Compounds, compositions thereof and their use as nematicides

Abstract

The present invention provides compounds of formula (I) or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof as well as their agricultural compositions and their use in the treatment or control of parasitic nematodes or nematode infection in crop plants.

Description

Field of the Invention

[0001] The present invention relates to compounds having nematicidal activity, agricultural compositions thereof, and the use of such compounds for treating or controlling parasitic nematodes or nematode infections in crops. Background of the Invention

[0003] Nematodes are active, flexible, elongated organisms that live on moist surfaces or in liquid environments, including water films in soil and within the moist tissues of other organisms. Many species of nematodes have evolved into highly successful parasites of plants and animals, causing significant economic losses to agriculture. Nematodes are known to affect the yield, growth, and health of crops and plants. Physiological changes in host plant roots caused by nematode larvae and / or adults can lead to the formation of galls, which damage the root vascular system. Root elongation may cease completely, causing the root system to shrink and fail to provide adequate water and nutrients, leading to chlorosis and / or wilting of leaves, as well as stunted growth, all of which can result in low yields or even death. Furthermore, nematodes induce physiological effects that make plant roots more susceptible to attack by bacteria and / or fungi, including those to which plants are otherwise resistant. This attack can lead to severe secondary decay. Therefore, controlling plant-parasitic nematodes is crucial for achieving high crop yields.

[0004] Due to the widespread increase in anthelmintic resistance in nematodes, nematodes continue to pose a threat despite the availability of multiple therapeutic agents. There is a continuous need for new compounds that are more effective, cheaper, less toxic, safer for the environment, or have different mechanisms of action. Summary of the Invention

[0005] The present invention provides a compound of formula (I),

[0006]

[0007]

[0008] or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof,

[0009] Among them, ring A, R 1 , and 'm' are as defined in the detailed description. The present invention also relates to agricultural compositions of the compound of formula (I) and their use in treating or controlling parasitic nematodes or nematode infections of crops.

[0010] Description of the Invention

[0011] definition:

[0012] When describing the embodiments of the present invention, specific terminology has been selected for clarity. However, the present invention is not limited to the specific terminology selected, and it is understood that these specific terms encompass all technical equivalents that operate in a similar manner to achieve similar purposes. It is understood that any numerical ranges recited herein encompass all subranges therein. In addition, unless otherwise indicated, the percentages of components in the compositions are expressed as weight percentages.

[0013] The terms "a" or "an," as used herein, are defined as one or more. The terms "including" and / or "having," as used herein, are defined as comprising (ie, open language).

[0014] The term "salt" includes salts prepared from bases or acids, including inorganic or organic bases and inorganic or organic acids. Examples of such salts include, but are not limited to, acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, camphorsulfonate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, propionate, dodecyl sulfate, ethanesulfonate, fumarate, glucoheptonate, gluconate, glutamate, glycolamidobenzenesulfonate, hexylresorcinate, hydrazine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothioate, iodide, thiocyanate ... Examples of salts derived from inorganic bases include, but are not limited to, aluminum, ammonium, calcium, copper, iron, ferrous, lithium, magnesium, manganous, potassium, sodium, and zinc.

[0015] The wavy lines used in this article Indicates the point of attachment of a bond to the rest of the molecule.

[0016] Certain compounds of this patent application can exist in stereoisomeric forms (e.g., diastereomers and enantiomers) and geometric configurations (E and Z configurations). With respect to all compounds described by general formula (I), this patent application covers these stereoisomeric forms, geometric configurations, and mixtures thereof. Within the scope of the synthesis or separation of specific stereoisomers taught by the prior art, the different stereoisomeric forms of this patent application can be separated from each other by methods known in the art, or a given isomer can be obtained by stereospecific or asymmetric synthesis. Tautomeric forms and mixtures of compounds described herein are also within the scope of consideration. It should also be understood that the compounds of the present invention can exist in solvated forms (e.g., hydrates) as well as unsolvated forms, and that the present invention covers all such forms.

[0017] Therefore, the present invention provides a compound of formula (I),

[0018]

[0019] or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, wherein

[0020] for

[0021]

[0022]

[0023] The compounds of the present invention or their agrochemically acceptable salts or N-oxides thereof are suitable for use alone, but are generally applied in the form of a composition wherein one or more compounds are suitably formulated into the composition, usually with at least one agrochemically acceptable excipient.

[0024] Therefore, the present invention also includes a composition for treating or controlling plant parasitic nematodes or nematode infections, the composition comprising an effective amount of one or more compounds of the present invention. In some embodiments, the one or more compounds of the present invention are present in an amount effective to treat or prevent nematode infections in plants.

[0025] In one embodiment, the present invention provides a compound of the formula:

[0026]

[0027]

[0028]

[0029] or an agrochemically acceptable salt or N-oxide thereof.

[0030] In one embodiment, the present invention provides a compound of the following formula:

[0031]

[0032] or an agrochemically acceptable salt or N-oxide thereof.

[0033] In one embodiment, the present invention provides a compound of the following formula:

[0034]

[0035] or an agrochemically acceptable salt or N-oxide thereof.

[0036] In one embodiment, the present invention provides a compound of the following formula:

[0037]

[0038] or an agrochemically acceptable salt or N-oxide thereof.

[0039] In one embodiment, the present invention provides a compound of the following formula:

[0040]

[0041] or an agrochemically acceptable salt or N-oxide thereof.

[0042] In one embodiment, the present invention provides an agricultural composition comprising a compound of formula (I),

[0043]

[0044] or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, and at least one agrochemically acceptable excipient, wherein

[0045] for

[0046]

[0047]

[0048] In one embodiment, the present invention provides an agricultural composition comprising a compound of the following formula:

[0049]

[0050]

[0051] or an agrochemically acceptable salt or N-oxide thereof, and at least one agrochemically acceptable excipient.

[0052] In one embodiment, the present invention provides an agricultural composition comprising a compound of the following formula:

[0053]

[0054] or an agrochemically acceptable salt or N-oxide thereof, and at least one agrochemically acceptable excipient.

[0055] In one embodiment, the present invention provides an agricultural composition comprising a compound of the following formula:

[0056]

[0057] or an agrochemically acceptable salt or N-oxide thereof, and at least one agrochemically acceptable excipient.

[0058] In one embodiment, the present invention provides an agricultural composition comprising a compound of the following formula:

[0059]

[0060] or an agrochemically acceptable salt or N-oxide thereof, and at least one agrochemically acceptable excipient.

[0061] In one embodiment, the present invention provides an agricultural composition comprising a compound of the following formula:

[0062]

[0063] or an agrochemically acceptable salt or N-oxide thereof, and at least one agrochemically acceptable excipient.

[0064] According to one embodiment, the agricultural composition comprises one or more agrochemically acceptable excipients, selected from one or more of surfactant, disintegrant, filler or carrier or diluent, spreading agent, colorant, anticaking agent, bonding agent, buffer or pH adjusting agent or neutralizing agent, pigment, stabilizer, defoamer or defoamer, penetrant, structurant, wetting agent, adhesive, antifreeze or freezing point depressant, chelating agent or complexing agent or sequestrant, preservative. However, it will be appreciated by those skilled in the art that, without departing from the scope of the invention, other agrochemically acceptable excipients may be used. These agrochemically acceptable excipients are commercially produced and can be obtained by multiple companies.

[0065] According to one embodiment, the surfactant used in the composition of the present invention includes one or more of an emulsifier, a wetting agent and a dispersant. According to one embodiment, the surfactant used in the composition includes one or more of an anionic surfactant, a nonionic surfactant and a polymeric surfactant.

[0066] Anionic surfactants include one or more of the following, but are not limited to: fatty acid salts, polycarboxylates, alkyl ether sulfates, alkyl sulfates, alkyl aryl sulfates, alkyl aryl sulfonates, aryl sulfonates, lignin sulfonates, alkyl diphenyl oxide disulfonates, polystyrene sulfonates, alkyl phosphate salts, alkyl aryl phosphates, styryl aryl phosphates, polyoxyethylene alkyl ether sulfate salts, sodium α-olefin sulfonate, alkylbenzene sulfonate or its salt, sodium lauroyl sarcosinate, sulfosuccinate, polyacrylate, alkyl ether phosphate, polyoxyethylene alkyl aryl phosphate salts, sulfosuccinate-monoesters and other diesters. Phosphate esters, isopropyl and butyl derivatives of alkylnaphthalenesulfonates, alkyl aryl ether phosphates, polyoxyethylene aryl ether phosphate salts, monoalkyl sulfosuccinates, aromatic hydrocarbon sulfonates, lauryl ammonium sulfate, soaps, soap substitutes, sodium alkyl sulfates, sodium lauryl sulfate, sodium dodecylbenzenesulfonate, sodium laurate, sodium laureth sulfate, sodium nonanoyloxybenzenesulfonate, alkyl carboxylates, sodium stearate, α-olefin sulfonates, naphthalenesulfonates, alkylnaphthalenesulfonic acid fatty acid salts, naphthalenesulfonic acid condensates-sodium salts, fatty alcohol sulfates, alkylnaphthalenesulfonic acid condensates-sodium salts, naphthalenesulfonic acid condensates with formaldehyde, or alkylnaphthalenesulfonates condensed with formaldehyde or its salts or derivatives. However, it will be understood by those skilled in the art that different anionic surfactants may be used without departing from the scope of the present invention.

[0067] Nonionic surfactants or polymeric surfactants include one or more but are not limited to polyol esters, polyol fatty acid esters, ethoxylated and propoxylated fatty alcohols, EO and PO block copolymers, diblock, triblock copolymers; polysorbates, alkyl polysaccharides, polyoxyethylene glycol, sorbitan derivatives, sorbitan fatty acid esters (Span) and their ethoxylated derivatives (Tween), cocamide monoethanolamine (MEA), decyl, narrow chain ethoxylates, oleyl alcohol, PEG-1 0, polysorbate, polysorbate 20, polysorbate 80, sorbitan, sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, stearyl alcohol, castor oil ethoxylate, polyethylene glycol ether, polyadduct of ethylene oxide and propylene oxide, polyoxyethylene sorbitan anhydride, fatty acid polyglycerol esters, polyoxyethylene alkyl ethers, polyoxyethylene alkyl aryl ethers, polyoxyethylene styryl aryl ethers, polyoxyethylene glycol alkyl ethers, alcohol ethoxylates (C6 to C 16 / 18Straight and branched alcohols), alcohol alkoxylates (various hydrophobes and EO / PO content and ratios), polyoxyethylene hydrogenated castor oil, salts or derivatives thereof. However, it will be understood by those skilled in the art that different nonionic surfactants or polymeric surfactants may be used without departing from the scope of the present invention.

