Imidopyridine thiophene acetamide compound as well as preparation method and application thereof
By developing an imidinethiophene acetamide compound, the problem of difficulty in preventing and controlling plant bacterial and nematode insects in the prior art is solved, and effective prevention and control of powdery mildew, rust and southern root knot nematodes is achieved.
Patent Information
- Application Number
- CN202311507722.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-11-09
- Publication Date
- 2025-03-18
AI Technical Summary
There is a lack of a drug in the prior art that can effectively prevent and control plant bacterial damage and target nematode insects. Especially in the fields of agriculture and forestry, existing nematode insecticides have resistance problems.
An imidinethiophene acetamide compound has been developed, with a specific structure of 8-chloro-N-[(2-thiopheneethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-formamide. This compound is prepared by specific synthetic methods and applied to pest control in agriculture, forestry or health fields.
This compound shows good bactericidal and nematodetic effects, can effectively prevent and treat plant diseases such as powdery mildew and rust, and has an 80-100% insecticidal effect on southern root knot nematodes.
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Figure CN119638689A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of fungicides, and specifically relates to an imidazole thiophene acetamide compound and a preparation method and application thereof. Background Art
[0002] my country is a large agricultural country. During the process of plant cultivation, plant fungal pests and nematode pests are inevitable problems. With the improvement of environmental requirements and the problem of agricultural fungicide resistance, it is urgent to develop a drug that can be used for both plant fungal pests and nematode control to meet production needs.
[0003] Underground nematodes mainly harm plant roots, causing the plant roots to form beaded knots of varying sizes. In severe cases, multiple knots are linked together to form nodules of varying sizes. When the plant is severely damaged, the leaves become small and yellow, the plant becomes dwarfed, and even wilts and dies. Root-knot nematodes mainly infect crop roots, but sometimes they also infect tubers, bulbs, underground fruit pods, and leaves of greenhouse crops (leaf galls). Plant root rots, hindering the supply of root nutrients to the aboveground parts, leading to nutritional imbalance and dwarfing of the aboveground parts of the plant, and the leaves gradually turn yellow and shrink. In severe cases, crop yields are reduced by more than 75%.
[0004] Imididine sulfonamide nematicides have been developed, and fluazaindolizine is a new sulfonamide nematicide developed by DuPont, which has a different mode of action from existing products. CN105175413 discloses the synthesis and application of the compound.
[0005]
[0006] The fungicidal activity of amide compounds has been reported, such as Pesticides. 2017, 56(08): 566-568, which discloses the synthesis of the compound fluopyram and its fungicidal activity.
[0007]
[0008] In the prior art, imidazole thiophene acetamide compounds have not been reported. Summary of the invention
[0009] The purpose of the present invention is to provide an imidazole thiophene acetamide compound and a preparation method and application thereof. The imidazole thiophene acetamide compound is 8-chloro-N-[(2-thiopheneethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide, which has good bactericidal and nematicidal abilities and can be used for the prevention and control of pests and diseases in agriculture, forestry or sanitation.
[0010] In order to solve the problems of the prior art, the technical solution adopted by the present invention is:
[0011] An imidazole thiophene acetamide compound, wherein the imidazole thiophene acetamide compound is 8-chloro-N-[(2-thiopheneethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide, and its structural formula is as follows:
[0012]
[0013] The preparation method of the above-mentioned imidinidine thiophene acetamide compound comprises the following steps:
[0014] Step 1, Preparation of 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride
[0015] 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carboxylic acid reacts with thionyl chloride to generate 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride. When the thionyl chloride is in large excess, the thionyl chloride is recovered after the reaction, or the reaction is carried out in an inert solvent, and the solvent is evaporated after the reaction to obtain the acid chloride;
[0016] Step 2, after 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride is dissolved in a solvent, it is reacted with 2-thiopheneethylamine under stirring at room temperature overnight in the presence of an organic base or an inorganic base to produce the target product 8-chloro-N-[(2-thiopheneethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide.
[0017] The reaction formula is as follows:
[0018]
[0019] As an improvement, the solvent in step 1 is toluene, ethylene dichloride, methylene chloride, or methyl isobutyl ketone.
