An amide bactericide compound and application thereof

Abstract

The application discloses a compound of formula I and stereoisomers and salts thereof, wherein R is selected from H, halogen, C1-C4 alkyl and C1-C4 haloalkyl. The compound has excellent bactericidal effect.

Description

Technical Field

[0001] This invention belongs to the field of agricultural fungicides, specifically relating to a novel amide fungicide. This invention also relates to compositions containing the compounds of this invention and their applications. Background Technology

[0002] Amide fungicides are a new class of fungicides with low efficacy and toxicity, characterized by good efficacy, long-lasting control, and the ability to increase rice seed setting rate. These fungicides exhibit strong systemic activity and long-lasting effect, showing good control against diseases caused by deuteromycetes and basidiomycetes, such as sheath blight, smut, and damping-off. Amide fungicides generally work by inhibiting the activity of mitochondrial respiratory chain complex II (succinate-ubiquinone oxidoreductase) in pathogenic fungi, thus preventing the transfer of electrons from succinate to ubiquinone, resulting in the inability to synthesize ATP normally and ultimately leading to fungal death due to energy depletion.

[0003] Amide bactericides have become a hot research topic. More and more amide compounds with lower toxicity and greater environmental safety are being researched and developed. Summary of the Invention

[0004] This invention discloses a novel amide compound with excellent bactericidal activity, which can be used as a fungicide for crops.

[0005] Specifically, this invention discloses a compound of formula I, its stereoisomers, and its salts.

[0006]

[0007] I,

[0008] R is selected from H, halogens, C1-C4 alkyl groups and C1-C4 haloalkyl groups.

[0009] This invention also provides a method for preparing compound of formula I, its stereoisomers, and its salts, comprising reacting the acylated product obtained after reacting formula II and an acylation reagent with a compound of formula III to prepare compound I. The synthetic route is as follows:

[0010]

[0011] The molecule is selected from H, halogens, C1-C4 alkyl groups and C1-C4 haloalkyl groups.

[0012] The present invention also discloses a composition comprising the compounds of the present invention.

[0013] The compounds or compositions of the present invention have good applications in the prevention and control of plant diseases. Beneficial effects

[0014] The compounds of this invention exhibit superior bactericidal effects compared to existing amide compounds. Detailed Implementation

[0015] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated components or steps, without excluding other substances or steps.

[0016] Furthermore, to better illustrate the present invention, numerous specific details are provided in the following detailed embodiments.

[0017] Those skilled in the art will understand that the present invention can be practiced even without certain specific details. In some embodiments, materials, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0018] When the compounds of the present invention can exist in tautomer form, the meanings stated above and below shall apply where applicable.

[0019] The term "compound" should be understood to also include the corresponding tautomers, even if these tautomers are not explicitly mentioned in each case.

[0020] If the compounds of Formula I described in this invention have functional groups that can be ionized, they can also be used as agricultural salts or mixtures thereof.

[0021] In this invention, the halogen is typically fluorine, chlorine, bromine, or iodine, preferably fluorine, bromine, or chlorine. Correspondingly, this also applies to halogens combined with other structures, such as alkyl halogens. Alkyl halogens preferably have a chain length of 1 to 6 carbon atoms, more preferably a chain length of 1 to 4 carbon atoms. Examples of C1-C4 alkyl halogens include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl, and 2,2,2-trichloroethyl; preferably fluoromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, difluorochloromethyl, and dichlorofluoromethyl.

[0022] C1-C6 indicates the presence of 1 to 6 carbon atoms. The alkyl group appearing in the definition of substituent can be straight-chain or branched, and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, n-butyl, sec-butyl, isobutyl, or tert-butyl. The alkoxy group is derived from the mentioned alkyl group. Alkoxy groups are, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, and tert-butoxy; methoxy and ethoxy are preferred.

[0023] This invention first discloses a compound of formula I, its stereoisomers, and its salts.

[0024]

[0025] I,

[0026] R is selected from H, halogens, C1-C4 alkyl groups and C1-C4 haloalkyl groups.

[0027] In a preferred embodiment, R is a halomethyl group, preferably fluoromethyl, difluoromethyl, or trifluoromethyl.

[0028] The compounds particularly preferred in this invention are: .

[0029] In this specification, if there are any differences between chemical names and chemical structures, the structure is preferred. Generally, the compounds of this invention can be prepared by the methods described herein, unless further specified. The following synthetic schemes and examples are provided to further illustrate the content of this invention.

[0030] The compound of formula I of this invention was synthesized by the following synthetic scheme:

[0031]

[0032] R is selected from H, halogens, C1-C4 alkyl groups and C1-C4 haloalkyl groups.

