A non-bipyridyl salt herbicide and its preparation method and application

Abstract

The present invention discloses a non-bipyridyl salt herbicide, its preparation method, and application. Specifically, the present invention provides a diene diamine compound having a structure of Formula I or a tricyclic diene piperazine structure of Formula II. The non-bipyridyl salt compound can be converted into paraquat or diquat under light and air conditions, exhibiting comparable herbicidal properties to paraquat or diquat without significant toxicity. Therefore, the non-bipyridyl salt compound of the present invention can serve as a non-toxic alternative to paraquat or diquat as a herbicide. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the field of pesticides, and in particular to a diene diamine or tricyclic diene piperazine herbicide, a preparation method thereof, and uses thereof. Background Art

[0002] Weeds pose a serious threat to sustainable food production. Herbicides play an irreplaceable role in ensuring global food security. Paraquat (PQ; 1,1-dimethyl-4,4-dipyridinium) dichloride is a non-selective herbicide that has been widely used in over 120 countries since the 1960s due to its rapid, highly effective, broad-spectrum weed control, ability to preserve root systems, rapid inactivation upon contact with soil, and relatively low cost. Due to its high environmental safety and high weed control effectiveness, PQ remains an irreplaceable herbicide.

[0003] However, the high toxicity of PQ to humans has become a serious social problem. The high mortality rate from PQ poisoning is due to its inherent toxicity and the lack of effective treatment. PQ has caused thousands of deaths worldwide due to suicide and accidental poisoning. Data indicate that PQ causes 2,000 toxic ingestions annually, with a mortality rate of 50-90%. Due to this practical challenge, many countries have restricted or banned the use of PQ as a herbicide.

[0004] Several methods have been reported to reduce the toxicity of PQ to humans and animals and to develop antidotes for PQ. For example, PQ can be mixed with emetics or PQ-loaded supramolecular vesicles such as pillar[6]arenes and curubit[8]uril can be used to develop user-safe PQ preparations. Due to its strong ability to complex with PQ, curubit[8]uril is also considered a specific antidote. Many antioxidants such as naringin, lysine acetylsalicylic acid, selenium, quercetin, vitamin C, and sodium salicylate are used as antioxidant strategies to treat PQ poisoning. However, to date, these intervention strategies have not significantly reduced the mortality rate of PQ poisoning, and the development of non-toxic and effective herbicides as PQ alternatives remains of great practical significance.

[0005] In view of this, there is an urgent need in the art for a non-toxic, practical, cost-effective, and high-performance herbicide to replace the highly toxic paraquat. Summary of the Invention

[0006] An object of the present invention is to provide a non-toxic, practical, cost-effective and high-performance herbicide as a substitute for paraquat or diquat.

[0007] Another object of the present invention is to provide a method for preparing a novel herbicide.

[0008] Another object of the present invention is to provide a method for removing weeds in farmland.

[0009] In a first aspect, the present invention provides a compound having a structure represented by Formula I or Formula II, and its pesticide-acceptable salts, enantiomers, diastereomers, optical isomers, tautomers, racemates, deuterated derivatives, or combinations thereof, for use in preparing a botanical pesticide (preferably a herbicide):

[0010]

[0011] in,

[0012] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 Each is independently selected from the group consisting of hydrogen, halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)O(C1-C6)alkyl, -S(O) p (C1-C6)alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, and -NRaRb;

[0013] p is 0, 1, or 2;

[0014] Ra and Rb are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy;

[0015] R6' and R7' are each independently selected from the group consisting of H, C1-C6 alkyl, and C1-C6 haloalkyl.

[0016] In another preferred embodiment, the compound has a structure shown in Formula I, wherein,

[0017] R1, R2, R3, R4, R5, R6, R7, R8 are each independently selected from the group consisting of hydrogen, halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)O(C1-C6)alkyl, -S(O) p (C1-C6)alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, and -NRaRb;

[0018] R9, R 10 Each is independently selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and C1-C6 haloalkyl;

[0019] Ra and Rb are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl.

[0020] In another preferred embodiment,

[0021] R1, R2, R3, R4, R5, R6, R7, and R8 are each independently selected from the group consisting of hydrogen, halogen, and cyano;

[0022] R9, R 10 Each is independently selected from the following group: C1-C6 alkyl, C3-C6 cycloalkyl.

[0023] In another preferred embodiment, R1, R2, R3, R4, R5, R6, R7, and R8 are all H, and R9, R 10 It is a C1-C4 alkyl group.

[0024] In another preferred embodiment, the compound has the structure shown in Formula II, and

[0025] R1, R2, R3, R4, R5, R8, R9, R 10 Each is independently selected from the group consisting of hydrogen, halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl;

[0026] R6' and R7' are each independently selected from the following group: H, C1-C6 alkyl.

[0027] In another preferred embodiment, R1, R2, R3, R4, R5, R8, R9, R 10 , R6', and R7' are all H.

[0028] In another preferred embodiment, the compound is selected from the following group:

[0029]

[0030] In a second aspect of the present invention, a method for preparing a compound of Formula I or Formula II is provided, comprising the steps of:

[0031]

[0032] In an aqueous solution, reacting a compound of formula Ia or a compound of formula IIa with a reducing agent to obtain a compound of formula I or a compound of formula II; wherein the reducing agent is a borohydride or H2;

[0033] wherein X is selected from Cl or Br.

[0034] In another preferred embodiment, when the reducing agent is H2, the reaction is carried out in the presence of a hydrogenation catalyst; preferably, the hydrogenation catalyst is selected from the following group: Pd, Ni.

[0035] In another preferred embodiment, the borohydride is selected from the group consisting of potassium borohydride, sodium borohydride, or a combination thereof.

[0036] In another preferred embodiment, in the method, the molar ratio of the compound of formula Ia or formula IIa to the borohydride is 1:(2-5), preferably 1:(3-4).

[0037] In another preferred embodiment, the reaction temperature is 10-40°C; preferably 15-30°C; and / or

[0038] In another preferred embodiment, the reaction time is 10-30 min; preferably 15-20 min.

[0039] In another preferred embodiment, the compound of formula Ia is 1,1-dimethyl-4,4'-bipyridinium dichloride.

[0040] In another preferred embodiment, the compound of formula IIa is 1,1'-ethylene-2,2'-bipyridinium dibromide.

[0041] In another preferred embodiment, the method further comprises the step of separating and purifying the reaction product after the reaction is completed.

