Preparation method and application of a pyridinium macrocyclic crystallization partner

Abstract

The present invention belongs to the technical field of crystal synthesis and structural identification, and specifically relates to a method for preparing a novel pyridinium macrocyclic crystallization partner and its application. To prepare a novel crystallization partner with simple synthesis, ease of operation, and wide adaptability for structural identification of organic molecules, the present invention provides a novel pyridinium macrocyclic crystallization partner and its preparation method. This pyridinium macrocyclic crystallization partner is simple to prepare and has high yield. It can be directly used to cultivate host-guest crystals, and the cultivation process does not require high temperatures, making the operation more convenient. Furthermore, the preparation method of this crystallization partner utilizes readily available raw materials, exhibits good reproducibility, high yield, and a wide range of applications, suggesting promising application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of crystal synthesis and structure identification, and particularly relates to a preparation method and application of a pyridinium macrocyclic crystallization partner. Background Art

[0002] Structural elucidation is crucial for the discovery and drug development of unknown natural compounds. Currently, the most commonly used structural analysis methods for natural product structures include single crystal X-ray diffraction (SCD), chiral nuclear magnetic resonance (NMR), chiral optical methods (ECD / VCD), and organic synthesis. However, while these spectroscopic techniques can be used for structural determination, identifying novel and complex natural products remains challenging due to their limitations. For example, single crystal X-ray diffraction (SCD) provides atomic-level structural information, including accurate information on atom types, bond lengths, bond angles, relative stereochemistry, absolute configuration, and molecular arrangement within the crystal. It is considered the most direct and reliable method. However, SCD also has limitations, being suitable only for identifying high-quality single crystals of suitable size. Powders, amorphous solids, liquids, volatile substances, or oily compounds are not suitable for such analysis. This has become a bottleneck restricting the development of X-ray crystallography.

[0003] Before structural identification, the main methods to help molecules crystallize are the "crystal sponge" method and the crystallization partner method. Among them, the crystal sponge method is to immerse the crystal in a solution of organic molecules so that the organic molecules are regularly arranged in the crystal to achieve the purpose of determining the structure of the organic molecules. The crystallization partner method is to bind the organic molecules to the crystallization partner by covalent or non-covalent bonds to help them crystallize. For example, the research group of Clemens Richert at the University of Stuttgart in Germany proposed the use of "adamantane crystallization partner" to solve the crystallization problem of small molecules. However, this method can only form cocrystals with liquid guests, the structure is small, and high temperature is required, resulting in its limited scope of application.

[0004] Therefore, it is of great significance to prepare crystallization partners with simple synthesis, easy operation and wide adaptability for the structural identification of organic molecules. Summary of the Invention

[0005] In order to overcome the deficiencies of the above-mentioned prior art, the present invention proposes a pyridinium macrocyclic crystallization partner and a preparation method thereof. The preparation method of the crystallization partner is simple, the raw materials are readily available, and the method has good reproducibility, high yield, a wide range of applicability, and good application prospects.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] The first aspect of the present invention provides a pyridinium macrocyclic crystallization partner, wherein the chemical formula of the pyridinium macrocyclic crystallization partner is C 48 H 42 N6P4F 24 , the structural formula is as follows:

[0008]

[0009] The second aspect of the present invention provides a method for preparing the pyridinium macrocyclic crystallization partner described in the first aspect, the preparation method comprising the following steps:

[0010] S1. Under an inert gas atmosphere, a solvent was added to 2,6-dibromoaniline, 4-pyridineboric acid, tetrakis(triphenylphosphine)palladium and K2CO3. After heating under reflux, the mixture was extracted with dichloromethane. The organic layer was collected, washed with water, brine, and dried, and the solvent was removed by filtration. The mixture was then separated by silica gel column chromatography to obtain compound 1, whose structural formula is shown below:

[0011]

[0012] S2. Dissolve the compound 1 and α,α′-dibromo-p-xylene prepared in step S1 in an organic solvent, combine the two solutions, and heat under reflux until a large amount of yellow precipitate is generated. Collect the precipitate by filtration, wash, and dry to obtain a pyridinium macrocyclic compound C1·Br4, whose structural formula is shown below:

[0013]

[0014] S3, dissolving C1·Br4 in water, adding excess NH4PF6 to generate a yellow precipitate, filtering, washing and drying to obtain the pyridinium macrocyclic compound C1·(PF6)4;

[0015] S4. Dissolving the pyridinium macrocyclic compound C1·(PF6)4 in an organic solvent, and then placing the mixture in an ether atmosphere for vapor diffusion at room temperature, and crystallizing the pyridinium macrocyclic crystallization partner.

[0016] The preparation method of the pyridinium macrocyclic crystallization partner of the present invention is simple to operate, has readily available raw materials, good reproducibility, high yield, and a wide range of applications, indicating good application prospects.

[0017] Preferably, in step S1, the equivalent ratio of the 2,6-dibromoaniline to 4-pyridineboric acid is 1:3 to 5 (preferably 1:3); with 2,6-dibromoaniline as 1 equivalent, the equivalent of the tetrakis(triphenylphosphine)palladium is 0.08 to 0.1 (preferably 0.08); with 2,6-dibromoaniline as 1 equivalent, the equivalent of the K2CO3 is 10 to 15 (preferably 10).

