Polyether modified amphiphilic carboxylic acid derivative and application thereof in nano pesticide

Abstract

The invention relates to the technical field of organic synthesis and fine chemical engineering, in particular to a polyether modified amphiphilic carboxylic acid derivative and application thereof in nano pesticides. The polyether modified amphiphilic carboxylic acid derivative provided by the invention can be used for preparing a completely water-based spinosad nano preparation under the condition of not using any organic solvent. The preparation can form a transparent nano-scale dispersion liquid after being diluted with water, and the transparent nano-scale dispersion liquid is sprayed after being diluted with water according to a recommended use amount. No organic solvent participates in preparation and use links, so that the hidden danger of human health is effectively reduced, and meanwhile, the ecological environment pressure is relieved.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis and fine chemical industry, and in particular to the design and synthesis of a polyether-modified amphiphilic carboxylic acid derivative and the application of the same in a water-based nano pesticide preparation. Background Art

[0002] Pesticides are an important means of production to ensure food production and are an indispensable key input in agricultural production. Pesticide formulations affect the transmission efficiency and biological activity of active ingredients by regulating the drug delivery pathway, and are closely related to pesticide utilization, pesticide environmental behavior characteristics, and biosafety effects.

[0003] Spinosad is a natural macrolide pesticide derived from actinomycetes. Saccharopolyspora spinosa Extracted from the culture fluid produced by fermentation. Due to its natural source and low toxicity, it has been widely used to control pests on field crops and vegetable crops, and has significant control effects on pests such as lepidopterans, thrips and diamondback moth. Among the commercialized preparations of spinosad, the most common is the water suspension, which requires a long period of mechanical grinding so that the spinosad particles are evenly dispersed in water under the joint action of various adjuvants such as wetting agents and dispersants, thereby forming a stable suspension. The pesticide particles in the suspension are usually 1~5 μm. Such large-sized particles cannot fully deposit the active ingredients in the target area effectively, causing most of the active ingredients to be lost during the application process. According to statistics, the effective utilization rate of traditional pesticide preparations is less than 0.1%. Therefore, the current spinosad preparations face the problems of complex preparation process and low utilization rate of active ingredients.

[0004] Nanopesticide formulations provide a promising formulation optimization solution. The nano-size effect helps to enhance the leaf penetration and resistance to photolysis of pesticides, which can not only improve the utilization rate of pesticides, but also reduce the risks to the environment and human health during the preparation and use of pesticides. However, it is still a technical challenge to prepare completely water-based nano-formulations without using any organic solvents. Summary of the invention

[0005] In view of this, the purpose of the present invention is to provide a design and synthesis of a polyether-modified amphiphilic carboxylic acid derivative and its application in a water-based nanopesticide formulation. The polyether-modified amphiphilic carboxylic acid derivative provided by the present invention can prepare a completely water-based spinosad nanopesticide formulation without using any organic solvent.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions: The present invention provides a polyether-modified amphiphilic carboxylic acid derivative having a structure shown in Formula 1: Formula 1.

[0007] The present invention provides a method for synthesizing the polyether-modified amphiphilic carboxylic acid derivatives described in the above scheme, comprising the following steps: The alcohol ether compound having the structure shown in Formula 2 and maleic anhydride are mixed and then subjected to an esterification reaction to obtain the polyether-modified amphiphilic carboxylic acid derivative; Formula 2.

[0008] Preferably, the mass ratio of the alcohol ether compound to maleic anhydride is 2.0-2.5:1.

[0009] Preferably, the temperature of the esterification reaction is 90-95° C., and the time is more than 3 h.

[0010] The present invention provides the use of the polyether-modified amphiphilic carboxylic acid derivatives described in the above scheme as surfactants in the preparation of water-based nano pesticide preparations.

[0011] The invention provides a spinosad water-based nano preparation comprising water, spinosad and the polyether-modified amphiphilic carboxylic acid derivative described in the above scheme.

[0012] Preferably, the mass content of the polyether-modified amphiphilic carboxylic acid derivative in the spinosad water-based nanoformulation is 4-5%.

[0013] Preferably, the mass content of spinosad in the spinosad water-based nanoformulation is 4-5%.

[0014] Preferably, the average particle size of the spinosad water-based nanoformulation is 45.61±0.5 nm.

