CN107759581B

CN107759581B - Substituted benzoyl isoxazole compound or tautomer, salt, preparation method, herbicidal composition and application thereof

Info

Publication number: CN107759581B
Application number: CN201711002420.3A
Authority: CN
Inventors: 连磊; 征玉荣; 何彬; 彭学岗; 金涛; 崔琦; 刘娜
Original assignee: Qingdao Kingagroot Chemical Compound Co Ltd
Current assignee: Qingdao Kingagroot Chemical Compound Co Ltd
Priority date: 2017-10-24
Filing date: 2017-10-24
Publication date: 2021-05-14
Anticipated expiration: 2037-10-24
Also published as: WO2019080227A1; CN107759581A

Abstract

The invention belongs to the technical field of pesticides, and particularly relates to a substituted benzoyl isoxazole compound or tautomer, salt, a preparation method, a herbicidal composition and application thereof. The substituted benzoyl isoxazole compound or the tautomer and the salt thereof are shown as a general formula I-1:

in the formula, R₁R₂N represents

R represents

Description

Substituted benzoyl isoxazole compound or tautomer, salt, preparation method, herbicidal composition and application thereof

Technical Field

The invention belongs to the technical field of pesticides, and particularly relates to a substituted benzoyl isoxazole compound or tautomer, salt, a preparation method, a herbicidal composition and application thereof.

Background

Weed control is a crucial step in achieving efficient agricultural practices, despite the wide variety of herbicides available on the market, for example, patent CN101981016A discloses a 4- (3-aminobenzoyl) -5-cyclopropylisoxazole of formula (i):

table A discloses X is Cl and Y is CF₃Compounds of formulae (I), (II), (III), (IV; WO97/46530A1 discloses as herbicides ketones of the general formula I:

however, due to the expanding market, the resistance of weeds, the life span of the drugs, and the economic nature of the drugs, and the growing environmental importance, scientists are required to research and develop new herbicide varieties with high efficiency, safety, economy, and different modes of action.

Disclosure of Invention

In order to develop a medicinal active substance with higher medicinal property, wider active spectrum and better safety, the invention provides a substituted benzoyl isoxazole compound or tautomer, salt, a preparation method, a herbicidal composition and application thereof.

The technical scheme adopted by the invention is as follows:

a substituted benzoyl isoxazole compound or tautomer and salt thereof, which is shown as a general formula I-1:

in the formula,

R₁R₂n represents

Wherein,

het is selected from the group consisting of three-to eight-membered heterocycles containing, as ring members, in addition to the C and the N atom in position 1, 0 to 3 of the following atoms or groups: o, NR_b、S、SO、SO₂、C＝O、C＝NR_bOr C ═ NOR_b；

R_bSelected from hydrogen, C_1～6Alkyl, halo C_1～6Alkyl radical, C_2～6Alkenyl, halo C_2～6Alkenyl radical, C_1～6Alkoxy radical C_1～6Alkyl, halo C_1～6Alkoxy radical C_1～6Alkyl radical, C_1～6Alkylcarbonyl, halo C_1～6Alkylcarbonyl group, C_1～6Alkylsulfonyl radical, C_1～6Alkoxycarbonyl group, C_1～6Alkylamino carbonyl, C_1～6Alkyl carbonyl radical C_1～6Alkyl radical, C_1～6Alkoxycarbonyl radical C_1～6Alkyl radical, C_1～6Alkylamino carbonyl group C_1～6Alkyl, unsubstituted or substituted by 1-3 substituents independently selected from halogen, nitro, cyano, C_1～6Alkyl, halo C_1～6Alkyl radical, C_1～6Alkoxy, halo C_1～6Alkoxy radical, C_1～6Aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, arylsulfonyl, arylmethyl, heteroarylmethyl substituted with a group selected from alkylcarbonyl;

R_aone or more groups selected from the following groups: hydrogen, halogen, cyano, nitro, hydroxy, carboxy, amino, C₁-C₆Alkylsulfonyl radical, C_1～6Alkyl, halo C_1～6Alkyl radical, C_2～6Alkenyl, halo C_2～6Alkenyl radical, C_1～6Alkoxy, halo C_1～6Alkoxy radical, C_1～6Alkylamino radical, C_2～6Alkenyloxy, halogeno C_2～6Alkenyloxy radical, C_2～6Alkenylamino, halogeno C_2～6Alkenylamino radical, C_1～6Alkylcarbonyl, halo C_1～6Alkylcarbonyl group, C_1～6Alkoxycarbonyl group, C_1～6Alkylamino carbonyl, C_1～6Alkoxy radical C_1～6Alkyl, halo C_1～6Alkoxy radical C_1～6Alkyl radical, C_1～6Alkylcarbonyloxy C_1～6Alkyl radical, C_1～6Alkoxy radical C_1～6Alkoxy, halo C_1～6Alkoxy radical C_1～6Alkoxy radical, C_1～6Alkoxycarbonyl radical C_1～6Alkoxy radical, C_1～6Alkylcarbonyloxy, halo C_1～6Alkylcarbonyloxy, C_1～6Alkylcarbonylamino, C_1～6Alkylsulfonyloxy, C_1～6Alkylsulfonylamino group, C_1～6Alkyl carbonyl radical C_1～6Alkoxy, unsubstitutedOr substituted by 1-3 substituents independently selected from halogen, nitro, cyano, C_1～6Alkyl, halo C_1～6Alkyl radical, C_1～6Alkoxy radical, C_1～6Aryl, heteroaryl, arylcarbonyloxy, arylsulfonyloxy, arylmethyloxy, heteroarylmethyloxy, arylcarbonylamino, arylsulfonylamino, arylmethylamino or heteroarylmethylamino substituted with a group in alkylcarbonyl;

r represents

Wherein R is₁₁Selected from hydrogen, C₁-C₆Alkyl radical, C₃-C₆Cycloalkyl, halo C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Alkylcarbonyl group, C₁-C₆Alkoxycarbonyl group, C₁-C₆Alkylthio, 6-10 membered aryl with or without halogen substitution, 5-10 membered heteroaryl with or without halogen substitution containing 1-3O, S, N heteroatoms, n-0-2.

