Pentafluoro-beta-nitrostyrene-hexamethylbenzene co-crystal and preparation method and application thereof

Abstract

The present application relates to a kind of five fluorine-β-nitrophenylethylene·hexamethyl benzene eutectic crystal and its preparation and application, belong to chemical synthesis technical field.The five fluorine-β-nitrophenylethylene·hexamethyl benzene eutectic crystal compound crystal disclosed in the present application is triclinic system, P-1 space group, and cell parameter is α=85.886 (3) °, β=87.902 (3) °, γ=79.644 (2) °, nitrophenylethylene is a kind of common antipathogenic microorganism drug, and the eutectic crystal formed by hexamethyl benzene can regulate the oxidation-reduction potential of nitrophenylethylene by non-covalent bond effect, and then can improve its physical and chemical properties and drug activity, has good potential application value in the field of organic chemistry, medicinal chemistry and crystal chemistry.

Description

Technical Field

[0001] This invention relates to the field of medicinal chemistry, specifically to a pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic and its preparation method, as well as its application in the preparation of antibacterial drugs. Background Technology

[0002] In recent years, various pathogenic fungi have been continuously affecting and interfering with human life. These pathogens include Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, which can easily reside on the human body surface, leading to infections. Pathogenic fungi are more likely to reside on the body surface of people with weakened immune systems, thus rapidly triggering systemic infections.

[0003] Based on the type of pathogenic fungus and the mechanism of disease induction, commonly used antifungal drugs mainly fall into three categories: echinocandins, azoles, and polyenes. Nitrostyrene derivatives have been reported to possess specific antifungal and antitumor activities, as well as metabolic inhibitory effects. 4-Bromo-β-nitrostyrene is also a broad-spectrum bactericide, widely used as an antibacterial and antifungal agent in cutting fluids, cosmetics (emollients), coatings, and emulsions, and also for industrial water treatment, oil reinjection water, and pulp sterilization and algae control. Furthermore, aromatic compounds containing nitroolefins are a novel class of functional organic compounds that inhibit bacterial quorum sensing and reduce the activity of related enzymes. In these compounds, the electron-withdrawing nitro functional groups, in conjunction with vinyl and aromatic functional groups, act on the active sites of enzyme proteins related to quorum sensing in bacteria. Through non-covalent interactions such as NO2...π and π...π between small molecule compounds and enzyme proteins, bacterial quorum sensing can be effectively regulated without affecting normal bacterial growth.

[0004] Due to the increasing resistance of fungi, the efficacy of active pharmaceutical ingredients (APIs) is declining. Therefore, synthesizing novel antibacterial drugs that enhance drug activity has become a growing focus for chemists and medical researchers. Drug polymorphism is one promising method for providing or improving drug activity. Nitrostyrene and its derivatives have been used as long-term antimicrobial agents. Studies have shown that the antibacterial and antifungal activities of these drugs stem from their ability to inhibit cancer cell proliferation and induce programmed cell death, suppressing cancer cell growth during the G2 / M phase of the cell cycle. Their antibacterial activity is correlated with the redox potential of the compound. Therefore, regulating the redox potential of β-nitrostyrene may also have a positive effect on improving its drug activity. Accordingly, novel antibacterial drugs can be synthesized by improving the electron density of the benzene ring, thereby affecting the electron density distribution of the nitro and ethylene functional groups. Hexamethylbenzene is a commonly used chemical reagent. At low concentrations (<50 ppm), this compound exhibits certain antibacterial activity. Furthermore, the presence of six electron-donating methyl functional groups in its molecular structure allows the high-electron-density benzene ring to readily form non-covalent π...π stacking interactions with electron-deficient aromatic benzene rings, thus regulating the synthesis of non-covalent structures. Pentafluoro-β-nitrostyrene, used as a long-term antimicrobial agent, exhibits antibacterial activity correlated with its redox potential. The pentafluoro-β-nitrostyrene (PFNEB) molecule contains an electron-deficient benzene ring, five fluorine atoms, an ethylene double bond, and a nitro functional group. Both the nitro and fluorine atoms are active pharmaceutical ingredients or key functional groups. As a derivative of nitrostyrene, it can serve as a broad-spectrum bactericide. However, this type of compound is a yellow liquid at room temperature, highly volatile, and difficult to store. Moreover, due to fungal resistance, the efficacy of single-active antibacterial agents gradually decreases with use. Summary of the Invention