[0015] The present invention provides a method for preparing the spinosad water-based nano-preparation of the above scheme, comprising the following steps: mixing spinosad, a polyether-modified amphiphilic carboxylic acid derivative and water to obtain the spinosad water-based nano-preparation.

[0016] The present invention provides a polyether-modified amphiphilic carboxylic acid derivative having a structure shown in Formula 1. At room temperature, the polyether-modified amphiphilic carboxylic acid derivative and spinosad are stirred in water, and a stable spinosad water-based nanoformulation is obtained efficiently and environmentally friendly 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-sized assembly structure during interface bending. By simple stirring at room temperature, the polyether-modified amphiphilic carboxylic acid derivative can interact with spinosad to achieve efficient self-assembly, thereby effectively dispersing spinosad into a nano state in water to form a transparent spinosad water-based nano delivery system.

[0017] The present invention provides a water-based nanopesticide preparation, which can form a transparent nano-scale dispersion after being diluted with water. The preparation can be sprayed after being diluted with water according to the recommended usage amount. It is easy to use, effectively reduces hidden dangers to human health, and alleviates ecological environmental pressure. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Flow chart of preparing polyether-modified amphiphilic carboxylic acid derivatives according to Example 1; Figure 2 This is the H NMR spectrum of the polyether-modified amphiphilic carboxylic acid derivative prepared in Example 1; Figure 3 This is the infrared spectrum of the polyether-modified amphiphilic carboxylic acid derivative prepared in Example 1; Figure 4 This is a scanning electron microscope image of a water-based nanoformulation of spinosad; Figure 5 This is an atomic force microscopy image of the water-based nanoformulation of spinosad; Figure 6 This is the particle size distribution diagram of the water-based nanoformulation of spinosad; Figure 7 These are actual photos of the water-based nanoformulations of spinosad prepared in Comparative Example 1 and Application Example 1 at the end point of the preparation. DETAILED DESCRIPTION

[0019] The present invention provides a polyether-modified amphiphilic carboxylic acid derivative having a structure shown in Formula 1: Formula 1.

[0020] The polyether-modified amphiphilic carboxylic acid derivative provided by the invention can prepare a completely water-based spinosad nano-preparation without using any organic solvent.

[0021] The present invention provides a method for synthesizing the polyether-modified amphiphilic carboxylic acid derivatives described in the above scheme, comprising the following steps: The alcohol ether compound having the structure shown in Formula 2 and maleic anhydride are mixed and then subjected to an esterification reaction to obtain the polyether-modified amphiphilic carboxylic acid derivative; Formula 2.

[0022] In the present invention, unless otherwise specified, the raw materials used are commercially available products well known in the art.

[0023] In the present invention, the alcohol ether compound of the structure described in Formula 2 is preferably prepared by referring to the method disclosed in "CN 116253626 A An alcohol ether compound and its application in water-based nanopesticide preparation".

[0024] In the present invention, the mass ratio of the alcohol ether compound to maleic anhydride is preferably 2.0-2.5:1, and in a specific embodiment may be 2.0:1 or 2.5:1.

[0025] In the present invention, the temperature of the esterification reaction is preferably 90-95°C, and in specific embodiments may be 90°C, 91°C, 92°C, 93°C, 94°C or 95°C; the time of the esterification reaction is preferably more than 3 h, more preferably 3-4 h.

[0026] The present invention provides the use of the polyether-modified amphiphilic carboxylic acid derivatives described in the above scheme in the preparation of water-based nano pesticide preparations. In the present invention, the pesticide preferably includes spinosad.

[0027] The invention provides a spinosad water-based nano preparation comprising water, spinosad and the above-mentioned polyether-modified amphiphilic carboxylic acid derivative.

[0028] In the present invention, the mass content of the polyether-modified amphiphilic carboxylic acid derivative in the spinosad water-based nanoformulation is preferably 4-5%, and in specific embodiments it can be 4%, 4.3%, 4.5%, 4.8% or 5%; the mass content of spinosad in the spinosad water-based nanoformulation is preferably 4-5%, and in specific embodiments it can be 4%, 4.3%, 4.5%, 4.8% or 5%.

[0029] In the present invention, the average particle size of the spinosad water-based nanoformulation is preferably 45.61±0.5 nm.

