CN118047703A - A trifluoroethylthio or trifluoroethylsulfinyl-containing meta-diamide compound and its preparation method and application - Google Patents

Abstract

The invention belongs to the technical field of agricultural pesticides, and in particular relates to a m-diamide compound containing trifluoroethylthio or trifluoroethylsulfinyl and having a structural formula shown in a general formula I, a preparation method thereof and application of the m-diamide compound containing trifluoroethylthio or trifluoroethylsulfinyl in preparation of agricultural pesticides:

Description

A diamide compound containing trifluoroethylthio or trifluoroethylsulfinyl groups and its preparation method and application

Technical Field

The invention belongs to the technical field of agricultural pesticides, and specifically relates to a diamide compound containing a trifluoroethylthio group or a trifluoroethylsulfinyl group, a preparation method thereof, and an application thereof in preparing agricultural pesticides.

Background technique

As the global population continues to grow, human demand for food is increasing. Pesticides can effectively improve food production and quality, so they have become the research target of universities and research institutes. As an important member of the pesticide family, insecticides occupy a huge market share. However, due to the large-scale and unreasonable abuse of chemical pesticides in recent years, pest resistance has continued to rise. Therefore, finding highly efficient, low-toxic, and environmentally friendly insecticides has become an urgent need.

Broflanilide (molecular structure shown above), a diamide insecticide that acts on γ-aminobutyric acid (GABA) receptors and was launched in 2020, is a rising star representative of diamide insecticides. When it binds to the insect GABA receptor target receptor, it regulates chloride ion channels, inhibits neurotransmission, causes a depolarization effect, and thus affects the life activities of insects, thereby achieving the purpose of rapid insect killing. At the same time, due to the huge difference in drug sensitivity of GABA receptors between insects and mammals, broflanilide has become a highly selective green insecticide.

A large number of pesticide research and development works with bromofenac as the lead compound and structural modification have been launched. Trifluoroethylthio or trifluoroethylsulfinyl is the active fragment of common agricultural insecticide acaricides, such as Bisulflufen and Flupentiofenox are typical representative compounds containing trifluoroethylthio or trifluoroethylsulfinyl active fragments. The sulfur atom in trifluoroethylthio or trifluoroethylsulfinyl has always been the focus of research by pesticide workers due to its diverse biological activities and structural characteristics that are easy to derivatize. It can not only make the corresponding compounds have a wide range of biological activities, but also provide reaction sites for the environmental degradation of drugs, which can effectively improve the physical properties and biological activity of the compounds. The present invention is committed to introducing trifluoroethylthio or trifluoroethylsulfinyl active fragments into bromofenac to replace its trifluoromethyl group. The diverse molecular structures help prevent the generation of pest resistance and explore its synthetic path and biological activity. At present, there are no reports on the preparation method and use of diamide compounds containing trifluoroethylthio or trifluoroethylsulfinyl groups, which has great research space and value.

Summary of the invention

The object of the present invention is to provide a diamide compound containing a methylthio group or a sulfur oxide, and a preparation method and application thereof. The compound has good insecticidal activity and can be used for the integrated prevention and control of various insect pests.

To achieve the above purpose, the solution adopted by the present invention is as follows:

In the first aspect, the present invention provides a trifluoroethylthio or trifluoroethylsulfinyl-containing diamide compound having a structural formula as shown in general formula I:

Where:

_R1 is selected from hydrogen, chlorine or bromine;

m is 0 or 1.

In a second aspect, the present invention also provides a method for preparing the above-mentioned diamide compound containing trifluoroethylthio or trifluoroethylsulfinyl, and the reaction scheme is shown in the following formula:

A method for preparing a trifluoroethylthio or trifluoroethylsulfinyl-containing diamide compound as claimed in claim 1, characterized in that the reaction route is as shown below:

In the formula, R ₁ and m are as defined in claim 1;

The preparation method of this reaction route comprises the following steps:

The compound of formula A is refluxed in thionyl chloride for 3 to 6 hours to prepare the corresponding fresh acyl chloride, and the acyl chloride and the compound of formula B are reacted in an organic solvent at -20°C to reflux temperature for 2 to 18 hours under the action of potassium iodide to obtain a compound of formula I (m=0; R ₁ =H); wherein the organic solvent is selected from one or more of methanol, ethanol, propanol, isopropanol, dichloromethane, acetonitrile, tetrahydrofuran, chloroform, 1,4-dioxane, dimethyl sulfoxide or N,N-dimethylformamide and 1,3-dimethyl-2-imidazolone.