Preferably, Het is selected from 3 to 8 nitrogen-containing heterocyclic groups containing 1 to 3 heteroatoms, such as 4 to 8 membered lactamyl, imidazolyl, pyrazolyl, containing in the ring, in addition to C, the N atom in position 1 and 1 or 2C ═ O, 1 to 3 atoms or groups as ring members: o, NR_b、S、SO、SO₂A five or six membered heterocyclic ring of (a); r_aIs selected from C_1～4Alkyl radical, C_1～4Alkoxy, nitro, halogen, cyano, amino, C_1～6Alkylamino radical, C_1～6One or more groups in an alkylsulfonyl group; r_bSelected from hydrogen, C_1～6Alkyl, halo C_1～6One or more groups in an alkyl group;

R₁₁selected from hydrogen, C₁-C₆Alkyl radical, C₃-C₆Cycloalkyl, halo C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Alkylcarbonyl group, C₁-C₆Alkoxycarbonyl group, C₁-C₆Alkylthio, 6-10 membered aryl with or without halogen substitution, 5-10 membered heteroaryl with or without halogen substitution containing 1-3O, S, N heteroatoms, n-0-2.

More preferably, Het is selected from butyrolactam, valerolactam, caprolactame, enantholactam, piperazinonyl, morpholinonyl, thiomorpholinonyl, imidazolyl, pyrazolyl, valerolactam, caprolacton, caprylyl, and caprylyl,

R_aSelected from fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, nitro, cyano, amino, C_1～6Alkylamino radical, C₁-C₆One or more groups in an alkylsulfonyl group; r_bSelected from hydrogen, C_1～6Alkyl, halo C_1～6One or more groups in an alkyl group;

R₁₁selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, methylcarbonyl, ethylcarbonyl, methoxycarbonyl, ethoxycarbonyl, methylthio, ethylthio, with or without halogen substitution

The salt is potassium salt, sodium salt, ammonium salt, calcium salt, pyridine salt or choline salt.

In the definitions of the compounds of the general formula given above, the terms used are collectively defined as follows:

the aryl is 6-10-membered aryl, including phenyl or naphthyl and the like; the heteroaryl group is a 5-to 10-membered heteroaryl group containing 1 to 3O, S, N heteroatoms, such as pyridyl, pyrimidinyl, pyrazinyl, furyl, thienyl, pyrrolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, oxadiazolyl, thiadiazolyl, pyridazinyl, triazinyl, quinolyl, quinoxalyl, indolyl, benzotriazolyl, benzothienyl, benzofuryl, isoquinolyl, tetrahydroquinolyl and the like.

In the compounds of the invention, all tautomers and mixtures thereof in any ratio are included.

The salt is an agriculturally and pharmaceutically acceptable salt, and preferably is an acid addition salt prepared by reacting the compound with a chemically acceptable acid, or a salt generated by reacting a compound with an acidic group and a basic compound. Wherein, the acid is preferably selected from inorganic acid (such as hydrochloric acid, sulfuric acid, phosphoric acid or hydrobromic acid, etc.) and organic acid (such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid or benzoic acid, etc.); the basic compound is preferably selected from sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate, and the like. The pharmaceutically acceptable salts are easily separated and can be purified by conventional separation methods, such as solvent extraction, dilution, recrystallization, column chromatography, preparative thin layer chromatography, and the like.

A process for preparing said substituted benzoylisoxazoles or tautomers, salts thereof, comprising the steps of:

reacting a compound of formula II with a hydroxylamine salt such as hydroxylamine hydrochloride in a suitable solvent such as ethanol, methanol, isopropanol, DMF or acetonitrile, a suitable base such as sodium/potassium acetate, sodium/potassium hydroxide, sodium/potassium tetrabutoxide, sodium/potassium carbonate at a temperature in the range from room temperature up to the boiling point of the solvent to produce a compound of formula I having the chemical equation:

wherein X is C1-C6 alkoxy, C1-C6 alkylamino, or the like.

A herbicidal composition comprising as an active ingredient at least one of said substituted benzoylisoxazoles or tautomers, salts thereof.

The weight percentage of the active component is 0.1-99%.

A method for controlling harmful plants, which comprises applying a herbicidally effective amount of at least one of said substituted benzoylisoxazoles or tautomers, salts thereof or of said herbicidal compositions on plants or in the area of harmful plants.

The application of the substituted benzoyl isoxazole compound or at least one of the tautomer and the salt thereof or the herbicidal composition in controlling weeds.

The substituted benzoyl isoxazole compound or the tautomer and the salt thereof are used for controlling weeds in useful crops, and preferably the useful crops are transgenic crops or crops treated by genome editing technology.

The compounds of formula I-1 according to the invention have outstanding herbicidal activity against a large number of economically important monocotyledonous and dicotyledonous harmful plants. The active substances according to the invention are also effective against perennial weeds which grow from rhizomes, or other perennial organs and are difficult to control. In this connection, it is generally immaterial whether the substance is used before sowing, before germination or after germination. Mention is made in particular of representative examples of the monocotyledonous and dicotyledonous weed groups which the compounds of the invention can control, without being restricted to a defined species. Examples of weed species for which the active substance acts effectively include monocotyledons: annual avena, rye, grass, alopecurus, farris, barnyard grass, digitaria, setaria and sedge, and perennial agropyron, bermudagrass, cogongrass and sorghum, and perennial sedge.

With regard to dicotyledonous weed species, the action can be extended to species such as the annual cleavers, viola, veronica, picea, chickweed, amaranthus, sinapis, ipomoea, sida, matricaria and abutilon species, and the perennial weeds cyclocarya, thistle, sorrel and artemisia. The active substances according to the invention are effective in controlling harmful plants, such as barnyard grass, sagittaria, alisma, eleocharis, saccharum and cyperus, in this particular condition of sowing of rice. If the compounds of the present invention are applied to the soil surface before germination, seedlings of weeds can be completely prevented before the weeds grow out, or the weeds stop growing when they grow out of cotyledons and finally die completely after three to four weeks. The compounds of the invention are particularly active against plants such as, for example, alpinia, sesamum indicum, polygonum convolvulus, chickweed, veronica vinifera, veronica albo, viola tricolor and amaranth, cleavers and kochia.