[0068] According to one embodiment, the dispersant used in the composition includes, but is not limited to, one or more nonionic dispersants selected from polyvinyl pyrrolidone, polyvinyl alcohol, polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, ethoxylated fatty acids, fatty alcohol ethoxylates, alkyl ethoxylates, EO-PO blocks and graft copolymers; however, it should be understood by those skilled in the art that different nonionic dispersants may be used without departing from the scope of the present invention.

[0069] According to one embodiment, the dispersant used in the composition includes, but is not limited to, an anionic dispersant selected from one or more of the following: tris(styrylphenol)polyoxyethylene ether phosphate, lignin sulfonate, phenylnaphthalene sulfonate, alkali metal salts, alkylaryl sulfonate, alkyl sulfonate, a mixture of naphthalenesulfonic acid urea formaldehyde condensate sodium salt and phenolsulfonic acid formaldehyde condensate sodium salt, polycarboxylate, sodium alkylbenzene sulfonate, sodium salt of sulfonated naphthalene, sodium naphthalenesulfonate formaldehyde condensate, condensate of arylsulfonic acid and formaldehyde, polyaromatic hydrocarbon sulfonate, sodium alkylaryl sulfonate, and kraft lignin. However, it should be understood by those skilled in the art that different anionic dispersants may be used without departing from the scope of the present invention.

[0070] According to one embodiment, the wetting agent used in the composition includes, but is not limited to, one or more of the following: phenol naphthalene sulfonate, alkyl naphthalene sulfonate, sodium alkyl naphthalene sulfonate, sodium naphthalene sulfonate, dibutyl naphthalene sulfonic acid, alkyl aryl sulfonate, sodium dioctyl sulfosuccinate, polyoxyethoxylated fatty alcohols, alkyl sulfonate, alkyl benzene sulfonate, alkyl ether phosphate, alkyl ether sulfate, and alkyl sulfosuccinic acid monoester, salts thereof, or derivatives thereof. However, it should be understood by those skilled in the art that different wetting agents may be used without departing from the scope of the present invention.

[0071] According to one embodiment, the carrier used in the composition of the present invention includes, but is not limited to, one or more solid carriers, fillers, or diluents. According to another embodiment, the carrier includes a mineral carrier, a plant carrier, a synthetic carrier, or a water-soluble carrier. However, it will be understood by those skilled in the art that different carriers may be used without departing from the scope of the present invention.

[0072] Solid carriers include natural minerals such as clays (e.g., china clay, acid clay), kaolins (e.g., kaolinite, dickite, nacrite), synthetic and diatomaceous earth silica, mica (e.g., pyrophyllite), talc, silica (e.g., cristobalite) and quartz (e.g., attapulgite and sepiolite), vermiculite, synthetic laponite, pumice, bauxite, hydrated alumina, perlite, sodium bicarbonate, limestone, natural and synthetic silicates, silica, surface-modified silica, zeolites, diatomaceous earth, loess, thenardite, white carbon, slaked lime, synthetic silicic acid, starch, modified starch, cellulose, plant carriers (e.g., cellulose, rice husks, wheat flour, wood flour, starch, rice bran, wheat bran and soy flour), sodium caseinate, sucrose, thenardite, potassium pyrophosphate, tripolyphosphate, or derivatives or mixtures thereof.

[0073] According to one embodiment, the defoaming agent or defoaming agent used in the composition of the present invention includes but is not limited to one or more of silicon dioxide, siloxane, silicon dioxide, polydimethylsiloxane, alkyl polyacrylate, ethylene oxide / propylene oxide copolymer, silicone oil, magnesium stearate or its derivatives. Preferred defoaming agents include silicone emulsions (e.g., SRE, Wacker, or Rhodia ), long-chain alcohols, fatty acids, fluorine-containing organic compounds. However, it will be understood by those skilled in the art that different defoaming agents may be used without departing from the scope of the present invention.

[0074] According to one embodiment, the pH adjusting agent, buffer or neutralizing agent used in the composition includes organic or inorganic type acid and base and mixtures thereof. According to another embodiment, the pH adjusting agent, buffer or neutralizing agent includes but is not limited to one or more of organic acid, inorganic acid and alkali metal compound or its salt, derivative. According to one embodiment, organic acid includes but is not limited to one or more of citric acid, malic acid, adipic acid, fumaric acid, maleic acid, succinic acid and tartaric acid, or its salt, derivative, and monobasic salt, dibasic salt or ternary salt of these acids or their derivatives. According to one embodiment, inorganic acid salt includes but is not limited to one or more of alkali metal salts, such as sodium chloride, sodium nitrate, potassium nitrate, sodium sulfate, potassium sulfate, sodium monohydrogen phosphate, potassium monohydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, etc. A mixture can also be used to prepare pH adjusting agent, buffer or neutralizing agent. However, it should be understood by those skilled in the art that different pH adjusting agents can be used without departing from the scope of the present invention.

[0075] According to one embodiment, the anti-caking agent used in the composition includes but is not limited to one or more of the following: polysaccharides, fumed silica and precipitated silica (white carbon black), petroleum resin, Soap L sodium stearate, 700 polyoxyethylene (100) stearyl ether, sodium acetate, sodium metasilicate, sodium alkyl sulfosuccinate or its derivatives. However, it should be understood by those skilled in the art that different anti-caking agents can be used without departing from the scope of the present invention.

[0076] According to one embodiment, the spreading agent used in the composition includes, but is not limited to, a copolymer of maleic acid and a styrene compound, a (meth)acrylic acid copolymer, a fatty alcohol, a vegetable oil (e.g., cottonseed oil) or an inorganic oil, a petroleum fraction, a trisiloxane, a modified trisiloxane, or a derivative thereof. However, it will be understood by those skilled in the art that different spreading agents may be used without departing from the scope of the present invention.

[0077] According to one embodiment, the adhesive used in the composition includes, but is not limited to, one or more of the following: paraffin wax, polyamide resin, polyacrylate, polyoxyethylene, wax, latex, polyvinyl pyrrolidone, gum (e.g., xanthan gum), vegetable oil (e.g., cottonseed oil), inorganic oil, petroleum fraction, modified trisiloxane, polyethylene glycol, synthetic resin emulsion, salts thereof, or derivatives thereof. However, it will be understood by those skilled in the art that different adhesives may be used without departing from the scope of the present invention.

[0078] According to one embodiment, the structuring agent used in the composition includes, but is not limited to, one or more of a thickener, a viscosity modifier, a tackifier, a suspending aid, a rheology modifier, or an anti-settling agent. The structuring agent can prevent the active ingredient particles from settling after long-term storage.

[0079] According to one embodiment, the structuring agent used in the composition includes, but is not limited to, one or more of the following substances: polyacrylic acid, polysaccharide, cellulose derivative, copolymer of cellulose derivative, polyvinyl alcohol and its derivatives; clay, such as kaolin, montmorillonite, attapulgite; gum, such as guar gum, xanthan gum, gelatin, dextrin, fumed silica, a mixture of fumed silica and fumed alumina; swellable polymer, polyethylene glycol, stachyose; cellulose, such as hemicellulose, carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl ethyl cellulose, hydroxyethyl propyl cellulose, methyl hydroxyethyl cellulose, methyl cellulose; plant starch, such as corn starch and potato starch. However, it should be understood by those skilled in the art that different structuring agents can be used without departing from the scope of the present invention.

[0080] Preferred structurants include one or more of xanthan gum, aluminum silicate, hydroxypropyl methylcellulose, carboxymethylcellulose, methylcellulose, polysaccharides, alkaline earth metal silicates, clays, gelatin, and polyvinyl alcohol.

[0081] According to one embodiment, the antifreeze or freezing point depression agent used in the composition includes, but is not limited to, one or more polyols, such as ethylene glycol, diethylene glycol, dipropylene glycol, propylene glycol, glycerol, monohydric alcohol or polyhydric alcohol, glycol ether, glycerol. However, it should be understood by those skilled in the art that different antifreeze agents may be used without departing from the scope of the present invention.

[0082] According to one embodiment, the chelating agents or complexing agents or sequestrants used in the composition include, but are not limited to, one or more polycarboxylic acids such as polyacrylic acid and various hydrolyzed poly(methyl vinyl ether / maleic anhydride); N-hydroxyethyliminodiacetic acid, nitrilotriacetic acid (NTA), N,N,N',N'-ethylenediaminetetraacetic acid, N-hydroxyethyl-N,N',N'-ethylenediaminetriacetic acid and N,N,N',N",N"-diethylenetriaminepentaacetic acid; α-hydroxy acids such as citric acid, tartaric acid and glucose; Gluconic acid; orthophosphate, disodium phosphate, monosodium phosphate; condensed phosphates, such as sodium tripolyphosphate, tetrasodium pyrophosphate, sodium hexametaphosphate and sodium tetrapolyphosphate; ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), N-hydroxyethylethylenediaminetriacetic acid (HEDTA), ethylenediaminediacetic acid (EDDA), ethylenediaminebis(o-hydroxyphenylacetic acid) (EDDHA), cyclohexanediaminetetraacetic acid (CDTA), fulvic acid, uric acid, nucleic acids, cyclodextrin, humic acid, pyrophosphate. However, it will be understood by those skilled in the art that different chelating agents may be used without departing from the scope of the present invention.

[0083] According to one embodiment, the penetrant used in the composition includes, but is not limited to, one or more of alcohol, glycol, glycol ether, ester, amine, alkanolamine, amine oxide, quaternary ammonium compound, triglyceride, fatty acid ester, fatty acid ether, N-methylpyrrolidone, dimethylformamide, dimethylacetamide or dimethyl sulfoxide, polyoxyethylene trimethylolpropane monooleate, polyoxyethylene sorbitan monooleate, polyoxyethylene trimethylolpropane dioleate, polyoxyethylene trimethylolpropane trioleate, and polyoxyethylene sorbitan hexaoleate. However, it will be understood by those skilled in the art that different penetrants may be used without departing from the scope of the present invention.

