Polyether-modified amphiphilic carboxylic acid derivatives and their use in nano-pesticides

Abstract

The present application relates to the field of organic synthesis and fine chemical technology, and particularly relates to a polyether modified amphiphilic carboxylic acid derivative and application thereof in nano pesticide. The polyether modified amphiphilic carboxylic acid derivative provided by the present application can be used to prepare a completely water-based polyoxin nano preparation without using any organic solvent. After being diluted with water, the preparation can form a transparent nanoscale dispersion liquid, and is sprayed after being diluted with water according to a recommended use amount. Since no organic solvent is involved in the preparation and use process, the human health hidden danger is effectively reduced, and the ecological environment pressure is also reduced.

Description

Technical Field

[0001] This invention relates to the fields of organic synthesis and fine chemical technology, and in particular to the design and synthesis of a polyether-modified amphiphilic carboxylic acid derivative and its application in water-based nanopesticide formulations. Background Technology

[0002] Pesticides, as essential production materials for ensuring grain yield, are indispensable key inputs in agricultural production. Pesticide formulations affect the transport efficiency and biological activity of active ingredients by regulating drug delivery pathways, and are closely related to pesticide utilization, pesticide environmental behavior characteristics, and biosafety effects.

[0003] Spinosad is a natural macrolide biological pesticide found in actinomycetes. Saccharopolyspora spinosa It is extracted from the culture broth produced during fermentation. Due to its natural source and low toxicity, it has been widely used to control pests on field crops and vegetable crops, showing significant control effects against lepidopteran insects, thrips, and diamondback moths. Among commercially available spinosad formulations, the most common is the water suspension. This formulation requires prolonged mechanical grinding to ensure that the spinosad particles are uniformly dispersed in water under the combined action of various adjuvants such as wetting agents and dispersants, thus forming a stable suspension. The pesticide particles in the suspension are typically 1–5 μm in size. These large particles cannot effectively deposit the active ingredient in the target area, resulting in the loss of most of the active ingredient during application. Statistics show that the effective utilization rate of traditional pesticide formulations is less than 0.1%. Therefore, current spinosad formulations face the problems of complex preparation processes and low utilization rates of the active ingredient.

[0004] Nanopesticide formulations offer a promising approach to formulation optimization. The nanosize effect helps enhance pesticide foliar penetration and resistance to photodegradation, thereby improving pesticide utilization and reducing the environmental and human health risks associated with pesticide preparation and application. However, preparing fully water-based nanoformulations without the use of any organic solvents remains a technological challenge. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide a design and synthesis of polyether-modified amphiphilic carboxylic acid derivatives and their application in water-based nanopesticide formulations. The polyether-modified amphiphilic carboxylic acid derivatives provided by this invention can prepare fully water-based spinosad nanoparticle formulations without the use of any organic solvents.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a polyether-modified amphiphilic carboxylic acid derivative having the structure shown in Formula 1:

[0008] Formula 1.

[0009] The application provides a synthesis method of the polyether-modified amphiphilic carboxylic acid derivative.

[0010] The alcohol ether compound having the structure shown in Formula 2 is mixed with maleic anhydride to perform an esterification reaction, so that the polyether-modified amphiphilic carboxylic acid derivative is obtained.

[0011] Formula 2.

[0012] Preferably, the mass ratio of the alcohol ether compound to maleic anhydride is 2.0-2.5:1.

[0013] Preferably, the esterification reaction is performed at a temperature of 90-95 DEG C for more than 3 hours.

[0014] The application provides an application of the polyether-modified amphiphilic carboxylic acid derivative as a surfactant in preparation of a water-based nano pesticide preparation.

[0015] The application provides a polyfenarimol water-based nano preparation, which comprises water, polyfenarimol and the polyether-modified amphiphilic carboxylic acid derivative.

[0016] Preferably, the mass content of the polyether-modified amphiphilic carboxylic acid derivative in the polyfenarimol water-based nano preparation is 4-5%.

[0017] Preferably, the mass content of the polyfenarimol in the polyfenarimol water-based nano preparation is 4-5%.

