Dithiobenzoylpyrazole compound, and preparation method therefor and use thereof

Abstract

Disclosed in the present invention are a dithiobenzoylpyrazole compound, and a preparation method therefor and the use thereof. The dithiobenzoylpyrazole compound is a compound as represented by formula (I), a stereoisomer thereof, or an agriculturally acceptable salt of the compound as represented by formula (I) or the stereoisomer thereof. The compound has a good herbicidal activity and high selectivity to rice, and can be safely used for weed control in rice fields.

Description

A dithiobenzoylpyrazole compound, its preparation method and application Technical Field

[0001] This invention belongs to the field of herbicides, specifically relating to a dithiobenzoylpyrazole compound, its preparation method, and its application. Background Technology

[0002] Barnyard grass and Echinochloa crus-galli are important weeds in paddy fields. Especially with the development of planting technology, their control has become the key to the yield of paddy fields. Although there are many commercial paddy field herbicides, such as ALS inhibitors (such as penoxsulam and flufenoxuron) and ACCase inhibitors (such as oxazolidinyl and cyhalofop-butyl), the problem of barnyard grass resistance is becoming increasingly serious with large-scale application.

[0003] Modern agriculture faces significant challenges in managing resistant weeds in rice paddies. These weeds develop resistance to commonly used herbicides through various mechanisms, including target site mutations and enhanced metabolic detoxification, leading to the gradual ineffectiveness of traditional control methods. Furthermore, resistant weeds compete with rice for water, nutrients, and sunlight, severely impacting crop growth and yield, increasing management costs, and potentially causing herbicide damage. In addition, the spread of resistant weeds can disrupt the ecological balance of farmland, affecting the number and activity of natural enemies, and hindering sustainable agricultural development.

[0004] Currently known HPPD herbicides are mainly classified into pyrazoles, triones, and isoxazoles. Before 2000, Japanese companies successively reported three pyrazole herbicides for use in rice paddies: pyrazosulfuron (3000 g ai / ha) in 1979, bensulfuron-methyl (2500-4000 g ai / ha) in 1985, and pyrazosulfuron-methyl (1600 g ai / ha) in 1990.

[0005] These herbicides are effective against barnyard grass, but they have significant drawbacks, such as low activity, a narrow spectrum of weed control, and application rates exceeding 1500g per hectare. They also pose a potential risk to non-target organisms in paddy fields. High-dose use not only increases costs but may also have negative environmental impacts, such as affecting soil microbial communities or aquatic ecosystems. Over time, long-term use of these herbicides can lead to weed community succession and the emergence of resistant weeds, thus reducing long-term weed control effectiveness.

[0006] Furthermore, the government mandates reduced pesticide use and increased efficiency to ensure agricultural production safety. However, the herbicides developed in Japan clearly do not meet the needs of the Chinese market. Therefore, there is an urgent need to develop new rice paddy herbicides that do not exhibit cross-resistance with existing mainstream herbicides. These new herbicides should possess higher activity and better safety profiles.

[0007] Chinese patent CN88101455A discloses compounds containing methanesulfonyl groups, with representative compounds including KC-1 to KC-3 listed below. These compounds exhibit high herbicidal activity and are safe for corn. However, research has found that these compounds are only safe for corn and lack selectivity for rice, making them unsuitable for weed control in rice paddies and severely limiting their application scope. Summary of the Invention

[0008] The purpose of this invention is to provide a dithiobenzoylpyrazole compound based on the prior art. This compound has excellent herbicidal activity and high selectivity for rice, and can be safely applied to weed control in rice fields.

[0009] Another object of the present invention is to provide a method for preparing dithiobenzoylpyrazole compounds and their application in weed control.

[0010] The objective of this invention can be achieved through the following measures:

[0011] A dithiobenzoylpyrazole compound, which is a compound of formula (I) or a stereoisomer thereof, or an agriculturally acceptable salt of a compound of formula (I) or a stereoisomer thereof.

[0012] In formula (I),

[0013] X1 is selected from halogens;

[0014] X2 is selected from C1-C6 alkyl, C3-C6 cycloalkyl, or C6-C6 alkyl. 14 Aryl C1-C6 alkyl;

[0015] X3 is selected from C1-C6 alkylsulfonyl groups;

[0016] R1 is selected from C1-C6 alkyl groups;

[0017] R2 is selected from hydrogen or C1-C6 alkyl groups;

[0018] Q is selected from -C(O)NR3R4;

[0019] R3 and R4 may be the same or different, and are independently selected from C1-C6 alkyl groups;

[0020] n is selected from 0, 1, or 2.

[0021] In a preferred embodiment, the dithiobenzoylpyrazole compound of the present invention is a compound of formula (II) or a stereoisomer thereof, or an agriculturally acceptable salt of a compound of formula (II) or a stereoisomer thereof.

[0022] in,

[0023] X2 is selected from one of C1-C6 alkyl, C3-C6 cycloalkyl-substituted C1-C4 alkyl;

[0024] n is selected from 0, 1, or 2;

[0025] R1 is selected from C1-C6 alkyl groups;

[0026] R2 is selected from hydrogen or C1-C6 alkyl groups.

[0027] In a preferred embodiment, X2 is selected from C2-C4 alkyl, C3-C5 cycloalkyl-substituted C1-C3 alkyl.

[0028] In another preferred embodiment, X2 is selected from C2-C3 alkyl, C1-C3 alkyl substituted with C3 cycloalkyl.