[0084] According to one embodiment, the humectant is selected from (but not limited to) one or more polyoxyethylene / polyoxypropylene copolymers, particularly block copolymers. Other humectants include propylene glycol, monoethylene glycol, hexylene glycol, butylene glycol, ethylene glycol, diethylene glycol, polyethylene glycol, polypropylene glycol, glycerol, and the like; and polyol compounds such as propylene glycol ethers and their derivatives. However, those skilled in the art will appreciate that different humectants may be used without departing from the scope of the present invention.

[0085] According to one embodiment, the stabilizer used in the agricultural composition includes, but is not limited to, one or more peroxides (e.g., hydrogen peroxide and organic peroxides), zeolites, antioxidants (e.g., phenolic compounds, phosphoric acid compounds, ethylenediaminetetraacetic acid (EDTA), sodium sulfite, citric acid, citrate, etc.). However, it should be understood by those skilled in the art that other conventionally known stabilizers may be used without departing from the scope of the present invention.

[0086] According to one embodiment, the preservative is selected from one or more of formic acid and derivatives of 2H-isothiazol-3-one (so-called isothiazolinone derivatives), such as alkylisothiazolinone (e.g. 2-methyl-2H-isothiazol-3-one, MIT; chloro-2-methyl-2H-isothiazol-3-one, CIT), benzisothiazolinone (e.g. 1,2-benzisothiazol-3(2H)-one, BIT, which can be used as Type commercially available from Arch Biocides Ltd.) or 2-methyl-4,5-trimethylene-2H-isothiazol-3-one (MTIT), commercially available from Arch Biocides Ltd. or from Thor Chemie RS and from Lanxess MK, sodium propionate, sodium benzoate, propyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, potassium sorbate, potassium benzoate, phenylmercuric nitrate, phenylethyl alcohol, sodium, ethyl parahydroxybenzoate, methyl parahydroxybenzoate, butyl parahydroxybenzoate, benzyl alcohol, benzethonium chloride, cetylpyridinium chloride. Antioxidants include, but are not limited to, one or more imidazoles and imidazole derivatives (e.g., urocanic acid), 4,4′-thiobis-6-tert-butyl-3-methylphenol, 2,6-di-tert-butyl-p-cresol (BHT), pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)]propionate; and amine antioxidants. However, those skilled in the art will appreciate that other conventionally known preservatives may be used without departing from the scope of the present invention.

[0087] According to one embodiment, the pigments and colorants are selected from, but not limited to, synthetic chemicals from different manufacturers. The pigments and colorants can be water-soluble or water-insoluble and exist in the form of lakes. The dye can be a solvent dye, an acid dye, or a basic dye. Examples of such products include, but are not limited to, Unisperse Red 3855, Pigmosol Agro Red 3785, and pigment 15. However, it will be appreciated by those skilled in the art that other conventionally known pigments and colorants can be used without departing from the scope of the present invention.

[0088] According to one embodiment, the disintegrants used in the agricultural composition include, but are not limited to, one or more inorganic water-soluble salts, such as sodium chloride; water-soluble organic compounds, such as agar, hydroxypropyl starch, carboxymethyl starch ether, tragacanth gum, cross-linked sodium carboxymethyl cellulose, sodium tripolyphosphate, sodium hexametaphosphate, metal stearates, cellulose powder, dextrin, methacrylate copolymers, XL-10 (cross-linked polyvinyl pyrrolidone), polyvinyl pyrrolidone. However, it should be understood by those skilled in the art that other conventionally known disintegrants may be used without departing from the scope of the present invention.

[0089] According to one embodiment, the adhesive or binder used in the agricultural composition includes, but is not limited to, one or more of maltodextrin, carbohydrates (e.g., monosaccharides, disaccharides, oligosaccharides, and polysaccharides), complex organic matter, synthetic organic polymers or derivatives thereof, and combinations thereof. However, it should be understood by those skilled in the art that other conventionally known adhesives may be used without departing from the scope of the present invention.

[0090] According to one embodiment, the content of the agrochemically acceptable excipient ranges from 0.1% w / w to 98% w / w of the total composition. According to another embodiment, the content of the agrochemically acceptable excipient ranges from 0.1% w / w to 95% w / w of the total composition.

[0091] According to one embodiment, the agricultural composition is in the form of a solid, a liquid, a gel or a paste.

[0092] According to one embodiment, the solid agricultural composition may include powders, granules and dusts.

[0093] According to one embodiment, the agricultural composition may be in the form of a powder, including wettable powders and dispersible powders. According to one embodiment, the composition may be in the form of a granule, including broadcast granules, water-disintegrating granules, spheronized granules, pellets, extruded granules, and water-dispersible granules.

[0094] According to one embodiment, the composition is preferably water-dispersible granules, wettable powder, broadcasting granules, water-disintegrable granules or spheronized granules.

[0095] According to one embodiment, the composition is preferably a solid composition in the form of granules, including spheronized granules, extruded granules, water-disintegrating granules, wettable powders, water-dispersible granules, dustable powders (DP), powders for dry seed treatment (DS), water-disintegrating tablets or water-dispersible powders for slurry seed treatment (WS).

[0096] According to one embodiment, the liquid composition may include a suspension, an emulsion, a liquid suspension, a flow concentrate, an emulsifiable concentrate, a seed dressing, a suspoemulsion, or an aqueous emulsion. In another embodiment, the compound of the present invention may be suspended, emulsified, or dissolved in the liquid composition. Examples of particularly suitable formulation types include solutions, soluble concentrates (e.g., SL, LS), dispersible concentrates (DC), suspensions and suspension concentrates (e.g., SC, oil dispersions (OD), OF, FS), emulsifiable concentrates (e.g., EC), emulsions (e.g., EW, EO, ES, microemulsions (ME) and suspoemulsions (SE), suspension concentrates (FS) for seed treatment, and ultra-low volumes (ULV).

[0097] According to one embodiment, the liquid composition may include a liquid suspension or suspension concentrate (SC); suspoemulsion (SE), oil dispersion (OD), flowable concentrate (FC), or suspension concentrate (FS) for seed treatment, ultra low volume (ULV).

[0098] According to one embodiment, the composition has a particle size ranging from 0.1 micrometer to 50 micrometers. According to one embodiment, the composition is in the form of granules having a size ranging from 0.025 to 6 millimeters.

[0099] According to one embodiment, the composition is in the form of spherical granules, broadcasting granules, water-disintegrating granules or extruded granules, wherein the size of the granules ranges from 0.025 to 6 mm.

[0100] According to one embodiment, the granules are dispersed into microparticles with a size ranging from 0.1 microns to 50 microns.

[0101] In one embodiment, the present invention provides an agricultural composition comprising a compound of the present invention in an amount ranging from 1% w / w to 95% w / w of the total composition, and at least one agrochemically acceptable excipient in an amount ranging from 1% w / w to 99% w / w of the total composition, wherein the size of the microparticles is in the range of 0.1 microns to 50 microns.

[0102] In one embodiment, the present invention provides an agricultural composition comprising a compound of the present invention in the range of 1% w / w to 95% w / w of the total composition, at least one agrochemically acceptable excipient in the range of 1% w / w to 99% w / w of the total composition, wherein the size of the microparticles is in the range of 0.1 microns to 50 microns, and the size of the granules is in the range of 0.025 to 6 mm.

[0103] According to one embodiment, the present invention relates to a method for preparing an agricultural composition of the present invention, comprising a compound of the present invention in an amount ranging from 1% w / w to 95% w / w of the total composition and at least one agrochemically acceptable excipient in an amount ranging from 1% w / w to 99% w / w of the total composition.

[0104] In one embodiment, the present invention includes a method of treating or controlling parasitic nematodes or nematode infestations in plants comprising administering one or more compounds of the present invention.

[0105] In one embodiment, the present invention includes a method of treating or controlling parasitic nematodes or nematode infestations in plants comprising administering a composition of one or more compounds of the present invention.

[0106] In another embodiment, the present invention also encompasses the use of one or more compounds of the present invention for treating or controlling plant parasitic nematodes or nematode infections.

[0107] In another embodiment, the present invention also includes the use of a combination of one or more compounds of the present invention for treating or controlling plant parasitic nematodes or nematode infections.

[0108] The present invention also includes the use of a combination of one or more compounds of the present invention in the preparation of a medicament for treating or controlling plant parasitic nematodes or nematode infections.

[0109] In one embodiment, the present invention includes a method of treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of formula (I).

[0110]

[0111] or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, wherein

[0112] for

[0113]

[0114]

[0115] In one embodiment, the present invention includes a method of treating or controlling parasitic nematodes or nematode infestations in plants comprising administering a compound of the formula:

[0116]

[0117]

[0118] or an agrochemically acceptable salt or N-oxide thereof.

[0119] In one embodiment, the present invention comprises a method of treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of the formula

[0120]

[0121] or an agrochemically acceptable salt or N-oxide thereof.

[0122] In one embodiment, the present invention comprises a method of treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of the formula

[0123]

[0124] or an agrochemically acceptable salt or N-oxide thereof.

[0125] In one embodiment, the present invention comprises a method of treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of the formula

[0126]

[0127] or an agrochemically acceptable salt or N-oxide thereof.

[0128] In one embodiment, the present invention comprises a method of treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of the formula

[0129]

[0130] or an agrochemically acceptable salt or N-oxide thereof.

[0131] In another embodiment, the present invention provides an agricultural composition for treating or controlling parasitic nematodes or nematode infections in plants, wherein the composition comprises a compound of formula (I),

[0132]

[0133] or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, and at least one agrochemically acceptable excipient, wherein

[0134] for

[0135]

[0136]

[0137] In another embodiment, the present invention provides the use of an agricultural composition for treating or controlling parasitic nematodes or nematode infections in plants, wherein the composition comprises a compound of the formula:

[0138]

[0139]

[0140]

[0141] or an agrochemically acceptable salt or N-oxide thereof, and at least one agrochemically acceptable excipient.