[0018] Preferably, the average particle size of the polyfenarimol water-based nano preparation is 45.61+0.5 nm.

[0019] The application provides a preparation method of the polyfenarimol water-based nano preparation, which comprises the following steps: mixing and stirring polyfenarimol, the polyether-modified amphiphilic carboxylic acid derivative and water to obtain the polyfenarimol water-based nano preparation.

[0020] The present application provides a polyether modified amphiphilic carboxylic acid derivative with the structure shown in formula 1. The polyether modified amphiphilic carboxylic acid derivative and the polyoxin are stirred in water at room temperature, and a stable polyoxin water-based nano preparation is obtained in a high-efficiency and environmentally friendly manner without using any organic solvent. The polyether modified amphiphilic carboxylic acid derivative has abundant hydrophilic groups (such as carboxyl groups and ether bonds) and self-assembly properties, which enable it to form a stable small-size assembly structure in the interfacial bending process. By simple stirring at room temperature, the polyether modified amphiphilic carboxylic acid derivative can interact with the polyoxin to realize high-efficiency self-assembly, thereby effectively dispersing the polyoxin into a nano state in water to form a transparent polyoxin water-based nano delivery system.

[0021] The present application provides a water-based nano pesticide preparation, which can form a transparent nanoscale dispersion liquid after being diluted with water, and is convenient to use after being diluted with water according to the recommended use amount, thereby effectively reducing the hidden danger to human health and relieving the pressure on the ecological environment. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 Flow chart for preparing the polyether modified amphiphilic carboxylic acid derivative of Example 1;

[0023] Figure 2 NMR hydrogen spectrum of the polyether modified amphiphilic carboxylic acid derivative prepared in Example 1;

[0024] Figure 3 Infrared spectrum of the polyether modified amphiphilic carboxylic acid derivative prepared in Example 1;

[0025] Figure 4 Scanning electron microscope image of the polyoxin water-based nano preparation;

[0026] Figure 5 Atomic force microscope image of the polyoxin water-based nano preparation;

[0027] Figure 6 Particle size distribution graph of the polyoxin water-based nano preparation;

[0028] Figure 7 Actual photos of the polyoxin water-based nano preparations prepared in Comparative Example 1 and Application Example 1 at the preparation endpoint. DETAILED DESCRIPTION

[0029] The present application provides a polyether modified amphiphilic carboxylic acid derivative with the structure shown in formula 1:

[0030] Formula 1.

[0031] The polyether modified amphiphilic carboxylic acid derivative provided by the application can prepare a completely water-based polyoxin nanofomulation without using any organic solvent.

[0032] The application provides a synthesis method of the polyether modified amphiphilic carboxylic acid derivative described in the above scheme, comprising the following steps:

[0033] The alcohol ether compound having the structure shown in formula 2 is mixed with maleic anhydride to perform an esterification reaction, so that the polyether modified amphiphilic carboxylic acid derivative is obtained.

[0034] Formula 2.

[0035] In the application, the raw materials used are all commercially available products well known in the art without special instructions.

[0036] In the application, the alcohol ether compound having the structure shown in formula 2 is preferably prepared by referring to the method disclosed in “CN 116253626 A Alcohol ether compound and its application in water-based nanofarmulation”.

[0037] In the application, the mass ratio of the alcohol ether compound to maleic anhydride is preferably 2.0-2.5:1, and in specific embodiments, can be 2.0:1 or 2.5:1.

[0038] In the application, the temperature of the esterification reaction is preferably 90-95℃, and in specific embodiments, can be 90℃, 91℃, 92℃, 93℃, 94℃ or 95℃; the time of the esterification reaction is preferably more than 3 h, and more preferably 3-4 h.

[0039] The application provides an application of the polyether modified amphiphilic carboxylic acid derivative described in the above scheme in preparing a water-based nanofarmulation. In the application, the pesticide preferably includes polyoxin.

[0040] The application provides a polyoxin water-based nanofarmulation, which comprises water, polyoxin and the polyether modified amphiphilic carboxylic acid derivative.