Although the compounds of the invention have excellent herbicidal activity against monocotyledonous and dicotyledonous weeds, they are not at all harmful or only insignificantly harmful to the important economic crop plants, such as wheat, barley, rye, rice, maize, sugar beet, cotton and soybean. Especially good compatibility with cereal crops such as wheat, barley and maize, especially wheat. The compounds according to the invention are therefore very suitable for selectively controlling unwanted vegetation in agricultural crops or ornamental plants.

Due to their herbicidal properties, these active substances can be used for controlling harmful plants in the cultivation of genetically engineered plants which are known or are to occur. Transgenic plants often have advantageous traits, such as resistance to specific insecticides, particularly to specific herbicides, resistance to plant diseases or to microorganisms pathogenic to plant diseases, such as specific insects or microorganisms of fungi, bacteria or viruses. Other specific traits are related to the conditions of the product, such as quantity, quality, storage stability, composition and specific ingredients. Thus, it is known that the resulting transgenic plant products have an increased starch content or an improved starch quality or a different fatty acid composition.

The compounds of the formula I-1 according to the invention or their salts are preferably used for economically important transgenic crops and ornamentals, for example cereals, such as wheat, barley, rye, oats, millet, rice, cassava and maize, or for the cultivation of sugar beet, cotton, soybeans, rapeseed, potatoes, tomatoes, peas and other vegetable plants. The compounds of the formula I-1 are preferably used as herbicides for cultivating useful plants which are resistant to the action of the herbicide or which are resistant to the toxic action of the herbicide by genetic engineering.

Conventional methods for breeding plants having improved shape over known plants include, for example, conventional mating methods and mutant breeding. In other words, new plants with improved traits may be obtained by means of methods of genetic engineering (see, for example, EP-0221044A, EP-0131624A). For example, several methods have been described:

the modification of crop plants by genetic engineering in order to improve starch synthesis in plants (e.g.WO 92/11376, WO 92/14827, WO 91/19806);

transgenic crop plants which are resistant to particular herbicides, to glufosinate herbicides (e.g. EP-0242236A, EP-0242246A) or to glyphosate-type herbicides (WO 92/00377), or to sulfonylurea-type herbicides (EP-0257993A, US-5013659A);

transgenic crop plants, such as cotton, which produce Bacillus thuringiensis toxins (Bt toxins) which protect against attack on plants by specific pests (EP-0142924A, EP-0193259A);

-transgenic crop plants with improved fatty acid composition (WO 91/13972).

A number of molecular biotechnologies are known which enable the production of transgenic plants with improved traits (see, for example, Sambrook et al, 1989, molecular amplification, second edition of the laboratory Manual, Cold spring harbor laboratory publications in the United states, Cold spring harbor, New York; or Winnacker "Gene und Klone" [ genes and clones ], VCH Weinheim, second edition 1996 or Christou, "trends in plant science" 1(1996) 423-431)). In order to carry out the manipulation of genetic engineering, it is possible to introduce nucleic acid molecules into plasmids, which undergo mutations or sequence changes by recombination of DNA sequences. Using standard methods as described above, it is possible, for example, to exchange substrates, remove partial sequences or add natural or synthetic sequences. In order to ligate the DNA fragments to each other, it is possible to attach a binder or a linker to the fragments.

Plant cells of reduced activity gene products can be prepared, for example, by expressing at least one suitable antisense-RNA, sense-RNA to achieve a cosuppression effect, or by expressing at least one suitably configured ribozyme which specifically cleaves transcripts of the gene products.

For this purpose, it is possible to use DNA molecules which contain the entire coding sequence of the gene product, including any flanking sequences which may be present, and to use DNA molecules which contain only a part of the coding sequence which has to be long enough to achieve an antisense effect in the cell. Sequences that are highly homologous but not identical to the coding sequence of the gene product may also be used.

When expressing the nucleic acid molecule in a plant, the synthetic protein can be localized in any desired plant cell compartment. However, for localization in a specific chamber, it is possible, for example, to link the coding region to a DNA sequence in order to ensure localization in a specific location. These sequences are known to those skilled in the art (see, for example, Braun et al, EMBO J.11(1992) 3219-3227; Wolter et al, Proc. Natl. Acad. Sci. USA85(1988), 846-850; Sonnewald et al Plant J.1(1991), 95-106).

Transgenic plant cells can be recombined into whole plants using known techniques. The transgenic plant may be of any desired plant variety, i.e., monocotyledonous and dicotyledonous plants. In this way, it is possible to obtain transgenic plants with improved traits by overexpressing, inhibiting or suppressing homologous (═ natural) genes or gene sequences, or by expressing heterologous (═ external) genes or gene sequences.

When the active substances according to the invention are used on transgenic crops, in addition to the harmful-plant-inhibiting effects observed on other crops, special effects are often observed on the corresponding transgenic crops, for example an improved or enlarged spectrum of weed control, improved application rates in the application, preferably a good combination of resistance of the transgenic crop and herbicide performance, and an influence on the growth and yield of the transgenic crop plants. The invention therefore also provides for the use of the compounds as herbicides for controlling harmful plants in transgenic crop plants.

In addition, the compound of the invention can obviously regulate the growth of crop plants. These compounds are used to target the control of plant components and to promote harvesting, such as desiccation and stunting of plants, by regulating the metabolism of plants involved. They are also suitable for regulating and inhibiting undesirable vegetation without destroying the growth of the crop plants. Inhibiting plant growth plays a very important role in many monocotyledonous and dicotyledonous crop plants, since this reduces or completely prevents lodging.

