1 is 0.1±0.01 mol / L; The molar ratio of the compound 1 to the KCNO is 12:105.

5.

5. The method for preparing a nine-membered macrocyclic compound according to claim 3, characterized in that: The reaction solution is subjected to solid-liquid separation, and the obtained solid is washed and dried to obtain compound 2, which specifically includes: The reaction solution was subjected to solid-liquid separation, and the obtained solid was washed with water and acetone in sequence, and dried to obtain compound 2.

6. The method for preparing a nine-membered macrocyclic compound according to claim 3, characterized in that: The compound 2 is dissolved in formic acid, and then water and glyoxal are added to perform reflux reaction, and then solid-liquid separation, liquid spin drying, washing and drying are performed to obtain compound 3, which specifically includes: The compound 2 is dissolved in formic acid and then water is added at 98-102° C. for reflux reaction, and then glyoxal is added for reflux reaction for 5±0.5h, and then solid-liquid separation is performed after cooling, and the liquid is spin-dried and washed with water, and dried to obtain compound 3; Wherein, the molar ratio of the compound 2 to the glyoxal is 14.6:29.

3.

7. The method for preparing a nine-membered macrocyclic compound according to claim 3, characterized in that: The compound 3 is dissolved in hydrochloric acid, and then a formaldehyde solution is added for reflux reaction to obtain a mixed solution, which specifically includes: The compound 3 is dissolved in 9 mol / L hydrochloric acid, and then a formaldehyde solution is added to react under reflux at 98-102° C. for 9-10 hours to obtain a mixed solution; Wherein, the molar ratio of the compound 3 to formaldehyde is 1:

2.

8. The method for preparing a nine-membered macrocyclic compound according to claim 3, characterized in that: The method of separating the benzyl cucurbitacin [3,6] from the mixed solution specifically comprises: Add formic acid to the mixed solution to dissolve the solid matter, then add silica gel and spin-dry to obtain a mixture; The mixture was loaded into a silica gel column, eluted with a formic acid:acetic acid solution with a volume ratio of 1:1.5, separated and spin-dried to obtain a crude product containing phenylcucurbitacin [3,6]; The crude product containing phenylcucurbitacin [3,6] was washed with acetone:water solution in a volume ratio of 1:1, and the solid was spin-dried after centrifugation; Trifluoroacetic acid was added to the solid after spin drying, followed by centrifugation. The supernatant was spin dried and washed with 1 mol / L NaOH aqueous solution, stirred for 4-5 hours, and then centrifuged, washed and dried to obtain the phenyl cucurbitacin-containing solid [3,6].

9. The method for preparing a nine-membered macrocyclic compound according to claim 8, characterized in that: The mass ratio of the silica gel to the compound 3 is 7:1.5008.

10. Use of a nine-membered macrocyclic compound as claimed in claim 1 or 2 as a detection reagent or impurity adsorbent for or in the preparation of pyridine compounds.

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