Preferably, the reaction route is as shown below:

In the formula, R ₁ , m, and are as defined in claim 1;

The preparation method of this reaction route comprises the following steps:

The compound of formula I (m=0; R ₁ =H) is reacted with N-bromosuccinimide (NBS) and a base in an organic solvent at -20°C to reflux temperature for 2 to 48 hours to obtain a compound of formula I (m=0; R ₁ =Br);

The alkali is selected from one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate and potassium carbonate;

The organic solvent is selected from one or more of methanol, dichloromethane, acetonitrile, tetrahydrofuran, chloroform, 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide and 1,3-dimethyl-2-imidazolone.

Preferably, the reaction route is as shown below:

The compound of formula I (m=0; R ₁ =Br) is reacted with hydrogen peroxide and trifluoroacetic acid in an organic solvent at 0°C to reflux temperature for 2 to 18 hours to obtain the compound of formula I (m=1; R ₁ =Br).

In a third aspect, the present invention also provides a use of the above-mentioned diamide compound containing a trifluoroethylthio group or a trifluoroethylsulfinyl group in the preparation of an agricultural insecticide, wherein the insecticide is an insecticide for killing lepidopteran pests and hemiptera, etc.; or, the insecticide is an insecticide for killing diamondback moth and aphids.

In a fourth aspect, the present invention further provides an insecticide composition comprising the above-mentioned trifluoroethylthio or trifluoroethylsulfinyl-containing diamide compound as an active ingredient and a pharmaceutically acceptable carrier.

Preferably, the formulation of the insecticide composition is selected from any one of emulsifiable concentrate, suspension, wettable powder, dust, granule, aqueous solution, poison bait, mother solution and mother powder.

In order to prevent the development of insecticide resistance, it is imperative to develop novel meta-diamide molecules with diverse structures and excellent insecticidal activity. The present invention introduces a high insecticidal activity fragment trifluoroethylthio or trifluoroethylsulfinyl into the parent structure of bromofenac (a type of meta-diamide) insecticide, replaces the trifluoromethyl group therein, and synthesizes a meta-diamide compound containing trifluoroethylthio or trifluoroethylsulfinyl for the first time. The derivative combines the characteristics of the diamide structure and the trifluoroethylthio or trifluoroethylsulfinyl group structure, and has excellent insecticidal activity.

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

The invention provides a novel trifluoroethylthio or trifluoroethylsulfinyl-containing diamide compound (compound of general formula I). The derivative has good and extensive insecticidal activity due to the combination of the characteristics of a diamide structure and a trifluoroethylthio or trifluoroethylsulfinyl group structure, has a control effect on pests such as diamondback moth and alfalfa aphid, can be used as an active component of an insecticidal composition, is used for preparing agricultural insecticides, and can be applied to the prevention and control of insect pests.

Detailed ways

The present invention is further described below in conjunction with examples, the purpose of which is to better understand the content of the present invention and embody the essential characteristics of the present invention, and therefore the examples cited should not be regarded as limiting the scope of protection of the present invention. It is also particularly pointed out here that the specific experimental methods and equipment involved in the examples are conventional methods or implemented under the conditions recommended by the manufacturer's instructions unless otherwise specified, and the reagents involved are commercially available unless otherwise specified.

Example 1

The structural formula and preparation method of compound I-1 2-fluoro-3-(N-methylbenzamide)-N-(2-((2,2,2-trifluoroethyl)thio)-4-(heptafluoroisopropyl)phenyl)benzamide are shown below.

Step 1: Preparation of 2-((2,2,2-trifluoroethyl)thio)aniline

Weigh 2.00g (15.98mmol) of 2-aminobenzenethiol and dissolve it in 10mL N,N-dimethylformamide (DMF), add 6.60g (47.9mmol) of potassium carbonate, add 3.70g (17.6mmol) of trifluoroiodoethane dropwise under stirring, heat under reflux in an oil bath for 4h, and monitor the reaction progress by TLC. After the reaction is completed, add 300mL of water to the reaction system, extract with ethyl acetate, combine the organic phases, concentrate under reduced pressure, and purify by column chromatography (eluent is ethyl acetate: petroleum ether = 1:30) to obtain 2-((2,2,2-trifluoroethyl)thio)aniline.

Step 2: Preparation of 4-(heptafluoroisopropyl)-2-((2,2,2-trifluoroethyl)thio)aniline

Weigh 1.00g (4.83mmol) 2-((2,2,2-trifluoroethyl)thio)aniline in a 100mL single-mouth bottle, add 0.93g (5.31mmol) 85% hydrosulfite powder, 0.16g (0.48mmol) tetrabutylammonium sulfate, then add 25mL of water and ethyl acetate respectively, add 0.93g (5.31mmol) sodium bicarbonate under stirring, add stirring for 10min, then continue to add 2.86g (9.66mmol) heptafluoro-2-iodopropane dropwise to the bottle, monitor the reaction process by TLC, reflux for about 12h, and then the reaction is completed. Separate the organic phase, extract the inorganic phase with ethyl acetate three times, combine the ethyl acetate phases and concentrate under reduced pressure, and purify the crude product by column chromatography (eluent is ethyl acetate: petroleum ether = 1:30) to obtain the product 4-(perfluoropropyl)-2-((2,2,2-trifluoroethyl)thio)aniline.