The compounds of the present invention can be applied using general formulations, and wettable powders, concentrated emulsions, sprayable solutions, powders or granules can be used. Thus the present invention also provides herbicidal compositions comprising the compounds of formula I-1. The compounds of formula I-1 can be formulated in a variety of ways depending on the usual biological and/or chemical physical parameters. Examples of suitable formulation choices are: wettable Powders (WP), water Soluble Powders (SP), water soluble concentrates, Emulsion Concentrates (EC), emulsions dispersed in water (EW), for example, oil-in-water and water-in-oil (EW), sprayable solutions, Suspension Concentrates (SC), dispersible oil suspensions (OD), suspensions with oil or water as diluent, solutions of miscible oils, powders (DP), Capsule Suspensions (CS), core (cutting) compositions, granules for spreading and soil application, spray granules, coated granules and absorbent granules, water dispersible granules (WG), water Soluble Granules (SG), ULV (ultra low volume) formulations, microcapsules and wax preparations. These individual formulation types are known and described in, for example, Winnacker-Kuchler, "Chemische Techologie" [ Chemicals Process ], Vol.7, C.Hauser Verlag Munich, 4 th edition 1986; wade van Valkenburg, "Pesticide Formulations," Marcel Dekker, n.y., 1973; martens, "Spray Drying" handbook, 3 rd edition 1979, g.

The necessary formulation auxiliaries, such as inerts, surfactants, solvents and other additives, are likewise known and are described in the documents mentioned below, for example in Watkins, "handbook of powdered diluents pesticides and carriers", second edition, Darland book Caldwell n.j.; h.v.01phen, "entry to clay colloid chemistry," second edition, j.wiley and Sons, n.y.; marsden, second edition "solvent guide", Interscience, n.y.1963; "annual report of detergents and emulsifiers" by McCutcheon, MC issues, Ridgewood n.j.; sisley and Wood, "surfactant encyclopedia", chemical publishing company, n.y.1964;

is/are as follows

[ ethylene oxide adduct surfactant]，Wiss.Verlagagesell.Stuttgart 1976；Winnacker-

"Chemische technology" [ chemical Process]Volume 7, c.hauser Verlag Munich, 4 th edition 1986.

Wettable powders can be uniformly dispersed in water and, in addition to the active substance, include diluents or inert substances, ionic and nonionic surfactants (wetting agents, dispersants), such as polyethoxylated alkylphenols, polyethoxylated fatty alcohols, polyoxyethylated fatty amines, fatty alcohol polyglycol ether sulfates, alkylsulfonates, alkylphenylsulfonates, sodium lignosulfonates, sodium 2,2 '-dinaphthylmethane-6, 6' -disulfonate, sodium dibutylnaphthalenesulfonate or sodium oleoylmethyltaurate. To prepare wettable powders, the active substances of the herbicides are finely ground, for example using customary instruments, such as hammer mills, fan mills and jet mills, with simultaneous or sequential incorporation of the adjuvants.

Emulsions are prepared by dissolving the active substance in an organic solvent, such as butanol, cyclohexanone, dimethylformamide, xylene or higher boiling aromatics or hydrocarbons or mixtures of solvents, and adding one or more ionic and/or nonionic surfactants (emulsifiers). Examples of emulsifiers which may be used are calcium alkylarylsulfonates, for example calcium dodecylbenzenesulfonate, or nonionic emulsifiers, for example polyglycol esters of fatty acids, alkylarylpolyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide-ethylene oxide condensation products, alkyl polyethers, sorbitan esters, for example sorbitan fatty acid esters, or polyoxyethylene sorbitan esters, for example polyoxyethylene sorbitan fatty acid esters.

The active substance and finely divided solid substances, for example talc, natural clays such as kaolin, bentonite and pyrophyllite, or diatomaceous earth, are ground to give a powder. Water or oil based suspensions may be prepared, for example, by wet milling using a commercially available bead mill, with or without the addition of a surfactant of the other formulation type described above.

For preparing emulsions, for example oil-in-water Emulsions (EW), it is possible to use aqueous organic solvents, using stirrers, colloid mills and/or static mixers, and, if desired, to add surfactants of another formulation type as described above.

Granules are prepared by spraying the active substance onto the adsorbate, granulating with inert material, or concentrating the active substance onto the surface of a carrier, for example sand, kaolinite, and granulating the inert material with a binder, for example polyvinyl alcohol, sodium polyacrylate or mineral oil. Suitable active substances can be granulated by the process for preparing fertilizer granules, if desired mixed with fertilizers. The preparation of water-suspendable granules is carried out by customary methods, for example spray-drying, fluidized-bed granulation, millstone granulation, mixing using high-speed mixers and extrusion without solid inert materials.

For the preparation of granules using a millstone, a fluidized bed, an extruder and Spray coating, see the following processes, for example "Spray Drying handbook", third edition 1979, g.goodwin ltd, london; browning, "Agglomeration", chemical and engineering 1967, page 147 ff; "Perry's handbook of Engineers of chemistry", fifth edition, McGraw-Hill, New York 1973, pages 8-57. If formulations for crop protection products are to be known, see, for example, G.C. Klingman, "Weed Control as a Science", John Wiley and Sons, New York, pages 196181-96 and J.D. Freyer, S.A. Evans, "Weed Control Manual", fifth edition, Blackwell Scientific rules, Oxford university 1968, pages 101-103.

Agrochemical formulations generally comprise from 0.1 to 99%, in particular from 0.1 to 95%, by weight of active substance of the formula I-1. The concentration of active substance in wettable powders is, for example, from about 10 to 99% by weight, with usual formulation components making up the remainder to 100% by weight. The concentration of the active substance in the emulsion concentrate may be about 1 to 90%, preferably 5 to 80% by weight. Powder formulations contain from 1 to 30% by weight of active, usually preferably from 5 to 20% by weight of active, whereas sprayable solutions contain from about 0.05 to 80%, preferably from 2 to 50% by weight of active. The content of active substance in the aqueous suspension granules depends primarily on whether the active substance is liquid or solid, and the auxiliaries, fillers and the like used in granulation. The content of active substance in the water-suspendable granule formulation is, for example, between 1 and 95% by weight, preferably between 10 and 80% by weight.