[0041] In the application, the mass content of the polyether modified amphiphilic carboxylic acid derivative in the polyoxin water-based nanofarmulation is preferably 4-5%, and in specific embodiments, can be 4%, 4.3%, 4.5%, 4.8% or 5%; the mass content of polyoxin in the polyoxin water-based nanofarmulation is preferably 4-5%, and in specific embodiments, can be 4%, 4.3%, 4.5%, 4.8% or 5%.

[0042] In the application, the average particle size of the polyoxin water-based nanofarmulation is preferably 45.61±0.5 nm.

[0043] The application provides a preparation method of the poly-myxin water-based nano preparation.

[0044] In the application, the mixing and stirring is preferably carried out at room temperature; the application does not have special requirements for the rate and time of the mixing and stirring, and when the turbid solution becomes transparent, the water-based nano pesticide preparation is obtained.

[0045] The polyether-modified amphiphilic carboxylic acid derivative and the application thereof in the water-based nano pesticide preparation are described in detail below with reference to examples, but they should not be understood as limitations to the protection scope of the application.

[0046] Example 1

[0047] The polyether-modified amphiphilic carboxylic acid derivative is prepared according to the flowchart shown in the figure: Figure 1

[0048] (1) 500 g of 4-hydroxyvalerophenone is heated to 110°C under nitrogen, vacuum dehydrated for 1 hour, then cooled and 2% of sodium hydroxide based on the total mass of 4-hydroxyvalerophenone and ethylene oxide (EO) is added, heated to 80°C under nitrogen, 1.5 kg of EO is added, and the reaction is completed at 120°C and 0.04 MPa. The temperature is lowered and the material is discharged to obtain a 4-pentanoyl phenol polyoxyethylene ether crude product.

[0049] 2.0 kg of 4-pentanoyl phenol polyoxyethylene ether crude product and 500 g of deionized water are heated to 70°C, 5% (5% of the total mass of 4-pentanoyl phenol polyoxyethylene ether crude product and deionized water) activated carbon adsorbent is added after stirring for 0.5 hours, and then slowly vacuum dehydrated for 0.5 hours. The dehydration time is 6 hours, and after dehydration, the temperature is lowered to 60°C and filtered to obtain a 4-pentanoyl phenol polyoxyethylene ether pure product.

[0050] (2) 310 g of 4-pentanoyl phenol polyoxyethylene ether pure product and 400 mL of tetrahydrofuran (THF) are placed in a four-necked flask, the reaction solution is cooled to 10°C, and a solution of n-butylmagnesium chloride in THF (350 mL, 2M) is added dropwise under nitrogen protection. The reaction is completed after 2 hours of dropping. The reaction solution is raised to room temperature and reacted overnight. When the water bath is cooled, 10% dilute hydrochloric acid is added dropwise to the reaction solution to adjust the pH to 5-6. After stirring, the organic liquid is extracted with ethyl acetate (EA) (300 mL x 3), and then desalted and dehydrated with saturated brine. After desolventizing, a brown viscous liquid is obtained, which is an alcohol ether compound with the structure shown in formula 2.

[0051] ​(3) 635 g of the alcohol ether compound and 254 g of maleic anhydride were added into a 2,000 mL three-necked flask, and after being heated and melted, the reaction was kept at 90°C. The acid value was measured at intervals, and when the reaction time reached 3 h, the reaction was stopped, and a polyether modified amphiphilic carboxylic acid derivative was obtained.

[0052] The polyether modified amphiphilic carboxylic acid derivative was subjected to nuclear magnetic resonance, and the MestReNova software was used for analysis. After baseline correction and phase processing, the hydrogen spectrum was integrated and peak analysis was performed, and the hydrogen spectrum was as shown in Figure 2 As shown in Figure 2 , the a proton and the b proton were chemically shifted to the low field, and were split into d peaks with a coupling constant of 8.9 Hz, which were AA'BB' spin-coupled spin protons in the benzene ring, and the shielding effect of the oxygen-containing group on the adjacent position caused the chemical shift of the b proton to be smaller than that of the a proton. In addition, the chemical shift of the c proton containing the oxygen-containing methylene was relatively large, and was split into t peaks; the chemical shift of the d proton was smaller; the e proton signal had high symmetry and was overlapped at 3.64 ppm; f, g, and h were methylene proton signals, and were coupled and split into multiple peaks, and were located in the range of 1.2-1.7 ppm, which were preliminarily assigned according to the chemical shift of the aliphatic chain; the i proton signal was a methyl proton signal, and was split into t peaks. J, k, l, and m were olefin proton signals, and because the chemical environments of the two ends of the olefin protons were similar, the chemical shifts of the olefin proton signals were relatively small, and some were overlapped, and were m peaks. According to the above information, it can be basically confirmed that it is the expected structure.