Step 3: Preparation of 2-fluoro-3-(N-methylbenzamide)-N-(2-((2,2,2-trifluoroethyl)thio)-4-(heptafluoroisopropyl)phenyl)benzamide

1.86 g (6.80 mmol) of 2-fluoro-3-(N-methylbenzamido)benzoic acid was weighed and dissolved in 15 mL of thionyl chloride solution. After reacting for 5 h under reflux conditions, the solvent was removed under reduced pressure to prepare fresh acid chloride for use.

The new acid chloride was dissolved in 20 mL of acetonitrile, and 1.69 g (10.21 mmol) of potassium iodide and 2.55 g (6.8 mmol) of 4-(heptafluoroisopropyl)-2-((2,2,2-trifluoroethyl)sulfur)aniline were added under stirring. The reaction system was then heated to reflux, and the reaction progress was monitored by TLC. The reaction was completed in about 7 hours, and the organic solvent was distilled off under reduced pressure, and extracted with water and dichloromethane. The organic layer was retained, concentrated under reduced pressure, and purified by column chromatography (the eluent ratio was ethyl acetate: petroleum ether = 1:6) to obtain the target product I-1.

Example 2

The structural formula and preparation method of compound I-2N-(2-bromo-6-((2,2,2-trifluoroethyl)thio)-4-(heptafluoroisopropyl)phenyl)-2-fluoro-3-(N-methylbenzamide)benzamide are shown below.

1.00 g (1.59 mmol) of the compound I-1 prepared in Example 1 was dissolved in acetonitrile, 0.24 g (1.70 mmol) of K ₂ CO ₃ was added under an ice bath, and after stirring for 5 min, 0.28 g (1.59 mmol) of NBS was added in batches, and the temperature was slowly raised to reflux state. The reaction process was monitored by TLC, and the reaction was completed after about 3 h. After the reaction was completed, the organic solvent was distilled off under reduced pressure, and water and dichloromethane were used for extraction. The organic layer was retained, concentrated under reduced pressure, and purified by column chromatography (the eluent ratio was ethyl acetate: petroleum ether = 1:6) to obtain the target product I-2.

Example 3

The structural formula and preparation method of compound I-3 2-fluoro-3-(N-methylbenzamide)-N-(2-((2,2,2-trifluoroethyl)sulfinyl)-4-(heptafluoroisopropyl)phenyl)benzamide are shown below.

0.13 g (0.18 mmol) of compound I-2 prepared in Example 2 and 0.34 g (0.54 mmol) of hydrogen peroxide were dissolved in 10 mL of trifluoroacetic acid, and then the system was stirred and reacted at room temperature for about 12 hours (TLC monitoring). After the reaction was completed, the organic solvent was removed by distillation under reduced pressure, and the system was dissolved in dichloromethane, and then washed with alkali, washed with salt, and dried, and the organic phase was concentrated under reduced pressure, and purified by column chromatography (the eluent ratio was ethyl acetate: petroleum ether = 1:2) to obtain I-3.

Table 1 below lists the structures, physical properties, H NMR spectra and mass spectrometry data of some compounds of formula I.

Table 1 Structures, physical properties, H NMR data and mass spectra of some compounds of general formula I

Insecticidal activity test:

Examples of biological activity tests of the compound of formula I and the control drug bromofenac, with the test targets being Plutella xylostella and Aphis craccivora Koch.

Feeding conditions:

Diamondback moth: raised indoors on radish seedlings at a temperature of 22±2°C and a light intensity of 12L:12D;

Alfalfa aphids: Raised indoors with broad bean seedlings at a temperature of 22±2℃ and a light intensity of 12L:12D.

experiment method:

1. Preparation of medicine

The original drug was dissolved in DMF to prepare a 1% stock solution, and diluted with distilled water containing 0.1% Tween 80 to prepare the corresponding concentration for use.

2. Experimental treatment methods

Activity test of diamondback moth: Use the dipping method, take an appropriate amount of radish leaves and soak them in the medicine for 30 seconds, then place them in a plastic petri dish lined with filter paper to dry naturally in the shade, and put 8 2-year-old diamondback moths in each dish and place them in an observation room at 25℃. Observe after 48 hours, touch the insect body with a brush, and if there is no reaction, it is considered dead. Repeat 3 times, and set up a blank control without adding the medicine.