The active substance formulations mentioned may additionally comprise tackifiers, wetting agents, dispersants, emulsifiers, penetrants, preservatives, antifreezes, solvents, fillers, carriers, colorants, antifoams, evaporation inhibitors and generally customary pH and viscosity regulators in all cases.

On the basis of these formulations, it is also possible to mix them with other insecticide active substances, such as insecticides, acaricides, herbicides and fungicides, and also with safeners, fertilizers and/or plant growth regulators, either premixed or mixed in containers.

Suitable active substances which can be mixed with the active substances according to the invention in a compounded or tank-mixed formulation are, for example, the substances known from "the world Wide Specification of New agricultural chemical products", from the national agricultural science and technology Press, 2010.9 and the documents cited therein. For example, the herbicidal active substances mentioned below may be mixed with the mixtures of the formula I (remarks: name of the compound, either by common name according to the International organization for standardization (ISO), or by chemical name, where appropriate with a code number): acetochlor, butachlor, alachlor, propisochlor, metolachlor, s-metolachlor, pretilachlor, propyzamide, pretilachlor, napropamide, R-levulinyl-propyzamide, propanil, mefenacet, dibenzamide, diflufenican, flumetsulam, bromobutyrolac, dimethenamid, mefenacet, metazachlor, isoxaflutole, ryegrass methyl ester, loflutolane, diacrylamide, pethoxamide, butachlor, propisochlor, cyprosulfamide, flumetsulam, heptanoyl, isobutramine, propyzamide, terbutamid, dimethenamid, larvamide, trimethylcyclam, clofenamid, propyzamide, penoxulamide, carpronide, diflormid, trinitrol, butachlor, butafenacet, butachlor, benfluralin, bencarbzamide, pencyhalonil, metolachlor, bencarbzamide, pencyhalonil, buta, Grazing amine, bensulfuron, quinoxalamine, bensulfuron-methyl, naproxen, acetochlor, naphazel, thiachlor, pyraflufen, bensulfuron-methyl, prochloraz, clofenamide, butamidam, flupiram, atrazine, simazine, prometryn, cyanazine, simetryn, ametryn, prometryn, ipratron, flurazin, terbutryn, triazineone-flumetsulam, ciprofloxacin, glycazine, pradapazine, prometryn, simatong, azidezin, diuron, isopentetryn, cycloprozine, ametryn, terbuthylazine, terbuton, metocloprid, cyanazine, bentazon, clonazine, atrazine, metribuzin, cyanuric acid, indaziflazaflam, chlorsulfuron, meturon, bensulfuron, chlorimuron, tribenuron-methyl, thifensulfuron-methyl, pyrazosulfuron-methyl, sulfosulfuron-methyl, sulfometuron, Cinosulfuron, triasulfuron, sulfometuron-methyl, nicosulfuron, ethametsulfuron, amidosulfuron, ethoxysulfuron, cyclosulfamuron, rimsulfuron, azimsulfuron, primisulfuron-methyl, flusulfuron-methyl, flupyrsulfuron-methyl, epoxysulfuron, imazosulfuron, primisulfuron-methyl, prosulfuron, sulfosulfuron, trifloxysulfuron, triflusulfuron, metsulfuron-methyl sodium, flupyrazosulfuron, methisulfuron-methyl, primisulfuron, propysilfuron (Propyrisulfuron), metribusulfuron, acifluorfen-methyl, fomesafen, lactofen, fluoroglycofen-ethyl, oxyfen, prosulfuron, benfuresafen, trifloxysulfuron, metofen-ethyl, metofen, trifloxysulfuron, fluroxypyr, fluridone, benfop, benfluridone, benfurazolin, benfluridone, benfurbenflur, Dimethofen, oxyfluorfen, clofenflurate, Halosafen, chlortoluron, isoproturon, linuron, diuron, sifenuron, fluometuron, benzthiauron, methabenzuron, prosulfuron, sulfosulfuron, clomauron, clodinafuron, clofensulfuron, metoxuron, bromuron, metoxuron, meturon, fensulfuron, prosulfuron, subtilon, cuarone, metolachlor, cycloaroron, cyclouron, thifluuron, buthiuron, kuron, cumuron, metoxuron, methamidothion, metominosulfuron, trifolium, isoxafluron, isoxauron, moneuronon, aniron, methicuron, chloretron, clotururon, teuron, benuron, pennison, phenmedibensulfuron, bensulfuron, benazolin, propham, buthan, thiuron, buthan, benazolin, buthan, benazolin, buthan, benazol, Thiobencarb, merthiolane, diclofop, triallate, penoxsulam, pyributicarb, dichlorfon, edifenphos, ethiofen, prosulfocarb, clenbuterol, prosulfocarb, dichotomene, thiobencarb, promethazine, Isopolinate, Methiobencarb, 2, 4-d butyl ester, 2 methyl 4-sodium chloride, 2, 4-d isooctyl ester, 2 methyl 4-chloroisooctyl ester, 2, 4-d sodium salt, 2, 4-d dimethylamine salt, 2 methyl 4-chloroethyl thioester, 2 methyl 4 chloride, 2, 4-d propionic acid, 2, 4-d propionate, 2, 4-d butyric acid, 2 methyl 4-chloropropionic acid, 2 methyl 4-chlorobutyric acid, 2,4, 5-d nasal discharge, 2,4, 5-d propionic acid, 2,4, 5-d butyric acid, 2 methyl 4-chloropropionic acid, 2 methyl 4-d propionic acid, 2-d propionic acid, 2-cloroprionic acid, triclocarb, triclopyr, triclop, Aminodiclofenac, metocloprofenac, diclofop-methyl, fluazifop-p-butyl, haloxyfop-methyl, haloxyfop-p-butyl, quizalofop-ethyl, quizalofop-p-ethyl, fenoxaprop-p-ethyl, propaquizafop-ethyl, fenoxaprop-ethyl, clodinafop-ethyl, benazolin, clodinafop-ethyl, haloxyfop-methyl, benazolin, propalaxyl, butyfen-ethyl, chloroethafloxacin, aminofluanid, benazolin, dichlofop-ethyl, methamphetalin, propamocarb-ethyl, benfop-methyl, thiophosphine, pirimiphos-methyl, benfop-ethyl, benazolin, benfop-methyl, imax-methyl, mefenofos, mefeno, Imazamox ammonium salt, imazapic acid, imazamethabenz ester, fluroxypyr, clopyralid, picloram, triclopyr, dithiopyr, haloxydine, triclopyril, thiazopyr, fluridone, aminopyralid, diflufenzopyr, butoxyethyl triclopyr, Clodinate, sethoxydim, clethodim, cycloxydim, clethodim, topramezone, Buthidazole, metribuzin, hexazinone, metamitron, metribuzin, amitridione, Amibuzin, bromoxynil, octanoyl ioxynil, dichlobenitrile, pyraclonil, hydroxybensulam, Iodobonil, flumetsulam, penoxsulam, clofenapyr, pyraclonil, pyraflufen-ethyl, pyraoxystrobin, flumetsulam, pyraclonil, pyraoxystrobin, isoxathion, pyriftalid, pyriminobac-methyl, pyrithiobac-methyl, benzobicylon, mesotrione, sulcotrione, Tembotrione, Tefuryltrione, Bicyclopyrone, ketodradox, isoxaflutole, isoxaclomazone, fenoxasulfofone, methiozoline, isopyrafen, pyraflufen, pyrazote, difenzoquat, pyrazoxazole, pyroxaflutole, pyroxsulam, pyraclofos, pyraclonil, amicarbazone, carfentrazone, flumiclone, sulfentrazone, bencarane, bisphenomezone, butafenacil, isoxaflutole, cyclam, triclopyr, fluroxypyr, flumethazine, parnaprox, flumiclone, flumethol, carfentrazone, carzone, carfentrazone, car, Fluazifop-methyl, pyriminostrobin, bromopicrin, didaphylm, pyridaben, Pyridafol, quinclorac, chloroquine, bentazon, pyridate, oxaziclomefone, benazolin, clomazone, isoprox, isoproxypyrim, propyribac, cumylfen, clomazone, sodium chlorate, thatch, trichloroacetic acid, monochloroacetic acid, hexachloroacetone, tetrafluoropropionic acid, mequat, bromophenol oxime, triazasulam, imazazole, flurtamone, mesotrione, ethofumesate, pyrimethanil, clodinafop-methyl, clodinium, pyributaine, benfurazolin, meton, metamitron, metolachlor, dichlorvofen, triclopyr, aloac, Dietmquat, Etpronil, ipriflam, iprimazam, iprodione, Trizopyr, Thiaclonifen, chlorpyrifos, pyradifquat, chlorpyrifos, propiram, pyradifurone, pyradifon, pyradifurone, pyrazone, thion, pyrazone, clomazone, fenclorim, cloquintocet-mexyl, mefenpyr-diethyl, DOWFAUC, UBH-509, D489, LS 82-556, KPP-300, NC-324, NC-330, KH-218, DPX-N8189, SC-0744, DOWCO535, DK-8910, V-53482, PP-600, MBH-001, KIH-9201, ET-751, KIH-6127 and KIH-2023.