[0053] The polyether modified amphiphilic carboxylic acid derivative was subjected to infrared testing, and the results were as shown in Figure 3 From the figure, it can be seen that the peak type of 3429 cm -1 was relatively wide, which was the absorption peak of the carboxyl group in the structure of the sample, the peak at 2873 cm -1 was the stretching vibration absorption peak of the methyl methylene in the structure, the peak was relatively strong, indicating that the content of the methyl methylene in the structure was relatively high, the absorption peak at 2351 cm -1 was the infrared absorption of the double bond in the structure, the absorption peak at 1708 cm -1 was the infrared absorption of the carbonyl group in the structure, the benzene ring skeleton in the structure of the sample had four bands, and the absorption peaks were respectively at 1634 cm -1 , 1597 cm -1 , 1506 cm -1 and 1456 cm -1 , and the ether bond absorption peak in the structure of the sample was at 1098 cm -1 . Through the analysis of the infrared spectrum, the structure of the sample was finally determined.

[0054] Application Example 1

[0055] Weigh 0.238 g of spinosad technical and 0.227 g of polyether-modified amphiphilic carboxylic acid derivative and dissolve them in 4.535 g of water. Stir the solution at room temperature, with a stirring speed of 600 rpm for 15 min. The turbid solution becomes transparent, and spinosad water-based nano-formulation is obtained.

[0056] Figure 4 , Figure 5 The images are scanning electron microscope (SEM) and atomic force microscope (AFM) images of the spinosad water-based nano-formulation. Various morphological characterization results show that the spinosad water-based nano-formulation is a uniform sphere. Figure 6 The particle size distribution of spinosad water-based nanoparticles was statistically analyzed, and the spherical particle size was approximately 45 nm.

[0057] Comparative Example 1

[0058] The only difference from Application Example 1 is that the polyether-modified amphiphilic carboxylic acid derivative is replaced with an alcohol ether compound with the structure shown in Formula 2 to prepare spinosad water-based nano-formulations;

[0059] Equation 2.

[0060] Photographs of the spinosad water-based nano-formulations prepared in Comparative Example 1 and Application Example 1 at the preparation endpoint are shown below. Figure 7 As shown, by Figure 7 It can be seen that the spinosad water-based nano-formulation prepared using the polyether-modified amphiphilic carboxylic acid derivative provided by this invention becomes clear and transparent; while the formulation prepared using the comparative alcohol ether compound shows that the drug has hardly been incorporated into the system, resulting in a turbid, layered state. It is clearly visible from the appearance that the comparative alcohol ether compound is incompatible with the spinosad system.

[0061] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A multi-myiocidin water-based nano-formulation, characterized in that, Consists of water, spinosad and polyether modified amphiphilic carboxylic acid derivatives; the polyether modified amphiphilic carboxylic acid derivatives have the structure shown in formula 1: The mass content of polyether modified amphiphilic carboxylic acid derivatives in the spinosad water-based nano-preparation is 4-5%; The mass content of spinosad in the spinosad water-based nano-preparation is 4-5%; The average particle size of the spinosad water-based nano-preparation is 45.61±0.5nm; The preparation method of the spinosad water-based nano-preparation consists of the following steps: mixing and stirring spinosad, polyether modified amphiphilic carboxylic acid derivatives and water to obtain the spinosad water-based nano-preparation.

2. A method of preparing a polyoxin water-based nano-formulation according to claim 1, consisting of the following steps: Mixing and stirring spinosad, polyether modified amphiphilic carboxylic acid derivatives and water to obtain the spinosad water-based nano-preparation.

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