Pyridine thiophene acetamide compound as well as preparation method and application thereof

Abstract

The invention discloses a pyridine thiophene acetamide compound as well as a preparation method and application thereof. 4-(trifluoromethyl) pyridine-3-formic acid reacts with thionyl chloride to generate 4-(trifluoromethyl) pyridine-3-formyl chloride, and the 4-(trifluoromethyl) pyridine-3-formyl chloride reacts in organic alkali such as pyridine, alkyl substituted pyridine, triethylamine, tripropylamine, saturated alkyl substituted amine, triethylamine, trimethylamine and the like to generate 4-(trifluoromethyl) pyridine-3-formyl chloride. The target product N-[(2-thiophene ethyl]-4-(trifluoromethyl) pyridine-3-formamide with the structural formula of # imgabs0 is generated by reacting 4-(trifluoromethyl) pyridine-3-formamide with 2-thiophene ethylamine under the catalysis of sodium carbonate, potassium carbonate, sodium hydroxide, sodium bicarbonate and the like. The compound disclosed by the invention has nematicidal activity, can be used for preventing and treating underground nematodes of plants, and has a good application prospect.

Description

Technical Field

[0001] The invention belongs to the field of killing plant nematodes, and specifically relates to a pyridinethiophene acetamide compound and a preparation method and application thereof. Background Art

[0002] 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%.

[0003] Imididine sulfonamide nematicides have been developed, and fluazaindol izine 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.

[0004]

[0005] In the prior art, there is no report on pyridinethiopheneacetamide compounds with the structure shown in the present invention. Summary of the invention

[0006] The object of the present invention is to provide a pyridinethiopheneacetamide compound and a preparation method and application thereof. The pyridinethiopheneacetamide compound can be used for the prevention and treatment of agricultural and forestry nematodes.

[0007] In order to solve the problems of the prior art, the technical solution adopted by the present invention is as follows:

[0008] A pyridinethiopheneacetamide compound, wherein the pyridinethiopheneacetamide compound is N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide, and the structural formula is as follows:

[0009]

[0010] The preparation method of the above-mentioned pyridinethiopheneacetamide compound comprises the following steps:

[0011] Step 1, 4-(trifluoromethyl)pyridine-3-carboxylic acid reacts with thionyl chloride to generate 4-(trifluoromethyl)pyridine-3-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 4-(trifluoromethyl)pyridine-3-carbonyl chloride;

[0012] Step 2: After the 4-(trifluoromethyl)pyridine-3-carbonyl chloride prepared in step 1 is dissolved in a solvent, it is reacted with 2-thiopheneethylamine in the presence of an organic base or an inorganic base at room temperature overnight to generate the target product N-[(2-thiopheneethyl]-4-(trifluoromethyl)pyridine-3-carboxamide.

[0013] The reaction formula is as follows:

[0014]

[0015] As an improvement, the solvent in step 1 is toluene, ethylene dichloride, methylene chloride, or methyl isobutyl ketone.

[0016] As an improvement, the solvent in step 2 is selected from dichloromethane, chloroform, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, N,N-dimethylformamide or dimethyl sulfoxide; the organic base is pyridine, alkyl-substituted pyridine, triethylamine, tripropylamine or saturated alkyl-substituted amine; and the inorganic base is sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide, or sodium bicarbonate.

[0017] The above-mentioned pyridinethiopheneacetamide compounds are used in the preparation of insecticides for underground nematodes of plants.

[0018] A nematicidal composition comprises an active component and an agricultural or forestry acceptable carrier, wherein the active component is the pyridinethiopheneacetamide compound according to claim 1, and the weight content of the active component is 1-99%.

[0019] The above method for controlling underground nematodes of plants comprises applying the above nematicidal composition at an effective dosage of 10 g to 1000 g per hectare to control underground nematodes of plants.

[0020] Specifically, the nematicidal composition of the present invention can be applied in the form of a preparation. The compound N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide is used as an active ingredient, dissolved or dispersed in a carrier or formulated into a preparation so that it is easier to disperse when used as a nematicide. For example, it can be made into a wettable powder or an emulsifiable concentrate. In these compositions, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can be added. According to the actual situation, a suitable surfactant, plant growth regulator or fertilizer, etc. can be added.

[0021] Beneficial effects:

[0022] The present invention discloses a pyridinethiophene acetamide compound and a preparation method and application thereof. The pyridinethiophene acetamide compound is N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide, which can be applied to the prevention and treatment of agricultural and forestry nematodes and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The H NMR spectrum of N-[(2-thienylethyl)-4-(trifluoromethyl)pyridine-3-carboxamide 1 H NMR (400 MHz, CDCl 3 ). DETAILED DESCRIPTION

[0024] 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.

[0025] The reaction formula is:

[0026]

[0027] The compound of general formula I can be obtained by referring to the preparation method described in the literature "World Pesticides", 2019, 41(3): 54-56.

[0028] The compound of general formula II is a commercially available product.

[0029] Example 14 Synthesis of 4-(Trifluoromethyl)-pyridine-3-carbonyl chloride

[0030] The reaction formula is:

[0031]

[0032] Under nitrogen protection, 4-(trifluoromethyl)pyridine-3-carboxylic acid (9.6 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 1 hour of dropwise addition, 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 9.7 g of acyl chloride with a yield of 93%.