When used, the commercially available formulations are diluted in the usual manner, if desired, for example in wettable powders, concentrated emulsions, suspensions and granules suspended in water, using water. Powders, granules for soil application or solutions for spreading and spraying generally do not require further dilution with inert substances before use. The amount of the compound of formula I-1 required to be used varies with the external conditions, such as temperature, humidity, the nature of the herbicide used, and the like. It may vary widely, for example between 0.001 and 1.0kg/ha, or more of active substance, but preferably between 0.005 and 750g/ha, in particular between 0.005 and 250 g/ha.

Detailed Description

The following examples are intended to illustrate the invention and should not be construed as limiting it in any way. The scope of the invention is indicated by the appended claims.

In view of the economic and diversity of the compounds, we prefer to synthesize some of the compounds, a selection of which are listed in table 1 below. Specific compound structures and corresponding compound information are shown in table 1. The compounds in table 1 are only for better illustrating the present invention, but not for limiting the present invention, and it should not be understood to limit the scope of the above-mentioned subject matter of the present invention to the following compounds for those skilled in the art.

Table 1 Structure of Compounds and methods of use thereof¹HNMR data

Several methods for preparing the compounds of the present invention are illustrated in the schemes and examples below. The starting materials are commercially available or can be prepared by methods known in the literature or as shown in detail. It will be appreciated by those skilled in the art that other synthetic routes may also be utilized to synthesize the compounds of the present invention. Although specific starting materials and conditions for the synthetic route are described below, they can be readily substituted with other similar starting materials and conditions, and variations or modifications of the preparation process of the present invention, such as various isomers of the compounds, are included in the scope of the present invention. In addition, the preparation methods described below may be further modified in accordance with the present disclosure using conventional chemical methods well known to those skilled in the art. For example, protecting the appropriate groups during the reaction, and the like.

The following process examples are provided to facilitate a further understanding of the methods of preparation of the present invention, and the particular materials, species and conditions used are intended to be further illustrative of the invention and are not intended to limit the reasonable scope thereof. The reagents used in the synthesis of the compounds indicated in the following table are either commercially available or can be readily prepared by one of ordinary skill in the art.

Examples of representative compounds are as follows:

a process for preparing compound 001:

10g of 60% NaH is suspended in 50mL of dry DMF, 21.2g of 2-pyrrolidone is slowly added with stirring, after the addition is finished, the mixture is stirred for 30min at room temperature, then 24.3g of compound A1 is slowly added, the temperature is raised to 80 ℃, and the reaction is stirred for 3 h. Most DMF is evaporated under reduced pressure, the residual liquid is diluted by adding 100mL of water, the pH value is adjusted to about 3 by dilute hydrochloric acid, and ethyl acetate is used for extraction. The organic phase was washed successively with water, saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to give 26.2g of A2 as a pale yellow solid with an HPLC purity of 95%.