[0033] Compound I is prepared by reacting the compound of formula II with an acylating reagent to form an acyl chloride compound, which is then combined with the compound of formula III. The acylating reagent is selected from thionyl chloride and oxalyl chloride. The reaction is preferably carried out in a solvent, which includes aromatic hydrocarbons such as benzene, xylene, and toluene; chlorinated hydrocarbons such as chlorobenzene, vinyl chloride, chloroform, and dichloromethane; the reaction temperature is 20-80°C; and the reaction is preferably carried out in the presence of a base, which is triethylamine, pyridine, potassium carbonate, sodium carbonate, etc., but is not limited to these.

[0034] Those skilled in the art will recognize that the chemical reactions described in this invention can be suitably used to prepare many other compounds of this invention, and that other methods for preparing the compounds of this invention are considered to be within the scope of this invention. For example, the synthesis of those non-illustrative compounds according to this invention can be successfully accomplished by those skilled in the art through modification methods, such as by appropriately protecting interfering groups, by utilizing other known reagents (in addition to those described in this invention), or by making some conventional modifications to the reaction conditions. Furthermore, the reactions disclosed in this invention or the known reaction conditions are also generally accepted to be applicable to the preparation of other compounds of this invention.

[0035] The present invention also provides a composition comprising a compound of formula I of the present invention and at least one adjuvant selected from surfactants, solid diluents and liquid diluents.

[0036] The application of the compounds or compositions described in this invention in the prevention and control of plant diseases.

[0037] The compounds of this invention are generally used as the active ingredient of a fungicide in a composition, i.e., a formulation, and typically also include a pesticide-acceptable surfactant and a carrier. The carrier can be a solid carrier or a liquid carrier.

[0038] The solid carriers include natural or synthetic clays and silicates, such as natural silica and diatomaceous earth; magnesium silicates, such as talc; magnesium aluminum silicates, such as kaolinite, kaolin, montmorillonite and mica; silica, calcium carbonate, light calcium carbonate; calcium sulfate; limestone; sodium sulfate; ammonium salts, such as ammonium sulfate, hexamethylenediamine and urea, etc.

[0039] The liquid carriers include water and organic solvents. When water is used as a solvent or diluent, the organic solvents can also be used as auxiliaries or antifreeze additives. Useful liquefied gaseous fillers or carriers are those liquids that are gaseous at standard temperatures and pressures, such as aerosol propellants, like halogenated hydrocarbons, and butane, propane, nitrogen, and carbon dioxide, etc. Suitable organic solvents include aromatic hydrocarbons, such as benzene, xylene, toluene, etc.; chlorinated hydrocarbons, such as chlorobenzene, vinyl chloride, chloroform, dichloromethane, etc.; aliphatic hydrocarbons, such as petroleum fractions, cyclohexane, light mineral oils; alcohols, such as isopropanol, butanol, ethylene glycol, glycerol, and cyclohexanol, etc.; and their ethers and esters; ketones, such as acetone, cyclohexanone, and dimethylformamide and N-methylpyrrolidone; vegetable oils, such as soybean oil, rapeseed oil, and cottonseed oil, etc., but not limited to these.

[0040] Suitable surfactants (adjuvants, emulsifiers, dispersants, protective colloids, wetting agents, and binders) include all common ionic and nonionic substances, such as ethoxylated nonylphenol, polyalkylene glycol ethers of straight-chain or branched alcohols, reaction products of alkylphenols with ethylene oxide and / or propylene oxide, reaction products of fatty acid amines with ethylene oxide and / or propylene oxide, as well as fatty acid esters, alkyl sulfonates, alkyl sulfates, alkyl ether sulfates, alkyl ether phosphates, aryl sulfates, ethoxylated arylalkylphenols (such as tristyryl-phenol-ethoxylate), and ethoxylated and propoxylated arylalkylphenols such as sulfated and phosphorylated arylalkylphenol-ethoxylates and -ethoxy and -propoxylates. The presence of a surfactant is necessary if one of the active ingredients and / or one of the inert carriers is insoluble in water and the application is carried out in water.

[0041] The compositions of this invention can be applied in their formulation or in the form of use prepared therefrom, such as aerosols, capsule suspensions, thermal fogging concentrates, encapsulated granules, fine granules, seed coating agents for seed treatment, powders that can be sprinkled, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, large granules, microgranules, oil-dispersible powders, oil-miscible flow concentrates, oil-miscible liquids, gaseous agents (under pressure), gas-producing products, foaming agents, pastes, suspension concentrates, emulsion concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, powders and granules, water-soluble and water-dispersible granules or tablets, water-soluble or water-dispersible powders for seed treatment, wettable powders, natural and synthetic substances impregnated with active substances, and microcapsules in polymers and seed coating materials.