[0142] Nematodes include parasitic nematodes such as root knot nematodes, cyst nematodes and lesion nematodes. The term "nematode" encompasses eggs, larvae, nymphs and adults of nematodes. Parasitic nematodes include, but are not limited to, the following species: root-knot nematodes (Meloidogyne spp.), such as Meloidogyne hapla (northern root-knot nematode), Meloidogyne incognita (southern root-knot nematode), Meloidogyne javanica (Javan root-knot nematode), Meloidogyne arenaria (peanut root-knot nematode), etc.; cyst nematodes, such as Globodera rostochiensis (potato golden nematode) and other Globodera species; Heterodera avenae (oat cyst nematode), Heterodera glycines (soybean cyst nematode), Heterodera schachtii (beet cyst nematode), Heterodera trifolii (clover cyst nematode), etc.; seed gall nematodes (Anguinas spp.); stem and leaf nematodes (Aphelenchoides spp.); sting nematodes (Belonolaimus longicaudatus, etc.); pine wood nematodes (Bursaphelenchus xylophilus, etc.); ring nematodes (Criconema, Criconemella, Criconemoides, Mesocriconema, etc.); stem ball nematodes (Ditylenchus destructor, Ditylenchus dipsaci, etc.); cone-bodied nematodes (Dolichodorus spp.); spiral nematodes (Helicotylenchus multicinctus, etc.); sheath nematodes (Hemicycliophora, Hemicriconemoides, etc.); lance-shaped nematodes (Hoploaimus spp.); pseudo root-knot nematodes (Nacobbus spp.); needle nematodes (Longidorus elongatus, etc.); short-bodied nematodes (Pratylenchus neglectus, Pratylenchus penetrans, etc.); piercing nematodes (Radopholus similis, etc.); kidney-shaped nematodes (Rotylenchus robustus, Rotylenchulus reniformis, etc.); thick root nematodes (Trichodorus, Paratrichodorus, etc.); dwarf nematodes (Tylenchorhynchus claytoni, etc.); citrus nematodes (Tylenchulus spp.); dagger nematodes (Xiphinema spp.); other plant-parasitic nematodes (such as Subanguina, Hypsoperine, Macroposthonia, Punctodera, Quinisulcius, etc.).

[0143] In the context of treating or controlling parasitic nematodes or nematode infestations in plants, an effective amount of one or more compounds of the present invention is an amount that reduces the nematode infestation in the plant, for example, as compared to the nematode infestation in the plant in the absence of application of one or more compounds of the present invention. The reduction in infestation can be assessed, for example, by measuring the number of viable or live nematodes in the plant and / or observing or assessing the extent of the disease, disorder, or condition caused by the nematode infestation.

[0144] The dosage of the compound of the present invention in plants depends on a variety of factors, such as its pharmacodynamic properties, route of administration, age, health and weight / mass of the plant, nature and extent of symptoms, frequency of treatment, and type of concurrent treatment (if any). The initial dosage of the compound of the present invention may be adjusted as needed based on the therapeutic effect.

[0145] In some embodiments, one or more compounds of the present invention are applied to plants at any suitable application rate, and one skilled in the art can select a suitable application rate. Factors to consider include, for example, the type of plant, the type of nematode, the type of plant disease, disorder, or condition, the severity of the nematode infestation, the severity of the plant disease, disorder, or condition, the age of the plant, the activity of the one or more compounds in the application, and the concentration of the one or more compounds in the application, or a combination thereof.

[0146] In some embodiments, the foliage of the plant and / or the soil surrounding the plant is contacted with one or more application compounds.

[0147] In some embodiments, nematodes infect plants and one or more compounds are applied to soil or plants. In some embodiments, one or more compounds are applied to soil before planting. In some embodiments, one or more compounds are applied to soil after planting. In some embodiments, one or more compounds are applied to soil using a drip irrigation system. In some embodiments, one or more compounds are applied to soil using an irrigation system. In some embodiments, one or more compounds are applied to plant roots or plant foliage (e.g., leaves, stems). In some embodiments, one or more compounds are plowed into soil or applied in a ditch. In some embodiments, one or more compounds are applied to seeds. In some embodiments, one or more compounds are applied as seed coating.

[0148] In one embodiment, the present invention also provides a method for protecting seeds from parasitic nematodes, comprising contacting the seeds with an effective amount of a compound of formula (I) or an agrochemically acceptable salt or N-oxide thereof (eg, as a composition described herein).

[0149] In addition, the composition of the present invention is also suitable for drip irrigation or sprinkler irrigation in addition to being suitable for application methods of other agricultural compositions.

[0150] According to one embodiment, specifically provided are compounds of formula (I) that reduce nematode populations by more than 90% at concentrations such as 100, 200, 250, 300, 500, or 1000 ppm compared to untreated controls.

[0151] According to one embodiment, there is provided a compound of formula (I) that reduces nematode populations by more than 80% at a concentration of, for example, 100, 200, 250, 300, 500 or 1000 ppm compared to an untreated control.

[0152] According to one embodiment, there is provided a compound of formula (I) that reduces nematode populations by more than 50% at a concentration of, for example, 100, 200, 250, 300, 500 or 1000 ppm compared to an untreated control.

[0153] In certain embodiments, nematode infestation plants, and one or more compositions are applied to soil or plants. In certain embodiments, one or more compositions are applied to soil before planting. In certain embodiments, one or more compositions are applied to soil after planting. In one embodiment, one or more compositions are applied to soil using a drip irrigation system. In certain embodiments, one or more compositions are applied to soil using an irrigation system. In certain embodiments, one or more compositions are applied to plant roots or plant foliage (e.g., leaves, stems). In certain embodiments, one or more compositions are plowed into soil or applied in a ditch. In certain embodiments, one or more compositions are applied to seeds.

[0154] In one embodiment, the method of the present application comprises applying the one or more compositions by a method selected from, but not limited to, pre-plant application, post-plant application, as a feed additive, drench, or foliar application.

[0155] In one embodiment, the term "plant" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, leaves, and fruits.

[0156] In one embodiment, the plant is a cultivated plant. In certain embodiments, the plant is a crop. In a further embodiment, the plant includes but is not limited to soybean, cotton, flax, hemp, jute, corn, tobacco, nuts, almonds, coffee, tea, pepper, grapevine, hops, wheat, barley, rye, oats, rice, corn, sorghum, apple, pear, plum, peach, banana, plantain, cherry, strawberry, raspberry, blackberry, beans, lentils, peas, soybean, rape, mustard, poppy, olive, sunflower, coconut, castor, cocoa, peanut, spinach, asparagus, lettuce, cabbage, carrot, onion, tomato, potato, bell pepper, cucumber, melon, pumpkin, sugarcane, beet, fodder beet, avocado, cinnamon, camphor, orange, tangerine, lemon, lime, grapefruit, latex plant, ornamental plant and / or turf grass.

[0157] Preparation method

[0158] The compounds described herein, including compounds of formula (I) and specific examples, are prepared using techniques known to those skilled in the art according to the reaction sequence shown in Scheme 1. In addition, specific bases, reagents, solvents, etc. are mentioned in the scheme, but it should be understood that other suitable bases, reagents, etc. can also be used, which are also included in the scope of the present invention. Modifications to the reaction conditions (such as temperature, reaction duration or a combination thereof) are also considered part of the present invention. The compounds obtained using the general reaction sequence may not be pure enough. These compounds can be purified using any organic compound purification method known to those skilled in the art, for example, crystallization, silica gel or alumina column chromatography, using different solvents mixed in appropriate proportions. All possible stereoisomers are included in the scope of the present invention.

[0159] Option 1:

[0160]

[0161] The compound of formula (I) can be prepared as shown in Scheme 1 by reacting a compound of formula (A) or a salt thereof with a compound of formula (B) or a salt thereof. The reaction can be carried out in the presence of a suitable base or in the absence of a base. The reaction can be carried out in the presence of a solvent or a solvent mixture at a suitable temperature range (e.g., -10°C to 100°C) to obtain a compound of formula (I). Suitable solvents include, but are not limited to, water, alcohol (methanol, ethanol, n-propanol, isopropanol, n-butanol or isobutanol), tetrahydrofuran, ethyl acetate and acetonitrile or a mixture thereof. Suitable bases may include, but are not limited to, organic bases (e.g., trimethylamine or diisopropylethylamine). Suitable bases may include, but are not limited to, inorganic bases (e.g., LiOH, NaOH, Na2CO3, KOH, KHCO3, K2CO3, Cs2CO3 or CsOH).

[0162] Example:

[0163] Example 1: (E)-N 2 Preparation of -{[2-(trifluoromethyl)phenyl]methylene}-L-arginine

[0164]

[0165] 2-Trifluoromethylbenzaldehyde (1 g) was added to a slurry of L-arginine (0.95 g) in ethanol (25 ml), and the mixture was stirred at room temperature for 6 hours. The resulting solid was filtered, washed with n-hexane (20 ml), and dried under high vacuum to give 1.08 g of (E)-N 2 -{[2-(trifluoromethyl)phenyl]methylene}-L-arginine as a solid). 1H NMR(400MHz,DMSO-d6)δ1.40-1.51(m,2H),1.69-1.74(m,1H),1.91-1.94( m,1H),3.08-3.09(m,2H),3.77(t,J=6.8Hz,1H),7.40-8.00(brs,4H),7.63 (t,J=7.2Hz,1H),7.72(t,J=7.6Hz,1H),7.78(d,J=7.6Hz,1H),8.16(d,J= 7.6Hz, 1H), 8.52 (d, J = 2.4Hz, 1H), 9.44 (s, 1H); ESI-MS: m / z331.10 (M+H)+.

[0166] Example 2: (E)-N 2 Preparation of -{[3-(trifluoromethyl)phenyl]methylene}-L-arginine

[0167]

[0168] 3-Trifluoromethylbenzaldehyde (1 g) was added to a solution of L-arginine (0.95 g) in ethanol (15 ml), stirred at room temperature for 5 hours, then n-hexane (15 ml) was added and stirred at room temperature for 2 hours. The resulting solid was filtered, washed with n-hexane (10 ml), and dried under high vacuum to obtain 1.59 g of (E)-N 2 -{[3-(Trifluoromethyl)phenyl]methylene}-L-arginine solid. 1H NMR (400MHz, DMSO-d6) δ1.47-1.52(m 2H),1.68-1.73(m,1H),1.90-1.94(m,1H),3.80-3.12(m,2H),3.75(t,J=6.8Hz,1H),7.20-7.90(br s,4H),7.71(t,J=7.6Hz,1H),7.77(d,J=8.0Hz,1H),8.01(d,J=7.6Hz,1H),8.05(s,1H),8.35(s,1H),9.39(br s,1H); ESI-MS: m / z331.10(M+H)+.