[0020] As an improvement, the solvent used to dissolve the 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride in step 2 is dichloromethane, chloroform, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, N,N-dimethylformamide or dimethyl sulfoxide.
[0021] As an improvement, the organic base in step 2 is pyridine, alkyl-substituted pyridine, triethylamine, tripropylamine, or saturated alkyl-substituted amine, and the inorganic base is sodium carbonate, potassium carbonate, sodium hydroxide, or sodium bicarbonate.
[0022] Application of the above-mentioned imidinidine thiophene acetamide compounds in the preparation of bactericidal or nematode compositions.
[0023] A fungicide or nematode composition comprises an active ingredient and an agriculturally or forestry acceptable carrier, wherein the active ingredient is 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide as claimed in claim 1, and the weight content of the active ingredient is 1-99%.
[0024] The above-mentioned fungicide or nematode compound is used in the preparation of products related to the prevention or treatment of cucumber powdery mildew, wheat powdery mildew, cucumber downy mildew or soybean rust. The fungicide or nematode composition is applied to the disease to be controlled or the medium where it grows at an effective dose of 100 grams to 1000 grams per hectare.
[0025] A method for controlling underground nematodes of plants, wherein the above compound is applied to control underground nematodes of plants at an effective dosage of 10g-1000g per hectare, preferably 100g-1000g per hectare.
[0026] Beneficial effects:
[0027] Compared with the prior art, the present invention provides an imidazole thiophene acetamide compound and a preparation method and application thereof. The imidazole thiophene acetamide compound has high bactericidal and nematicidal effects. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Figure 1 The H NMR spectrum of 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide 1 H NMR (400 MHz, CDCl3). DETAILED DESCRIPTION
[0029] The present invention is further described below in conjunction with specific embodiments. Synthesis examples and biological test results can be used to further illustrate the present invention, but are not intended to limit the present invention.
[0030] The 2-ethylaminothiophene (general formula (II)) used in the following examples is a commercially available product.
[0031] Example 1 Synthesis of 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride
[0032] Among them, 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride (general formula (I)) is prepared by referring to the preparation method described in World Pesticides, 2019, 41(3):54-56. The reaction formula is:
[0033]
[0034] Under nitrogen protection, 8-chloro-6-(trifluoromethyl)-imidazole [1,2a] pyridine-2-carboxylic acid (13.3 g, 0.05 mol), 80 ml of dichloroethane and N-formylpiperidine (0.45 g, 0.004 mol) were added to a 250 mL four-necked round-bottom flask equipped with a mechanical stirrer, a condenser, a constant pressure dropping funnel and a thermometer. A solution of thionyl chloride (9.5 g, 0.08 mol) dissolved in 20 ml of dichloroethane was added dropwise at room temperature. After the addition was completed in 1 hour, the mixture was kept at room temperature for 1 hour, and then heated to reflux for 2 hours. The excess thionyl chloride and solvent dichloroethane were evaporated to obtain 13 g of solid with a yield of 91.9%.
[0035] Example 2 Synthesis of 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide
[0036] The reaction formula is:
[0037]
[0038] The acid chloride obtained in Example 1 was dissolved in 100 mL of ethyl acetate, cooled to 5°C, and triethylamine (6.1 g, 0.06 mol) was added dropwise. After the addition of triethylamine, 2-ethylaminothiophene (6.4 g, 0.05 mol) was added dropwise at 5°C. The mixture was stirred at room temperature overnight. After the reaction was complete, the mixture was washed with 100 mL of water and concentrated to obtain a solid. The solid was washed with 100 mL of ether and dried to obtain 16.2 g of a light brown solid powder with a yield of 86.8%, a melting point of 196-198°C, and a 1H NMR (400MHz, CDC13) δ: 3.18(t,2H), 3.74(t,2H), 6.91(d,1H), 7.16(s,1H), 7.26(s,1H), 7.66(d,1H), 7.48(s,1H), 8.31(s,1H), 8.49(s,1H).