26g of Compound A2, 5g of concentrated sulfuric acid and 200mL of anhydrous methanol were mixed and heated under reflux overnight. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with 100mL of water and extracted with dichloromethane. The organic phase was washed successively with water, saturated sodium bicarbonate solution, saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to give 25g of a pale yellow liquid A3.

20g of Compound A3, 5g of cyclopropylmethanone and 150mL of anhydrous toluene were mixed, and 7g of sodium tert-butoxide was slowly added with stirring, and after the addition, the mixture was refluxed overnight with increasing temperature. After the reaction, the temperature was lowered to 0 ℃, 100mL of water was added, the pH was adjusted to about 3 with dilute hydrochloric acid, and the mixture was separated. The organic phase was washed successively with water, saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The crude product was distilled under reduced pressure to give 14.8g of a pale yellow liquid A4.

3.73g of Compound A4, 4.9g of triethyl orthoformate were mixed with 10mL of acetic anhydride and reacted under reflux with stirring for 3 hours. The reaction solution was concentrated under reduced pressure. To the residue was added 10mL of dry toluene, and the mixture was concentrated to remove volatile substances, whereby 4.3g of Compound A5 was obtained as a red liquid.

4.3g of Compound A5, 0.74g of hydroxylamine hydrochloride, 1.5g of sodium acetate and 10mL of ethanol were mixed and stirred at room temperature for 2.5 h. The solution was diluted with water, extracted with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to give 3.0g of a pale yellow solid with a yield of 75.5% and a purity of 95% by HPLC.

The preparation method of the compound 002 comprises the following steps:

10g of 60% NaH is suspended in 50mL of dry DMF, 28.7g of 5-methoxy-2-pyrrolidone is slowly added with stirring, after the addition is finished, the mixture is stirred for 30min at room temperature, then 24.3g of compound A1 is slowly added, the temperature is raised to 80 ℃, and the reaction is stirred for 3 h. Most DMF is evaporated under reduced pressure, the residual liquid is diluted by adding 100mL of water, the pH value is adjusted to about 3 by dilute hydrochloric acid, and ethyl acetate is used for extraction. The organic phase was washed successively with water, saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to give 27.1g of A6 as a pale yellow solid with an HPLC purity of 97%.

25.0g of Compound A6 was mixed with 50mL of thionyl chloride, heated under reflux for 2 hours, and excess thionyl chloride was distilled off under reduced pressure to give 26.5g of A7 as a pale yellow liquid. The crude product was used in the next reaction without purification.

13.5g of t-butyl acetoacetate and 3.8g of anhydrous lithium chloride were added to 30mL of THF, cooled to 0 ℃ in an ice bath, and stirred for 1 hour while 20g of pyridine was slowly dropped thereinto under stirring. A mixed solution of 25g of Compound A7 and 100mL of THF was added dropwise. After the dripping is finished, the temperature is increased and the reflux is carried out for 8 hours. After the reaction, the temperature was lowered to 0 ℃ and 100mL of water was added, and the pH was adjusted to about 3 with dilute hydrochloric acid, followed by liquid separation. The organic phase was washed successively with water, a saturated sodium bicarbonate solution and a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and the residue obtained by concentration was mixed with 60mL of trifluoroacetic acid and stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and the residual solution was diluted with ethyl acetate, washed successively with water, a saturated sodium bicarbonate solution, and a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give 20g of a pale yellow liquid A8.

3.8g of Compound A8, 1.5mL of N, N-dimethylformamide dimethyl acetal and 15mL of 1, 2-dichloroethane are mixed and stirred at reflux overnight. The reaction mixture was concentrated under reduced pressure to obtain 4.4g of compound A9 in an orange-red viscous state.

4.4g of Compound A9, 0.74g of hydroxylamine hydrochloride, 1.5g of sodium acetate and 10mL of ethanol were mixed and stirred at room temperature for 2.5 h. The solution was diluted with water, extracted with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was purified by column chromatography to give 2.63g of a pale yellow solid with a yield of 65.8% and a purity of 95% by HPLC.

Evaluation of biological Activity:

the activity level criteria for harmful plant destruction (i.e. growth control rate) are as follows:

10 level: death is complete;

and 9, stage: the growth control rate is more than 95 percent;

and 8, stage: the growth control rate is more than 90%;

and 7, stage: the growth control rate is more than 80 percent;

and 6, level: the growth control rate is more than 70%;

and 5, stage: the growth control rate is more than 60 percent;

4, level: the growth control rate is more than 50%;

and 3, level: the growth control rate is more than 20 percent;

and 2, stage: the growth control rate is 5-20%;

level 1: the growth control rate is below 5%;

level 0: no effect is produced.

The growth control rate is the fresh weight control rate.

Placing monocotyledon and dicotyledon weed seeds in a plastic pot filled with soil, then covering 0.5-2 cm of soil, enabling the monocotyledon and dicotyledon weed seeds to grow in a good greenhouse environment, processing test plants in a 4-5 leaf period after sowing for 2-3 weeks, respectively dissolving the tested compound of the invention with acetone, then adding Tween 80, diluting the solution into a solution with a certain concentration by using a certain amount of water, and spraying the solution onto the plants by using a spray tower. The weeds were cultured in the greenhouse for 3 weeks after application, and the experimental effects of the weeds after 3 weeks are shown in Table 2.

TABLE 2 post-emergence weed test

Number of Compounds	Chickweed	Descurainia sophia	Abutilon
				1	10	10	10
2	8	9	8
				9	10	10	10
10	9	9	9
				12	8	9	9
14	10	10	10
				16	10	10	10
17	10	10	10
				18	10	10	10
20	10	10	10
				21	10	10	10
23	10	10	10
				24	10	10	10
35	8	8	9
				38	10	10	10
44	10	10	10
				45	10	10	10
46	10	10	10
				47	10	10	10
48	10	10	10
				60	10	10	10
65	10	10	10
				66	10	10	10
68	10	10	10
				69	10	10	10
70	8	9	9
				74	10	10	10
75	10	10	10
				85	10	10	10
92	10	10	10
				93	10	10	10
94	10	10	10
				95	10	10	10

Note: the application dosage is 300 g/hectare of effective components.