[0042] In a third aspect of the invention, there is provided an agricultural composition comprising:

[0043] (a) as an active ingredient, a compound of formula I or II as described in the first aspect of the present invention, a pesticidally acceptable salt, enantiomer, diastereomer, optical isomer, tautomer, racemate, deuterated derivative thereof, or a combination thereof; and

[0044] (b) an optional oxidizing agent; preferably, the oxidizing agent is selected from the group consisting of an oxidizing agent (preferably chloranil, chloramine T, hydrogen peroxide, bleaching powder, hydrosulfite, potassium monopersulfate complex salt), a metal catalyst (preferably copper, iron, nickel, molybdenum, ruthenium, manganese, palladium or platinum metal), or a combination thereof; and

[0045] (c) a pesticide-acceptable carrier and / or excipient; wherein the preferred carrier is selected from the group consisting of water, aqueous NaCl solution; and

[0046] (d) optional auxiliary agents; wherein the auxiliary agent is selected from the group consisting of molecular sieves, surfactants, protective colloids, adhesives, thickeners, thixotropic agents, penetrants, chelating agents, dyes, colorants, polymers, or combinations thereof.

[0047] In another preferred embodiment, the content of the active ingredient in the agricultural composition is 0.01-99.99 wt%.

[0048] In another preferred embodiment, the oxidation aid is [{Cu(Sal)2(MeCN)}2].

[0049] In a fourth aspect of the invention, a weed control method is provided, comprising the steps of applying a compound according to Formula I or Formula II, or the agricultural composition according to the third aspect of the invention, to the surface of the weeds or plants to be removed, or to the soil or environment surrounding the weeds or plants under conditions of light and oxygen:

[0050]

[0051] in,

[0052] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 Each is independently selected from the group consisting of hydrogen, halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)O(C1-C6)alkyl, -S(O) p (C1-C6)alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, and -NRaRb;

[0053] p is 0, 1, or 2;

[0054] Ra and Rb are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy;

[0055] R6' and R7' are each independently selected from the group consisting of H, C1-C6 alkyl, and C1-C6 haloalkyl.

[0056] In a fifth aspect of the present invention, there is provided a compound represented by the following formula II:

[0057]

[0058] in,

[0059] R1, R2, R3, R4, R5, R8, R9, R 10 Each is independently selected from the group consisting of hydrogen, halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)O(C1-C6)alkyl, -S(O) p(C1-C6)alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, and -NRaRb;

[0060] p is 0, 1, or 2;

[0061] Ra and Rb are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy;

[0062] R6' and R7' are each independently selected from the group consisting of H, C1-C6 alkyl, and C1-C6 haloalkyl;

[0063] Preferably, the compound is

[0064] In a fifth aspect of the present invention, a method for preparing paraquat or diquat is provided, comprising the steps of:

[0065] In the presence of light and oxygen, the compound represented by Formula 2 or Formula 3 reacts to produce paraquat or diquat;

[0066]

[0067] In another preferred embodiment, the method comprises the steps of:

[0068] At 60-100° C., in a first solvent, in the presence of an oxidant and a catalyst, the compound represented by Formula 2 or Formula 3 reacts to obtain paraquat or diquat.

[0069] In another preferred embodiment, the oxidant is selected from the following group: chloranil, chloramine T, hydrogen peroxide, bleaching powder, hydrosulfite, potassium monopersulfate complex salt, oxygen, air, or a combination thereof.

[0070] In another preferred embodiment, the oxidant is chloranil.

[0071] In another preferred embodiment, the catalyst is selected from the group consisting of copper, iron, nickel, molybdenum, ruthenium, manganese, palladium, platinum, or a combination thereof.

[0072] In another preferred embodiment, the catalyst is selected from the group consisting of [{Cu(Sal)2(MeCN)}2], metal chlorides, metal bromides, or a combination thereof; preferably [{Cu(Sal)2(MeCN)}2].

[0073] In another preferred embodiment, the metal chloride is selected from the group consisting of ferric chloride, copper chloride, or a combination thereof.

[0074] In another preferred embodiment, the metal bromide is selected from the group consisting of ferric bromide, copper bromide, or a combination thereof.

[0075] In another preferred embodiment, the amount of the oxidant is 0.2-0.6 of the molar amount of the compound represented by Formula 2 or Formula 3.

[0076] In another preferred embodiment, the amount of the catalyst used is 0.01-0.1 of the molar amount of the compound represented by Formula 2 or Formula 3.

[0077] In another preferred embodiment, the first solvent is selected from the following group: water, C2-C6 nitrile solvents, C1-C6 ketone solvents, or a combination thereof.

[0078] In another preferred embodiment, the first solvent is selected from the group consisting of water, MeCN, acetone, or a combination thereof.

[0079] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] Figure 1 The trend graphs showing the quantitative analysis and cyclic voltammetry detection of the conversion of dienediamine compounds to PQ under light and air conditions are shown.

[0081] Figure 2 The results show that the dienediamine compounds have herbicidal properties against creeping weeds.

[0082] Figure 3 The results showed that the dienediamine compounds had herbicidal properties against calamus.

[0083] Figure 4 The herbicidal properties of the dienediamine compounds against Arabidopsis thaliana were shown.

[0084] Figure 5 The herbicidal effects of diquat and its reduced form tricyclodienepiperazine were demonstrated.

[0085] Figure 6 The effects of dienediamine compounds and PQ on the survival rate and body weight of mice are shown.

[0086] Figure 7 The data of various biochemical indicators are shown in mice injected intraperitoneally with dienediamine compounds and PQ 48h later.

[0087] Figure 8 Shows the changes in various organs of mice 48 hours after intraperitoneal injection of dienediamine compounds and PQ.

[0088] Figure 9Shown are the transmission electron microscopy results of various organs of mice 48 hours after intraperitoneal injection of dienediamine compounds and PQ.

[0089] Figure 10 The ROS levels of cells after direct contact of dienediamine compounds and PQ on A549 cells, COS-7 cells, and Hep G2 cells are shown.

[0090] Figure 11 The cell apoptosis after direct contact of diene diamine compounds and PQ on A549 cells, COS-7 cells and Hep G2 cells is shown. DETAILED DESCRIPTION

[0091] After extensive and in-depth research, the inventors have discovered a non-toxic, practical, cost-effective, and excellently performing dienediamine herbicide having structural formula I or tricyclic dienepiperazine having structural formula II. The herbicide of the present invention does not function as an electron transfer agent, and its toxicity in systematic in vivo and in vitro evaluations is significantly lower than that of paraquat or diquat, with toxicity comparable to that of a normal saline control group. The herbicide of the present invention can be effectively converted into an effective active ingredient under natural sunlight and air conditions, achieving highly effective weed control. Based on this, the inventors completed the present invention.

