Indane picolinamide compound as well as preparation method and application thereof
By developing indanpyridinamide compound N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridin-3-formamide, the problem of lack of effective fungicides in the prior art was solved, and effective prevention and control of plant fungal diseases was achieved, and wide application prospects were achieved.
Patent Information
- Application Number
- CN202311492070.9
- 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
Indanpyridinamide compounds and their applications have not yet appeared in the prior art, and it is difficult to effectively solve the bacterial agent needs for resistance problems in agriculture and forestry.
A indanpyridinamide compound, specifically N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridin-3-formamide, was developed, and a preparation method and application thereof were provided for bactericidal as an active ingredient.
This compound has good bactericidal activity, can effectively prevent and control plant fungal diseases, and has a wide range of application prospects in agriculture, forestry and sanitation.
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Figure CN119638619A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of fungicides, and specifically relates to an indane pyridine amide compound and a preparation method and application thereof. Background Art
[0002] The problem of agricultural fungicide resistance has always accompanied the use of fungicides and has also driven the continuous research and development of the pesticide industry. Therefore, it is necessary to continuously invent new and improved compounds and compositions with fungicidal activity. 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.
[0003]
[0004] Fluopyram
[0005] In the prior art, there is no report on indane pyridine amide compounds and their application. Summary of the invention
[0006] The object of the present invention is to provide an indane pyridine amide compound and a preparation method and application thereof. The indane pyridine amide compound is specifically N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide, which has good bactericidal activity as an active ingredient and can be used for the prevention and treatment of diseases in agriculture, forestry or health.
[0007] In order to solve the problems of the prior art, the technical solution adopted by the present invention is:
[0008] An indane pyridine amide compound, wherein the indane pyridine amide compound is N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide, and its structural formula is as follows:
[0009]
[0010] A method for preparing indane pyridine amide compounds comprises the following steps: 4-(trifluoromethyl)-pyridine-3-carboxylic acid reacts with thionyl chloride to generate 4-(trifluoromethyl)-pyridine-3-carbonyl chloride; 4-(trifluoromethyl)-pyridine-3-carbonyl chloride reacts with 7-fluoro-1,1,3-trimethyl-4-aminoindan under the catalysis of an organic base or an inorganic base to generate a target product, N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide.
[0011] The above method specifically comprises the following steps:
[0012] 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 the acyl chloride;
[0013] Step 2, dissolving the 4-(trifluoromethyl)-pyridine-3-carbonyl chloride prepared in step 1 in a solvent, adding an organic base or an inorganic base and a 7-fluoro-1,1,3-trimethyl-4-aminoindan solution, and carrying out a catalytic reaction at room temperature overnight to generate the target product N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide.
[0014] The reaction formula is as follows:
[0015]
[0016] As an improvement, the solvent in step 1 is toluene, ethylene dichloride, methylene chloride, or methyl isobutyl ketone.
[0017] As an improvement, 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 base is an organic base such as pyridine, alkyl-substituted pyridine, triethylamine, tripropylamine or saturated alkyl-substituted amine; the inorganic base is such as sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide or sodium bicarbonate.
[0018] The indanyl pyridine amide compounds are used in the preparation of drugs for controlling agricultural diseases or forestry diseases.
[0019] A fungicide composition comprises an active component and a carrier acceptable to agriculture or forestry, wherein the active component is the indanyl pyridine amide compound and the weight content thereof is 1-99%.
[0020] A method for controlling plant diseases, comprising applying the fungicide composition at an effective dosage of 10g-1000g per hectare to the disease to be controlled or the medium where it grows.
[0021] As an improvement, the disease is wheat powdery mildew, cucumber powdery mildew, soybean rust or cucumber downy mildew.
[0022] As an improvement, the effective dose is 100g-500g per hectare applied to the disease to be controlled or the medium in which it grows.
[0023] Beneficial effects:
[0024] The invention provides an indane pyridine amide compound and a preparation method and application thereof. The indane pyridine amide compound is N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide, has fungicidal activity, can be used for preventing and controlling plant fungal diseases, and has good application prospects.
[0025] The bactericidal composition of the present invention is dissolved or dispersed in a carrier or formulated as a preparation as an active component so as to be more easily dispersed when used as a bactericidal agent. 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 appropriate surfactants, plant growth regulators or fertilizers, etc. can be added according to actual conditions. BRIEF DESCRIPTION OF THE DRAWINGS
[0026] Figure 1 The H NMR spectrum of N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide 1 H NMR (400 MHz, CDCl3). DETAILED DESCRIPTION
[0027] 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.
[0028] Reaction:
[0029]
[0030] 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.
[0031] The compound of general formula II is a commercially available product.
[0032] Example 14 Synthesis of 4-(Trifluoromethyl)-pyridine-3-carbonyl chloride
[0033] The reaction formula is:
[0034]
[0035] 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%.
[0036] Example 2 Synthesis of N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide
[0037] The acyl 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, a solution of 7-fluoro-1,1,3-trimethyl-4-aminoindane (9.7 g, 0.05 mol) dissolved in 30 mL of ethyl acetate 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 15.6 g of off-white solid powder. The yield is 85%, the melting point is 155-156℃, 1HNMR (400MHz, CDC13) δ: 0.06(s,6H), 1.47(d,3H), 1.74(d,1H), 2.32(d,1H), 3.4(m,1H), 6.95(d,1H), 7.31(d,1H), 7.34(d,1H), 7.72(d,1H), 8.97(d,1H), 8.98(s,1H), 9.02(s,1H).