[0039] Example 38 Synthesis of 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide The acid chloride obtained in Example 1 was dissolved in 100 mL of dichloromethane, cooled to 5°C, and tributylamine (11.1 g, 0.06 mol) was added dropwise. After the addition of tributylamine, 2-ethylaminothiophene (6.4 g, 0.05 mol) was added dropwise at 5°C. The mixture was stirred at room temperature overnight. After the reaction was complete, the mixture was washed with 100 mL of water and concentrated to obtain a solid. The solid was washed with 100 mL of ether and dried to obtain 15.5 g of a light brown solid powder with a yield of 82.9%, a melting point of 196-198°C, and a 1H NMR (400MHz, CDC13) δ: 3.18(t,2H), 3.74(t,2H), 6.91(d,1H), 7.16(s,1H), 7.26(s,1H), 7.66(d,1H), 7.48(s,1H), 8.31(s,1H), 8.49(s,1H).
[0040] Example 4 Synthesis of 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide The acid chloride obtained in Example 1 was dissolved in 100 mL of N,N-dimethylformamide, cooled to 5°C, and pyridine (4.8 g, 0.06 mol) was added dropwise. After the addition of pyridine, 2-ethylaminothiophene (6.4 g, 0.05 mol) was added dropwise at 5°C. The mixture was stirred at room temperature overnight. After the reaction was complete, 200 mL of water was added and the solid was filtered to obtain a solid. The solid was washed with 100 mL of ether and dried to obtain 14.8 g of a light brown solid powder with a yield of 79.1%. The melting point was 196-198°C, and the reaction mixture was 1H NMR (400MHz, CDC13) δ: 3.18(t,2H), 3.74(t,2H), 6.91(d,1H), 7.16(s,1H), 7.26(s,1H), 7.66(d,1H), 7.48(s,1H), 8.31(s,1H), 8.49(s,1H).
[0041] Example 58 Synthesis of 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide
[0042] The acyl chloride obtained in Example 1 was dissolved in 100 mL of N, N-dimethylformamide, cooled to 5°C, and potassium carbonate (8.3 g, 0.06 mol) was added in batches. After potassium carbonate was added, 2-ethylaminothiophene (6.4 g, 0.05 mol) was added dropwise at 5°C, and stirred at room temperature overnight. After the reaction was complete, 200 mL of water was added, and the solid was filtered to obtain a solid. The solid was washed with 100 mL of ether and dried to obtain 13.7 g of a light brown solid powder with a yield of 73.4%, a melting point of 196-198°C, and a 1H NMR (400MHz, CDC13) δ: 3.18(t,2H), 3.74(t,2H), 6.91(d,1H), 7.16(s,1H), 7.26(s,1H), 7.66(d,1H), 7.48(s,1H), 8.31(s,1H), 8.49(s,1H).
[0043] Example 6 Synthesis of 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide The acid chloride obtained in Example 1 was dissolved in 100 mL of ethyl acetate and cooled to 5°C. 2-ethylaminothiophene (6.4 g, 0.05 mol) was added dropwise. After the addition was completed, 30% sodium hydroxide solution (8 g, 0.06 mol) was added dropwise. The temperature was not higher than 5°C. After the addition was completed, the mixture was stirred at room temperature overnight. After the reaction was complete, the mixture was washed with 100 mL of water and concentrated to obtain a solid. The solid was washed with 100 mL of ether and dried to obtain 15.1 g of a light brown solid powder with a yield of 81%. The melting point was 196-198°C, and the reaction mixture was dried for 1 h. NMR (400MHz, CDC13) δ: 3.18(t,2H), 3.74(t,2H), 6.91(d,1H), 7.16(s,1H), 7.26(s,1H), 7.66(d,1H), 7.48(s,1H), 8.31(s,1H), 8.49(s,1H).
