A 4,4'-bipyridyl ester salt compound and its preparation method and application

Abstract

The present invention provides a 4,4'-bipyridyl ester salt compound and its preparation method and application. The following steps are included: 4,4'-bipyridyl, compound 1 and compound 2 are respectively dissolved in a solvent; the obtained solutions are mixed and the reaction is stirred at a constant temperature; after the reaction is completed, an anti-solvent is added for crystallization, suction filtration is performed, and the precipitate is collected, washed and dried to obtain a 4,4'-bipyridyl ester salt compound. Wherein, compound 1 and compound 2 respectively include one or more of methyl 2-chloroacetate, methyl 2-bromoacetate, ethyl 2-chloroacetate and ethyl 2-bromoacetate. The 4,4'-bipyridyl ester salt compound provided by the present invention has high-efficiency herbicidal performance under neutral conditions and can be used as an active substance for controlling weeds in the soil environment; in an acidic environment, it can be rapidly degraded to avoid harm to the human body. It has significant advantages such as a simple synthesis method, low production cost, high yield, and no harmful residual substances left after use, and can be used as a safe and friendly new herbicide.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and pesticides, and particularly relates to a 4,4'-bipyridyl ester salt compound and a preparation method and application thereof. Background Art

[0002] Paraquat (1,1'-dimethyl-4,4'-bipyridinium cation salt, methyl viologen ((C 12 H 14 N2) 2+ ) is a broad-spectrum, contact, non-selective herbicide. Upon entering plant cells, it mediates redox cycling and continuously produces highly cytotoxic reactive oxygen species, ultimately leading to cell death. Due to its rapid weed control, low cost, and immediate soil inactivation, it is currently registered and widely used in over 90 countries worldwide, with no alternatives currently available.

[0003] However, paraquat's extreme toxicity to humans has hindered its further development as a herbicide. Once in the body, paraquat competes with diamines and polyamines, entering tissues, particularly lung tissue, through active transport mechanisms across cell membranes. Concentrations can reach 10 to 90 times those in plasma, ultimately causing severe damage to multiple organs and irreversible pulmonary fibrosis. Precisely due to paraquat's safety concerns, as of 2020, over 20 countries, including China, have strictly restricted or banned its use.

[0004] Therefore, the development of paraquat-derivative herbicides that are non-toxic to humans but still effective in killing weeds is a current research focus. Ingestion and gastric absorption are the primary modes of paraquat poisoning in humans. Given the extremely acidic nature of gastric acid (the pH of pure gastric juice is between 0.9 and 1.5), developing paraquat-derivative herbicides that can undergo acid-responsive degradation to reduce or even eliminate toxicity would effectively lower the mortality rate following ingestion.

[0005] In summary, the development of paraquat derivatives that are stable and have herbicidal activity under neutral conditions but degrade into attenuated or even non-toxic substances in the acidic environment of gastric acid has important research and application value. Summary of the Invention

[0006] The present invention aims to provide a 4,4'-bipyridyl ester salt compound, which has many advantages such as good herbicidal effect, low production cost, simple synthesis process and safety to humans, and has broad application prospects.

[0007] To achieve the above objectives, the present invention provides a 4,4'-bipyridyl ester salt compound comprising the general structural formula shown in Formula I:

[0008]

[0009] Wherein, X is any one of F, Cl, Br, and I, n1 and n2 are both not greater than 6, and R1 and R2 are any alkanes with a carbon number not greater than 6.

[0010] Another object of the present invention is to provide a method for preparing a 4,4'-bipyridyl ester salt compound, comprising the following steps: dissolving 4,4'-bipyridyl, compound 1 and compound 2 in a solvent respectively; mixing the obtained solutions and stirring the mixture at a constant temperature for reaction; after the reaction is completed, adding an excess anti-solvent to the reactants for crystallization at room temperature, filtering, collecting the precipitate, washing and drying to obtain a 4,4'-bipyridyl ester salt compound.