[0018] Preferably, in step S2, the equivalent ratio of the compound 1 to α,α′-dibromo-p-xylene is 1:1 to 2, preferably 1:1.

[0019] Preferably, in step S1, the temperature of the heating reflux reaction is 120-150° C., and the time is 12-20 hours; preferably, the reaction is carried out at 120° C. for 12 hours.

[0020] Preferably, in step S2, the temperature of the heating reflux reaction is 80-100° C., and the time is 24-48 hours; preferably, the reaction is carried out at 80° C. for 24 hours.

[0021] Preferably, in step S1, the silica gel column chromatography separation is eluted with a mobile phase of CH2Cl2:CH3OH=100:1, 50:1, 30:1, and the eluate of the CH2Cl2:CH3OH=30:1 portion is collected.

[0022] Preferably, in step S4, the gas phase diffusion time is 2 to 4 days.

[0023] Preferably, the organic solvent in step S2 is acetonitrile, and its amount is based on the ability to completely dissolve the solute.

[0024] Preferably, the amount of water in step S3 is based on the amount that can completely dissolve the solute.

[0025] Preferably, the silica gel column chromatography separation in step S1 is performed using a 200-mesh silica gel column.

[0026] The third aspect of the present invention provides the use of the pyridinium macrocyclic crystallization partner described in the first aspect in the structural identification of organic molecules.

[0027] The pyridinium macrocyclic crystallization partner of the present invention can be directly used for the cultivation of host-guest crystals. The cultivation process does not require high temperature, making the operation more convenient and having good application prospects.

[0028] Preferably, the organic molecules include but are not limited to benzoic acid, succinic acid, benzaldehyde, methyl salicylate, phenylboronic acid, and anisene.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] (1) The method for preparing the pyridinium macrocyclic crystalline partner is easy to operate, has simple synthesis steps, and eliminates the need for a complex purification process; the prepared crystalline partner has high purity and can be directly used to test the structure of the guest molecule.

[0031] (2) The raw materials for preparing the pyridinium macrocyclic crystallization partner are readily available, and the preparation method has good reproducibility and high yield.

[0032] (3) This pyridinium macrocyclic crystallization partner can be used not only for the structural identification of liquid natural products, but also for the structural identification of solid states and mixtures.

[0033] The present invention provides a new idea for the structural identification of organic molecules and opens up new uses for pyridinium macrocyclic crystallization partners. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The synthetic route of the intermediate 2,6-di(pyridin-4-yl)aniline is shown below;

[0035] Figure 2 This is the hydrogen spectrum of the intermediate 2,6-di(pyridin-4-yl)aniline;

[0036] Figure 3 Carbon spectrum of the intermediate 2,6-di(pyridin-4-yl)aniline;

[0037] Figure 4 is the mass spectrum of the intermediate 2,6-di(pyridin-4-yl)aniline;

[0038] Figure 5 The synthetic route of pyridinium macrocycle C1·(PF6)4 is shown;

[0039] Figure 6 This is the hydrogen spectrum of the pyridinium macrocycle C1·Br4;

[0040] Figure 7 This is the carbon spectrum of the pyridinium macrocycle C1·Br4;

[0041] Figure 8 This is the mass spectrum of the pyridinium macrocycle C1·Br4;

[0042] Figure 9 is the mass spectrum of pyridinium macrocycle C1·(PF6)4;

[0043] Figure 10 Figure 1 shows the experimental results of the pyridinium macrocyclic crystallization partner provided in Example 6, including: the chemical structure of benzoic acid (a), the asymmetric unit of the crystal (b), the host-guest interaction (c), and the unit cell packing (d);

[0044] Figure 11 This is a diagram showing the experimental results of the pyridinium macrocyclic crystallization partner provided in Example 7, including: the chemical structure of succinic acid (a), the asymmetric unit of the crystal (b), the host-guest interaction (c), and the unit cell stacking (d);

[0045] Figure 12Figure 1 shows the experimental results of the pyridinium macrocyclic crystallization partner provided in Example 8, including: the chemical structure of benzaldehyde (a), the asymmetric unit of the crystal (b), the host-guest interaction (c), and the unit cell stacking (d);

[0046] Figure 13 Figure 1 shows the experimental results of the pyridinium macrocyclic crystallization partner provided in Example 9, including: the chemical structure of methyl salicylate (a), the asymmetric unit of the crystal (b), the host-guest interaction (c), and the unit cell stacking (d);

[0047] Figure 14 Figure 10 shows the experimental results of the carbopyridinium macrocyclic crystallization partner provided in Example 10, including: the chemical structure of phenylboronic acid (a), the asymmetric unit of the crystal (b), the host-guest interaction (c), and the unit cell stacking (d);

[0048] Figure 15 The experimental results of the carbpyridinium macrocyclic crystallization partner provided in Example 11, including: the chemical structure of anisene (a), the asymmetric unit of the crystal (b), the host-guest interaction (c), and the unit cell stacking (d). DETAILED DESCRIPTION

[0049] The following is a further description of specific embodiments of the present invention. It should be noted that the description of these embodiments is intended to facilitate understanding of the present invention and does not constitute a limitation of the present invention. In addition, the technical features involved in the various embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

[0050] The experimental methods in the following examples are conventional methods unless otherwise specified, and the experimental materials used in the following examples are commercially available unless otherwise specified.