[0005] To address the technical problems of pentafluoro-β-nitrostyrene being a yellow liquid at room temperature, being volatile, difficult to store, and having a low efficacy of single-active antibacterial ingredients with use, this invention utilizes the non-covalent space π...π stacking effect to introduce the high-density electron antibacterial material hexamethylbenzene into pentafluoro-β-nitrostyrene, and screens four methods to prepare pentafluoro-β-nitrostyrene·hexamethylbenzene cocrystals.

[0006] To achieve the above objectives, the present invention employs the following technical solution:

[0007] Different cocrystal forms of the same drug can result in different physical and chemical properties of the drug molecules, such as drug activity, solubility, dissolution rate, melting point, stability, and tablet compressibility. These properties are crucial for the efficacy of a drug. The first aspect of this invention is the preparation of a pentafluoro-β-nitrostyrene-hexamethylbenzene cocrystal, the structural formulas of pentafluoro-β-nitrostyrene and hexamethylbenzene being shown in general formula 1:

[0008]

[0009] The molar ratio of the eutectic component pentafluoro-β-nitrostyrene to hexamethylbenzene is 1:1.

[0010] The pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic proposed in this invention is triclinic, space group P-1, and its cell parameters are as follows: α=85.886(3)°, β=87.902(3)°, γ=79.644(2)°,

[0011] The triclinic crystal system of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic proposed in this invention comprises one pentafluoro-β-nitrostyrene molecule and one hexamethylbenzene molecule in each independent unit. The aromatic benzene ring and vinyl group of the pentafluoro-β-nitrostyrene form two non-covalent π...π stacking interactions with the two adjacent hexamethylbenzene rings from both sides. The centroid distances of the two stacking interactions in the π-π system are respectively... and

[0012] One of the components of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic proposed in this invention, pentafluoro-β-nitrostyrene, is prepared by heating pentafluorobenzaldehyde and nitromethane in the organic solvent methanol under normal pressure.

[0013] The second aspect of this invention is the preparation of pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic using the following four methods:

[0014] Method 1: Direct evaporation of solution: Hexamethylbenzene is completely dissolved in an organic solvent, pentafluoro-β-nitrostyrene is added to the solution, the temperature is lowered, and the resulting mixture is allowed to stand for 32-64 hours to separate and crystallize, thus obtaining the crystalline product.

[0015] Method 2: Liquid-phase diffusion method: Dissolve hexamethylbenzene in isopropanol solution, add ethyl acetate solution of pentafluoro-β-nitrostyrene to the hexamethylbenzene solution to form liquid layers, let the layered solution stand for 32-64 hours to obtain the crystalline product.

[0016] Method 3: Gas-phase diffusion method: Pentafluoro-β-nitrostyrene and hexamethylbenzene are dissolved in dichloromethane. The solution system is sealed and stored in an ether bath. After standing at room temperature for 32-64 hours, the crystallized product is obtained.

[0017] Method 4: Sublimation method: A solid-liquid mixture of hexamethylbenzene and pentafluoro-β-nitrostyrene is subjected to vacuum sublimation, and a powdery eutectic is obtained after 16 to 32 hours.

[0018] Preferably, the molar ratio of pentafluoro-β-nitrostyrene to hexamethylbenzene used in the preparation of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic is 1:1.