Alfalfa aphid activity test: About 30 alfalfa aphid nymphs were placed on a broad bean leaf disc and sprayed with a Potter spray tower with a spray volume of 2.5 mL. After treatment, they were placed in a 25°C observation room for cultivation. The results were investigated after 48 hours. The insects were touched with tweezers, and those without reaction were considered dead. A blank control without the addition of the drug was also set up.

3. Data statistics and analysis

The number of deaths of each treated target was counted, and the mortality rate was calculated and corrected. It was divided into four levels: A, B, C, and D. The mortality rate was 100%-75% for level A, 74%-50% for level B, 49%-25% for level C, and 24%-0% for level D. The test results are shown in Table 2.

Table 2 Insecticidal activity levels of some compounds of general formula I against oriental armyworm and diamondback moth

Note: - Not tested

As can be seen from Table 2, the trifluoroethylthio or trifluoroethylsulfinyl-containing meta-diamide compounds of the present invention have certain insecticidal activity against the lepidopteran pests Plutella xylostella and the hemiptera alfalfa aphid, especially compound I-3 maintains the same insecticidal activity as the lead compound bromofenac at the same test concentration. It is particularly noteworthy that compound I-3 still has a 100% lethal effect on Plutella xylostella at a test concentration of 0.625 mg/L, and it is worth further exploring its insecticidal activity and toxicity. It shows that the trifluoroethylthio or trifluoroethylsulfinyl-containing meta-diamide compounds provided by the present invention have excellent insecticidal activity against Plutella xylostella, and can be used as potential insecticide molecular structures for in-depth exploration.

Claims (6)

1. A kind of diamide compound containing trifluoro ethylthio or trifluoro ethylsulfinyl, has the structural formula as shown in formula I:

wherein:

R ₁ is selected from hydrogen, chlorine or bromine;

m is 0 or 1.

2. A process for the preparation of a trifluoroethylthio-or trifluoroethylsulfinyl-containing metadiamide according to claim 1, wherein the reaction scheme is as follows:

wherein R ₁, m are as defined in claim 1;

the preparation method of the reaction route comprises the following steps:

Refluxing the compound of the formula A in thionyl chloride for 3-6 hours to prepare corresponding fresh acyl chloride, and reacting the acyl chloride with the compound of the formula B in an organic solvent at the temperature of minus 20 ℃ to the reflux temperature for 2-18 hours under the action of potassium iodide to obtain a compound of the formula I (m=0, R ₁ =H);

wherein the organic solvent is selected from one or more of methanol, ethanol, propanol, isopropanol, dichloromethane, acetonitrile, tetrahydrofuran, chloroform, 1,4 dioxane, dimethyl sulfoxide or N, N-dimethylformamide and 1, 3-dimethyl-2-imidazolone.

3. The preparation method according to claim 2, wherein the reaction route is represented by the following formula:

wherein R ₁, m are as defined in claim 1;

the preparation method of the reaction route comprises the following steps:

Reacting a compound of formula I (m=0, r ₁ =h) with N-bromosuccinimide (NBS) and a base in an organic solvent at-20 ℃ to reflux temperature for 2-48 hours to obtain a compound of formula I (m=0, r ₁ =br);

The alkali is selected from one or more of sodium hydroxide, sodium bicarbonate, sodium carbonate and potassium carbonate;

The organic solvent is selected from one or more of methanol, dichloromethane, acetonitrile, tetrahydrofuran, chloroform, 1,4 dioxane, dimethyl sulfoxide, N-dimethylformamide and 1, 3-dimethyl-2-imidazolone.

4. The preparation method according to claim 2, wherein the reaction route is represented by the following formula:

wherein R ₁, m are as defined in claim 1;

the preparation method of the reaction route comprises the following steps:

The compound of formula I (m=0; r ₁ =br) is reacted in an organic solvent under the conditions of 0 ℃ to reflux temperature for 2 to 18 hours by the action of hydrogen peroxide and trifluoroacetic acid to obtain the compound of formula I (m= 1;R ₁ =br).

5. Use of a m-diamide compound containing a trifluoroethylthio group or a trifluoroethylsulfinyl group according to claim 1 for the preparation of an agricultural insecticide, wherein the insecticide is an insecticide for killing lepidopteran pests, hemipteran pests, etc.;

Or the pesticide is a pesticide for killing plutella xylostella and aphid.

6. A pesticidal composition comprising the trifluoroethylthio-or trifluoroethylsulfinyl-containing metadiamide compound according to claim 1 as an active ingredient and a pharmaceutically acceptable carrier.