Preparation method and application of 2,4-di-tert-butylphenol-betaine eutectic

Abstract

The present invention is applicable to the field of agricultural production technology, and provides a preparation method and application of a 2,4-di-tert-butylphenol-betaine eutectic. The present invention adopts a eutectic strategy through crystal engineering technology, significantly improves the thermal stability and solubility of 2,4-di-tert-butylphenol, and reduces its volatility. The 2,4-di-tert-butylphenol-betaine eutectic synthesized by the present invention, compared with 2,4-di-tert-butylphenol, significantly improves the growth inhibition of farmland weeds such as ryegrass, foxtail grass, water barnyard grass, purslane, Amaranthus retroflexus and Bidens pilosa, showing great potential in the long-term inhibition of agricultural weeds. In addition, 2,4-di-tert-butylphenol and betaine are both natural source ingredients, environmentally friendly and low cost. At the same time, the present invention effectively reduces the amount of organic solvent used by grinding-induced self-assembly method, further reduces production costs, and thus improves the feasibility of developing it into a commercial product.

Description

Technical Field

[0001] The invention belongs to the technical field of agricultural production, and in particular relates to a preparation method and application of a 2,4-di-tert-butylphenol-betaine eutectic. Background Art

[0002] Weeds have long posed a serious threat to crop yield and quality, and chemical herbicides have been widely used and achieved remarkable results. However, in order to cope with the increasingly serious problem of resistant weeds and a series of environmental challenges, it is necessary to explore new weed control strategies. Allelopathic inhibition among plants has the potential to be developed into an efficient and environmentally friendly strategy in the field of weed control. By utilizing secondary metabolites secreted by specific plants, weed growth and development can be inhibited.

[0003] 2,4-di-tert-butylphenol is a natural small molecule compound derived from a variety of plants. It has plant allelopathic effects and herbicidal effects. It has excellent allelopathic inhibitory activity on seed germination and seedling growth of various weeds such as barnyard grass, so it is regarded as an ideal alternative to traditional chemical herbicides. However, the low thermal stability, high volatility and poor water solubility of 2,4-di-tert-butylphenol limit its practical application. At present, there are no research reports on the application formulation of 2,4-di-tert-butylphenol.

[0004] Cocrystals are solid complexes formed by the self-assembly of active pharmaceutical ingredients (API) and suitable cocrystal formers (CCF) in stoichiometric ratios under specific conditions based on supramolecular chemistry principles. They present supramolecular structures with the help of hydrogen bonds or other non-covalent interactions, thereby converting low-melting point compounds into stable crystalline forms. In recent years, cocrystal systems based on plant essential oils and their active ingredients have attracted the interest of researchers. Compared with single active ingredients, cocrystals have the advantages of excellent thermal stability, controllable release rate and high solubility.

[0005] Based on the above background, the present invention proposes a preparation method and application of 2,4-di-tert-butylphenol-betaine co-crystal. Summary of the invention

[0006] The object of the present invention is to provide a preparation method and application of 2,4-di-tert-butylphenol-betaine co-crystal, aiming to solve the problems raised in the above background technology.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] A method for preparing a 2,4-di-tert-butylphenol-betaine eutectic comprises the following steps:

[0009] Weigh 2,4-di-tert-butylphenol and betaine, put them in an agate mortar and grind them until the mixture is in a uniform white powder state; transfer the ground mixture to a conical flask, slowly add a methanol-dichloromethane mixed solution until the solid is completely dissolved; seal the bottle mouth with plastic wrap, poke small holes in the plastic wrap, place the conical flask in a fume hood, and wait for the solvent to slowly evaporate to obtain a single crystal of 2,4-di-tert-butylphenol-betaine eutectic.

[0010] Furthermore, the molar ratio of 2,4-di-tert-butylphenol to betaine is 2:1.

[0011] Furthermore, in the step of placing in an agate mortar and grinding, the grinding time is 15 min.

[0012] Furthermore, the methanol-dichloromethane mixed solution consists of methanol and dichloromethane in a volume ratio of 1:1.

[0013] A use of the 2,4-di-tert-butylphenol-betaine co-crystal prepared according to the above-mentioned preparation method of the 2,4-di-tert-butylphenol-betaine co-crystal as a weed inhibitor in inhibiting weed growth.