[0092] the term

[0093] Each alkyl moiety, alone or as part of a larger group such as alkoxy, alkylthio, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl, can be straight or branched. Typically, the alkyl group is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, tert-butyl, n-pentyl, neopentyl, or n-hexyl.

[0094] The term "alkyl" generally refers to a C1-C6 alkyl group, which refers to a straight or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or a similar group, preferably a C1-C4 alkyl group or a C1-C3 alkyl group; more preferably a C1-C2 alkyl group (such as methyl).

[0095] Alkenyl and alkynyl moieties may be in the form of straight or branched chains, and the alkenyl moieties may be of (E)- or (Z)-configuration. Alkenyl and alkynyl moieties may contain one or more double and / or triple bonds in any combination; but preferably contain only one double bond (for alkenyl) or only one triple bond (for alkynyl).

[0096] The term "C2-C6 alkenyl" refers to a straight or branched alkenyl group having 2 to 6 carbon atoms, such as vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, or the like.

[0097] The term "C2-C6 alkynyl" refers to a straight chain or branched chain alkynyl group having 2 to 6 carbon atoms, such as ethynyl, propynyl, or the like.

[0098] Typically, alkenyl or alkynyl is C2-C4 alkenyl or C2-C4 alkynyl, more specifically ethenyl (vinyl), prop-2-enyl, prop-3-enyl (allyl), ethynyl, prop-3-ynyl (propargyl), or prop-1-ynyl. Preferably, the term "cycloalkyl" refers to cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0099] As used herein, the term "aryl" preferably refers to phenyl.

[0100] The terms "heteroaryl" and "heteroaryl ring" (alone or as part of a larger group (e.g., heteroaryl-alkyl-)) are ring systems containing at least one heteroatom and can be in monocyclic or bicyclic form. Preferably, a monocyclic ring will contain 1, 2, or 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. Typically, as used herein, the term "heteroaryl" includes furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, and triazinyl rings, which may or may not be substituted as described herein.

[0101] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. The term "halogenated" refers to a group substituted by one or more of the above halogen atoms, which may be the same or different, such as trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.

[0102] The same applies correspondingly to halogen in the context of other definitions, such as haloalkyl or halophenyl.

[0103] Haloalkyl radicals having a chain length of 1 to 6 carbon atoms are, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl, heptafluoro-n-propyl, and perfluoro-n-hexyl.

[0104] The term "alkoxy" preferably has 1 to 6 carbon atoms. Typically, the alkoxy group is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy or one of the pentoxy or hexoxy isomers, preferably methoxy and ethoxy. It should be understood that two alkoxy substituents can be present on the same carbon atom.

[0105] Typically, the term "haloalkoxy" is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy or 2,2,2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.

[0106] Exemplary "C1-C6 alkyl-S-(alkylthio)" include methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0107] Exemplary “C1-C6 alkyl-S(O)-(alkylsulfinyl)” include methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0108] Exemplary "C1-C6 alkyl-S(O)2-(alkylsulfonyl)" include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0109] The compounds of the present invention may contain one or more asymmetric centers and thus occur as racemates, racemic mixtures, single enantiomers, diastereomeric compounds, and single diastereomers. The presence of asymmetric centers depends on the nature of the various substituents on the molecule. Each such asymmetric center will independently produce two optical isomers, and all possible optical isomers and diastereomeric mixtures and pure or partially purified compounds are included within the scope of the present invention. The present invention includes all isomeric forms of the compounds.

[0110] The term "light conditions" refers to the presence of visible light in the environment, preferably natural light conditions, such as sunlight.

[0111] The term "oxygen presence condition" refers to the presence of sufficient oxygen in the environment to convert the herbicide composition of the present invention into the corresponding active ingredient (paraquat or diquat). In a preferred embodiment, the oxygen may be present in an air environment.

[0112] The term "pesticide-acceptable salt" refers to a salt whose anion is known and acceptable to form a pharmaceutically acceptable salt of a nematicide. Preferably, the salt is water-soluble. Suitable acid addition salts formed from the compound of formula (I) include salts formed with inorganic acids, such as hydrochlorides, phosphates, sulfates, and nitrates; and salts formed with organic acids, such as acetates and benzoates.

[0113] The term "weeds" includes undesirable crop species such as volunteer crops, including conventional and genetically modified volunteer crops through mutation or transgenic methods. For example, in a turfgrass crop, such as a golf course environment, creeping bentgrass putting green turf may be considered "volunteer" if it is found on a flat fairway area planted with a different grass variety. Similarly, the grasses listed below may be considered weeds when found in inappropriate locations.

[0114] As used herein, the term "room temperature" refers to 5-45°C, preferably 10-30°C; more preferably 25±2°C.

[0115] Unless otherwise specified, when paraquat (or PQ) is mentioned herein, it refers to 1,1-dimethyl-4,4-dipyridinium, or a salt thereof with a halogen anion.

[0116] Non-bipyridyl herbicides

[0117] The term "active ingredient" or "active substance" or "active compound" refers to a dienediamine compound having a structure of Formula I or a compound having a tricyclic dienepiperazine structure as shown in Formula II, and its pesticide-acceptable salts, enantiomers, diastereomers, optical isomers, tautomers, racemates, deuterated derivatives, or combinations thereof;

[0118]

[0119] in,

[0120] R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 Each is independently selected from the group consisting of hydrogen, halogen, cyano, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)O(C1-C6)alkyl, -S(O) p (C1-C6)alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, and -NRaRb;

[0121] p is 0, 1, or 2;

[0122] Ra and Rb are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy;

[0123] R6' and R7' are each independently selected from the group consisting of H, C1-C6 alkyl, and C1-C6 haloalkyl.

[0124] The dienediamine compound or tricyclic dienepiperazine compound of the present application has herbicidal activity comparable to that of paraquat or diquat, but is significantly less toxic to animals than PQ or diquat. Therefore, the compound has great potential and can be widely used in green agriculture worldwide, and can prevent deaths caused by PQ or diquat.