Experiments show that the compound generally has better weed control effect, particularly has good effect on main broadleaf weeds such as descurainia sophia, chickweed, piemarker and the like widely occurring in corn and wheat fields, and has good commercial value. In particular, we have noted that it has extremely high activity against broadleaf weeds such as descurainia sophia which are resistant to ALS inhibitors. In addition, the compound of the invention has good activity and crop safety for key weeds in direct seeding and transplanting paddy fields under the condition of proper dosage.

Comparative experiment:

the test conditions after seedling are the same as above, and the test dosage is 50 g/hectare; the observation time was 20 days after the test.

TABLE 3 comparative experimental results

Table 4 comparative experimental results

TABLE 5 comparative experimental results

As can be seen from tables 3 to 5, the compounds of the present invention are clearly superior to the comparative compounds in herbicidal activity.

Meanwhile, a plurality of tests show that the compound has good selectivity on gramineous lawns such as zoysia japonica, bermuda grass, tall fescue, blue grass, ryegrass, seashore paspalum and the like, and can prevent and kill a plurality of key gramineous weeds and broadleaf weeds. Tests on soybeans, cotton, sunflower, potatoes, fruit trees, vegetables and the like under different application modes also show excellent selectivity and commercial value.

Claims

1. A substituted benzoyl isoxazole compound or a salt thereof, which is shown as a general formula I-1:

in the formula,

R₁R₂n represents

Wherein,

selected from 4-to 8-membered lactam group, imidazolyl group, pyrazolyl group,

R_bSelected from hydrogen, C_1～6Alkyl, halo C_1～6Alkyl radical, C_2～6Alkenyl, halo C_2～6Alkenyl radical, C_1～6Alkylcarbonyl or halo C_1～6An alkylcarbonyl group;

R_aselected from hydrogen, halogen, amino, C₁-C₆Alkylsulfonyl radical, C_1～6Alkyl, halo C_1～6Alkyl radical, C_2～6Alkenyl, halo C_2～6Alkenyl radical, C_1～6Alkoxy, halo C_1～6Alkoxy radical, C_1～6Alkylamino radical, C_2～6Alkenyloxy, halogeno C_2～6Alkenyloxy radical, C_2～6Alkenylamino, halogeno C_2～6Alkenylamino radical, C_1～6Alkylcarbonyl, halo C_1～6Alkylcarbonyl group, C_1～6Alkoxy radical C_1～6Alkyl or halo C_1～6Alkoxy radical C_1～6An alkyl group;

r represents

Wherein R is₁₁Selected from hydrogen, C₁-C₆Alkyl radical, C₃-C₆Cycloalkyl, halo C₁-C₆Alkyl or C₁-C₆Alkoxycarbonyl, n-0-2.

2. A substituted benzoylisoxazole compound or its salt according to claim 1, which is characterized in that:

selected from 4-to 8-membered lactam group, imidazolyl group, pyrazolyl group,

R_aSelected from hydrogen, C_1～4Alkyl radical, C_1～4Alkoxy, halogen, amino, C_1～6Alkylamino or C_1～6An alkylsulfonyl group;

R_bselected from hydrogen, C_1～6Alkyl or halo C_1～6An alkyl group;

R₁₁selected from hydrogen, C₁-C₆Alkyl radical, C₃-C₆Cycloalkyl, halo C₁-C₆Alkyl or C₁-C₆Alkoxycarbonyl, n-0-2.

3. A substituted benzoylisoxazole compound or its salt according to claim 1, which is characterized in that:

selected from butyrolactam, valerolactam, caprolactame, enantholactam, imidazolyl, pyrazolyl,

R_aSelected from hydrogen, fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, amino, C_1～6Alkylamino or C₁-C₆An alkylsulfonyl group;

R_bselected from hydrogen, C_1～6Alkyl or halo C_1～6An alkyl group;

R₁₁selected from hydrogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, cyclopropyl, methoxycarbonyl or ethoxycarbonyl.

4. A substituted benzoylisoxazole compound or its salt according to any one of claims 1 to 3, which is characterized in that: the salt is potassium salt, sodium salt, ammonium salt, calcium salt, pyridine salt or choline salt.

5. A substituted benzoylisoxazole compound or a salt thereof, which is selected from any one of the following compounds:

6. a process for the preparation of a substituted benzoylisoxazole compound according to any one of claims 1 to 4 or a salt thereof, comprising the steps of:

reacting a compound of formula II with a hydroxylamine salt to produce a compound of formula I, wherein the chemical reaction equation is as follows:

wherein X is C1-C6 alkoxy or C1-C6 alkylamino, R is₁R₂N and R₁₁Is as defined in any one of claims 1 to 4.

7. A herbicidal composition characterized by: containing at least one of the substituted benzoylisoxazoles or salts thereof according to any one of claims 1 to 5 as an active ingredient.

8. A herbicidal composition according to claim 7, characterized in that: the weight percentage of the active component is 0.1-99%.

9. A method for controlling harmful plants, which comprises applying a herbicidally effective amount of at least one of the substituted benzoylisoxazoles or their salts according to any one of claims 1 to 5 or of the herbicidal composition according to claim 7 or 8 to the plants or to the area of the harmful plants.

10. Use of at least one of the substituted benzoylisoxazoles or their salts according to any one of claims 1 to 5 or the herbicidal composition according to claim 7 or 8 for controlling weeds.

11. The use according to claim 10, wherein the substituted benzoylisoxazoles or their salts are used for controlling weeds in crops of useful plants.

12. The use according to claim 11, wherein the useful crop is a transgenic crop or a crop treated with genome editing techniques.