[0169] Example-3: (E)-N 2 Preparation of -[(4-chloro-2-hydroxyphenyl)methylene]-L-arginine

[0170]

[0171] L-arginine (1.07 g) was added to a solution of 4-chloro-2-hydroxybenzaldehyde (1.0 g) in ethanol (20 ml), stirred at room temperature for 18 h, and the resulting solid was filtered, washed with n-hexane (20 ml), and dried under high vacuum to obtain 1.28 g (E)-N 2 -[(4-Chloro-2-hydroxyphenyl)methylene]-L-arginine solid. 1 HNMR (400MHz, DMSO-d6) δ1.44-1.51(m,2H),1.75-1.91(m,2H),3.08-3.10(m,2H),3.91(t,J=6.4Hz,1H),6.54(dd,J=2.0,6.4H z,1H),6.65(d,J=1.6Hz,1H),7.28(d,J=8.4Hz,1H),7.44(brs,4H),8.41(brs,1H),9.39(brs,1H),14.53(brs,1H); ESI-MS: m / z 313.10(M+H) + .

[0172] Example-4: (E)-N 2 Preparation of -[(6-chloro-2-hydroxyphenyl)methylene]-L-arginine

[0173]

[0174] L-arginine (1.07 g) was added to a solution of 6-chloro-2-hydroxybenzaldehyde (1.0 g) in ethanol (20 ml) and stirred at room temperature for 4 hours. The solid was filtered, washed with n-hexane (20 ml), and dried under high vacuum to obtain 1.64 g (E)-N2 -[(6-Chloro-2-hydroxyphenyl)methylene]-L-arginine solid. 1 HNMR(400MHz,DMSO-d6)δ1.45-1.54(m,2H),1.76-1.95(m,2H),3.10-3.16(m,2H),4.06(t,J=6.4Hz,1H),6.64-6.67(m,2H), 7.22(dd,J=0.4,8.0Hz,1H),7.55(brs,4H),8.72(d,J=5.6Hz,1H),9.33(brs,1H),15.25(brs,1H); ESI-MS:m / z313.50(M+H) + .

[0175] Example-5: (E)-N 2 Preparation of -[(3-fluoro-2-hydroxyphenyl)methylene]-L-arginine

[0176]

[0177] 3-Fluoro-2-hydroxybenzaldehyde (1 g) was added to a slurry of L-arginine (1.18 g) in ethanol (20 ml) and stirred at room temperature for 4 hours. The resulting solid was filtered, washed with n-hexane (20 ml), and dried under high vacuum to obtain 1.54 g of (E)-N 2 -[(3-Fluoro-2-hydroxyphenyl)methylene]-L-arginine solid. 1 HNMR(400MHz,DMSO-d6)δ1.46-1.76(m,2H),1.78-1.96(m,2H),3.10-3.20(m,2H),3.96(t,J=6.8Hz,1H),6.3 4-6.39(m,1H),7.04-7.48(m,2H),7.25-8.0(brs,4H),8.44(s,1H),9.35(s,1H),14.40(brs,1H); ESI-MS:m / z 297.20(M+H)+.

[0178] Example-6: (E)-N 2 Preparation of -[(4-fluoro-2-hydroxyphenyl)methylene]-L-arginine

[0179]

[0180] 4-Fluoro-2-hydroxybenzaldehyde (1 g) was added to a solution of L-arginine (1.18 g) in ethanol (25 ml) and stirred at room temperature under nitrogen for 3 hours. The reaction mixture was filtered, washed with n-hexane (10 ml), and dried under high vacuum to obtain 1.36 g of (E)-N 2-[(4-Fluoro-2-hydroxyphenyl)methylene]-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.48-1.51(m,2H),1.76-1.90(m,2H),3.09-3.11(m,2H) ,3.91(t,J=6.0Hz,1H),6.28-6.35(m,2H),7.29(t,J=8.4Hz,1H),7.20-7.80(br s,4H),8.36(s,1H),9.36(s,1H),14.45(s,1H); ESI-MS: m / z297.10(M+H)+.

[0181] Example-7: (E)-N 2 Preparation of -[(5-fluoro-2-hydroxyphenyl)methylene]-L-arginine

[0182]

[0183] 5-Fluoro-2-hydroxybenzaldehyde (1 g) was added to a slurry of L-arginine (1.18 g) in ethanol (20 ml) and stirred at room temperature for 5 hours. The solid was filtered, washed with n-hexane (20 ml), and dried under high vacuum to obtain 1.57 g of (E)-N 2 -[(5-Fluoro-2-hydroxyphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.46-1.51(m,2H),1.70-1.76(m,1H),1.89-1.93(m,1H),3.07-3.09(m,2H),3.78(t,J=6.4Hz,1H),6.8 0-6.84(m,1H),7.12-7.18(m,1H),7.26-7.29(m,1H),7.30-7.90(brs,4H),8.42(s,1H),9.57(s,1H),14.06(s,1H); ESI-MS:m / z 297.40(M+H)+.

[0184] Example-8: (E)-N 2 Preparation of -[(6-fluoro-2-hydroxyphenyl)methylene]-L-arginine

[0185]

[0186] 1 g of 6-fluoro-2-hydroxybenzaldehyde was added to a solution of 1.18 g of L-arginine in ethanol (25 ml) and stirred at room temperature under nitrogen for 3 hours. The solid was filtered, washed with 10 ml of n-hexane, and dried under high vacuum to obtain 1.61 g of (E)-N 2-[(6-Fluoro-2-hydroxyphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.46-1.49(m,2H),1.74-1.80(m,1H),1.87-1.94(m,1H),3.09-3.11(m,2H),4.00(t, J=6.0Hz,1H),6.31-6.36(dd,J=7.6,2.4Hz,1H),6.48(d,J=8.8Hz,1H),7.23(dd,J=8.4,7.6Hz,1H),7.42(br s,4H),8.60(d,J=4.8Hz,1H),9.40(s,1H),14.75(s,1H); ESI-MS:m / z 297.40(M+H) + .

[0187] Example-9: (E)-N 2 Preparation of -[(2-hydroxy-3-methoxyphenyl)methylene]-L-arginine

[0188]

[0189] o-Vanillin (4.59 g) was added to a solution of L-arginine (5.0 g) in ethanol (25 ml) and stirred at room temperature for 6 hours under nitrogen protection. n-Hexane (50 ml) was added to the reaction mixture and stirred at room temperature for 1 hour. The product was filtered, washed with n-hexane (50 ml), and dried under high vacuum to obtain 9.10 g of (E)-N 2 -[(2-hydroxy-3-methoxyphenyl)methylene]-L-arginine as solid). 1 HNMR(400MHz,DMSO-d6)δ1.49-1.59(m,2H),1.71-1.80(m,1H),1.88-1.93(m,1H),3.05-3.15(m, 2H),3.73(s,3H),3.85(t,J=6.4Hz,1H),6.55(t,J=8.0Hz,1H),6.87-6.89(m,2H),7.20-8.01(br s,4H),8.36(s,1H),9.53(br s,1H),14.25(br s,1H); ESI-MS:m / z 309.10(M+H) + .

[0190] Example-10: (E)-N 2 Preparation of -[(2-hydroxy-5-methoxyphenyl)methylene]-L-arginine

[0191]

[0192] L-arginine (1.09 g) was added to a solution of 2-hydroxy-5-methoxybenzaldehyde (1.0 g) in ethanol (25 ml), and the reaction mixture was stirred at room temperature for 2 hours. The solid was filtered, washed with n-hexane (25 ml), and dried under high vacuum to obtain 1.57 g of (E)-N 2 -[(2-Hydroxy-5-methoxyphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.46-1.51(m,2H),1.69-1.74(m,1H),1.90-1.95(m,1H),3.05-3.10(m,2H),3.33(s,3H),3.75(t,J=6.4Hz,1H) ,6.76(d,J=8.8Hz,1H),6.90(dd,J=2.8,6.0Hz,1H),7.00(s,1H),7.44(brs,4H),8.40(s,1H),9.51(brs,1H),13.56(s,1H); ESI-MS: m / z 309.20(M+H) + .

[0193] Example-11: (E)-N 2 Preparation of -[(2-hydroxy-6-methoxyphenyl)methylene]-L-arginine

[0194]

[0195] L-arginine (1.09 g) was added to a solution of 2-hydroxy-6-methoxybenzaldehyde (1.0 g) in ethanol (25 ml), and the reaction mixture was stirred at room temperature for 18 hours. The solid was filtered, washed with n-hexane (25 ml), and dried under high vacuum to obtain 1.03 g of (E)-N 2 -[(2-Hydroxy-6-methoxyphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.40-1.51(m,2H),1.68-1.77(m,1H),1.85-1.90(m,1H),3.00-3.10(m,2H),3.78(s,3H),3.88(t,J=6.4Hz,1H),6.12(d, J=8.0Hz,1H),6.24(d,J=8.8Hz,1H),7.16(t,J=8.0Hz,1H),7.60(brs,4H),8.59(s,1H),9.47(brs,1H),14.84(brs,1H); ESI-MS: m / z309.10(M+H) + .

[0196] Example-12: (E)-N 2 Preparation of -[(2,4-dihydroxy-6-methylphenyl)methylene]-L-arginine

[0197]

[0198] L-arginine (1.09 g) was added to a solution of 2,4-dihydroxy-6-methylbenzaldehyde (1.0 g) in ethanol (20 ml), and the reaction mixture was stirred at room temperature for 12 hours. The solid was filtered, washed with n-hexane (25 ml), and dried under high vacuum to obtain 0.91 g of (E)-N 2 -[(2,4-Dihydroxy-6-methylphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.45-1.55(m,2H),1.68-1.95(m,2H),2.20(s,3H),3.05-3.14(m,2H),3.91(t,J=6. 4Hz,1H),6.50(s,1H),7.01(s,1H),7.60(brs,4H),8.59(s,1H),9.47(brs,1H),14.84(brs,1H); ESI-MS:m / z 309.20(M+H) + .

[0199] Example 13: (E)-N 2 Preparation of -[(2,4-dimethoxyphenyl)methylene]-L-arginine

[0200]

[0201] L-arginine (1 g) was added to a solution of 2,4-dimethoxybenzaldehyde (1.0 g) in ethanol (25 ml) and stirred at room temperature for 16 hours. The solid was filtered, washed with n-hexane (50 ml), and dried under high vacuum to obtain 1.70 g of (E)-N 2 -[(2,4-Dimethoxyphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.48-1.62(m,3H),1.80-1.91(m,1H),3.03-3.07(m,2H),3.60(t,J=6.4Hz,1H),3.80(s,3H),3.87 (s,3H),6.54-6.59(m,2H),7.04(brs,2H),7.75(d,J=8.4Hz,1H),7.90(brs,2H),8.44(s,1H),9.50(brs,1H); ESI-MS:m / z 323.30(M+H) + .