[0042] The formulations described in this invention may also contain other components, such as other fungicides, insecticides, herbicides, plant growth regulators, attractants, acaricides, nematicides, fertilizers, and safeners, which can be formulated together with liquid fertilizers or solid or granular fertilizer carriers such as ammonium nitrate and urea, or mixed with fine sand or soil.

[0043] This invention relates to the use of the compound or a composition containing the compound as a fungicide in agriculture or horticulture for controlling or preventing diseases in beneficial plants.

[0044] Within the scope of this invention, useful plants include the following plant species: cereals (wheat, barley, rye, oats, rice, corn, sorghum, and related species); sugar beets (sugar beets and forage sugar beets); pome fruits, stone fruits, and soft fruits (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, and blackberries); legumes (lentils, beans, peas, soybeans); oil crops (rapeseed, mustard, olives, sunflowers, coconuts, castor oil plants, cocoa beans, peanuts, or soybeans); and cucurbits (pumpkins, cucumbers, melons). ; fiber plants (cotton, flax, hemp, jute); citrus fruits (oranges, lemons, grapefruits, tangerines); vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, red peppers); laurel plants (avocados, camphor, camphor) or plants such as tobacco, nuts, coffee, eggplant, sugarcane, tea, pepper, grapevines, hops, bananas, and natural rubber plants, along with turf, ornamental and forest plants such as flowers, shrubs, broad-leaved trees or evergreen trees such as conifers, and plant propagation materials.

[0045] The dosage of the composition described in this invention varies depending on weather conditions, formulation, timing of application, method of application, area of ​​application, and target crop.

[0046] Preparation Examples

[0047] The present invention will be further described below with reference to the embodiments. Unless otherwise specified, the raw materials, reagents, etc. used to prepare the compounds of the present invention are commercially available or can be prepared by conventional methods in the art.

[0048] Example 1: Synthesis of N-(3-isopropoxyphenyl)-2-methylsulfonyl-4-(trifluoromethyl)benzamide (PPN-FL-01)

[0049]

[0050] In a 1000 mL reaction flask equipped with a stirrer, reflux condenser, and thermometer, N2 was introduced, followed by the addition of 100 mL dichloroethane, 0.1 mol 2-methylsulfonyl-4-trifluoromethylbenzoic acid, and 0.1 g DMF. The mixture was heated to reflux, and 0.12 mol thionyl chloride was added dropwise over 2 hours. HPLC analysis showed that 2-methylsulfonyl-4-trifluoromethylbenzoic acid was <0.5%. After the reaction was complete, 0.2 mol pyridine was added, followed by 100 mL dichloroethane. 0.2 mol m-isopropoxyaniline was added dropwise at 0°C over 2 hours. The mixture was then slowly heated to room temperature and reacted for 10 hours. HPLC analysis confirmed the reaction was complete. 200 mL ethyl acetate and 100 mL water were added, and the mixture was stirred for 20 minutes. After standing and separating the layers, the organic phase was desolvated, and crystallized from ethyl acetate to obtain a white solid product with a purity of 98% and a yield of 70%.

[0051] 1 H NMR (500 MHz, DMSO) δ 10.72 (s, 1H,H-1), 8.27 (m, 2H,H-2, H-2'), 7.99 (d, J = 7.7 Hz, 1H,H-3), 7.33 (m, 1H,H-4), 7.25 (t, J = 8.1 Hz, 1H,H-5), 7.18 (d, J = 8.0 Hz, 1H,H-6), 6.71 (dd, J = 8.1, 1.9 Hz, 1H,H-7), 4.63 – 4.52 (m,J = 6.0 Hz,1H,H-8), 3.47 (s, 3H,H-9), 1.28 (d, J = 6.0 Hz, 6H,H-10).

[0052] Example 2 Synthesis of N-(3-isopropoxyphenyl)-2-methylsulfonyl-4-(trifluoromethyl)benzamide

[0053] In a 1000 mL reaction flask equipped with a stirrer, reflux condenser, and thermometer, N2 was introduced, followed by the addition of 100 mL dichloroethane, 0.1 mol 2-methylsulfonyl-4-trifluoromethylbenzoic acid, and 0.1 g DMF. The mixture was heated to reflux, and 0.12 mol oxaloyl chloride was added dropwise over 2 hours. HPLC analysis showed that 2-methylsulfonyl-4-trifluoromethylbenzoic acid was <0.5%. After the reaction was complete, 0.2 mol pyridine was added, followed by 100 mL dichloroethane. 0.2 mol m-isopropoxyaniline was added dropwise at 0°C over 2 hours. The mixture was then slowly heated to room temperature and reacted for 10 hours. HPLC analysis confirmed the reaction was complete. 200 mL ethyl acetate and 100 mL water were added, and the mixture was stirred for 20 minutes. After standing and separating the layers, the organic phase was desolvated, and crystallized from ethyl acetate to obtain a white solid product with a purity of 98% and a yield of 65%.