[0019] Pentafluoro-β-nitrostyrene is an extremely electron-deficient aromatic ring system, while hexamethylbenzene is an electron-rich molecular system. Both molecules are relatively planar and can form a eutectic structure through non-covalent interactions. Furthermore, these non-covalent interactions can further modulate the redox potential of nitrostyrene, thereby improving its pharmacological activity. This allows the components of the eutectic to exhibit better physicochemical and pharmaceutical properties as antibacterial agents, showing inhibitory effects against Staphylococcus aureus, Escherichia coli, and Proteus vulgaris.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The pentafluoro-β-nitrostyrene molecule has a benzene ring with five strongly electron-withdrawing fluorine atoms, plus an electron-withdrawing nitro group in the vinyl group, giving the compound an extremely electron-deficient aromatic ring system. This facilitates non-covalent interactions (π...π and NO2...π) with other planar compounds rich in π electrons. The hexamethylbenzene molecule has six electron-donating methyl groups surrounding the benzene ring, making the benzene ring system electron-rich. Furthermore, both pentafluoro-β-nitrostyrene and hexamethylbenzene are relatively planar molecules, making π...π conjugated stacking between them possible. This allows for the formation of new cocrystal drug molecules through non-covalent stacking, creating structurally favorable conditions for cocrystal synthesis. Based on this synthetic design concept, this patent obtained a novel pentafluoro-β-nitrostyrene / hexamethylbenzene cocrystal with a P-1 spatial stacking mode through four different crystallization processes. This cocrystal structure helps improve the bioavailability of this chemical as an antibacterial drug.

[0022] This invention synthesizes a pentafluoro-β-nitrostyrene·hexamethylbenzene cocrystal, which, compared to single-component antibacterial drugs, is less prone to inducing drug resistance. The pentafluoro-β-nitrostyrene·hexamethylbenzene cocrystal exhibits more stable physicochemical properties than single-component pentafluoro-β-nitrostyrene, remaining solid at room temperature and pressure, making it easy to store and use. The non-covalent bonds between the two components of the cocrystal further regulate the redox potential of nitrostyrene, contributing to improved antibacterial efficacy. Each component in the cocrystal, as an antibacterial agent, exhibits superior pharmaceutical properties and possesses excellent antibacterial activity, showing great potential for application in the biological and pharmaceutical fields. This invention prepares the pentafluoro-β-nitrostyrene·hexamethylbenzene cocrystal using direct solvent evaporation, liquid-phase diffusion, gas-phase diffusion, and sublimation methods. All synthetic routes are simple, low-cost, and pollution-free, demonstrating promising practical applications. Attached Figure Description

[0023] Figure 1 The thermal ellipsoid diagram shows the spatial distribution of the smallest asymmetric unit cell of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic, which contains one pentafluoro-β-nitrostyrene and one hexamethylbenzene molecule.

[0024] Figure 2 This is a schematic diagram of the three-dimensional spatial structure of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic crystal, formed by intermolecular non-covalent bonds of CH...F, NO2...π and π...π.

[0025] Figure 3 X-ray powder diffraction pattern of pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic.

[0026] Figure 4 The infrared absorption spectrum is that of pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic.

[0027] Figure 5 This is a gas chromatography-mass spectrometry (GC-MS) chromatogram of pentafluoro-β-nitrostyrene.

[0028] Figure 6 The high-resolution mass spectrum of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic is shown.

[0029] Figure 7 The high-resolution mass spectrum of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic is shown.

[0030] Figure 8 The thermogravimetric spectrum of pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic is shown. Detailed Implementation

[0031] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0032] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings of this invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments of the invention described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover a non-exclusive inclusion; for example, a process, method, system, product, or apparatus that comprises a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products, or apparatus.