[0038] Example 3 Synthesis of N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide
[0039] 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, a solution of 7-fluoro-1,1,3-trimethyl-4-aminoindane (9.7 g, 0.05 mol) dissolved in 30 mL of dichloromethane 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 g of off-white solid powder. The yield is 82%, the melting point is 155-156℃, 1HNMR (400MHz, CDC13) δ: 0.06(s,6H), 1.47(d,3H), 1.74(d,1H), 2.32(d,1H), 3.4(m,1H), 6.95(d,1H), 7.31(d,1H), 7.34(d,1H), 7.72(d,1H), 8.97(d,1H), 8.98(s,1H), 9.02(s,1H).
[0040] Example 4 Synthesis of N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide
[0041] 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, a solution of 7-fluoro-1,1,3-trimethyl-4-aminoindane (9.7 g, 0.05 mol) dissolved in 30 mL of N, N-dimethylformamide 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. The solid was filtered to obtain a solid. The solid was washed with 100 mL of ether and dried to obtain an off-white solid powder 13. .7g, yield 75%, melting point 155-156℃, 1HNMR (400MHz, CDC13) δ: 0.06(s,6H), 1.47(d,3H), 1.74(d,1H), 2.32(d,1H), 3.4(m,1H), 6.95(d,1H), 7.31(d,1H), 7.34(d,1H), 7.72(d,1H), 8.97(d,1H), 8.98(s,1H), 9.02(s,1H).
[0042] Example 5 Synthesis of N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide
[0043] 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 the addition of potassium carbonate, a solution of 7-fluoro-1,1,3-trimethyl-4-aminoindane (9.7 g, 0.05 mol) dissolved in 30 mL of N, N-dimethylformamide 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 an off-white solid powder. 13g, yield 71%, melting point 155-156℃, 1HNMR (400MHz, CDC13) δ: 0.06(s, 6H), 1.47(d, 3H), 1.74(d, 1H), 2.32(d, 1H), 3.4(m, 1H), 6.95(d, 1H), 7.31(d, 1H), 7.34(d, 1H), 7.72(d, 1H), 8.97(d, 1H), 8.98(s, 1H), 9.02(s, 1H).
[0044] Example 6 Synthesis of N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide
[0045] The acid chloride obtained in Example 1 was dissolved in 100 mL of ethyl acetate, cooled to 5°C, and a solution of 7-fluoro-1,1,3-trimethyl-4-aminoindane (9.7 g, 0.05 mol) dissolved in 30 mL of ethyl acetate was added dropwise. After the addition was completed, a 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 12.4 g of off-white solid powder with a yield of 68%, a melting point of 155-156°C, and a temperature of 1H NMR (400MHz, CDC13) δ: 0.06 (s, 6H), 1.47 (d, 3H), 1.74 (d, 1H), 2.32 (d, 1H), 3.4 (m, 1H), 6. 95(d,1H), 7.31(d,1H), 7.34(d,1H), 7.72(d,1H), 8.97(d,1H), 8.98(s,1H), 9.02(s,1H).
[0046] Bactericidal activity assay
[0047] 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:
[0048]
[0049] 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.
[0050] 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. An indane pyridine amide compound, characterized in that: The indan pyridine amide compound is N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide, and its structural formula is shown below:
2. A method for preparing the indane pyridine amide compound according to claim 1, characterized in that: The following steps are involved: 4-(Trifluoromethyl)-pyridine-3-carboxylic acid reacts with thionyl chloride to generate 4-(trifluoromethyl)-pyridine-3-carbonyl chloride, and 4-(trifluoromethyl)-pyridine-3-carbonyl chloride reacts with 7-fluoro-1,1,3-trimethyl-4-aminoindan in the presence of an organic base or an inorganic base to generate the target product N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide.
3. The method according to claim 2, characterized in that The specific steps include: 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 the acyl chloride; Step 2, dissolving the 4-(trifluoromethyl)-pyridine-3-carbonyl chloride prepared in step 1 in a solvent, adding an organic base or an inorganic base and a 7-fluoro-1,1,3-trimethyl-4-aminoindan solution, and carrying out a catalytic reaction at room temperature overnight to generate the target product N-(7-fluoro-1,1,3-trimethyl-4-indanyl)-4-trifluoromethylpyridine-3-carboxamide.
4. The method according to claim 3, characterized in that: In step 1, the solvent is toluene, ethylene dichloride, methylene chloride, or methyl isobutyl ketone.
5. The method according to claim 3, 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 base is an organic base such as pyridine, alkyl substituted pyridine, triethylamine, tripropylamine or saturated alkyl substituted amine; the inorganic base is such as sodium carbonate, potassium carbonate, potassium hydroxide, sodium hydroxide or sodium bicarbonate.
6. Use of the indane pyridine amide compound according to claim 1 in the preparation of drugs for controlling agricultural diseases or forestry diseases.
7. A bactericidal composition, characterized in that: The fungicide composition comprises an active component and an agricultural or forestry acceptable carrier, wherein the active component is the indane pyridine amide compound according to claim 1, and the weight content of the active component is 1-99%.
8. A method for controlling plant diseases, characterized in that: The fungicidal composition according to claim 7 is applied to the disease to be controlled or the medium where it grows at an effective dosage of 10 g to 1000 g per hectare.
9. The method for controlling plant diseases according to claim 8, characterized in that: The disease is wheat powdery mildew, cucumber powdery mildew, soybean rust or cucumber downy mildew.
10. The method for controlling plant diseases according to claim 8, characterized in that: The effective dose is 100g-500g per hectare applied to the disease to be controlled or the medium in which it grows.