[0051] Example 1 Preparation of pyridinium macrocyclic crystallization partner

[0052] (1) 2,6-Dibromoaniline (1 g, 3.98 mmol), 4-pyridineboronic acid (1.47 mg, 11.96 mmol), tetrakis(triphenylphosphine)palladium (0.37 g, 0.32 mmol), and K2CO3 (5.50 g, 39.8 mmol) were placed in a 250 mL round-bottom flask. Anhydrous DMF (100 mL) was added to the reaction system under N2 atmosphere, and the mixture was refluxed at 120°C for 12 h. After the reaction was completed, the mixture was cooled to room temperature and extracted three times with dichloromethane (3 × 30 mL). The organic layers were combined, washed twice with water (2 × 30 mL), washed once with 10% salinity brine, and dried over anhydrous Na2SO4. Na2SO4 was filtered using a Buchner funnel, and the filtrate was concentrated under reduced pressure to remove the solvent. The mixture was then separated by silica gel column chromatography (using a 200-mesh silica gel column with a mobile phase of CH2Cl2:CH3OH = 100:1, 50:1, and 30:1, and the eluent with CH2Cl2:CH3OH = 30:1 was collected) to obtain compound 1 as a light yellow solid (735 mg, yield: 74.6%).

[0053] The compound 1 obtained in step (1) is the intermediate 2,6-di(pyridin-4-yl)aniline, and its synthesis route is shown in Figure 1 , hydrogen spectrum see Figure 2 , the NMR data are: 1 H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 4.6 Hz, 4H, Hd), 7.45 (d, J = 4.6 Hz, 4H, Hc), 7.16 (d, J = 7.5 Hz, 2H, Hb), 6.94 (t, J = 7.4 Hz, 1H, Ha), 3.88 (s, 2H, He). The carbon spectrum of the intermediate is shown in Figure 3 , the NMR data are: 13 C NMR (101MHz,CDCl3)δ150.50,147.35,140.26,130.54,125.35,124.10,118.84. The mass spectrum of the intermediate is shown in Figure 4 ,from Figure 4 It can be clearly observed that m / z = [M+H] + =248.1180 quasi-molecular ion peak, its structural formula is shown in Formula I:

[0054]

[0055] (2) Compound 1 (500 mg, 2.02 mmol) was weighed and dissolved in acetonitrile (200 mL) and placed in a 500 mL reaction flask. Separately, α,α′-dibromo-p-xylene (530 mg, 2.02 mmol) was dissolved in acetonitrile (50 mL). The acetonitrile solution of α,α′-dibromo-p-xylene was slowly added dropwise to the reaction flask using a dropping funnel (100 mL). The mixture was refluxed at 80°C for 24 h. A large amount of yellow precipitate was produced. The mixture was cooled to room temperature, filtered, and collected. The precipitate was washed with acetonitrile three times and dried in vacuo to obtain pyridinium macrocycle C1·Br4 as a yellow solid (1058 mg, yield 51.2%).

[0056] The synthetic route of the pyridinium macrocycle C1·Br4 obtained in step (2) is shown in Figure 5 The hydrogen spectrum of pyridinium macrocycle C1·Br4 is shown in Figure 6 , the NMR data are: 1 H NMR (400 MHz, D2O) δ 8.89 (d, J = 6.6 Hz, 8H), 8.21 (d, J = 6.6 Hz, 8H), 7.64 (d, J = 11.9 Hz, 8H), 7.47 (d, J = 7.7 Hz, 4H), 7.13 (t, J = 7.7 Hz, 2H), 5.86 (s, 8H). The carbon spectrum of the pyridinium macrocycle C1·Br4 is shown in Figure 7 , the NMR data are: 13 C NMR (151 MHz, D2O) δ 156.73, 144.30, 141.62, 134.68, 134.66, 133.51, 133.47, 130.25, 128.13, 123.01, 119.79, 63.48. The mass spectrum of pyridinium macrocycle C1·Br4 is shown in Figure 8 ,from Figure 8 It can be clearly observed that m / z = [M+H] + =1019.0277 quasi-molecular ion peak, its structural formula is shown in Formula II:

[0057]

[0058] (3) C1·Br4 (200 mg, 0.19 mmol) was dissolved in H2O (100 mL) and an excess of NH4PF6 was added thereto. A yellow precipitate was immediately formed, which was filtered, washed with H2O, and dried in vacuo to afford the pyridinium macrocycle C1·(PF6)4 as a yellow solid (205 mg, 81.3%).

[0059] The synthetic route of the pyridinium macrocycle C1·(PF6)4 obtained in step (3) is shown in Figure 9 The mass spectrum of pyridinium macrocycle C1·(PF6)4 is shown in Figure 10 ,from Figure 10It can be clearly observed that m / z = [M+H] + =1283.2108 quasi-molecular ion peak, its structural formula is shown in formula III:

[0060]

[0061] (4) The obtained C1·(PF6)4 solid was completely dissolved in 0.5 mL of acetonitrile, placed in a liquid phase vial and then stored in a 20 mL glass bottle. 2 mL of isopropyl ether was added, the mixture was sealed, and the mixture was placed at room temperature for static incubation to allow vapor diffusion. After 2 days, yellow block crystals were obtained.