[0125] Examples of weeds that can be removed by the diene diamine compounds and tricyclic diene piperazine compounds of the present application include, but are not limited to: creeping weed, Arabidopsis thaliana, and calamus. After the diene diamine compounds and tricyclic diene piperazine come into contact with the surface of weeds, they react in sunlight and air to form paraquat and diquat, respectively. Both paraquat and diquat are non-selective herbicides that have a significant killing effect on weeds and green plants such as grasses, sedges, broadleaf weeds, Asteraceae, Polygonaceae weeds, and Leguminosae. The diene diamine compounds or tricyclic diene piperazine compounds are mainly used in:

[0126] 1) Orchard weeds: Cirsium arvense var. integrifolium, Cirsium japonicum Fisch. ex DC., Conyza japonica, Artemisia lavandulaefolia, Cerastium arvense L., Xanthium strumarium L., Herb of Spanish needles, Bidens bipinnata, Artemisia hedinii Ostenf. et Pauls, Digitaria sanguinalis (L.) Scop., Setaria viridis, Eleusine indica (L.) Gaertn., Avena fatua, Vicia hirsuta, Capsella bursa-pastoris, Euphorbia helioscopia).

[0127] 2) Paddy field weeds: Monochoria vaginalis, Ammannia baccifera, Echinochloa crusgalli; Alternanthera philoxeroides, Ophiopogon japonicus, Chrysopogon aciculatus, Eleocharis dulcis, Paspalum paspaloides, and Sagittaria pygmaea;

[0128] 3) Wheat field weeds: Aster (Aster tataricus Lf), Erigeron annuus, Youngia japonica, Erigeron philadelphicus L., Cirsium arvensevar. integrifolium, Gnaphalium affine D. Don, Hemistepta lyrata (Bunge) Bunge, Sonchus oleraceus L, Lapsana apogonoides, Alopecurus japonicus Steud., Beckmannia syzigachne, Sclerochloa dura, Polypogon fugax Nees ex Steud., Alopecurus aequalis Sobol., Poa pratensis L., Avena fatua), Roegneria kamoji, ryegrass (Lolium perenne);

[0129] 4) Weeds in cotton fields: Common weeds include Eleusine indica (L.) Gaertn., Portulaca oleracea L., Digitaria sanguinalis (L.) Scop., Eclipta prostrata, Chenopodium quinoa, Acalypha australis, Sonchus arvensis, Echinochloa crusgalli, Cyperus rotundus, Imperata cylindrica (L.) Beauv., Bolboschoenus planiculmis, Cynodon dactylonlon, Suaeda glauca (Bunge) Bunge, and Cirsium arvense. var.integrifolium), Amaranthus retroflexus L., Setaria viridis, Solanum nigrum L., Sonchus oleraceus L., Convolvulus arvensis L., Polygonum aviculare L., Parthenocissus tricuspidata (Sieb. & Zucc.) Planch., Commelina diffusa, Ipomoea nil (Linnaeus) Roth, Amaranthus viridis, Abutilon theophrasti Medicus, Chloris virgata Sw., Amaranthus roxburghianus, Hibiscus trionum, Xanthium strumarium), Cyperus microiria, Daucus carota L., Digitaria ciliaris (Retz.) Koel., Digitaria chrysoblephara, Eragrostis pilosa, Leptochloa chinensis (L.)Nees), Setaria glauca (L.) Beauv., Cirsium japonicum Fisch.ex DC., Erigeroncanadensis, Taraxacum mongolicum Hand.-Mazz., Artemisia scoparia, Humulus scandens (Lour.) Merr., Physalis minima;

[0130] 5) Cornfield weeds: Digitaria sanguinalis (L.) Scop., Leptochloachinensis (L.) Nees, Portulaca oleracea L., Eleusine indica (L.) Gaertn., etc.

[0131] 6) Weeds in tobacco fields: Common weeds include Acalypha australis, Polygonum lapathifolium L., Echinochloa crusgalli, Cardamine hirsuta L., Digitaria sanguinalis (L.) Scop., Alopecurus aequalis Sobol., and Mazus pumilus.

[0132] Examples of weeds that can be removed by the diene diamine compounds and tricyclic diene piperazine herbicides of the present application include, but are not limited to: Cynodon dactylonlon, Arabidopsis thaliana, Acorus calamus L., Digitaria sanguinalis (L.) Scop., Eleusine indica (L.) Gaertn., Eragrostis cilianensis, Portulaca oleracea L., Malachium aquaticum (L.) Fries., Stellaria media (L.) Cyr, Alternanthera Sessilis (Linn.) DC., Cyperus rotundus, Imperata cylindrica (L.) Beauv., Oplismenus serrata compositus (L.) Beauv.), Phragmites australis (Cav.) Trin.ex Steud, Galium spurium L., Polygonum convolvulus, Solanum nigrum L., Vicia gigantea Bge., Convolvulus arvensis L., Galeopsis bifida Boenn., Polygonum lapathifolium L., Polygonum bungeanum Turcz, Amaranthus retroflexus L., Commelina communis L., Elsholtzia ciliata (Thunb.) Hyland., Thlaspiarvense L., Vicia sepium L., Descurainia sophia(L.)Webb.ex Prantl), Calystegia hederacea Wall, Avena fatua, Arrhenatherum elatius(L.)Presl, Aegilops tauschii Coss., Alopecurus aequalisSobol.), Japanese wheatgrass (Alopecurus japonicas Steud.), webgrass (Aponogetonmadagascariensis), barnyard grass (Echinochloa crusgalli), bluegrass (Poa annua L.), foxtail grass (Setaria viridis(L.)Beauv.), water centipede (Kyllinga brevifolia Rottb.), Cyperus difformis L., sunshine sedge (Fimbristylis miliacea(L.)Vahl), water sedge (Juncellus serotinus), broken rice sedge (Cyperus iria), red-scaled flat sedge (Pycreussanguinolentus), bull grass (Bulbostylis barbata(Rotth.)Kunth), firefly rush (Scirpusjuncoides Roxb.), flat-stem grass (Scirpus Green weeds such as planiculmis (Fr.) Schmidt, Japanese bonegrass (Ajuganipponensis Makino), dandelion (Taraxacum mongolicum Hand.-Mazz.), meadowfowl (Poapratensis L.), sedge grass (Lycopodiastrum casuarinoides), poinsettia (Euphorbia pulcherrima Willd. et Kl.), pineapple (Ananas comosus (Linn.) Merr.), hot pepper (Polygonum hydropiper L.), wild mustard (Raphanus raphanistrum), bitter vine (Celastrus angulatus Maxim.), cardamine hirsuta L., echinacea (Echinacea purpurea (Linn.) Moench), and inula japonica (Inula japonica Thunb).