[0014] Furthermore, the weeds are ryegrass, foxtail grass, water barnyard grass, purslane, Amaranthus retroflexus and Bidens pilosa.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] 1. The present invention adopts a co-crystallization strategy through crystal engineering technology to significantly improve the thermal stability and solubility of the natural active ingredient 2,4-di-tert-butylphenol and reduce its volatility.

[0017] 2. The present invention synthesizes 2,4-di-tert-butylphenol-betaine eutectic, which significantly improves the growth inhibition effect on farmland weeds such as ryegrass, Setaria viridis, Echinochloa crus-galli, Portulaca oleracea, Amaranthus retroflexus and Bidens pilosa, compared with 2,4-di-tert-butylphenol, showing great potential in the long-term inhibition of agricultural weeds.

[0018] 3. The 2,4-di-tert-butylphenol and betaine used in the present invention are both natural ingredients, and the prepared co-crystals reduce the risks to the agricultural environment and human health. In addition, these two ingredients have been industrialized and have low material costs. At the same time, the present invention effectively reduces the amount of organic solvents used through the grinding-induced self-assembly method, further reduces production costs, and thus improves the feasibility of developing it into a commercial product. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1It is a single crystal state of 2,4-di-tert-butylphenol-betaine cocrystal.

[0020] Figure 2 This is the powder X-ray diffraction pattern of 2,4-di-tert-butylphenol-betaine co-crystal.

[0021] Figure 3 Single crystal X-ray diffraction characterization of 2,4-di-tert-butylphenol-betaine co-crystal; (a) is the molecular assembly in the co-crystal (the molar ratio of 2,4-di-tert-butylphenol molecules to betaine molecules is 2:1), and (b) is the unit cell structure along the a direction of the co-crystal.

[0022] Figure 4 Thermogravimetric and differential scanning calorimetric analyses of 2,4-di-tert-butylphenol and 2,4-di-tert-butylphenol-betaine co-crystals; wherein (a) is the thermogravimetric and differential scanning calorimetric analysis of 2,4-di-tert-butylphenol, and (b) is the thermogravimetric and differential scanning calorimetric analysis of 2,4-di-tert-butylphenol-betaine co-crystals. DETAILED DESCRIPTION

[0023] In order to have a clearer understanding of the technical features, purposes and beneficial effects of the present invention, the technical solution of the present invention is now described in detail below, but it should not be construed as limiting the applicable scope of the present invention.

[0024] The specific implementation of the present invention is described in detail below in conjunction with specific embodiments.

[0025] Example 1, preparation of 2,4-di-tert-butylphenol-betaine eutectic;

[0026] Method 1: Weigh 2,4-di-tert-butylphenol (4.12 g, 0.02 mol) and betaine (1.17 g, 0.01 mol), place in an agate mortar, and grind for about 15 min until the mixture is in a uniform white powder state. Transfer the ground mixture to a conical flask, slowly add a methanol-dichloromethane mixed solution (v / v, 1:1) until the solid is completely dissolved, seal the bottle mouth with plastic wrap, pierce several small holes, and place in a fume hood. After the solvent slowly evaporates, the single crystal state of 2,4-di-tert-butylphenol-betaine cocrystal is obtained, which appears as colorless needle-shaped crystals ( Figure 1 ).

[0027] Method 2: Weigh 2,4-di-tert-butylphenol (105 mg, 0.02 mol) and dissolve it in dimethyl sulfoxide, and weigh betaine (167 mg, 0.01 mol) and dissolve it in methanol. Then mix the two solutions and stir the solution at a constant temperature (60°C) for 20 minutes. After stopping stirring, cool the system to room temperature and let the solution evaporate slowly. After about 20 days, a single crystal of 2,4-di-tert-butylphenol-betaine cocrystal is obtained, showing colorless needle-shaped crystals ( Figure 1 ).

[0028] Example 2, Characterization of the 2,4-di-tert-butylphenol-betaine co-crystal in Example 1;

[0029] 1) Powder X-ray diffraction characterization: Data were collected at room temperature using a BV Empyrean diffractometer with a copper target (λ = 1.54178 Å) at 40 kV and 100 mA, with a scan speed of 5° min -1 , the test range is 1.5°≤ 2θ ≤ 50°. In order to mitigate low-angle scattering, a beam blocker and anti-scattering air components are used. The test results are shown in Figure 2 As shown, the powder X-ray diffraction pattern shows that the 2,4-di-tert-butylphenol-betaine co-crystal has a diffraction angle of 2 θ There are significant characteristic peaks at values ​​of 5.2, 10.3, 12.9, 20.8 and 26.4.