[0033] The present invention will now be described in further detail with reference to the accompanying drawings:

[0034] Example 1: Preparation of PFNEB

[0035] The pentafluoro-β-nitrostyrene synthesized in this invention is prepared by appropriately modifying the solvent according to the method described in Organic Letters, 23(7), 2584-2589; 2021, replacing the methanol solvent in the original literature with a mixed solvent composed of glacial acetic acid and ethanolamine, as follows:

[0036] Pentafluorobenzaldehyde and nitromethane were added to a mixed solution of glacial acetic acid and ethanolamine, wherein the molar ratio of pentafluorobenzaldehyde to nitromethane was 1:1.0–1.5, and the molar ratio of glacial acetic acid to ethanolamine was 1.0:1.0. The mixed solution was stirred at room temperature to form a mixture, and then the temperature was slowly increased to 80–120°C and reacted for 8–12 hours. After the reaction, the temperature was lowered to room temperature to obtain the PFNEB component in the eutectic compound.

[0037] Example 2: Preparation of eutectic by direct solvent evaporation method

[0038] 162.1 mg of colorless, flaky hexamethylbenzene solid sample was placed in a crystallization culture flask. 15.0 mL of anhydrous ethanol solution was added at room temperature (20°C), and the mixture was sonicated until completely dissolved. Then, 239.0 mg of pentafluoro-β-nitrostyrene yellow liquid sample was slowly added dropwise while sonicating. After the addition was complete, the resulting mixture was sealed and placed in a crystallization incubator (5°C, 30% humidity) for 48 hours. Yellow blocky crystals appeared on the upper edge of the crystallization culture flask. After 72 hours, yellow blocky crystals appeared on both the upper edge and bottom of the flask. The crystallization culture flask was removed, the product was separated, dried under an infrared lamp, and weighed. The yield was 273.0 mg, with a yield of ~68%.

[0039] Example 3: Preparation of eutectic by liquid-phase diffusion method

[0040] 162.1 mg of colorless, flaky hexamethylbenzene solid sample was placed in a crystallization culture flask. 20.0 mL of isopropanol solution was added at room temperature (20°C), and the mixture was sonicated until completely dissolved. Then, 10 mL of a yellow ethyl acetate solution of pentafluoro-β-nitrostyrene (containing 239.0 mg of pentafluoro-β-nitrostyrene) was slowly added along the wall of the crystallization culture flask to create liquid stratification. After completion, the resulting mixture was sealed and allowed to stand in a natural environment for 48 hours. Yellow blocky crystals appeared in the middle and bottom of the crystallization culture flask. The crystallization culture flask was removed, the product was separated, dried under an infrared lamp, and weighed. The yield was 328.8 mg, with a yield of ~82%.

[0041] Example 4: Preparation of eutectic by vapor-phase diffusion method

[0042] 162.1 mg of colorless, flaky hexamethylbenzene solid and 239.0 mg of pentafluoro-β-nitrostyrene were placed in a crystallization flask. At room temperature (20°C), 20.0 mL of dichloromethane solution was added, and the mixture was sonicated until completely dissolved. The crystallization flask was then placed in a 50 mL ground glass bottle, and 15 mL of diethyl ether was carefully added to the outside of the bottle. The bottle was then sealed. The prepared solution and the ground glass bottle were left at room temperature for 48 hours. Yellow, blocky crystals appeared at the upper edge of the crystallization flask, and after 72 hours, yellow, blocky crystals appeared at the bottom. The crystallization flask was removed, the product separated, dried under an infrared lamp, and weighed. The yield was 348.9 mg, with a yield of approximately 87%.

[0043] Example 5: Preparation of eutectic by sublimation method

[0044] 162.1 mg of colorless, flake-shaped hexamethylbenzene solid sample and 239.0 mg of pentafluoro-β-nitrostyrene were placed in a Schranke vacuum sublimation reactor, which was maintained at a vacuum of 100 mBar. Cooling water at -5°C was circulated through the inner sublimation crystallizer, and the outer vacuum tube was heated in a 70°C oil bath for 2 hours. A yellow solid powder sample was obtained on the lower surface of the inner crystallizer. The crystallized sample was recovered. Yield: 256.6 mg, yield: 64.0%.