[0062] The crystal obtained in step (4) was subjected to single crystal X-ray diffraction analysis using an Agilent Gemini S ultra CCD diffractometer, and modeled and refined using OLEX2. The results showed that non-hydrogen atoms were anisotropically refined, and hydrogen atoms were fixed using a riding model. The chemical formula is C 48 H 42 N6P4F 24 The crystallographic parameters are shown in Table 1. As can be seen from the table, this crystallization partner has a clear cavity Can be used to include guest molecules.

[0063] Table 1 Crystallographic data of pyridinium macrocyclic crystallization partners

[0064]

[0065]

[0066] Example 2 Preparation of pyridinium macrocyclic crystallization partner

[0067] (1) 2,6-Dibromoaniline (1 g, 3.98 mmol), 4-pyridineboronic acid (1467.6 mg, 11.94 mmol), tetrakis(triphenylphosphine)palladium (265.7 mg, 0.23 mmol), and K2CO3 (6041.6 mg, 43.78 mmol) were placed in a 250 mL round-bottom flask. Anhydrous DMF (100 mL) was added to the reaction system under N2 atmosphere, and the mixture was refluxed at 130°C for 12 h. After the reaction was completed, the mixture was cooled to room temperature and extracted three times with dichloromethane (3 × 30 mL). The organic layers were combined, washed twice with water (2 × 30 mL), washed once with brine, and dried over anhydrous Na2SO4. The mixture was further filtered and concentrated under reduced pressure to remove the solvent, and then separated by silica gel column chromatography (using a 200-mesh silica gel column with a mobile phase of CH2Cl2:CH3OH=100:1, 50:1, and 30:1, and collecting the eluate with CH2Cl2:CH3OH=30:1) to obtain compound 1 as a light yellow solid (701.56 mg, yield: 71.2%).

[0068] (2) Compound 1 (500 mg, 2.02 mmol) was weighed and dissolved in acetonitrile (200 mL) and placed in a 500 mL reaction flask. Separately, α,α′-dibromo-p-xylene (639.8 mg, 2.42 mmol) was dissolved in acetonitrile (50 mL). The acetonitrile solution of α,α′-dibromo-p-xylene was slowly added dropwise to the reaction flask using a dropping funnel (100 mL). The mixture was refluxed at 80°C for 24 h. A large amount of yellow precipitate was produced. The mixture was cooled to room temperature, filtered, and collected. The precipitate was washed with acetonitrile three times and dried in vacuo to obtain pyridinium macrocycle C1·Br4 as a yellow solid (1029.5 mg, yield 49.8%).

[0069] (3) C1·Br4 (194 mg, 0.19 mmol) was dissolved in H2O (100 mL), and an excess of NH4PF6 was added thereto. A yellow precipitate was immediately formed, which was filtered, washed with H2O, and dried in vacuo to afford the pyridinium macrocycle C1·(PF6)4 as a yellow solid (190.2 mg, 80.6% yield).

[0070] (4) The obtained C1·(PF6)4 solid was completely dissolved in 0.5 mL of acetonitrile, placed in a liquid phase vial and then stored in a 20 mL glass bottle. 2 mL of isopropyl ether was added, the mixture was sealed, and the mixture was placed at room temperature for static incubation to allow vapor diffusion. After 2 days, yellow block crystals were obtained.

[0071] The structure was identified by referring to the method in Example 1. The results showed that the composition and structure were consistent with those of the crystallization partner obtained in Example 1.

[0072] Example 3 Preparation of Pyridinium Macrocyclic Crystallization Partner

[0073] (1) 2,6-Dibromoaniline (1 g, 3.98 mmol), 4-pyridineboronic acid (1958.2 mg, 15.92 mmol), tetrakis(triphenylphosphine)palladium (265.7 mg, 0.23 mmol), and K2CO3 (6590.9 mg, 47.7 mmol) were placed in a 250 mL round-bottom flask. Anhydrous DMF (100 mL) was added to the reaction system under N2 atmosphere, and the mixture was refluxed at 140°C for 15 h. After the reaction was completed, the mixture was cooled to room temperature and extracted three times with dichloromethane (3 × 30 mL). The organic layers were combined, washed twice with water (2 × 30 mL), washed once with brine, and dried over anhydrous Na2SO4. The mixture was further filtered and concentrated under reduced pressure to remove the solvent, and then separated by silica gel column chromatography (using a 200-mesh silica gel column with a mobile phase of CH2Cl2:CH3OH=100:1, 50:1, and 30:1, and collecting the eluate with CH2Cl2:CH3OH=30:1) to obtain compound 1 as a light yellow solid (647.36 mg, yield: 65.7%).

[0074] (2) Compound 1 (500 mg, 2.02 mmol) was weighed and dissolved in acetonitrile (200 mL) and placed in a 500 mL reaction flask. Separately, α,α′-dibromo-p-xylene (693.2 mg, 2.63 mmol) was dissolved in acetonitrile (50 mL). The acetonitrile solution of α,α′-dibromo-p-xylene was slowly added dropwise to the reaction flask using a dropping funnel (100 mL). The mixture was refluxed at 90°C for 30 h. A large amount of yellow precipitate was produced. The mixture was cooled to room temperature, filtered, and collected. The precipitate was washed with acetonitrile three times and dried in vacuo to obtain pyridinium macrocycle C1·Br4 as a yellow solid (946.8 mg, yield 45.8%).