[0030] 2) Single crystal X-ray diffraction characterization: Single crystal diffraction data were collected at room temperature using a SMART APEX2 diffractometer with a molybdenum target (λ = 0.71073 Å) radiation. Lorentz polarization and absorption correction were used during data collection. Data restoration was performed using APEX v3 software. The energy of the beam was set to 0.700 Å. The maximum full width at half maximum (FWHM) of the beam was 2.0 × 0.37 mm. 2 , photon flux is 1012-1013 ph s -1 . Diffraction intensities were collected by a Pilatus 2M detector and processed using XDS software. The crystal structure was directly analyzed using SHELXT and refined using the SHELXL tool in Olex2 using full-matrix least-squares methods, using anisotropic thermal shift parameters for all non-hydrogen atoms. Hydrogen bond parameters were generated by PLATON. Co-crystal data are shown in Table 1:

[0031] Table 1 Parameters of 2,4-di-tert-butylphenol-betaine cocrystal

[0032] wavelength 0.71073 Å Unit Cell a=12.037(6) Å α=111.631(12)° b=17.030(6) Å β=93.863(14)° c=18.569(7) Å γ=98.212(14)° temperature 275 K volume <![CDATA[3472(3) Å 3 ]]> Space group P-1 Overall molecular formula <![CDATA[C 33 H 55 NO 4 ]]> Number of molecules contained 4 Number of electrons 1168 Density (calculated) <![CDATA[1.013 mg / m 3 ]]> Absorption coefficient <![CDATA[0.065 mm -1 ]]> Diffraction index (h, k, l) range 14,20,22 Collecting diffraction points 12628 Maximum and minimum spectral transmittance 0.278，0.746 Maximum incident angle 25.35° Correction method T limits Data integrity 0.991 R value (all data) R = 0.1044, wR2 = 0.3314

[0033] The crystal structure obtained by analysis is as follows Figure 3As shown in (a) and (b), it can be seen that the molar ratio of 2,4-di-tert-butylphenol molecules to betaine molecules in the co-crystal is 2:1.

[0034] Example 3, thermal stability and volatility test of 2,4-di-tert-butylphenol-betaine co-crystal;

[0035] The melting point and thermal stability of 2,4-di-tert-butylphenol-betaine cocrystals were analyzed by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The experiment used a TA Q20 differential scanning calorimeter for data acquisition, and the equipment was calibrated with standard indium and zinc before use. In the experiment, a small amount of sample (5-10 mg) was placed in a pinhole sealed aluminum pan and heated at 10 ° C min in a nitrogen environment. -1 The heating was performed at a scanning rate of 1.5 ℃ / min. An empty pinhole pan was used as a reference. The data were analyzed by Stare software. In addition, the thermogravimetric analysis was performed on a Pyris TGA system. 10 mg of sample was placed in a standard alumina crucible and heated at 5 °C / min under nitrogen. -1 The scanning rate was heated from 30 ℃ to 300 ℃. The test results are shown in Figure 4 The results show that the melting point of 2,4-di-tert-butylphenol is 54.5°C, and it is completely volatilized when the temperature reaches 187.5°C; while the melting point of 2,4-di-tert-butylphenol-betaine eutectic increases to 137.6°C, and when the temperature reaches 200°C, its volatilization amount is only 65%.

[0036] Example 4, solubility test of 2,4-di-tert-butylphenol-betaine co-crystal;

[0037] The equilibrium solubility of 2,4-di-tert-butylphenol and 2,4-di-tert-butylphenol-betaine cocrystals was measured by the shake bottle method. In the experiment, excess 2,4-di-tert-butylphenol and 2,4-di-tert-butylphenol-betaine cocrystals were dissolved in distilled deionized water at 25°C, and the suspension was allowed to settle after shaking for 2 hours. The supernatant was filtered with a 0.45 μm polytetrafluoroethylene syringe filter, and then the 2,4-di-tert-butylphenol content in the supernatant was detected by high performance liquid chromatography. The solubility test results are shown in Table 2:

[0038] Table 2 Equilibrium solubility of 2,4-di-tert-butylphenol and 2,4-di-tert-butylphenol-betaine cocrystals

[0039] sample Solubility 2,4-Di-tert-butylphenol 0.029 g / L 2,4-Di-tert-butylphenol-betaine cocrystal 0.185 g / L

[0040] It can be seen from the data in Table 2 that the solubility of 2,4-di-tert-butylphenol in pure water is significantly improved by co-crystallization with betaine.