[0045] Example 6: Structural Characterization of the Eutectic

[0046] The co-crystal of (E)-1,2,3,4,5-pentafluoro-6-(2-nitrovinyl)benzene compound and 1,2,3,4,5,6-hexamethylbenzene (1:1) has the chemical formula C1. 20 H 20 F5NO2 has the following chemical structural formula:

[0047]

[0048] The compounds exhibiting the characteristics of a pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic were structurally characterized, and the X-ray diffraction pattern of the eutectic is shown in [reference needed]. Figure 3 X-ray diffraction data for the crystals were determined using a Bruker D8 Venture single-crystal diffractometer. GaK α radiation A graphite monochromator was used to collect diffraction data in ω-scan mode, followed by Lp factor correction and empirical absorption correction. The initial positions of all non-hydrogen atoms were determined using a direct method, then refined using the difference Fourier function method and least squares method to obtain the coordinates of all non-hydrogen atoms. The positions of hydrogen atoms were obtained using theoretical hydrogen addition, and the structure was corrected using full-matrix least squares method. Crystal parameters are shown in the table below, and the structure is shown in [reference needed]. Figure 1 and Figure 2 .

[0049] Table 1. Analysis of parameters and structure of pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic crystal.

[0050]

[0051]

[0052] a R1=Σ(||F o |-|F c ||) / Σ(|F o |); bwR2=[Σw(F o 2 -F c 2 ) 2 / Σw(F o 2 ) 2 ] 1 / 2

[0053] The infrared absorption spectrum of the eutectic is shown in [reference needed]. Figure 4 The gas chromatography-mass spectrometry chromatogram is shown below. Figure 5 , Figure 6-7 This is a high-resolution mass spectrum of the eutectic. Figure 8 This is the thermogravimetric spectrum of the eutectic.

[0054] In the crystal structure of this compound, the smallest asymmetric unit consists of a disordered pentafluoro-β-nitrostyrene molecule and a hexamethylbenzene molecule, both of which exhibit good planarity. The equation for the plane containing the 12 carbon atoms of hexamethylbenzene is: 0.87x - 0.45y + 0.204z + 1.968 = 0, with a root mean square deviation of only [value missing]. The equation for the plane containing the 16 non-hydrogen atoms of pentafluoro-β-nitrostyrene is: 0.83x - 0.494y + 0.261z + 5.405 = 0, with a root mean square deviation of only [value missing]. Hexamethylbenzene forms a π-π stacking interaction with pentafluoro-β-nitrostyrene. One side consists of a toluene ring and a benzene ring with five fluorine molecules, forming a highly conjugated π-π stack. The distance between the centroids of the rings is [missing information]. On the other side, a small conjugated π-π stacking is formed between the hexamethylbenzene ring and the nitrovinyl group, with a centroid distance of [missing information]. These two π-π stacking interactions alternate on both sides of the benzene ring, resulting in a one-dimensional stacking structure arranged along the lattice

[100] direction in the molecular space. The adjacent one-dimensional π-π stacks and the surrounding adjacent molecules form a three-dimensional stacking structure through the interaction of CH...F, halogen F...F and -NO2...F.

[0055] The smallest asymmetric unit in the PFNEB-hexamethylbenzene eutectic crystal structure consists of one PFNEB molecule and one hexamethylbenzene molecule, with the center-to-center distance between the benzene ring and the hexamethylbenzene ring in adjacent PFNEB molecules being [missing information]. The centroid distance between adjacent vinyl groups and adjacent hexamethylbenzene rings is

[0056] The PFNEB and hexamethylbenzene eutectic in the triclinic crystal system has a "pedal" disorder in the smallest asymmetric unit. The ratio of the two parts is 0.87(1):0.13(1). The nitro and pentafluorophenyl groups are in trans mode relative to ethylene. The dihedral angle between the nitrovinyl group and the adjacent benzene ring plane is 1.08(1). o .