[0075] (3) Synthetic crystallization partner

[0076] C1·Br4 (194 mg, 0.19 mmol) was dissolved in H2O (100 mL), and an excess of NH4PF6 was added thereto. A yellow precipitate was immediately generated, which was filtered, washed with H2O, and dried in vacuo to give the pyridinium macrocycle C1·(PF6)4 as a yellow solid (180.9 mg, 76.7% yield).

[0077] (4) The obtained C1·(PF6)4 solid was completely dissolved in 0.5 mL of acetonitrile, placed in a liquid phase vial and then stored in a 20 mL glass bottle. 2 mL of isopropyl ether was added, the mixture was sealed, and the mixture was placed at room temperature for static incubation to allow vapor diffusion. After 2 days, yellow block crystals were obtained.

[0078] The experimental results show that the composition and structure of the crystal sponge are consistent with those obtained in Example 1.

[0079] Example 4 Preparation of Pyridinium Macrocyclic Crystallization Partner

[0080] (1) 2,6-Dibromoaniline (1 g, 3.98 mmol), 4-pyridineboronic acid (2446.1 mg, 19.9 mmol), tetrakis(triphenylphosphine)palladium (265.7 mg, 0.23 mmol), and K2CO3 (7151.0 mg, 51.74 mmol) were placed in a 250 mL round-bottom flask. Anhydrous DMF (100 mL) was added to the reaction system under N2 atmosphere, and the mixture was refluxed at 150°C for 18 h. After the reaction was completed, the mixture was cooled to room temperature and extracted three times with dichloromethane (3 × 30 mL). The organic layers were combined, washed twice with water (2 × 30 mL), washed once with brine, and dried over anhydrous Na2SO4. The mixture was further filtered and concentrated under reduced pressure to remove the solvent, and then separated by silica gel column chromatography (using a 200-mesh silica gel column with a mobile phase of CH2Cl2:CH3OH=100:1, 50:1, and 30:1, and collecting the eluate with CH2Cl2:CH3OH=30:1) to obtain compound 1 as a light yellow solid (593.1 mg, yield: 60.2%).

[0081] (2) Compound 1 (500 mg, 2.02 mmol) was weighed and dissolved in acetonitrile (200 mL) and placed in a 500 mL reaction flask. Separately, α,α′-dibromo-p-xylene (746.5 mg, 2.83 mmol) was dissolved in acetonitrile (50 mL). The acetonitrile solution of α,α′-dibromo-p-xylene was slowly added dropwise to the reaction flask using a dropping funnel (100 mL). The mixture was refluxed at 100°C for 35 h. A large amount of yellow precipitate was produced. The mixture was cooled to room temperature, filtered, and collected. The precipitate was washed with acetonitrile three times and dried in vacuo to obtain pyridinium macrocycle C1·Br4 as a yellow solid (901.3 mg, yield 43.6%).

[0082] (3) Synthetic crystallization partner

[0083] C1·Br4 (194 mg, 0.19 mmol) was dissolved in H2O (100 mL), and an excess of NH4PF6 was added thereto. A yellow precipitate was immediately generated, which was filtered, washed with H2O, and dried in vacuo to give the pyridinium macrocycle C1·(PF6)4 as a yellow solid (180.9 mg, 76.7% yield).

[0084] (4) The obtained C1·(PF6)4 solid was completely dissolved in 0.5 mL of acetonitrile, placed in a liquid phase vial and then stored in a 20 mL glass bottle. 2 mL of isopropyl ether was added, the mixture was sealed, and the mixture was placed at room temperature for static incubation to allow vapor diffusion. After 2 days, yellow block crystals were obtained.

[0085] The experimental results show that the composition and structure of the crystal sponge are consistent with those obtained in Example 1.

[0086] Example 5 Preparation of Pyridinium Macrocyclic Crystallization Partner

[0087] (1) 2,6-Dibromoaniline (1 g, 3.98 mmol), 4-pyridineboronic acid (2446.1 mg, 19.9 mmol), tetrakis(triphenylphosphine)palladium (265.7 mg, 0.23 mmol), and K2CO3 (8251.1 mg, 59.7 mmol) were placed in a 250 mL round-bottom flask. Anhydrous DMF (100 mL) was added to the reaction system under N2 atmosphere, and the mixture was refluxed at 150°C for 20 h. After the reaction was completed, the mixture was cooled to room temperature and extracted three times with dichloromethane (3 × 30 mL). The organic layers were combined, washed twice with water (2 × 30 mL), washed once with brine, and dried over anhydrous Na2SO4. The mixture was further filtered and concentrated under reduced pressure to remove the solvent, and then separated by silica gel column chromatography (using a 200-mesh silica gel column with a mobile phase of CH2Cl2:CH3OH=100:1, 50:1, and 30:1, and collecting the eluate with CH2Cl2:CH3OH=30:1) to obtain compound 1 as a light yellow solid (555.7 mg, yield: 56.4%).