[0011] The synthetic route of the 4,4'-bipyridyl ester salt compound of the present invention is shown in Formula II:

[0012]

[0013] In a preferred embodiment, the compound 1 and compound 2 respectively include one or more of methyl 2-chloroacetate, methyl 2-bromoacetate, ethyl 2-chloroacetate and ethyl 2-bromoacetate; more preferably, the compound 1 and compound 2 are the same substance.

[0014] In a preferred embodiment, the mass ratio of the 4,4'-bipyridine, compound 1 and compound 2 is 1:(1-4):(1-4); more preferably, the compound 1 and compound 2 are the same substance with the same mass.

[0015] In a preferred embodiment, the mass volume ratio of the 4,4'-bipyridine to the solvent is 1g:(2-10)ml; the mass volume ratio of the compound 1 to the solvent is 1g:(1-5)ml; the mass volume ratio of the compound 2 to the solvent is 1g:(1-5)ml; more preferably, the mass volume ratio of the compound 1 to the solvent is the same as the mass volume ratio of the compound 2 to the solvent.

[0016] In a preferred embodiment, the solvent includes one or more of methanol, ethanol, isopropanol, acetonitrile, acetone and chloroform; more preferably, the solvent used for the 4,4'-bipyridine, compound 1 and compound 2 is the same substance.

[0017] In a preferred embodiment, the constant temperature stirring reaction conditions are: constant temperature of 20-80° C., stirring rate of 200-1000 rpm, and reaction time of 3-72 h.

[0018] In a preferred embodiment, the anti-solvent includes one or more of dichloromethane, ethyl ether, hexane, petroleum ether, and cyclohexane.

[0019] In a preferred embodiment, the washing method is washing with diethyl ether 2-4 times; the drying method can adopt conventional methods known to those skilled in the art, such as vacuum drying.

[0020] Another object of the present invention is to provide an application of a 4,4'-bipyridyl ester salt compound, specifically comprising: the 4,4'-bipyridyl ester salt compound has a highly effective herbicidal property in a neutral environment and can be used as an active substance to control weeds in a soil environment;

[0021] The 4,4'-bipyridyl ester salt compound can be completely degraded in an acidic environment to avoid causing harm to the human body.

[0022] In a preferred embodiment, the soil environment includes one or more of fields, orchards, and grasslands.

[0023] In a preferred embodiment, the weeds include perennial and annual weeds.

[0024] In a preferred embodiment, the acidic environment has a pH below 6.0; more preferably, when the pH of the acidic environment is 2.0, the 4,4'-bipyridyl ester salt compound can be completely degraded within 8 hours.

[0025] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0026] 1. Compared with the traditional herbicide paraquat, the 4,4'-bipyridyl ester salt compound provided by the present invention has both high-efficiency herbicidal performance and acidic hydrolysis performance. After being ingested by the human body, the acidic gastric juice can promote its full degradation, which is highly safe for the human body and avoids harm to the human body after accidental ingestion. Therefore, it is a safe and friendly new herbicide.

[0027] 2. The 4,4'-bipyridyl ester salt compounds provided by the present invention also have significant advantages such as simple synthesis method, low production cost, high yield, and no harmful residual substances left after use. They help maintain the health of soil and water resources, thereby achieving green, environmentally friendly and sustainable agricultural development. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] These and / or other aspects and advantages of the present invention will become more apparent and more readily understood from the following detailed description of embodiments of the present invention in conjunction with the accompanying drawings, in which:

[0029] Figure 1 The 4,4'-bipyridyl ester salt prepared in Example 1 of the present invention 1 H NMR spectra;

[0030] Figure 2The hydrolysis of 4,4'-bipyridyl ester salt prepared in Example 1 of the present invention in simulated gastric acid conditions 1 H NMR spectra;