[0202] Example-14: (E)-N 2 Preparation of -{[2-hydroxy-5-(trifluoromethoxy)phenyl]methylene}-L-arginine

[0203]

[0204] L-arginine (0.81 g) was added to a solution of 2-hydroxy-5-(trifluoromethoxy)benzaldehyde (1.0 g) in ethanol (20 ml) and stirred at room temperature for 16 hours. After vacuum concentration, the mixture was crystallized in a mixed solvent of ethanol and n-hexane to obtain 1.21 g of (E)-N 2 -{[2-Hydroxy-5-(trifluoromethoxy)phenyl]methylene}-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.47-1.51(m 2H),1.74-1.80(m,1H),1.91-1.96(m,1H),3.00-3.11(m,2H),3.85(t,J=6.4Hz,1H),6.83(d,J=9.2Hz,1H) ,7.26-7.28(m,1H),7.43(s,1H),7.80(brs,4H),8.48(s,1H),9.48(brs,1H),14.56(brs,1H); ESI-MS:m / z 363.30(M+H) + .

[0205] Example-15: (E)-N 2 Preparation of -[(3-chloro-5-fluoro-2-hydroxyphenyl)methylene]-L-arginine

[0206]

[0207] L-arginine (0.95 g) was added to a solution of 3-chloro-5-fluoro-2-hydroxybenzaldehyde (1.0 g) in ethanol (25 ml) and stirred at room temperature for 16 hours. After filtration, the mixture was washed with n-hexane (25 ml) and dried under high vacuum to obtain 1.37 g of (E)-N 2 -[(3-Chloro-5-fluoro-2-hydroxyphenyl)methylene]-L-arginine solid. 1H NMR (400MHz, DMSO-d6) δ1.48-1.55(m2H),1.79-1.94(m,2H),3.10-3.15(m,2H),4.00(t,J=6.4Hz,1H),7.12(dd,J=3 .2,5.6Hz,1H),7.49(dd,J=3.2,5.2Hz,1H),7.64(brs,4H),8.45(s,1H),9.31(brs,1H),14.50(brs,1H); ESI-MS:m / z 331.60(M+H) + .

[0208] Example-16: (E)-N 2 Preparation of -[(4-methoxyphenyl)methylene]-L-arginine

[0209]

[0210] Anisaldehyde (7.82 g) was added to a solution of L-arginine (10 g) in water (80 ml) and stirred at room temperature for 7 hours. The solid was filtered, washed with water (50 ml), and dried under high vacuum to obtain 16.6 g of (E)-N 2 -[(4-Methoxyphenyl)methylene]-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.40-1.54(m,2H),1.64-1.69(m,1H),1.85-1.90(m,1H),3.08-3.09(m,2H ),3.65(t,J=6.0Hz,1H),3.77(s,3H),6.95(d,J=8.4Hz,2H),7.64(d,J=8.4Hz,2H),7.40-8.15(br s,4H),8.16(s,1H),9.25(br s,1H); ESI-MS:m / z 293.20(M+H) + .

[0211] Example-17: (E)-N 2 Preparation of -[(3-hydroxy-4-methoxyphenyl)methylene]-L-arginine

[0212]

[0213] L-arginine (1.09 g) was added to a solution of isovanillin (1.0 g) in ethanol (25 ml), and the reaction mixture was stirred at room temperature for 5 hours. The solid was filtered, washed with n-hexane (50 ml), and dried under high vacuum to obtain 0.86 g of (E)-N 2 -[(3-Hydroxy-4-methoxyphenyl)methylene]-L-arginine solid.1 HNMR (400MHz, DMSO-d6) δ1.40-1.52(m,2H),1.62-1.40(m,1H),1.83-1.91(m,1H),3.02-3.06(m,2H),3.62(t,J=6.4Hz,1H),3.44( brs,1H),3.86(s,3H),6.92(d,J=8.4Hz,1H),7.02(d,J=9.6Hz,1H),7.23(d,J=1.2Hz,1H),7.60(brs,5H),8.06(s,1H); ESI-MS:m / z 309.10(M+H) + .

[0214] Example-18: (E)-N 2 Preparation of -[(3-chloro-4-methoxyphenyl)methylene]-L-arginine

[0215]

[0216] 3-Chloro-p-methoxyanisaldehyde (1.5 g) was added to a slurry of L-arginine (1.45 g) in ethanol (30 ml) and stirred at room temperature for 16 hours. N-hexane (60 ml) was added to the reaction mixture and stirring was continued for 1 hour. The solid was filtered, washed with n-hexane (30 ml), and dried under high vacuum to obtain 1.68 g of (E)-N 2 -[(3-Chloro-4-methoxyphenyl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.41-1.51(m,2H),1.66-1.69(m,1H),1.85-1.88(m,1H),3.01-3.10(m,2H),3.66(t,J=6.4Hz,1H),3.89(s,3H),7.1 8(d,J=8.4Hz,1H),7.56(brs,2H),7.63(dd,J=1.6,6.8,1H),7.77(d,J=1.6Hz,1H),7.95(brs,2H),8.16(s,1H),9.32(brs.1H); ESI-MS: m / z 349.60(M+Na) + .

[0217] Example-19: Preparation of (E)-N 2 -{[4-(methylsulfanyl)phenyl]methylene}-L-arginine

[0218]

[0219] L-arginine (1.09 g) was added to a solution of 4-methylthiobenzaldehyde (1.0 g) in ethanol (40 ml), and the reaction mixture was stirred at room temperature for 4 hours. The solid was filtered, washed with n-hexane (50 ml), and dried under high vacuum to obtain 1.69 g of (E)-N 2 -{[4-Methylthiophenyl]methylene}-L-arginine solid. 1 HNMR (400MHz, DMSO-d6) δ1.47-1.50(m,2H),1.62-1.69(m,1H),1.84-1.89(m,1H),3.07-3.10(m,2H),3.20(s,3H),3.67(t,J= 6.4Hz,1H),7.28(d,J=8.4Hz,2H),7.45(brs,2H),7.64(d,J=8.4Hz,2H),8.01(brs,2H),8.19(s,1H),9.55(s,1H); ESI-MS:m / z 313.10(M+H) + .

[0220] Example-20: (E)-N 2 Preparation of -{[2-hydroxy-3-methoxy-5-(prop-2-en-1-yl)phenyl]methylene}-L-arginine

[0221]

[0222] L-arginine (0.86 g) was added to a solution of 2-hydroxy-3-methoxy-5-(prop-2-en-yl)benzaldehyde (1.0 g) in ethanol (25 ml), and the reaction mixture was stirred at room temperature for 16 hours. The solid was filtered, washed with n-hexane (20 ml), and dried under high vacuum to obtain 1.35 g of (E)-N 2 -{[2-Hydroxy-3-methoxy-5-(prop-2-en-1-yl)phenyl]methylene}-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.47-1.50(m,2H),1.70-1.90(m,2H),3.10-3.19( m,2H),3.24(d,J=6.4Hz,1H),3.42-3.45(m,1H),3.73(s,3H),3.81(t,J=5 .6Hz,1H),5.08-5.08(m,2H),5.89-5.99(m,1H),6.88(s,1H),6.72(s,1H) ,7.53(brs,4H),8.30(s,1H),9.49(brs,1H),14.14(brs,1H); ESI-MS:m / z 349.20(M+H) + .

[0223] Example-21: (E)-N 2 Preparation of -{[2,3-dimethoxy-5-(prop-2-en-1-yl)phenyl]methylene}-L-arginine

[0224]

[0225] L-arginine (0.81 g) was added to a solution of 2,3-dimethoxy-5-(prop-2-en-yl)benzaldehyde (1.0 g) in ethanol (20 ml), and the reaction mixture was stirred at room temperature for 4 hours. The solid was filtered, washed with n-hexane (50 ml), and dried under high vacuum to obtain 1.18 g of (E)-N 2 -{[2,3-Dimethoxy-5-(prop-2-en-1-yl)phenyl]methylene}-L-arginine solid. 1 HNMR(400MHz,DMSO-d6)δ1.45-1.50(m,2H),1.59-1.64(m,1H),1.88-1.91(m, 1H),3.02-3.14(m,2H),3.38(d,J=6.8Hz,2H),3.68(t,J=6.8Hz,1H),3.73(s,3 H),3.81(s,3H),5.03-5.13(m,2H),5.89-5.99(m,1H),6.93(d,J=2.0Hz,1H), 7.24(d,J=2.0Hz,1H),7.75(brs,4H),8.45(s,1H),9.57(brs,1H); ESI-MS:m / z 363.20(M+H) + .

[0226] Example-22: (E)-N 2 Preparation of -{[2-hydroxy-3-(prop-2-en-1-yl)phenyl]methylene}-L-arginine

[0227]

[0228] L-arginine (1.03 g) was added to a solution of 2-hydroxy-3-(prop-2-en-1-yl)benzaldehyde (1.0 g) in ethanol (10 ml), and the reaction mixture was stirred at room temperature for 16 hours. The solid was filtered, washed with n-hexane (25 ml), and dried under high vacuum to obtain 1.64 g of (E)-N 2 -{[2-Hydroxy-3-(prop-2-en-1-yl)phenyl]methylene}-L-arginine solid. 1H NMR(400MHz,DMSO-d6)δ1.48-1.53(m,2H),1.72-1.77(m,1H),1.90-1.95(m,1H ),3.09-3.18(m,2H),3.26-3.37(m,2H),3.81(t,J=5.6Hz,1H),4.99-5.08(m,2 H),5.92-6.02(m,1H),6.69(t,J=7.6Hz,1H),7.14(d,J=0.8Hz,1H),7.20(d,J= 0.8Hz,1H),7.42(brs,4H),8.41(s,1H),9.54(s,1H),14.62(s,1H); ESI-MS:m / z 319.5 (M+H) + .