[0088] (2) Compound 1 (500 mg, 2.02 mmol) was weighed and dissolved in acetonitrile (200 mL) and placed in a 500 mL reaction flask. Separately, α,α′-dibromo-p-xylene (1066.4 mg, 4.04 mmol) was dissolved in acetonitrile (50 mL). The acetonitrile solution of α,α′-dibromo-p-xylene was slowly added dropwise to the reaction flask using a dropping funnel (100 mL). The mixture was refluxed at 100°C for 48 h. A large amount of yellow precipitate was produced. The mixture was cooled to room temperature, filtered, and collected. The precipitate was washed three times with acetonitrile and dried in vacuo to obtain pyridinium macrocycle C1·Br4 as a yellow solid (862.1 mg, yield 41.7%).

[0089] (3) Synthetic crystallization partner

[0090] C1·Br4 (194 mg, 0.19 mmol) was dissolved in H2O (100 mL), and an excess of NH4PF6 was added thereto. A yellow precipitate was immediately generated, which was filtered, washed with H2O, and dried in vacuo to give the pyridinium macrocycle C1·(PF6)4 as a yellow solid (180.9 mg, 76.7% yield).

[0091] (4) The obtained C1·(PF6)4 solid was completely dissolved in 0.5 mL of acetonitrile, placed in a liquid phase vial and then stored in a 20 mL glass bottle. 2 mL of isopropyl ether was added, the mixture was sealed, and the mixture was placed at room temperature for static incubation to allow vapor diffusion. After 2 days, yellow block crystals were obtained.

[0092] The experimental results show that the composition and structure of the crystal sponge are consistent with those obtained in Example 1.

[0093] Example 6 Pyridinium Macrocyclic Crystallization Companion for Structural Identification of Benzoic Acid

[0094] The crystallization partner prepared in Example 1 was dissolved in acetonitrile (concentration of 1 mM), 200 μL was added to a 1.5 mL liquid phase vial, and 200 μL of benzoic acid dissolved in methanol (concentration of 2 mM) was added. The vial was capped and a needle was inserted into the cap. The solution was then slowly evaporated at room temperature for 3 days until yellow block crystals appeared.

[0095] Select a crystal of appropriate size (about 0.2mm×0.08mm×0.04mm), and then use Agilent Gemini SM Ltra CCD diffractometer to collect the diffraction data of the crystal. The diffraction data were collected under the condition of ray, and then the diffraction data were restored using the CrysAlisPro package. The restored diffraction data were used for structure analysis using the direct method in the SHEXLE package, and the structure was analyzed based on the F 2 The coordinates of each atom were refined by full matrix least squares method. All non-hydrogen atoms were anisotropic except for solvent molecules. The results of refinement are shown in Table 2. The X-ray diffraction results of the single crystal are shown in Figure 10 , including the chemical structures of benzoic acid (a) and ORTEP (b), the asymmetric unit of the crystal (c) and the crystal packing (d).

[0096] The experimental results in Table 2 demonstrate that the pyridinium macrocyclic crystallization partner prepared in Example 1 can stably encapsulate the target guest, obtain the single crystal structure of the guest-encapsulated crystal, and determine the structure of the guest molecule with convenient operation and high accuracy.

[0097] Table 2 Crystallographic data of the crystallization chaperone-benzoic acid complex after co-incubation of the crystallization chaperone with benzoic acid

[0098]

[0099]

[0100] Example 7: Use of a pyridinium macrocyclic crystallization partner for structural identification of succinic acid

[0101] The crystallization partner prepared in Example 1 was dissolved in acetonitrile (concentration of 1 mM), 200 μL was added to a 1.5 mL liquid phase vial, and 200 μL of succinic acid dissolved in methanol (concentration of 2 mM) was added. The vial was covered with a lid, a needle was inserted into the lid, and then slowly evaporated at room temperature for 5 days until yellow block crystals appeared.

[0102] Select a crystal of appropriate size (about 0.2mm×0.05mm×0.04mm), and then use Agilent Gemini SM Ltra CCD diffractometer to collect the diffraction data of the crystal. The diffraction data were collected under the condition of ray, and then the diffraction data were restored using the CrysAlisPro package. The restored diffraction data were used for structure analysis using the direct method in the SHEXLE package, and the structure was analyzed based on the F 2 The coordinates of each atom were refined by full matrix least squares method. All non-hydrogen atoms were anisotropic, except for solvent molecules. The results of the refinement are shown in Table 3, and the X-ray diffraction results of the single crystal are shown in Figure 11 , the chemical structures of succinic acid (a) and ORTEP (b), the asymmetric unit of the crystal (c) and the crystal packing (d).

[0103] The experimental results in Table 3 also prove that the carbazole crystal sponge prepared in Example 1 can stably encapsulate the target object, obtain the single crystal structure of the object-encapsulated crystal, and determine the structure of the object molecule with convenient operation and high accuracy.

[0104] Table 3 Crystallographic data of the crystallization partner-succinic acid complex after co-incubation of the crystallization partner with succinic acid

[0105]

[0106]

[0107] Example 8: Use of Pyridinium Macrocyclic Crystallization Partner for Structural Identification of Benzaldehyde

[0108] The crystallization partner prepared in Example 1 was dissolved in acetonitrile (concentration of 1 mM), 200 μL was added to a 1.5 mL liquid phase vial, and 200 μL of benzaldehyde solution dissolved in methanol (concentration of 2 mM) was added. The vial was covered with a lid, a needle was inserted into the lid, and then slowly evaporated at room temperature for 3 days until yellow block crystals appeared.