[0133] Agricultural compositions

[0134] The active substances of the present invention can be prepared into herbicidal compositions by conventional methods. These active compounds can be made into conventional formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with the active substance, microcapsules in polymers, coating compounds for seeds, and formulations for use with combustion devices, such as fumigation cartridges, fumigation pots and fumigation trays, as well as ULV cold mist and hot mist formulations.

[0135] These formulations can be produced by known methods, for example, by mixing the active compound with an extender, i.e., a liquid, liquefied gas, or solid diluent or carrier, and optionally a surfactant, i.e., an emulsifier and / or dispersant and / or foam former. When, for example, water is used as the extender, an organic solvent may also be used as an auxiliary agent.

[0136] If necessary, other active ingredients compatible with the herbicidal composition of the present invention may be added, for example, other herbicides, fungicides, plant growth regulators, antibiotics, insecticides, and fertilizers.

[0137] In a preferred embodiment, the content of the active ingredient is 1 to 99.99 weight % based on the total weight of the agricultural composition; preferably 5 to 95 weight %, for example, the content of the active ingredient is 10 weight %, 15 weight %, 20 weight %, 25 weight %, 30 weight %, 35 weight %, 40 weight %, 45 weight %, 50 weight %, 55 weight %, 60 weight %, 65 weight %, 70 weight %, 75 weight %, 80 weight %, 85 weight %, 90 weight %, etc.

[0138] The pesticide-acceptable carriers and / or excipients include, but are not limited to, surfactants, protective colloids, adhesives, thickeners, thixotropic agents, penetrants, chelating agents, dyes, colorants, polymers, and the like, and may also be other conventional adjuvants acting as carriers.

[0139] As used herein, a carrier refers to one or more organic, inorganic, natural, or synthetic substances. They facilitate the application of the active ingredient and are generally inert and agriculturally acceptable, particularly to the plants being treated. Carriers can be solid, such as clay, natural or synthetic silicates, silicon dioxide, resins, waxes, solid fertilizers, or liquid, such as water, alcohols, ketones, petroleum fractions, aromatic or waxy hydrocarbons, chlorinated hydrocarbons, and liquefied gas.

[0140] When a liquid solvent is used as a diluent or carrier, suitable diluents or carriers may include, for example: aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or dichloromethane; aliphatic hydrocarbons, such as cyclohexane or paraffins, such as mineral oil fractions; alcohols, such as ethanol or ethylene glycol and their ethers and lipids; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or less commonly used polar solvents, such as dimethylformamide and dimethyl sulfoxide, and water.

[0141] A diluent or carrier for liquefied gas refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide.

[0142] Solid carriers can be ground natural minerals such as kaolin, clay, talc, quartz, attapulgite, montmorillonite, or diatomaceous earth; and ground synthetic minerals such as highly dispersed silicic acid, alumina, and silicates. Solid carriers for particles are crushed and graded natural zircons such as calcite, marble, pumice, sepiolite, and dolomite, as well as particles synthesized from inorganic and organic coarse powders, and particles of organic materials such as sawdust, coconut shells, corn cobs, and tobacco stems.

[0143] Binders, such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or emulsions, such as gum arabic, polyvinyl alcohol and polyvinyl acetate.

[0144] Examples of the coloring agents include inorganic dyes such as iron oxide, cobalt oxide and Prussian blue; organic dyes such as azo dyes or metal phthalocyanine dyes; and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, aluminum and zinc.

[0145] The surfactant components of the present invention include emulsifiers, dispersants or wetting agents, which may be ionic or nonionic. Examples that may be mentioned are: polyacrylates, lignin sulfonates, phenolsulfonic acid or naphthalenesulfonates, polymers of ethylene oxide with aliphatic alcohols or with aliphatic acids or with aliphatic amines and with substituted phenols (especially alkylphenols or arylphenols), sulfosuccinates, taurine derivatives and alcohol phosphates or polyhydroxyethylated phenol phosphates, alkylsulfonates, alkylarylsulfonates, alkyl sulfates, lauryl ether sulfates, fatty alcohol sulfates, sulfated cetostearyl alcohol and sulfated fatty alcohol glycol ethers, and also condensates of naphthalene or naphthalenesulfonic acid with phenol and formaldehyde. Compounds, polyoxyethylene octylanisole, ethoxylated isooctyl ether, octylphenol or nonylphenol, alkylphenyl polyethylene glycol ether, tributylphenyl polyethylene glycol ether, tristearylphenyl polyethylene glycol ether, alkylaryl polyether alcohol, alcohol and fatty alcohol / ethylene oxide condensate, ethoxylated castor oil, polyoxyethylene alkyl ether, ethoxylated polyoxypropylene, lauryl alcohol polyethylene glycol ether acetal, sorbitol ester, lignin sulfite waste liquor, as well as proteins, denatured proteins, polysaccharides, hydrophobically modified starches, polyvinyl alcohol, polycarboxylates, polyoxyalkylates, polyvinylamine, polyvinylpyrrolidone and copolymers.

[0146] Preferably, the carrier and / or excipient is at least one of an emulsifier, a dispersant, a wetting agent, a spreader, a stabilizer, a defoaming agent, a synergist, a penetrant, an adhesive, a carrier and a filler.

[0147] Preferably, the formulation of the agricultural composition is at least one selected from wettable powders, soluble powders, emulsifiable concentrates, aqueous suspensions, dispersible oil suspensions, aqueous emulsions, microemulsions and water-dispersible granules.

[0148] The present invention does not particularly limit the specific methods for preparing various formulations of agricultural composition herbicides. Those skilled in the art can refer to the standard methods provided in "Modern Pesticide Formulation Processing Technology" (Edited by Liu Guangwen, Chemical Industry Press) to prepare herbicides of the desired formulation.

[0149] The components of the herbicide composition provided by the present invention can be stored mixed or separately. According to a preferred embodiment, the components of the agricultural composition forming the active ingredient in the herbicide are stored independently or two or more components are mixed and stored in the form of a tank mix for immediate use.

[0150] The agricultural herbicide composition of the present invention includes, but is not limited to, application to crops and / or weeds by methods such as spraying.

[0151] Preparation methods of diene diamine compounds and tricyclic diene piperazines

[0152] The compounds of the present invention having a structure represented by Formula I or Formula II can be prepared by the following method. However, the conditions of the method, such as the reactants, solvent, base, amount of the compound used, reaction temperature, reaction time, etc., are not limited to the following explanation. The compounds of the present invention can also be conveniently prepared by optionally combining various synthetic methods described in this specification or known in the art. Such combinations can be easily performed by those skilled in the art to which the present invention belongs.