[0033] Example 2 Synthesis of N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide

[0034] 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, and 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 12.8 g of a light gray solid powder with a yield of 85%. The melting point was 79-81°C, 1H NMR (400 MHz, CDC13) δ: 3.20 (t, 2H), 3.77 (m, 2H), 6.34 (s, 1H), 6.86 (d, 1H), 6.98 (t, 1H), 7.22 (d, 1H), 7.58 (d, 1H), 8.74 (s, 1H), 8.81 (d, 1H).

[0035] Example 3 Synthesis of N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide

[0036] The acyl 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 12.2 g of a light gray solid powder with a yield of 81%, a melting point of 79-81°C, and a 1H NMR (400MHz, CDC13) δ: 3.20(t,2H), 3.77(m,2H), 6.34(s,1H), 6.86(d,1H), 6.98(t,1H), 7.22(d,1H), 7.58(d,1H), 8.74(s,1H), 8.81(d,1H).

[0037] Example 4 Synthesis of N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide

[0038] The acyl 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, 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 11.3 g of a light gray solid powder with a yield of 75%, a melting point of 79-81°C, and a 1H NMR (400MHz, CDC13) δ: 3.20(t,2H), 3.77(m,2H), 6.34(s,1H), 6.86(d,1H), 6.98(t,1H), 7.22(d,1H), 7.58(d,1H), 8.74(s,1H), 8.81(d,1H).

[0039] Example 5 Synthesis of N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide

[0040] 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 overnight at room temperature. 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 10.7 g of a light gray solid powder with a yield of 71.5%, a melting point of 79-81°C, and a 1H NMR (400MHz, CDC13) δ: 3.20(t,2H), 3.77(m,2H), 6.34(s,1H), 6.86(d,1H), 6.98(t,1H), 7.22(d,1H), 7.58(d,1H), 8.74(s,1H), 8.81(d,1H).

[0041] Example 6 Synthesis of N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide

[0042] The acid chloride obtained in Example 1 was dissolved in 100 mL of ethyl acetate, cooled to 5°C, and 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, it was stirred at room temperature overnight. After the reaction was complete, it 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 12 g of light gray solid powder with a yield of 80%. The melting point was 79-81°C, and the reaction temperature was 1H NMR (400MHz, CDC13) δ: 3.20(t,2H), 3.77(m,2H), 6.34(s,1H), 6.86(d,1H), 6.98(t,1H), 7.22(d,1H), 7.58(d,1H), 8.74(s,1H), 8.81(d,1H).

[0043] Biological Activity Assay Examples

[0044] The biological activity of the compounds of the present invention against southern root-knot nematodes was tested by the second-instar larvae immersion method.

[0045] The N-[(2-thienylethyl]-4-(trifluoromethyl)pyridine-3-carboxamide 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 the 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 the solvent is used as a blank control. After the 96-well plate is placed in an incubator at 25° C. and cultured for 24 and 48 hours, the death situation is checked under a stereomicroscope and the mortality rate of the nematodes 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 compounds of the present invention to southern root-knot nematodes are 80-100%.

[0046] The above description is not intended to limit the present invention. Any technician familiar with the present invention may use the above disclosed technical content to change or modify it into an equivalent embodiment with equivalent changes. However, any simple modification, equivalent change and modification made to the above embodiment according to the technical essence of the present invention without departing from the technical solution of the present invention still belongs to the protection scope of the technical solution of the present invention.

Claims

1. A pyridinethiopheneacetamide compound, characterized in that: The pyridinethiopheneacetamide compound is N-[(2-thiopheneethyl]-4-(trifluoromethyl)pyridine-3-carboxamide, and the structural formula is as follows:

2. The method for preparing the pyridinethiopheneacetamide compound according to claim 1, characterized in that: The following steps are included: Step 1, 4-(trifluoromethyl)pyridine-3-carboxylic acid reacts with thionyl chloride to generate 4-(trifluoromethyl)pyridine-3-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 4-(trifluoromethyl)pyridine-3-carbonyl chloride; Step 2: After the 4-(trifluoromethyl)pyridine-3-carbonyl chloride prepared in step 1 is dissolved in a solvent, it is reacted with 2-thiopheneethylamine in the presence of an organic base or an inorganic base at room temperature overnight to generate the target product N-[(2-thiopheneethyl]-4-(trifluoromethyl)pyridine-3-carboxamide.

3. The method for preparing pyridinethiopheneacetamide compounds according to claim 2, characterized in that: The solvent described in step 1 is toluene, ethylene dichloride, methylene chloride, or methyl isobutyl ketone.

4. The method for preparing pyridinethiopheneacetamide compounds according to claim 2, characterized in that: In step 2, the solvent is selected from dichloromethane, chloroform, hexane, benzene, toluene, ethyl acetate, acetonitrile, tetrahydrofuran, dioxane, N,N-dimethylformamide or dimethyl sulfoxide; the organic base is pyridine, alkyl substituted pyridine, triethylamine, tripropylamine or saturated alkyl substituted amine; the inorganic base is sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide, or sodium bicarbonate.

5. Use of the pyridinethiopheneacetamide compound according to claim 1 in the preparation of an insecticide for underground nematodes of plants.

6. A nematicidal composition, characterized in that: The nematicidal composition comprises an active component and an agricultural or forestry acceptable carrier, wherein the active component is the pyridinethiopheneacetamide compound according to claim 1, and the weight content of the active component is 1-99%.

7. A method for controlling underground nematodes of plants, characterized in that: The nematicide composition according to claim 6 is applied to control underground nematodes of plants at an effective dosage of 10 g to 1000 g per hectare.

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