[0109] Select a crystal of appropriate size (about 0.3mm×0.05mm×0.05mm), and then use Agilent Gemini SUltra CCD diffractometer to collect the diffraction data of the crystal. The diffraction data were collected under the condition of ray, and then the diffraction data were restored using the CrysAlisPro package. The restored diffraction data were used for structure analysis using the direct method in the SHEXLE package, and the structure was analyzed based on the F 2The coordinates of each atom were refined by full matrix least squares method. All non-hydrogen atoms were anisotropic except for solvent molecules. The results of the refinement are shown in Table 4. The X-ray diffraction results of the single crystal are shown in Figure 12 The figure includes the chemical structures of benzaldehyde (a) and ORTEP (b), the asymmetric unit of the crystal (c) and the crystal packing (d).

[0110] The experimental results in Table 4 also prove that the carbazole crystal sponge prepared in Example 1 can stably encapsulate the target object, obtain the single crystal structure of the object-encapsulated crystal, and determine the structure of the object molecule with convenient operation and high accuracy.

[0111] Table 4 Crystallographic data of the crystallization partner-benzaldehyde complex after co-incubation of the crystallization partner with benzaldehyde

[0112]

[0113]

[0114] Example 9 Pyridinium Macrocyclic Crystallization Partner for Structural Identification of Methyl Salicylate

[0115] The crystallization partner prepared in Example 1 was dissolved in acetonitrile (concentration of 1 mM), 200 μL was added to a 1.5 mL liquid phase vial, and 200 μL of methyl salicylate solution (concentration of 2 mM) was added. The vial was covered with a lid, a needle was inserted into the lid, and then slowly evaporated at room temperature for 7 days until yellow needle-shaped crystals appeared.

[0116] Select a crystal of appropriate size (about 0.3mm×0.04mm×0.03mm), and then use Agilent Gemini SMLtra CCD diffractometer to collect the diffraction data of the crystal. The diffraction data were collected under the condition of F-ray, and then the diffraction data were restored using the CrysAlisPro program package. The restored diffraction data were used for structure analysis using the direct method in the SHEXLE program package, and the structure was analyzed based on the F-ray. 2 The coordinates of each atom were refined by full matrix least squares method. All non-hydrogen atoms were anisotropic except for solvent molecules. The results of refinement are shown in Table 5. The X-ray diffraction results of the single crystal are shown in Figure 13 , including the chemical structures of methyl salicylate (a) and ORTEP (b), the asymmetric unit of the crystal (c) and the crystal packing (d).

[0117] The experimental results in Table 5 also prove that the carbazole crystal sponge prepared in Example 1 can stably encapsulate the target object, obtain the single crystal structure of the object-encapsulated crystal, and determine the structure of the object molecule with convenient operation and high accuracy.

[0118] Table 5 Crystallographic data of crystallization partner-methyl salicylate complex after co-incubation of crystallization partner and methyl salicylate

[0119]

[0120]

[0121] Example 10 Pyridinium Macrocyclic Crystallization Partner for Structural Identification of Phenylboronic Acid

[0122] The crystallization partner prepared in Example 1 was dissolved in acetonitrile (concentration of 1 mM), 200 μL was added to a 1.5 mL liquid phase vial, and 200 μL of a methanol solution of phenylboronic acid (concentration of 2 mM) was added. The vial was covered with a lid, a needle was inserted into the lid, and then slowly evaporated at room temperature for 3 days until yellow block crystals appeared.

[0123] Select a crystal of appropriate size (about 0.3mm×0.06mm×0.04mm), and then use Agilent Gemini SMLtra CCD diffractometer to collect the diffraction data of the crystal. The diffraction data were collected under the condition of ray, and then the diffraction data were restored using the CrysAlisPro package. The restored diffraction data were used for structure analysis using the direct method in the SHEXLE package, and the structure was analyzed based on the F 2 The coordinates of each atom were refined by full matrix least squares method. All non-hydrogen atoms were anisotropic except for solvent molecules. The results of refinement are shown in Table 6. The X-ray diffraction results of single crystal are shown in Figure 14 The figure includes the chemical structures of phenylboronic acid (a) and ORTEP (b), the asymmetric unit of the crystal (c) and the crystal packing (d).

[0124] The experimental results in Table 6 also prove that the carbazole crystal sponge prepared in Example 1 can stably encapsulate the target object, obtain the single crystal structure of the object-encapsulated crystal, and determine the structure of the object molecule with convenient operation and high accuracy.

[0125] Table 6 Crystallographic data of the crystallization partner-phenylboronic acid complex after co-incubation of the crystallization partner with phenylboronic acid

[0126]

[0127] Example 11: Use of a pyridinium macrocyclic crystallization partner for the structural identification of anisene

[0128] The crystallization partner prepared in Example 1 was dissolved in acetonitrile (concentration of 1 mM), 200 μL was added to a 1.5 mL liquid phase vial, and 200 μL of aniseed solution (concentration of 2 mM) was added. The vial was capped and a needle was inserted into the cap. The solution was then slowly evaporated at room temperature for 6 days until yellow block crystals appeared.