[0031] Figure 3 This is a UV-Vis graph of the hydrolysis of 4,4'-bipyridyl ester salt prepared in Example 1 of the present invention under simulated gastric acid conditions;

[0032] Figure 4 This is a graph showing the weight changes of mice after feeding the 4,4'-bipyridyl ester salt prepared in Example 1 of the present invention before and after hydrolysis;

[0033] Figure 5 This is a diagram showing the weed control effect of the 4,4'-bipyridyl ester salt prepared in Example 1 of the present invention before and after hydrolysis. DETAILED DESCRIPTION

[0034] In order to enable those skilled in the art to better understand the present invention, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments. However, it should be understood that the protection scope of the present invention is not limited to the specific embodiments.

[0035] The embodiments of the present invention provide a 4,4'-bipyridyl ester salt compound and its preparation method and application, thereby solving the technical problem that traditional high-efficiency herbicides are extremely toxic to humans, which hinders their widespread application in the prior art.

[0036] The technical solution of this application is described in detail below through specific embodiments:

[0037] The present invention provides a 4,4'-bipyridyl ester salt compound comprising the general structural formula shown in Formula I:

[0038]

[0039] Wherein, X is any one of F, Cl, Br, and I, n1 and n2 are both not greater than 6, and R1 and R2 are any alkanes with a carbon number not greater than 6.

[0040] Unless otherwise specified, the technical means used in the present invention are conventional means well known to those skilled in the art. The various raw materials, reagents, instruments, and equipment used in the present invention can be purchased from the market or prepared by existing methods. Unless otherwise specified, the reagents used in the present invention are of analytical grade.

[0041] Example 1

[0042] In this example, 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridine]-1,1'-diimine bromide (wherein R1=R2=-CH3, n1=n2=1) was prepared. The specific steps are as follows:

[0043] 1.56 g (10.0 mmol) of 4,4'-bipyridine was dissolved in 10.0 mL of methanol and then added to a methanol (10.0 mL) solution containing 4.59 g (30.0 mmol) of methyl 2-bromoacetate. The mixture was heated to 50°C and stirred (600 rpm) for 24 h. After the reaction, 20.0 mL of diethyl ether was added to precipitate the product. The precipitate was filtered and washed three times with diethyl ether. The precipitate was vacuum dried to obtain 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridine]-1,1'-diimine bromide, weighing 3.92 g. The yield was calculated to be 84.8%.

[0044] The specific synthetic route is:

[0045]

[0046] The target compound of this example was characterized by nuclear magnetic resonance, and the results are as follows ( Figure 1 ):

[0047] 1 H NMR (400MHz, D2O, δppm): 9.01 (d, 4H), 8.53 (d, 4H), 5.61 (s, 4H), 3.76 (s, 6H).

[0048] Example 2

[0049] In this example, 1,1'-bis(2-ethoxy-2-oxyethyl)-[4,4'-bipyridine]-1,1'-diimine bromide (wherein R1=R2=-CH2CH3, n1=n2=1) was prepared. The specific steps are as follows:

[0050] 1.56 g (10.0 mmol) of 4,4'-bipyridine was dissolved in 10.0 mL of ethanol and added to an ethanol (10.0 mL) solution containing 5.01 g (30.0 mmol) of ethyl 2-bromoacetate under stirring at 600 rpm. The mixture was heated to 50°C and stirred for 24 h. After the reaction, 20.0 mL of diethyl ether was added to precipitate the product. The precipitate was filtered and then washed three times with diethyl ether. The precipitate was dried under vacuum to obtain 1,1'-bis(2-ethoxy-2-oxoethyl)-[4,4'-bipyridine]-1,1'-diimine bromide, weighing 4.28 g. The yield was calculated to be 87.3%.

[0051] The specific synthetic route is:

[0052]

[0053] The target compound of this example was characterized by nuclear magnetic resonance, and the results are as follows:

[0054] 1H NMR (400MHz, D2O, δppm): 9.01 (d, 4H), 8.53 (d, 4H), 5.59 (s, 4H), 4.20 (q, 4H), 1.18 (t, 6H).