[0041] Example 5, allelopathic activity test of 2,4-di-tert-butylphenol-betaine co-crystal;

[0042] Seed germination inhibition rate test: Set the concentration gradient of the sample to be tested to 0.25, 0.50, 1.00, 2.00, 4.00, and 8.00 mg / mL. Weigh 0.50 g of the compound, dissolve it in 5 mL of ethanol, and prepare a 0.10 g / mL mother solution for use. Spread a 9 cm sterile filter paper in a 9 cm sterile culture dish, add 5 mL of sterile distilled water, and then add 1.25, 2.5, 5, 10, 20, and 40 µL of the mother solution in turn and mix well. Use the same volume of sterile distilled water as a negative control, and repeat each treatment three times. Add 30 seeds to each culture dish and seal it. After a period of cultivation, observe and record the germination of the seeds. The effects of 2,4-di-tert-butylphenol-betaine cocrystals on the germination of different seeds are shown in Table 3:

[0043] Table 3 Seed germination rates of different weeds treated with 2,4-di-tert-butylphenol and 2,4-di-tert-butylphenol-betaine co-crystals

[0044] Ryegrass Setaria Echinochloa crusgalli purslane Amaranthus retroflexus ghost needle grass 2,4-Di-tert-butylphenol 55.0% 56.7% 78.3% 85.0% 41.7% 23.3% 2,4-Di-tert-butylphenol-betaine cocrystal 12.3% 9.6% 14.3% 21.7% 8.6% 4.4%

[0045] *Note: The application concentration is 0.5 mg / mL.

[0046] From the data in Table 3, it can be seen that compared with 2,4-di-tert-butylphenol alone, 2,4-di-tert-butylphenol-betaine co-crystals exhibit more significant phytotoxic effects, and can significantly increase the seed germination inhibition rate of farmland weeds such as ryegrass. Therefore, the co-crystal can be used as a potential agricultural weed inhibitor.

[0047] The above are only preferred embodiments of the present invention. It should be pointed out that, for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention. These should also be regarded as the protection scope of the present invention. These will not affect the effect of the implementation of the present invention and the practicality of the patent.

Claims

1. A method for preparing a 2,4-di-tert-butylphenol-betaine eutectic, characterized in that: The following steps are involved: Weigh 2,4-di-tert-butylphenol and betaine, put them in an agate mortar and grind them until the mixture is in a uniform white powder state; transfer the ground mixture to a conical flask, slowly add a methanol-dichloromethane mixed solution until the solid is completely dissolved; seal the bottle mouth with plastic wrap, poke small holes in the plastic wrap, place the conical flask in a fume hood, and wait for the solvent to slowly evaporate to obtain a single crystal of 2,4-di-tert-butylphenol-betaine eutectic.

2. The method for preparing the 2,4-di-tert-butylphenol-betaine eutectic according to claim 1, characterized in that: The molar ratio of the 2,4-di-tert-butylphenol to betaine is 2:

1.

3. The method for preparing the 2,4-di-tert-butylphenol-betaine eutectic according to claim 1, characterized in that: In the step of placing in an agate mortar and grinding, the grinding time is 15 min.

4. The method for preparing the 2,4-di-tert-butylphenol-betaine eutectic according to claim 1, characterized in that: The methanol-dichloromethane mixed solution consists of methanol and dichloromethane in a volume ratio of 1:

1.

5. Use of 2,4-di-tert-butylphenol-betaine co-crystal prepared by the preparation method of 2,4-di-tert-butylphenol-betaine co-crystal according to any one of claims 1 to 4 as a weed inhibitor in inhibiting weed growth, characterized in that: The weeds are ryegrass, foxtail grass, water barnyard grass, purslane, Amaranthus retroflexus and Bidens pilosa.

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