[0030] The present invention provides a method for preparing the spinosad water-based nanoformulation described in the above scheme, comprising the following steps: mixing and stirring spinosad, the above polyether-modified amphiphilic carboxylic acid derivative and water to obtain the spinosad water-based nanoformulation.

[0031] In the present invention, the mixing and stirring is preferably carried out at room temperature; the present invention has no special requirements on the rate and time of the mixing and stirring, and when the turbid solution becomes transparent, the water-based nanopesticide preparation is obtained.

[0032] The design, synthesis and application of the polyether-modified amphiphilic carboxylic acid derivatives provided by the present invention in water-based nanopesticide preparations are described in detail below in conjunction with the examples, but they should not be construed as limiting the scope of protection of the present invention.

[0033] Example 1 according to Figure 1 The process shown is to prepare polyether-modified amphiphilic carboxylic acid derivatives: (1) 500 g of 4-hydroxyvalerophenone (4'-Hydroxyvalerophenone) was heated to 110°C under nitrogen and vacuum dehydrated for 1 hour. The temperature was then lowered and sodium hydroxide accounting for 2% of the total mass of 4-hydroxyvalerophenone and ethylene oxide (EO) was added. The temperature was then raised to 80°C under nitrogen and 1.5 kg of EO was added. The reaction was completed at 120°C and 0.04 MPa. The temperature was then lowered and the crude product of 4-valerylphenol polyoxyethylene ether was obtained.

[0034] Heat 2.0 kg of crude 4-pentanoylphenol polyoxyethylene ether and 500 g of deionized water to 70°C, stir for 0.5 hour, add 5% (5% of the total mass of crude 4-pentanoylphenol polyoxyethylene ether and deionized water) activated carbon adsorbent, stir for another 0.5 hour, slowly vacuum dehydrate for 6 hours, and after dehydration, cool to 60°C and filter to obtain pure 4-pentanoylphenol polyoxyethylene ether.

[0035] (2) Place 310 g of pure 4-pentanoylphenol polyoxyethylene ether and 400 mL of tetrahydrofuran (THF) in a four-necked flask, cool the reaction solution to 10°C, and under nitrogen protection, dropwise add a THF solution of n-butylmagnesium chloride (350 mL, 2M) over 2 hours. The reaction solution is warmed to room temperature and reacted overnight. While cooling in a water bath, add 10% dilute hydrochloric acid to the reaction solution to adjust the pH to 5-6. Stir thoroughly, extract with ethyl acetate (EA) (300 mL×3), combine the extracted organic liquids, desalt and dehydrate with saturated brine, and obtain a brown viscous liquid after desolventization, which is the alcohol ether compound with the structure shown in Formula 2.

[0036] (3) Add 635 g of alcohol ether compound and 254 g of maleic anhydride into a 2,000 mL three-necked flask, heat to melt, and then keep warm at 90°C for reaction. Take samples at regular intervals to measure the acid value. When the reaction time reaches 3 h, stop the reaction to obtain a polyether-modified amphiphilic carboxylic acid derivative.

[0037] The polyether-modified amphiphilic carboxylic acid derivative was subjected to nuclear magnetic resonance and analyzed using MestReNova software. After baseline correction and phase processing, the hydrogen spectrum was integrated and peak-marked to obtain a hydrogen spectrum such as Figure 2 As shown. Figure 2As shown, the chemical shifts of protons a and b are low field, and split into peak d, with a coupling constant of 8.9 Hz. They are the spin-coupled protons of AA′BB′ in the benzene ring, and the shielding effect of the oxygen group on the adjacent position causes the chemical shift of proton b to be smaller than that of proton a; in addition, the chemical shift of proton c is larger, and it is split into peak t; the chemical shift of proton d is second; the symmetry of proton e is high, and it overlaps at 3.64ppm; f, g, and h are methylene proton signals, and the coupling splits into multiple peaks, located in the range of 1.2~1.7ppm, and they are preliminarily assigned according to the chemical shift of the aliphatic chain; the signal of proton i is a methyl proton signal, and it is split into peak t. J, k, l, and m are olefin proton signals. Because the chemical environments at both ends of the olefin protons are similar, the chemical shifts of the olefin proton signals are slightly different, partially overlapped, and present peak m. Based on the above information, it can be basically confirmed that it is the expected structure.