[0055] Effect Example 1

[0056] This embodiment uses 1 The hydrolysis kinetics of 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridine]-1,1'-diimine bromide prepared in Example 1 was tested by H NMR. The specific steps are as follows:

[0057] Dissolve 5.0 mg of 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridyl]-1,1'-diimine bromide in D2O, add phosphate buffer solution (PBS) to adjust the pH to 2.0, and measure the pH every 1 hour. 1 H NMR spectrum, measured for 8 hours, Figure 2 As can be seen from the figure, as the hydrolysis proceeds, the methyl peak (δ = 4.20 ppm) continuously moves to the high field until it almost disappears, indicating that in an acidic environment, the ester salt can be almost completely hydrolyzed to 1,1'-dicarboxymethyl-4,4'-bipyridinium bromide within 8 h.

[0058] Effect Example 2

[0059] This example uses UV-Vis to test the hydrolysis kinetics of 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridine]-1,1'-diimine bromide prepared in Example 1. The specific steps are as follows:

[0060] Dissolve 2.31 mg (5.0 μmol) of 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridyl]-1,1'-diimine bromide in an appropriate amount of PBS and adjust the solution to pH 2.0. After dissolution, use a glass rod to drain and transfer to a 100.0 mL volumetric flask. Wash the inner wall of the beaker with PBS 2 to 3 times, and transfer all the washings to the volumetric flask. After the volume is fixed, transfer an appropriate amount of the solution to a cuvette. Control the reaction temperature at 37°C and measure its UV-Vis spectrum every 1 hour for 8 hours. Figure 3 As can be seen from the figure, the maximum absorption wavelength of the pure substance before hydrolysis is 268nm, and the maximum absorption wavelength of the pure substance after hydrolysis is 282nm. As the hydrolysis progresses, the maximum absorption wavelength continuously red-shifts to a nearly constant value, indicating that in an acidic environment, the ester salt can be almost completely hydrolyzed to 1,1'-dicarboxymethyl-4,4'-bipyridinium bromide within 8 hours.

[0061] Effect Example 3

[0062] This example uses the biosafety of 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridine]-1,1'-diimine bromide prepared in Test Example 1. The specific steps are as follows:

[0063] 60.0 mg of 1,1'-bis(2-methoxy-2-oxoethyl)-[4,4'-bipyridyl]-1,1'-diimine bromide (ester group), 1,1'-dicarboxymethyl-4,4'-bipyridyl bromide (hydrolysis group), and 1,1'-dimethyl-4,4'-bipyridyl bromide (paraquat group) were dissolved in 5.0 mL of water, and 0.50 mL of each solution was administered orally to 15 different BALB / c mice (three groups, five mice in each group, mice weighing approximately 20 g, and the administration concentration was 300.0 mg / kg) after fasting for 10 h. Another 0.50 mL of deionized water was administered orally to five mice (control group). The survival rate and body weight of the mice in the four groups were recorded.

[0064] Two mice in the paraquat group died on the third day, and one each on the fourth, seventh, and ninth days. The mice in the other groups survived for more than 30 days. Their weight data are shown in the attached table. Figure 4 As shown, the ester group is very safe for mice.

[0065] Effect Example 4

[0066] In this example, toxicity tests were conducted on 1,1'-bis(2-methoxy-2-oxyethyl)-[4,4'-bipyridine]-1,1'-diimine bromide prepared in Example 1 and 1,1'-bis(2-ethoxy-2-oxyethyl)-[4,4'-bipyridine]-1,1'-diimine bromide prepared in Example 2. The specific steps are as follows:

[0067] (1) 3.0 g of each of 1,1'-bis(2-methoxy-2-oxyethyl)-[4,4'-bipyridine]-1,1'-diimine bromide (ester salt 1) and 1,1'-bis(2-ethoxy-2-oxyethyl)-[4,4'-bipyridine]-1,1'-diimine bromide (ester salt 2), as well as 1,1'-dicarboxymethyl-4,4'-bipyridine bromide (hydrolyzed group) generated by complete hydrolysis of ester salt 1 in an acidic environment at pH = 2.0, and paraquat were dissolved in 1.0 L of deionized water to prepare samples with an active ingredient of 3.0 g / L.