[0057] In summary, the eutectic organic compound with two benzene rings, one nitro group, one vinyl group, and six methyl groups as its smallest repeating unit belongs to the triclinic crystal system, space group P-1, and its unit cell parameters are as follows: α=85.886(3)°, β=87.902(3)°, γ=79.644(2)°, In the structural formula, the stoichiometric ratio of pentafluoro-β-nitrostyrene and hexamethylbenzene is 1:1.

[0058] Example 7: Antibacterial performance test of eutectic

[0059] 1.0 mg of the pentafluoro-β-nitrostyrene·hexamethylbenzene cocrystal product prepared by the above methods was added to a bacterial culture dish. The minimum inhibitory concentration (MIC) of the cocrystal product was determined to be 19.6 μg / mL (relative to Staphylococcus aureus). 1.0 mg of the pentafluoro-β-nitrostyrene product was added to a bacterial culture dish, and its MIC was determined to be 27.6 μg / mL (relative to Escherichia coli). 1.0 mg of the hexamethylbenzene sample was added to a bacterial culture dish, and its MIC was determined to be 55.9 μg / mL (relative to Proteus vulgaris). See the table below for details.

[0060] Table 2: Minimum inhibitory concentration (μg / ml) of pentafluoro-β-nitrostyrene·hexamethylbenzene on the reproduction of common bacteria

[0061]

[0062] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic, characterized in that, The molar ratio of pentafluoro-β-nitrostyrene to hexamethylbenzene in the eutectic is 1:1; the eutectic has a triclinic crystal system. P Space group -1, cell parameters are: a =7.9888(8)Å, b = 8.5807(9)Å, c = 13.5717(1)Å, α =85.886(3)°, β = 87.902(3)°, γ = 79.644(2)°, V = 912.55(16)Å 3 .

2. The pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic according to claim 1, characterized in that, The independent unit of the triclinic eutectic contains a pentafluoro-β-nitrostyrene molecule and a hexamethylbenzene molecule. The aromatic benzene ring and vinyl group of pentafluoro-β-nitrostyrene form two non-covalent π...π stacking interactions with the two adjacent hexamethylbenzene rings from both sides. The centroid distances of the two stacking interactions are 3.558(1) Å and 3.308(1) Å, respectively.

3. The method for preparing the pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic according to claim 1, characterized in that, Hexamethylbenzene was completely dissolved in anhydrous ethanol, and pentafluoro-β-nitrostyrene was added to form a mixed solution. The resulting mixed solution was cooled and allowed to stand for 32-64 hours to separate and crystallize, thus obtaining a pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic.

4. The method for preparing the pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic according to claim 1, characterized in that, Hexamethylbenzene was dissolved in isopropanol, and an ethyl acetate solution of pentafluoro-β-nitrostyrene was added to the hexamethylbenzene solution to form liquid layers. The layered solution was allowed to stand for 32-64 hours to obtain a pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic.

5. The method for preparing the pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic according to claim 1, characterized in that, Pentafluoro-β-nitrostyrene and hexamethylbenzene were dissolved in dichloromethane. The solution system was sealed and stored in an ether bath. After standing at room temperature for 32-64 hours, pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic was obtained.

6. The method for preparing the pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic according to claim 1, characterized in that, A solid-liquid mixture of hexamethylbenzene and pentafluoro-β-nitrostyrene was subjected to vacuum sublimation for 16-32 hours to obtain a powdered pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic.

7. The method for preparing pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic according to any one of claims 3 to 6, characterized in that, The molar ratio of pentafluoro-β-nitrostyrene to hexamethylbenzene is 1:

1.

8. The method for preparing pentafluoro-β-nitrostyrene·hexamethylbenzene eutectic according to claim 7, characterized in that, The preparation method of pentafluoro-β-nitrostyrene is as follows: pentafluorobenzaldehyde and nitromethane are heated and reacted in an organic solvent under normal pressure.

9. The use of the pentafluoro-β-nitrostyrene-hexamethylbenzene eutectic according to claim 1 or 2 in the preparation of antibacterial drugs.

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