[0054] 1 H NMR (500 MHz, DMSO) δ 10.72 (s, 1H,H-1), 8.27 (m, 2H,H-2, H-2'), 7.99 (d, J = 7.7 Hz, 1H,H-3), 7.33 (m, 1H,H-4), 7.25 (t, J = 8.1 Hz, 1H,H-5), 7.18 (d, J = 8.0 Hz, 1H,H-6), 6.71 (dd, J= 8.1, 1.9 Hz, 1H,H-7), 4.63 – 4.52 (m,J = 6.0 Hz,1H,H-8), 3.47 (s, 3H,H-9), 1.28 (d, J = 6.0 Hz, 6H,H-10).

[0055] Bioactivity assay

[0056] 1. Preparation of test reagents

[0057] 1.1 Experimental Materials and Reagents

[0058] PPN-FL-01 (98.5% technical grade), fluoxetine (98.5%), acetone (AC), Tween 80, water.

[0059] 1.2 Preparation of the drug

[0060] (1) Preparation of 1% PPN-FL-01 mother liquor: prepared using acetone as solvent.

[0061] (2) Preparation of 0.1% fluoroamide mother liquor: prepared using acetone as solvent.

[0062] (3) Preparation of 0.5% Tween 80 solution: Prepared with water as solvent, and used as an emulsifier solution.

[0063] (4) Preparation of test reagent: Prepare the required test concentration using the mother liquor and 0.5% Tween 80 solution.

[0064] (5) CK is a water blank control.

[0065] 2. Preparation of PDA culture medium:

[0066] (1) Weighing and boiling: Weigh 700g of peeled potatoes according to the culture medium formula. Cut the potatoes into small pieces and put them in a pot. Add 3500ml of water and heat on a heater until boiling. Maintain for 20-30 minutes. Filter the hot filtrate through a measuring cup using two layers of gauze. Discard the residue. Add water to the filtrate to bring it up to 3500ml.

[0067] (2) Heating and dissolving: Put the filtrate into a pot, add 70g of glucose and 55g of agar, then heat over low heat and stir constantly with a glass rod to prevent the agar from sticking to the bottom or overflowing. After the agar is completely dissolved, add water to the required amount.

[0068] (3) Dispensing: According to the experimental requirements, dispense the prepared culture medium into 250ml Erlenmeyer flasks (100ml) and 500ml Erlenmeyer flasks (300ml).

[0069] (4) High pressure sterilization: 121℃ for 20min.

[0070] 3. Testing Methods

[0071] The test compounds were prepared at concentrations of 0.0155 ppm, 0.125 ppm, and 0.50 ppm. Using the growth rate method, 11.11 ml of the prepared reagent was added to a conical flask containing 100 ml of culture medium, cooled to 50-60°C, and mixed thoroughly. The mixture was then poured into agar plates. After the plates cooled, a 6 mm diameter mycelial cake was inoculated into the center of each plate, and the plates were capped. Each treatment was repeated three times, and the plates were incubated in an incubator with 65% humidity and 25°C.

[0072] 4. Survey Time and Methods

[0073] Three days after application, the diameter of the colonies was measured using the cross-sectional method, and the average value was taken to calculate the inhibition rate of each treatment on the mycelial growth of rice sheath blight fungus.

[0074]

[0075] 5. Data analysis and statistics

[0076] The activity of the compounds is expressed in terms of fungal growth inhibition (0 = no growth inhibition, 80% to 99% means good to very good inhibition, 100% = complete inhibition).

[0077] Table 1. Data on the control efficacy of the compounds of this invention against rice sheath blight pathogen.

[0078]

[0079] As can be seen from Table 1 and the results, the bactericidal effect of the compound of the present invention is significantly better than that of fluoroamide at low concentrations.

[0080] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A compound of formula I and its salt, in, R is selected from C1-C4 haloalkyl groups.

2. The compound of formula I and its salt according to claim 1, characterized in that, R is a halomethyl group.

3. The compound of formula I and its salt according to claim 1, characterized in that, R represents fluoromethyl, difluoromethyl, and trifluoromethyl.

4. The compound of formula I and its salts according to claim 1, characterized in that, The compound is:

5. A method for preparing the compound of formula I according to any one of claims 1-4 and its salt, Its features are, The compound of formula I was prepared by reacting compounds of formula II and formula III, and the synthetic route is as follows: The R group is defined as described in claims 1-4.

6. A composition, characterized in that, It includes the compound according to any one of claims 1-4.

7. The use of the compound according to any one of claims 1-4 or the composition according to claim 6 in the prevention and control of plant diseases.

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