[0038] The polyether-modified amphiphilic carboxylic acid derivatives were subjected to infrared testing, and the results were as follows: Figure 3 As shown in the figure, it can be seen that 3429 cm -1 The broad peak is the absorption peak of the carboxyl group in the sample structure, with a wavelength of 2873 cm -1 The peak at 2351 cm is the stretching vibration absorption peak of the methyl methylene group in the structure. This peak is relatively strong, indicating that the content of methyl methylene in the structure is relatively high. -1 The absorption peak at 1708 cm -1 The absorption peak at is the infrared absorption of the carbonyl group in the structure. The benzene ring skeleton in the sample structure has four spectral bands, and the absorption peaks appear at 1634 cm -1 ,1597 cm -1 ,1506 cm -1 and 1456cm -1 The ether bond absorption peak in the sample structure appears at 1098 cm -1 . The structure of the sample was finally determined through infrared spectrum analysis.

[0039] Application Example 1 0.238 g of spinosad technical and 0.227 g of polyether-modified amphiphilic carboxylic acid derivative were weighed and dissolved in 4.535 g of water and stirred at room temperature. The rotation speed was controlled at 600 rpm for 15 min. The turbid solution became transparent to obtain a spinosad water-based nanoformulation.

[0040] Figure 4 , Figure 5 These are the scanning electron microscope and atomic force microscope images of the water-based nanoformulation of spinosad, and the results of various morphological characterizations show that the water-based nanoformulation of spinosad is a uniform sphere; Figure 6The particle size distribution of water-based nanoformulation of spinosad was statistically analyzed, and the spherical particle size was about 45 nm.

[0041] Comparative Example 1 The only difference from Application Example 1 is that the polyether-modified amphiphilic carboxylic acid derivative is replaced by an alcohol ether compound having a structure shown in Formula 2 to prepare a water-based nano-preparation of spinosad; Formula 2.

[0042] The actual photos of the water-based nano-preparation of spinosad prepared in Comparative Example 1 and Application Example 1 at the end of the preparation are as follows: Figure 7 As shown by Figure 7 It can be seen that the water-based nano-preparation of spinosad prepared by using the polyether-modified amphiphilic carboxylic acid derivative provided by the present invention becomes clear and transparent; while the preparation using the alcohol ether compound of the comparative example shows that the drug has hardly been integrated into the system and is in a turbid layered state. From the appearance, it can be clearly seen that the alcohol ether compound of the comparative example is incompatible with the spinosad system.

[0043] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A polyether-modified amphiphilic carboxylic acid derivative, characterized in that: It has the structure shown in formula 1: Formula 1.

2. The method for synthesizing the polyether-modified amphiphilic carboxylic acid derivative according to claim 1, comprising the following steps: The alcohol ether compound having the structure shown in Formula 2 and maleic anhydride are mixed and then subjected to esterification reaction to obtain the polyether-modified amphiphilic carboxylic acid derivative; Formula 2.

3. The preparation method according to claim 2, characterized in that: The mass ratio of the alcohol ether compound to maleic anhydride is 2.0-2.5:

1.

4. The preparation method according to claim 2 or 3, characterized in that: The temperature of the esterification reaction is 90-95° C. and the time is more than 3 h.

5. Use of the polyether-modified amphiphilic carboxylic acid derivative according to claim 1 as a surfactant in the preparation of a water-based nanopesticide preparation.

6. A water-based nano-preparation of spinosad, characterized in that: The invention comprises water, spinosad and the polyether-modified amphiphilic carboxylic acid derivative according to claim 1.

7. The water-based nanoformulation of spinosad according to claim 6, characterized in that: The mass content of the polyether-modified amphiphilic carboxylic acid derivative in the spinosad water-based nano preparation is 4-5%.

8. The water-based nanoformulation of spinosad according to claim 6 or 7, characterized in that: The mass content of spinosad in the water-based nanopesticide preparation is 4-5%.

9. The water-based nanoformulation of spinosad according to claim 7, characterized in that: The average particle size of the spinosad water-based nanoformulation is 45.61±0.5 nm.

10. The method for preparing the water-based nano-preparation of spinosad according to any one of claims 6 to 9, comprising the following steps: The spinosad, the polyether-modified amphiphilic carboxylic acid derivative and water are mixed and stirred to obtain the spinosad water-based nano preparation.

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