[0068] (2) Add equal amounts of the surfactant Triton-100 to the four groups of samples in step 1), shake well, ultrasonicate for 5 minutes, and evenly disperse the mixture into three small spray bottles.

[0069] (3) Take four pots of well-growing ryegrass and evenly spray the four groups of samples prepared in step 2) into them. Use plant light for 8 hours every day (lux = 7000) and take pictures to record the growth status of the plants. Figure 5 shown.

[0070] As shown in Examples 1-4, the 4,4'-bipyridyl ester salt provided by the present invention exhibits significant herbicidal efficacy comparable to paraquat under neutral conditions, while rapidly hydrolyzing in acidic environments, thus preventing harm to the body. Furthermore, animal experiments have also demonstrated the high safety of the 4,4'-bipyridyl ester salt provided by the present invention after hydrolysis. Therefore, it can be widely used as an active substance in the field of soil weed control.

[0071] The foregoing descriptions of specific exemplary embodiments of the present invention are for purposes of illustration and description. These descriptions are not intended to limit the invention to the precise forms disclosed, and it is apparent that many variations and modifications are possible in light of the foregoing teachings. The exemplary embodiments have been selected and described for the purpose of explaining the specific principles of the invention and their practical application, thereby enabling those skilled in the art to realize and utilize a variety of exemplary embodiments of the invention and various options and modifications. The scope of the invention is intended to be defined by the claims and their equivalents.

Claims

1. An application of a 4,4'-bipyridyl ester salt compound, characterized in that: The 4,4'-bipyridyl ester salt compound is used to control weeds in a soil environment in a neutral environment. In an acidic environment with a pH of 2.0, the 4,4'-bipyridyl ester salt compound can be completely degraded within 8 hours. The 4,4'-bipyridyl ester salt compound includes the general structural formula shown in Formula I: wherein X is any one of F, Cl, Br, and I, n1 and n2 are both not greater than 6, and R1 and R2 are any alkanes with a carbon number not greater than 6; The soil environment includes one or more of fields, orchards, and grasslands; The weeds include perennial and annual weeds; The 4,4'-bipyridyl ester salt compound is prepared by the following method: 4,4'-bipyridyl, compound 1 and compound 2 are dissolved in a solvent respectively; the obtained solutions are mixed and stirred at a constant temperature for reaction; after the reaction, an anti-solvent is added to the reactants for crystallization, filtered, and the precipitate is collected, washed and dried to obtain the 4,4'-bipyridyl ester salt compound; The compounds 1 and 2 respectively include one or more of methyl 2-chloroacetate, methyl 2-bromoacetate, ethyl 2-chloroacetate and ethyl 2-bromoacetate; the solvent includes one or more of methanol, ethanol, isopropanol, acetonitrile, acetone and chloroform; the anti-solvent includes one or more of dichloromethane, ether, hexane, petroleum ether and cyclohexane; The mass ratio of the 4,4'-bipyridine, compound 1 and compound 2 is 1:(1-4):(1-4); The mass volume ratios of the 4,4'-bipyridine, compound 1 and compound 2 to the solvent are 1 g:(2-10) ml, 1 g:(1-5) ml and 1 g:(1-5) ml respectively.

2. The use of the 4,4'-bipyridyl ester salt compound according to claim 1, wherein The constant temperature stirring reaction conditions are: constant temperature of 20-80° C., stirring rate of 200-1000 rpm, and reaction time of 3-72 h.

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