[0153] Specifically, the compounds of the present invention can be prepared by the following method:

[0154]

[0155] In an aqueous solution, reacting a compound of formula Ia or a compound of formula IIa with a reducing agent to obtain a compound of formula I or a compound of formula II; wherein the reducing agent is a borohydride or H2;

[0156] wherein X is selected from Cl or Br.

[0157] In one embodiment, when the reducing agent is H2, the reaction is carried out in the presence of a hydrogenation catalyst; preferably, the hydrogenation catalyst is selected from the group consisting of Pd and Ni.

[0158] In another preferred embodiment, the borohydride is selected from the group consisting of potassium borohydride, sodium borohydride, or a combination thereof. In another embodiment, in the method, the molar ratio of the compound of formula Ia or formula IIa to the borohydride is 1:(2-5), preferably 1:(3-4).

[0159] In another embodiment, the reaction temperature is 10-40°C; preferably 15-30°C; and / or

[0160] In another embodiment, the reaction time is 10-30 min; preferably 15-20 min.

[0161] In another embodiment, the compound of formula Ia is 1,1-dimethyl-4,4'-bipyridinium dichloride.

[0162] In another embodiment, the compound of formula IIa is 1,1'-ethylene-2,2'-bipyridinium dibromide.

[0163] In another embodiment, the method further comprises the step of separating and purifying the reaction product after the reaction is completed.

[0164] Compared with the prior art, the main advantages of the present invention include:

[0165] (1) The diene diamine compound and tricyclic diene piperazine structure of the present invention have herbicidal efficacy comparable to that of paraquat or diquat when used as herbicides, but their toxicity to animals is comparable to that of normal saline in the control group, and they are almost non-toxic. Therefore, they can be used as substitutes for paraquat or diquat.

[0166] (2) The diene diamine compound and tricyclic diene piperazine structure of the present invention exert herbicidal efficacy under natural light and air conditions.

[0167] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. The experimental methods in the following examples, for which specific conditions are not specified, are generally based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0168] Example 1 Preparation of Diene Diamine Compound 2

[0169]

[0170] Dissolve 1,1-dimethyl-4,4'-bipyridinium dichloride (100 g, 0.39 mol, 1.0 equiv.) in 400 mL of distilled water, add potassium borohydride (98.4 g, 1.17 mol, 3.0 equiv.), and stir at room temperature for 15 minutes. Extract three times with dichloromethane (200 mL), dry over anhydrous sodium sulfate, and evaporate to obtain a white solid (73.5 g, 96% yield). 1 H NMR (500MHz, D2O). δ5.62(t,1H),2.87(s,2H),2.45(t,2H),2.17(t,2H),2.12(s,3H). 13 C NMR(126MHz,D2O)δ133.5,119.5,53.4,50.6,43.8,24.8.HRMS(ESI)m / z calcd for C 12 H 21 N2[(M+H) + ]:193.1626,found:193.1703.

[0171] The method of the present invention can be used to produce the diene diamine compound on a large scale, with milder conditions and lower costs compared to existing small-scale production methods.

[0172] Example 2 Preparation of tricyclic diene piperazine (compound of formula 3)

[0173]

[0174] Dissolve 1,1'-ethylene-2,2'-bipyridinium dibromide (100 g, 0.35 mol, 1.0 equiv.) in 400 mL of distilled water and add potassium borohydride (56.7 g, 1.05 mol, 3.0 equiv.). Stir at room temperature for 15 minutes. Extract three times with dichloromethane (200 mL), dry over sodium sulfate, and evaporate to obtain a black solid (47.1 g, 70% yield). 1 H NMR (500MHz, CDCl3) δ5.6-5.5(m 4H), 3.1(m 2H), 2.8-2.7(m 2H), 2.6(m 2H), 2.4-2.3(m 2H), 2.0(m 2H), 1.9(m 2H), 1.8(m 2H); 13 C NMR (126MHz, CDCl3) δ124.0,123.8,61.9,54.0,53.98,29.0.

[0175] Example 3 The compound of formula 2 is transformed under the action of tetrachlorobenzoquinone

[0176]

[0177] 1,1'-Dimethyl-1,1',2,2',3,3',6,6'-octahydro-4,4'-bipyridine (100 mg, 0.52 mmol, 1.0 equiv.), chloranil (63.9 mg, 0.26 mmol, 0.5 equiv.), and [{Cu(Sal)2(NCMe)}2] (19.7 mg, 0.03 mmol, 0.05 equiv.) were added to 5 mL of acetone and heated to 40°C for 8 hours. The reaction mixture was rinsed twice with 20 mL of dichloromethane and filtered to obtain a black solid. The solid was then rinsed twice with 20 mL of methanol, dried over sodium sulfate, and evaporated to afford a yellow 1,1-dimethyl-4,4'-bipyridinium dichloride (128 mg, 96%). 1 H NMR (500MHz, D2O) δ8.91 (d, J = 5.7Hz, 1H), 8.39 (d, J = 4.8Hz, 1H), 4.37 (s, 2H). 13 CNMR(126MHz,D2O)δ149.8,146.2,126.6,48.3.HRMS(ESI)m / z calcd for C 12 H 14 N2[(M+2H) / 2]:93.0572,found:93.0573. The product was verified to be paraquat, indicating that the compound of formula 2 can be converted back into paraquat under oxidative conditions.

[0178] Example 4: Compound 2 is transformed under natural conditions

[0179]

[0180] Add 1,1'-dimethyl-1,1',2,2',3,3',6,6'-octahydro-4,4'-bipyridine (50 mg, 0.26 mmol, 1.0 equiv.) to 5 mL of normal saline and place under direct sunlight for 24 hours to obtain a yellow solid (40 mg, 63% yield). 1 H NMR (500MHz, D2O) δ8.91 (d, J = 5.7Hz, 1H), 8.39 (d, J = 4.8Hz, 1H), 4.37 (s, 2H). 13 C NMR(126MHz,D2O)δ149.8,146.2,126.6,48.3.HRMS(ESI)m / zcalcd for C 12 H 14 N2[(M+2H) / 2]:93.0572,found:93.0573. The product was confirmed to be paraquat.