[0044] Bactericidal activity assay
[0045] The fungicidal activity of the synthesized compounds was determined in vivo using a greenhouse pot experiment. For specific methods, please refer to the fungicide volume of the Standard Operating Procedures for Pesticide Biological Activity Tests compiled by Kang Zhuo and Gu Baogen, SOP-SC-1101 Cucumber Powdery Mildew Potting Method; SOP-SC-1120 Soybean Rust Potting Method; SOP-SC-1116 Wheat Powdery Mildew Potting Method; SOP-SC-1098 Cucumber Downy Mildew Potting Method. The results are as follows:
[0046]
[0047] In the table, A indicates that the control effect is 80% or more; B indicates that the control effect is 60-80% (excluding 80%); C indicates that the control effect is 40-60% (excluding 60%); and D indicates that the control effect is less than 40% (excluding 40%). It can be seen from the above results that the compounds of the present invention show good control effects on powdery mildew and rust.
[0048] Nematicidal activity assay
[0049] The biological activity of the compound obtained in the present invention against southern root-knot nematode was tested by the second-instar larvae immersion method.
[0050] The compound of the present invention is dissolved in an organic solvent and diluted to 100 mg / L by adding a 0.1% Triton aqueous solution. 100 μL of the drug solution and 100 μL of nematode solution (50 second-instar larvae) are mixed in a 96-well culture plate, and each treatment is repeated 3 times; a Triton aqueous solution containing only solvent is used as a blank control. After the 96-well plate is placed in an incubator at 25°C for 24 and 48 hours, the death situation is checked under a stereomicroscope and the nematode mortality rate is calculated. The calculation formula is: mortality rate (%) = number of dead nematodes (pieces) / total number of tested nematodes (pieces) × 100%; the indoor toxicity results of the compound of the present invention to southern root-knot nematodes are 80-100%.
[0051] Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, including combining various technical features in any other suitable manner. These simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.
Claims
1. Imidinidine thiophene acetamide compounds, characterized in that: The imidazole thiophene acetamide compound is 8-chloro-N-[(2-thiopheneethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide, and its structural formula is as follows:
2. The method for preparing the imidazole thiophene acetamide compound according to claim 1, characterized in that: The following steps are involved: Step 1, Preparation of 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carboxylic acid reacts with thionyl chloride to generate 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride. When the thionyl chloride is in large excess, the thionyl chloride is recovered after the reaction, or the reaction is carried out in an inert solvent, and the solvent is evaporated after the reaction to obtain the acid chloride; Step 2, after 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride is dissolved in a solvent, it is reacted with 2-thiopheneethylamine under stirring at room temperature overnight in the presence of an organic base or an inorganic base to produce the target product 8-chloro-N-[(2-thiopheneethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide.
3. The method for preparing the imidazole thiophene acetamide compound according to claim 2, characterized in that: In step 1, the solvent is toluene, ethylene dichloride, methylene chloride, or methyl isobutyl ketone.
4. The method for preparing imidazole thiophene acetamide compounds according to claim 2, characterized in that: The solvent used to dissolve 8-chloro-6-(trifluoromethyl)-imidazo[1,2a]pyridine-2-carbonyl chloride in step 2 is dichloromethane, chloroform, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, N,N-dimethylformamide or dimethyl sulfoxide.
5. The method for preparing imidazole thiophene acetamide compounds according to claim 2, characterized in that: In step 2, the organic base is pyridine, alkyl-substituted pyridine, triethylamine, tripropylamine, or saturated alkyl-substituted amine, and the inorganic base is sodium carbonate, potassium carbonate, sodium hydroxide, or sodium bicarbonate.
6. Use of the imidinidine thiophene acetamide compound according to claim 1 in preparing a bactericidal or nematode composition.
7. A bactericidal or nematode composition, characterized in that: The invention comprises an active ingredient and an agriculturally or forestry acceptable carrier, wherein the active ingredient is the 8-chloro-N-[(2-thienylethyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxamide as claimed in claim 1, and the weight content of the active ingredient is 1-99%.
8. Use of the fungicide or nematode composition according to claim 7 in the preparation of products for preventing or treating cucumber powdery mildew, wheat powdery mildew, cucumber downy mildew or soybean rust; the fungicide or nematode composition is applied to the disease to be controlled or the medium in which it grows at an effective dose of 100 g to 1000 g per hectare.
9. A method for controlling underground nematodes of plants, characterized in that: The fungicide or nematode composition according to claim 7 is applied to control underground nematodes of plants at an effective dosage of 10 g to 1000 g per hectare.