[0129] Select a crystal of appropriate size (about 0.3mm×0.06mm×0.04mm), and then use Agilent Gemini SMLtra CCD diffractometer to collect the diffraction data of the crystal. The diffraction data were collected under the condition of ray, and then the diffraction data were restored using the CrysAlisPro package. The restored diffraction data were used for structure analysis using the direct method in the SHEXLE package, and the structure was analyzed based on the F 2 The coordinates of each atom were refined by full matrix least squares method. All non-hydrogen atoms were anisotropic, except for solvent molecules. The results of the refinement are shown in Table 7, and the X-ray diffraction results of the single crystal are shown in Figure 15 The figure includes the chemical structure of anisene (a) and ORTEP (b), the asymmetric unit of the crystal (c) and the crystal packing (d).

[0130] The experimental results in Table 7 also prove that the pyridinium macrocyclic crystallization partner prepared in Example 1 can stably encapsulate the target guest, obtain the single crystal structure of the guest-encapsulated crystal, and determine the structure of the guest molecule with convenient operation and high accuracy.

[0131] Table 7 Crystallographic data of crystallization partner-anisene complex after co-incubation of crystallization partner and anisene

[0132]

[0133] The experimental results of Examples 6-11 demonstrate that the crystallization partner prepared by the present invention can be used to analyze the crystal structures of a variety of organic molecules that are difficult to identify using conventional methods. Successfully prepared crystals can be directly used to test the structure of guest molecules, simplifying the process. Furthermore, the preparation method of this crystallization partner is simple, the raw materials are readily available, and it exhibits good reproducibility and high yield, suggesting broad application prospects in molecular structure identification.

[0134] The embodiments of the present invention are described in detail above, but the present invention is not limited to the described embodiments. It is apparent to those skilled in the art that various changes, modifications, substitutions, and variations of these embodiments may be made without departing from the principles and spirit of the present invention, and the changes still fall within the scope of protection of the present invention.

Claims

1. A pyridinium macrocyclic crystallization partner, characterized in that The chemical formula of the pyridinium macrocyclic crystallization partner is C 48 H 42 N6P4F 24 , the structural formula is as follows: The pyridinium macrocyclic crystal partner is monoclinic, and its space group is P2 1 / c , the unit cell parameters are: a=15.28,b=10.88,c=15.79,α=γ=90°,β=101.77°, and the unit cell volume is 2. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 1, characterized in that: The following steps are involved: S1. Under an inert gas atmosphere, an organic solvent was added to 2,6-dibromoaniline, 4-pyridineboric acid, tetrakis(triphenylphosphine)palladium, and K2CO3. After heating under reflux, the mixture was extracted with dichloromethane. The organic layer was collected, washed with water, brine, and dried, and the solvent was removed by filtration. The mixture was then separated by silica gel column chromatography to obtain compound 1, whose structural formula is shown below: S2. Dissolve the compound 1 and α,α′-dibromo-p-xylene prepared in step S1 in an organic solvent, combine the two solutions, and heat under reflux until a large amount of yellow precipitate is generated. Collect the precipitate by filtration, wash, and dry to obtain a pyridinium macrocyclic compound C1·Br4, whose structural formula is shown below: S3, dissolving C1·Br4 in water, adding excess NH4PF6 to generate a yellow precipitate, filtering, washing and drying to obtain the pyridinium macrocyclic compound C1·(PF6)4; S4. Dissolving the pyridinium macrocyclic compound C1·(PF6)4 in an organic solvent, and then placing the mixture in an ether atmosphere for vapor diffusion at room temperature, and crystallizing the pyridinium macrocyclic crystallization partner.

3. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 2, wherein: In step S1, the equivalent ratio of the 2,6-dibromoaniline to 4-pyridineboric acid is 1:3-5; the equivalent of the tetrakis(triphenylphosphine)palladium is 0.08-0.1 with 2,6-dibromoaniline as 1 equivalent; and the equivalent of the K2CO3 is 10-15 with 2,6-dibromoaniline as 1 equivalent.

4. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 2, wherein: In step S2, the equivalent ratio of the compound 1 to α,α′-dibromo-p-xylene is 1:1-2.

5. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 2, wherein: In step S1, the temperature of the heating reflux reaction is 120-150° C., and the time is 12-20 hours.

6. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 2, wherein: In step S2, the heating reflux reaction temperature is 80-100° C. and the time is 24-48 hours.

7. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 2, wherein: In step S1, the silica gel column chromatography separation is performed with a mobile phase of CH2Cl2:CH3OH=100:1, 50:1, and 30:1, and the eluate of the CH2Cl2:CH3OH=30:1 portion is collected.

8. The method for preparing the pyridinium macrocyclic crystallization partner according to claim 2, wherein: In step S4, the gas phase diffusion time is 2 to 4 days.

9. Use of the pyridinium macrocyclic crystallization partner according to claim 1 in the structural identification of organic molecules, characterized in that: The organic molecules are benzoic acid, succinic acid, benzaldehyde, methyl salicylate, phenylboric acid, and anisene.

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