[0181] Example 5: Compound 3 is transformed under natural conditions

[0182]

[0183] Add 50 mg (50 mg, 0.26 mmol, 1.0 equiv.) of 1,4,6,7,9,12,12a,12b octahydrodipyridinium [1,2-a:2', 1'-c] pyrazine to 5 mL of normal saline and place under direct sunlight for 24 hours. A yellow solid is obtained. 1 HNMR(500MHz,D2O)δ9.1(dd,2H),8.8(dd,2H),8.7(m,2H),8.3-8.2(m,2H),5.2(d,4H). 13 CNMR (126 MHz, D2O) δ = 148.26, 147.0, 130.6, 128.3, 52.3, the product was confirmed to be the compound of formula 5.

[0184] Example 6 Conversion of Formula 2 Compound

[0185] The present invention also tests the quantitative analysis of the conversion of diene diamine compounds to PQ. The present invention provides two conversion methods, both of which can achieve this conversion.

[0186] Method I (small-scale conversion): In the presence of a catalyst and an oxidant, the compound of Formula 2 can be converted to varying degrees in different solvents at elevated temperatures. Specifically, at 80°C, using water as the solvent, [{Cu(Sal)2(NCMe)}2] (5%) as the catalyst, and tetrachlorobenzoquinone as the oxidant, the conversion rate can reach as high as 92%.

[0187]

[0188]

[0189]

[0190] Method II (large-scale conversion): Under light and air conditions, using physiological saline as solvent, the compound of formula 2 is converted into PQ. Figure 1 As shown, the compound of Formula 2 was exposed to light at 25°C and 40°C, respectively. The results showed that the diene diamine compound was hardly converted to PQ in the dark, but was converted to PQ under light conditions, with the conversion efficiency increasing as the temperature increased. After exposure to natural light at 40°C for 24 hours, the conversion rate of the diene diamine compound to PQ was approximately 63%, while the conversion rate was approximately 30% after exposure to natural light at 25°C for 24 hours. This suggests that the conversion of the compound of Formula 2 is light-dependent and has potential use as a slow-release herbicide.

[0191]

[0192]

[0193] Example 7 Evaluation of the herbicidal properties of the compound of formula 2

[0194] As is well known, creeping weeds, Arabidopsis thaliana, and Acorus calamus are naturalized green weeds in much of the world and are also invasive. Photosynthesis occurs throughout their leaves and fascicles. The compounds of this application can show good control effects on green weeds by interrupting photosynthesis. Therefore, creeping weeds, Acorus calamus, and Arabidopsis thaliana were selected as plant models to evaluate the herbicidal activity of the compounds of this application.

[0195] In air and sunlight, the compound of Formula 2 of the present application was sprayed on the leaf surface at concentrations of 1, 2, 4, and 8 times the PQ equivalent, respectively. Paraquat herbicide was used as a positive control, and a normal saline solution was sprayed as a blank control. The diameter of the observation area was 8 cm.

[0196] After 24 hours of spraying with PQ and various concentrations of dienediamine, the leaves of creeping grass, calamus and Arabidopsis began to wilt. Figure 2, 3, and 4. The herbicidal effect also increased with increasing concentration. It can also be seen that a slight delayed herbicidal effect was observed in the groups treated with the same or double dose of the compound of Formula 2. When the dosage concentration of the compound of Formula 2 was greater than twice that of PQ, the herbicidal activity of the compound of Formula 2 was similar to that of PQ at any time point after administration. This delayed herbicidal effect of the compound of Formula 2 may be due to the efficiency and yield of the conversion of the compound of Formula 2 to PQ in air and sunlight. However, regardless of the dosage concentration, the grass in all the herbicide-sprayed groups was completely withered and dried 120 hours after application. These data demonstrate the herbicidal activity of the compound of Formula 2, dienediamine.

[0197] Example 8 Evaluation of the Herbicidal Performance of the Compound of Formula 3

[0198] The compound of formula 3 of the present application was sprayed on the leaf surface in air and sunlight, with diquat herbicide as a positive control. The diameter of the observation area was 10 cm.

[0199] from Figure 5 As can be seen, three days after spraying (using concentration not given) the compound of formula 3, the leaves of the creeping weed began to wither. After five days, the leaves of the creeping weed were completely withered. The compound of formula 3 exhibited a herbicidal effect comparable to that of diquat, indicating that the compounds of the present application have herbicidal activity under the conditions used.

[0200] Example 9 In vivo safety assessment of the compound of formula 2

[0201] The optimal dose and time for the lethal level of PQ in mice were first determined by a single intraperitoneal injection of PQ at doses of 20, 30, 40, 50, and 60 (mg / kg). All mice survived for more than 168 hours at doses of 20 and 30 (mg / kg), but died within 27 to 113 hours at doses of 50 or 60 (mg / kg kg), and their body weight dropped significantly on the first day. In addition, a significant increase in lung injury scores was observed 24 hours after PQ administration, and the lung injury scores were highest at 48 hours compared to other time points. Therefore, 50 mg / kg was selected as the optimal dose. Mouse tissue samples were collected 48 hours after PQ administration.

[0202] In order to evaluate the safety of the compound of formula 2 of the present invention in vivo, an acute toxicity test was conducted on mice. Figure 6 As shown, 100% of the mice administered PQ (0.19 mmol / kg) died within 112 hours of PQ administration. In contrast, all mice in the Compound 2 group survived 168 hours after administration of the Compound 2 (0.19 mmol / kg). The weight of the mice in the PQ group continued to decrease, while the weight of the mice in the control group and the Compound 2 group continued to steadily increase.

[0203] like Figure 7 As shown, 48 hours after administration, compared with the control group and the dienediamine compound of Formula 2 group, the serum AST, ALT, SCr, BUN and uric acid (UA) levels and serum inflammatory cytokine levels (TNF-α, interleukin-1β, IL-6) in the mice in the PQ group were significantly increased; the SOD or CAT levels in the lung tissue were significantly decreased.

[0204] Meanwhile, the lung, liver and kidney weights per body weight of the PQ group were significantly higher than those of the control group and the dienediamine group of the compound of formula 2. In contrast, no significant changes in these parameters were detected between the control group and the dienediamine group of the compound of formula 2.

[0205] like Figure 8 As shown, mice 48 hours after PQ administration exhibited multiple organic injuries accompanied by significant inflammation, including pulmonary hemorrhage, extensive thickening of the alveolar septum, hepatic hemorrhage near the central vein, renal interstitial edema, renal tubular epithelial cell degeneration, and multifocal myocardial cell necrosis accompanied by inflammatory cell infiltration. In contrast, no obvious pathological damage was observed in these major tissues in the dapoxetine and control groups. Furthermore, the tissue injury scores of major organs in the PQ group were significantly higher than those in the control and dapoxetine groups.