[0229] Example-23: (E)-N 2 Preparation of -[(1H-indol-3-yl)methylene]-L-arginine

[0230]

[0231] Indole-3-carboxaldehyde (1.76 g) was added to a slurry of L-arginine (1.11 g) in ethanol (30 ml) and stirred at room temperature for 16 hours. The solid was filtered, washed with n-hexane, and dried under high vacuum to obtain 1.68 g of (E)-N 2 -[(1H-Indol-3-yl)methylene]-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.51-1.60(m,2H),1.63-1.70(m,1H),1.88-1.93(m,1H),3.09-3.16(m,2H) ,3.61(t,J=6.4Hz,1H),7.06(t,J=7.2Hz,1H),7.15(t,J=7.2Hz,1H),7.38(d,J=8.0Hz,1H),7.52(br s.2H),7.71(s,1H),8.01(brs,2H),8.25(d,J=8.0Hz,1H),8.39(s,1H),9.53(brs,1H),11.46(brs,1H); ESI-MS:m / z 302.10(M+H)+.

[0232] Example-24: (E)-N 2 Preparation of -[(2H-1,3-benzodioxol-5-yl)methylene]-L-arginine

[0233]

[0234] Piperonal (1 g) was added to a slurry of L-arginine (1.11 g) in ethanol (30 ml) and stirred at room temperature for 16 hours. N-hexane (30 ml) was added to the reaction mixture and stirring continued for 1 hour. The solid was filtered, washed with n-hexane, and dried under high vacuum to obtain 0.91 g of (E)-N 2 -[(2H-1,3-Benzodioxin-5-yl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.40-1.54(m,2H),1.61-1.66(m,1H),1.85-1.87(m,1H),3.07-3.09(m2H),3.64(t,J=6.4Hz,1H),6.06(d,J=4.4H z,2H),6.95(d,J=8.0Hz,1H),7.15(d,J=11.2Hz,1H),7.32(s,1H),7.49(brs,2H),7.56(brs,2H),8.13(s,1H),9.52(brs,1H); ESI-MS: m / z 307.30(M+H) + .

[0235] Example-25: (E)-N 2 Preparation of -[(furan-2-yl)methylene]-L-arginine

[0236]

[0237] Furfural (1.56 g) was added to a slurry of L-arginine (2 g) in ethanol (50 ml) and stirred at room temperature under nitrogen for 18 hours. The solvent was removed in vacuo, and n-hexane (20 ml) was added to the residue and stirred for 1 hour. The resulting solid was filtered, washed with n-hexane (10 ml), and dried under high vacuum to give 1.91 g of (E)-N 2 -[(Furan-2-yl)methylene]-L-arginine solid. 1 HNMR(400MHz,DMSO-d6)δ1.45-1.50(m,2H),1.60-1.67(m,1H),1.82-1.85(m,1H),3.07-3.09(m,2H),3.63(t,J=6.80Hz,1H),6.58 -6.9(m,1H),6.86(d,J=3.2Hz,1H),7.45(brs,2H),7.55(d,J=1.2Hz,1H),8.06(brs,2H),8.10(s,1H),9.45(brs,1H); ESI-MS:m / z 253.20(M+H) + .

[0238] Example-26: (E)-N 2 Preparation of -[(5-methylfuran-2-yl)methylene]-L-arginine

[0239]

[0240] L-arginine (1.5 g) was added to a solution of 5-methylfurfural (1.0 g) in ethanol (20 ml). The reaction mixture was stirred at room temperature for 16 hours. The solid was filtered, washed with ethanol (10 ml), and dried under high vacuum to give 1.99 g of (E)-N 2 -[(5-Methylfuran-2-yl)methylene]-L-arginine solid. 1 HNMR(400MHz,DMSO-d6)δ1.45-1.85(m,4H),2.31(s,3H),3.06-3.10(m,2H),3.57(t,J=6.4H z,1H),6.22(d,J=2.8Hz,1H),6.71(d,J=2.8Hz,1H),7.50(brs,5H),7.99(s,1H); ESI-MS:m / z 267.20(M) + .

[0241] Example-27: (E)-N 2 Preparation of -{[5-(hydroxymethyl)furan-2-yl]methylene}-L-arginine

[0242]

[0243] L-arginine (1.32 g) was added to a solution of 5-(hydroxymethyl)furan-2-carbaldehyde (1.0 g) in ethanol (25 ml). The reaction mixture was stirred at room temperature for 16 hours. The solid was filtered, washed with ethanol (10 ml) and n-hexane (25 ml), and then dried under high vacuum to give 1.71 g of (E)-N 2 -{[5-(Hydroxymethyl)furan-2-yl]methylene}-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.40-1.55(m,2H),1.60-1.67(m,1H),1.81-1.90(m,1H),3.04-3.12(m,2H),3.61(t,J=6.4Hz,1H),4.4 2(s,2H),5.50(brs,1H),6.39(d,J=2.8Hz,1H),6.77(d,J=2.4Hz,1H),7.48(brs,4H),8.09(s,1H),9.50(brs,1H); ESI-MS:m / z 283.20(M) + .

[0244] Example-28: (E)-N 2 Preparation of -[(naphthalen-1-yl)methylene]-L-arginine

[0245]

[0246] At room temperature, L-arginine (0.96 g) was added to a solution of 1-naphthaldehyde (1 g) in ethanol (15 ml). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The solid product was filtered, washed with cold ethanol (10 ml) and n-hexane (40 ml) in sequence, and dried under high vacuum to obtain 1.19 g of (E)-N 2 -[(Naphthalen-1-yl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.56(br s,2H),1.74-1.81(m,1H),1.97-2.05(m,1H),3.13-3.14(m,2H),3.82(t,J=6.4Hz,1H),7.34(br s,4H),7.55-7.63(m,3H),7.88(d,J=6.8Hz,1H),7.99(t,J=7.2Hz,2H)8.86(s,1H),9.17(d,J=8.4Hz,1H),9.79(br s,1H); ESI-MS: m / z 313.12(M+H) + .

[0247] Example-29: (E)-N 2 Preparation of -[(pyridin-3-yl)methylene]-L-arginine

[0248]

[0249] L-arginine (0.9 g) was added to a solution of nicotinaldehyde (1 g) in ethanol (10 ml) at room temperature. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The solid product was filtered, washed with cold ethanol (10 ml) and n-hexane (30 ml) in sequence, and dried under high vacuum to obtain 0.91 g of (E)-N 2 -[(Pyridin-3-yl)methylene]-L-arginine solid. 1H NMR (400MHz, DMSO-d6) δ1.46-1.52(m,2H),1.68-1.73(m,1H),1.90-1.93(m,1H),3.09(br s,1H),3.74(t,J=6.4Hz,1H),7.29(br s,5H),7.45(dd,J=5.0Hz,7.8Hz,1H),8.11(d,J=8.0Hz,1H),8.33(s,1H),8.61(dd,J=1.6Hz,4.8Hz,1H),8.86(s,1H),9.71(br s,1H); ESI-MS: m / z 264.20(M+H) + .

[0250] Example-30: (E)-N 2 Preparation of -[(naphthalen-2-yl)methylene]-L-arginine

[0251]

[0252] At room temperature, L-arginine (0.90 g) was added to a solution of 2-naphthaldehyde (1 g) in ethanol (10 ml). The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The solid product was filtered, washed with cold ethanol (10 ml) and n-hexane (40 ml) in sequence, and dried under high vacuum to obtain 1.13 g of (E)-N 2 -[(Naphthalen-2-yl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.49-1.556(m,2H),1.71-1.76(m,1H),1.94-1.97(m,1H),3.11(br s,2H),3.78(t,J=6.4Hz,1H),7.32(br s,4H),7.54-7.58(m,2H),7.92-7.96(m,3H),7.98-8.01(m,1H)8.17(s,1H),8.42(s,1H),9.80(br s,1H); ESI-MS:m / z 313.28(M+H) + .

[0253] Example-31: (E)-N 2 Preparation of -[(thiophen-3-yl)methylene]-L-arginine

[0254]

[0255] L-arginine (0.9 g) was added to a solution of thiophene-3-carboxaldehyde (1 g) in ethanol (10 ml) at room temperature. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The solid product was filtered, washed with cold ethanol (10 ml) and n-hexane (20 ml) in sequence, and dried under high vacuum to obtain 0.48 g of (E)-N 2 -[(Thien-3-yl)methylene]-L-arginine solid. 1 H NMR (400MHz, DMSO-d6) δ1.47(br s,2H),1.61-1.66(m,1H),1.84-1.88(m,1H),3.06-3.09(m,2H),3.62(t,J=6.4Hz,1H),7.33-7.60(br s,4H),7.43(d,J=4.4Hz,1H),7.55-7.56(m,1H),7.87(s,1H)8.25(s,1H),9.69(br s,1H); ESI-MS: m / z 269.40(M+H) + .

[0256] Example-32: (E)-N 2 Preparation of -{[2-methoxy-3-(prop-2-en-1-yl)phenyl]methylene}-L-arginine

[0257]

[0258] L-arginine (1.89 g) was added to a solution of 2-methoxy-3-(prop-2-en-1-yl)benzaldehyde (2 g) in isopropanol (20 ml) at room temperature. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. The solid product was filtered, washed with n-hexane (20 ml), and then dried under high vacuum to obtain 2.34 g of (E)-N 2 -{[2-methoxy-3-(prop-2-en-1-yl)phenyl]methylene}-L-arginine solid. 1HNMR(400MHz,DMSO-d6)δ1.50(br s,2H),1.66-1.71(m,1H),1.88-1.92(m,1H),3.09(d,J=6.4Hz,2H)3.40(d,J=6.4Hz,2H),3.72(s,3H),3.74- 3.76(m,1H),5.05-509(m,2H),5.93-6.01(m,1H),7.12(t,J=7.6Hz,1H),7.26(d,J=7.6Hz,1H),7.31-7.36(br s,4H),7.73(d,J=8.0Hz,1H),8.48(s,1H),9.70(br s,1H); ESI-MS:m / z 333.20(M+H) + .