[0206] Transmission electron micrographs of lung, liver, kidney, and heart were collected 48 hours after intraperitoneal injection of 0.19 mmol / kg paraquat or compound of Formula 2. Black arrows indicate damaged mitochondria. The electron micrograph scale bar for the heart group is 200 nm, and the electron micrograph scale bar for the other groups is 100 nm. Figure 9 As shown in the figure, transmission electron microscopy results showed mitochondrial damage such as swelling, vacuolization, blurring or fragmentation of mitochondrial cristae in the lung, liver, kidney and heart tissues of mice in the PQ group. No obvious mitochondrial structural damage was detected in either the diphenylamine group or the control group.

[0207] Upon entry into the human body, PQ is rapidly absorbed and distributed to the lungs, kidneys, liver, and muscles. Death from PQ ingestion often results from multi-organ failure, such as pulmonary edema, renal and hepatic failure. Therefore, we selected lung (A549), kidney (COS-7), and liver (Hep G2) cells to evaluate the direct cytotoxicity of PQ.

[0208] After 24 hours of co-culture with PQ, PQ showed direct cytotoxic effects on A549, Hep G2, and COS-7 cell lines in a dose-dependent manner. In contrast, after 24 hours of co-incubation with the compound of Formula 2, no significant changes in cell viability were detected in the above cells under the same concentration gradient. The half-maximal inhibitory concentration (IC50) was calculated to represent the cytotoxicity of the compound of Formula 2. The results are shown in Table 1:

[0209] Table 1 Toxicity of dienediamine and paraquat to three cell lines

[0210] A549 cells Hep G2 cells Cos-7 cells Paraquat PQ 322.3μM 131 μM 114.4μM Formula 2 diene diamine compound 5770μM 1358μM 1572μM

[0211] The results showed that the IC of the compound group of formula 2 was 50 The value was significantly higher than that of the PQ treatment group, and its IC 50 The value increased by dozens of times, indicating that the safety of dienediamine for organisms has been significantly improved.

[0212] The three cells were exposed to 100 μM PQ (100) and 100 μM compound of formula 2 for 18 h, and the intracellular reactive oxygen species (ROS) levels were detected by flow cytometry and DCF fluorescence (n=6). Figure 10 As shown, the ROS production in the PQ group was significantly increased compared with the Formula 2 compound group and the control group.

[0213] In addition, if Figure 11 As shown, after 24 hours of incubation, cells were stained with Annexin V-FITC and propidium iodide (PI) (n=6). Data are expressed as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

[0214] The results showed that compared with the PQ group, the apoptosis rate of cells in the Formula 2 group was significantly reduced. This result was consistent with the ROS level, which showed no significant difference.

[0215] summary

[0216] The present invention discovered for the first time that the compound of Formula 2 cannot be converted into PQ in air and darkness, but can be directly converted into PQ in the presence of air and sunlight. Furthermore, its herbicidal activity is comparable to that of PQ in natural sunlight and air. All of this evidence suggests that the conversion of the compound of Formula 2 to PQ is responsible for its high herbicidal activity.

[0217] The present invention also proves through in vivo and in vitro experiments that the toxicity of the compound of formula 2 to animals is significantly lower than that of PQ, and its toxicity level is equivalent to that of a normal control group using physiological saline, indicating that the compound of formula 2, dienediamine, is a non-toxic herbicide.

[0218] The bipyridine structure is the basis of PQ's electron transfer catalyst, which generates a large number of free radicals, leading to cellular damage. PQ induces a decrease in superoxide dismutase (SOD) and catalase (CAT) in lung tissue and an increase in recurrent oxygen species (ROS) in lung, kidney, and liver cells. In contrast, the pyridinium-treated group showed no significant changes in SOD and CAT levels in lung tissue or ROS production in cell lines.

[0219] In summary, the present invention creatively utilizes dienediamine 2 to prepare a herbicide composition, which can be effectively converted to PQ under natural sunlight and air conditions. Dienediamine not only exhibits herbicidal activity comparable to PQ but is also non-toxic. Therefore, dienediamine has great potential for widespread application in global green agriculture and can prevent PQ-induced mortality.

[0220] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A compound having a structure represented by Formula 1 or Formula 3, a pesticide-acceptable salt thereof, or a combination thereof, characterized in that: For the preparation of botanicals: in, R1, R2, R3, R4, R5, R6, R7, R8 are all H, and R9, R 10 It is a C1-C4 alkyl group.

2. The use according to claim 1, characterized in that The compound of formula I is selected from:

3. An agricultural composition, characterized in that include: (a) a compound of Formula I or Formula 3, a pesticidally acceptable salt thereof, or a combination thereof as an active ingredient; in, R1, R2, R3, R4, R5, R6, R7, R8 are all H, and R9, R 10 is a C1-C4 alkyl group; (b) optionally an oxidizing aid; and (c) pesticidally acceptable carriers and / or excipients; and (d) optional auxiliary agents; wherein the auxiliary agent is selected from the group consisting of molecular sieves, surfactants, protective colloids, adhesives, thickeners, thixotropic agents, penetrants, chelating agents, dyes, colorants, polymers, or combinations thereof.

4. The agricultural composition according to claim 3, wherein The oxidation aid is selected from the following group: an oxidant, a metal catalyst, or a combination thereof.

5. The agricultural composition according to claim 4, wherein The oxidants are chloranil, chloramine T, hydrogen peroxide, bleaching powder and potassium monopersulfate composite salt.

6. The agricultural composition according to claim 4, wherein The metal catalyst is copper, iron, nickel, molybdenum, ruthenium, manganese, palladium or platinum.

7. The agricultural composition according to claim 3, wherein The carrier is selected from the following group: water, NaCl aqueous solution.

8. A weed control method, characterized in that: The method comprises the steps of applying the compound of Formula 1 or Formula 3, or the agricultural composition of claim 3, to the surface of the grass or plant to be removed, or to the soil or environment around the grass or plant under the conditions of light and oxygen: in, R1, R2, R3, R4, R5, R6, R7, R8 are all H, and R9, R 10 It is a C1-C4 alkyl group.

9. A method for preparing paraquat or diquat, characterized in that: Including steps: At 60-100° C., in a first solvent, in the presence of an oxidant and a catalyst, the compound represented by Formula 2 or Formula 3 reacts to obtain paraquat or diquat; Wherein, the oxidant is chloranil; The catalyst is selected from the group consisting of [{Cu(Sal)2(MeCN)}2], metal chloride, metal bromide, or a combination thereof.

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