[0259] Example-33: (E)-N 2 Preparation of -[(7-methoxy-2H-1,3-benzodioxol-5-yl)methylene]-L-arginine

[0260]

[0261] At room temperature, 0.96 g of L-arginine was added to a solution of 1 g of 7-methoxy-2H-1,3-benzodioxole-5-carboxaldehyde (20 ml) in ethanol. The reaction mixture was stirred at room temperature under nitrogen for 18 hours. The solid product was filtered, washed with 20 ml of n-hexane, and dried under high vacuum to obtain 1.23 g of (E)-N 2 -[(7-Methoxy-2H-1,3-benzodioxol-5-yl)methylene]-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.46(br s,2H),1.63-1.65(m,1H),1.87-1.88(m,1H),3.05-3.37(m,2H),3.65(t,J =6.6Hz,1H),3.85(s,3H),6.05(s,2H),6.95(s,1H),7.04(s,1H),7.46(br s,3H),7.99(br s,1H),8.12(s,1H),9.48(br s,1H); ESI-MS:m / z 337.20(M+H) + .

[0262] Example-34: (E)-N 2 Preparation of -[(2H-1,3-benzodioxol-4-yl)methylene]-L-arginine

[0263]

[0264] At room temperature, 1.11 g of L-arginine was added to a 20 ml ethanol solution of 2H-1,3-benzodioxole-4-carboxaldehyde. The reaction mixture was stirred at room temperature under nitrogen for 18 hours. The solid product was filtered, washed with 20 ml of n-hexane, and dried under high vacuum to obtain 1.41 g of (E)-N 2 -[(2H-1,3-Benzodioxin-4-yl)methylene]-L-arginine solid. 1 H NMR(400MHz,DMSO-d6)δ1.47(br s,2H),1.63-1.72(m,1H),1.84-1.89(m,1H),3.07-3.09(m,2H),3.69(t,J=6.4Hz,1H),6.0 9(s,2H),6.85(t,J=7.6Hz,1H),6.95(d,J=8.0Hz,1H),7.26(d,J=7.6Hz,1H),7.52-7.91(br s,5H),8.32(s,1H),9.36(br s,1H); ESI-MS:m / z 307.20(M+H) + .

[0265] Example-35: Stability study of the compound of the present invention:

[0266] The compounds of the present invention were stored under the conditions shown in the table below [room temperature and accelerated storage conditions (ATS)] and their purity was assessed by HPLC. Properly packaged materials were handled according to the conditions described in the table below.

[0267] Table 1:

[0268]

[0269] The following examples illustrate the basic methods and versatility of the compositions of the present invention. It should be noted that the present invention is not limited to these examples. The form of the composition, excipients, and concentrations of the active ingredient and excipients can be substituted with any other form, excipient, and concentration encompassed by the present invention.

[0270] Example-36: General steps for preparing water-disintegrating granules (GR)

[0271] The compound of the present invention is ground in a jet mill to the desired granules of less than 50 microns, then all ingredients are added and mixed in a ribbon mixer to obtain a uniform powder. The required amount of water is added to the above mixture to form a mass, and the material is then granulated and dried in a suitable apparatus to obtain granules.

[0272] The following water-disintegrating granule (GR) composition was prepared according to Example 36.

[0273] Table 2:

[0274]

[0275] Example-37: General steps for preparing extruded granules (WG)

[0276] The compound of the present invention is mixed with a dispersant, a wetting agent, and an inert auxiliary material in a ribbon mixer and then ground to the desired particle size in a jet mill. The desired amount of water is added to the mixture to form a mass, which is then granulated in a suitable apparatus and dried to obtain granules.

[0277] The following extruded granule (WG) compositions were prepared according to Example 37.

[0278] Table 3

[0279]

[0280]

[0281] Example-38: General steps for preparing spray-dried granules (WG)

[0282] The compound of the present invention is mixed with all ingredients in 100 parts of water and ground to the desired particle size. The ground slurry is then spray-dried / fluid-bed-dried to obtain granules.

[0283] The following spray-dried granule (WG) compositions were prepared as in Example 38.

[0284] Table 4:

[0285]

[0286]

[0287] Example-39: General steps for preparing WP

[0288] The composite of the present invention is mixed with the required amount of dispersant, wetting agent and inert ingredients in a ribbon mixer. The mixed material is passed through a jet mill to reduce the particle size and the mixing is continued for 1 hour to obtain the product of the required composition.

[0289] The following wettable powder (WP) composition was prepared according to Example 39.

[0290] Table 5:

[0291]

[0292]

[0293] Example-40: General steps for preparing suspension concentrate (SC)

[0294] Mix the required amounts of surfactant and antifreeze with a certain amount of water. Add the compound of the present invention to the homogenized mixture and continue stirring for about 20 minutes until the mixture is completely homogenized. While continuing to homogenize, add half the amount of defoamer to obtain a liquid suspension. Subsequently, pass the resulting suspension through a wet grinder to reduce the particle size. Add the required amounts of thickener, preservative, balance water, and defoamer to obtain the desired product composition.

[0295] Example-41: General steps for preparing coated granules (GR)

[0296] The desired amounts of stabilizer, surfactant, colorant, and binder are mixed in a drum coater and heated to the desired temperature. The desired amount of river sand is added to the drum coater and mixed. The desired particle size of the compound of the present invention is added to a ribbon mixer and mixed to obtain the desired product composition.

[0297] Example-42: General Procedure for Preparing Powder for Dry Seed Treatment (DS)

[0298] The compound of the present invention is mixed with the required amount of pigment, wetting agent and inert ingredients in a ribbon mixer. The mixed material is passed through a jet mill to reduce the particle size and the mixing is continued for 1 hour to obtain the product of the desired composition.

[0299] Example-43: General Procedure for Preparing Water-Dispersible Powders (WS) for Slurry Processing

[0300] The compound of the present invention is mixed with the required amount of pigment, dispersant, wetting agent and inert ingredients in a ribbon mixer. The mixed material is passed through a jet mill to reduce the particle size and further mixed for 1 hour to obtain the product of the desired composition.

[0301] The following suspension concentrate (SC), coated granule (GR), dust for dry seed treatment (DS) and water dispersible powder for slurry treatment (WS) compositions were prepared according to Examples 40, 41, 42 and 43, respectively.

[0302] Table 6:

[0303]

[0304]

[0305] Example-43: Determination of Nematicidal Activity Against Meloidogyne spp.

[0306] The test compound (4 mg) was dissolved in 40 μl DMSO to prepare a stock solution with a concentration of 100,000 PPM. A clear solution was obtained after vortexing. A nematode suspension (250 μl) containing 70-100 root-knot nematode (Meloidogyne spp.) larvae (J2) was pipetted into each well of a 24-well bioassay plate. 1 ml of sterile water was pipetted into a new 2.5 ml Eppendorf microcentrifuge tube. The stock solution was added to a 2.5 ml Eppendorf microcentrifuge tube and prepared to the desired concentration (500 ppm) of the compound. Each treatment was repeated 4 times. The bioassay plate was placed in a humidity chamber at 22 ± 2 ° C and 70 ± 5% RH and cultured. The number of dead / inactive nematodes was counted under a microscope 24, 48, 72 and 96 hours after incubation, and the mortality rate was calculated.

[0307] Table 7: Rating table

[0308]

[0309]

[0310] Table 8: Biological results

[0311] Example No. Rating Example No. Rating Example No. Rating 1 A 13 C 25 A 2 A 14 B 26 A 3 B 15 C 27 B 4 B 16 A 28 B 5 A 17 C 29 B 6 A 18 B 30 A 7 A 19 B 31 B 8 A 20 A 32 B 9 C 21 A 33 B 10 B 22 A 34 B 11 A 23 B -- -- 12 C 24 B -- --

Claims

1. A compound of formula (I) or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, wherein for 2. The compound according to claim 1, wherein for 3. The compound according to claim 1, wherein 4. The compound according to claim 1, wherein The compound is selected from or an agrochemically acceptable salt or N-oxide thereof.

5. The compound of formula according to claim 1 or an agrochemically acceptable salt or N-oxide thereof.

6. The compound of formula according to claim 1 or an agrochemically acceptable salt or N-oxide thereof.

7. The compound of formula according to claim 1 or an agrochemically acceptable salt or N-oxide thereof.

8. The compound of formula according to claim 1 or an agrochemically acceptable salt or N-oxide thereof.

9. An agricultural composition comprising a compound of formula (I) or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, and at least one agrochemically acceptable excipient, wherein for 10. The agricultural composition according to claim 9, wherein The agrochemically acceptable excipient is selected from one or more of the following: surfactant, disintegrant, filler or carrier or diluent, spreading agent, colorant, anti-caking agent, binder, buffer or pH adjuster or neutralizer, pigment, stabilizer, defoamer or defoaming agent, penetrant, structurant, humectant, adhesive, antifreeze or freezing point depressant, chelating agent or complexing agent or multivalent sequestrant, preservative.

11. An agricultural composition comprising a compound of the formula or an agrochemically acceptable salt or N-oxide thereof and at least one agrochemically acceptable excipient.

12. An agricultural composition comprising a compound of the formula or an agrochemically acceptable salt thereof or an N-oxide thereof and at least one agrochemically acceptable excipient.

13. An agricultural composition comprising a compound of the formula or an agrochemically acceptable salt thereof or an N-oxide thereof and at least one agrochemically acceptable excipient.

14. An agricultural composition comprising a compound of the formula or an agrochemically acceptable salt thereof or an N-oxide thereof and at least one agrochemically acceptable excipient.

15. An agricultural composition comprising a compound of the formula or an agrochemically acceptable salt thereof or an N-oxide thereof and at least one agrochemically acceptable excipient.

16. The agricultural composition according to any one of claims 9 to 15, wherein The composition is in the form of a solid or liquid or a gel or a paste.

17. The agricultural composition according to claim 16, wherein The solid composition is in the form of spherical granules, extruded granules, water-disintegrating granules, wettable powders, water-dispersible granules, dustable powders, powders for dry seed treatment, water-disintegrating tablets or water-dispersible powders for slurry seed treatment.

18. The agricultural composition according to claim 16, wherein The liquid composition is in the form of a liquid suspension or suspension concentrate, suspoemulsion, oil dispersion, flowable concentrate or suspension concentrate for seed treatment, ultra low volume.

19. A method for treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of formula (I) or an agrochemically acceptable salt, stereoisomer, enantiomer, tautomer or N-oxide thereof, wherein for 20. A method of treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of the formula or an agrochemically acceptable salt or N-oxide thereof.

21. A method for treating or controlling plant parasitic nematodes or nematode infections comprising administering a compound of the formula or an agrochemically acceptable salt or N-oxide thereof.

22. A method for preparing a compound of formula (I), comprising mixing a compound of formula (A) with a compound of formula (B) in for

Images