[0029] In a more preferred embodiment, X2 is selected from C2-C3 alkyl and C1-C2 alkyl substituted with C3 cycloalkyl.

[0030] In a further preferred embodiment, X2 is selected from C2-C3 alkyl groups and cyclopropylmethyl groups.

[0031] In a further preferred embodiment, X2 is selected from ethyl, n-propyl, isopropyl, and cyclopropylmethyl.

[0032] In a preferred embodiment, R1 is selected from C1 to C4 alkyl groups.

[0033] In another preferred embodiment, R1 is selected from C1 to C3 alkyl groups.

[0034] In a more preferred embodiment, R1 is selected from C1 to C2 alkyl groups.

[0035] In a further preferred embodiment, R1 is selected from methyl or ethyl.

[0036] In a preferred embodiment, R2 is selected from hydrogen or C1-C4 alkyl groups.

[0037] In another preferred embodiment, R2 is selected from hydrogen or C1-C3 alkyl.

[0038] In a more preferred embodiment, R2 is selected from hydrogen or C1-C2 alkyl.

[0039] In a further preferred embodiment, R2 is selected from hydrogen or methyl.

[0040] In a preferred embodiment, when R2 is selected from hydrogen, R1 is selected from ethyl; when R2 is selected from methyl, R1 is selected from methyl.

[0041] In one specific embodiment, the dithiobenzoylpyrazole compounds of the present invention include the following compounds, their stereoisomers, agriculturally acceptable salts of each compound, and agriculturally acceptable salts of their stereoisomers:

[0042] This invention discloses a method for preparing compound (I) of the dithiobenzoylpyrazole class of compounds, specifically including the following steps:

[0043] The definitions of X1, X2, X3, R1, R2, Q, and n are as described above. In a preferred embodiment, X1 is Cl, X3 is -S(O)2CH3, and Q is a -C(=O)N(C2H5)2 group.

[0044] In our study of the structure-activity relationship of benzoylpyrazole compounds shown in formula (III), we found that although these compounds exhibit herbicidal activity against weeds such as barnyard grass, foxtail, cricket grass, crabgrass, millet, garland chrysanthemum, amaranth, knotweed, cocklebur, and sedge, they lack selectivity for rice. When applied to paddy fields, they severely impact rice growth and can even kill large areas of rice plants. However, we accidentally discovered that in these benzoylpyrazole compounds, when a -OC(=O)-N(C2H5)2 group is used at the 5' position of the pyrazole ring, an alkyl group is used at the 1' position, and chlorine is used at the 2 position and -CH2-S(O) is used at the 3 position of the benzene ring... n When the -X2 group, the 4-position is a methanesulfonyl group, and the 5 and 6-positions are hydrogen (i.e., the structure of formula (II)), the killing effect on rice can be unexpectedly completely eliminated. This makes the compound highly selective for rice while having high herbicidal activity, thus giving birth to the present invention.

[0045] Further research revealed that for benzoylpyrazole compounds represented by formula (III), the high selectivity for rice disappears when each substituent is outside the range claimed in this application, or when one of the groups is outside the range claimed in this application; clearly, the high selectivity for rice is highly dependent on each specific substituent and its combination.

[0046] Unless otherwise specified, the various groups and technical terms referred to in this application have the following meanings:

[0047] "Halogen" refers to a fluorine atom (F), a chlorine atom (Cl), a bromine atom (Br), or an iodine atom (I).

[0048] "C1-C6 alkyl" refers to a saturated aliphatic hydrocarbon group with 1-6 carbon atoms, including straight-chain and branched groups (the numerical range mentioned in this application, such as "1-6", refers to the group, which is an alkyl group and can contain 1, 2, 3, etc., up to 6 carbon atoms). As a preferred embodiment, the group can be further C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, C2-C4 alkyl, C2-C3 alkyl, etc. Specific examples of alkyl groups in this invention include, but are not limited to: methyl, ethyl, propyl, 2-propyl, n-butyl, isobutyl, tert-butyl, pentyl, etc.

[0049] "C3-C6 cycloalkyl" refers to a saturated cyclic aliphatic hydrocarbon group containing 3-6 carbon atoms. The numerical range mentioned in this application, such as "3-6," means that the cycloalkyl group can contain 3, 4, 5, or 6 carbon atoms as ring atoms. C3-C6 cycloalkyl groups can further be selected from C... 3-5 cycloalkyl, C 3-4 cycloalkyl, C 4-6 cycloalkyl, C 4-5 Cycloalkyl groups, etc. Specific cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0050] "C3-C6 cycloalkyl" indicates a group in which one or more hydrogen atoms in the alkyl group are replaced by one or more "C3-C6 cycloalkyl" groups. The "C3-C6" before cycloalkyl specifies that the cycloalkyl group has 3-6 carbon atoms. As a preferred embodiment, this group can be further substituted with C1-C6 alkyl groups (C3-C6 cycloalkyl-substituted), C1-C5 alkyl groups (C3-C6 cycloalkyl-substituted), C1-C4 alkyl groups (C3-C6 cycloalkyl-substituted), C1-C3 alkyl groups (C3-C6 cycloalkyl-substituted), C1-C2 alkyl groups (C3-C5 cycloalkyl-substituted), C1-C6 alkyl groups (C3-C5 cycloalkyl-substituted), C1-C4 alkyl groups (C3-C5 cycloalkyl-substituted), C1-C3 alkyl groups (C3-C4 cycloalkyl-substituted), C1-C4 alkyl groups (C3-C4 cycloalkyl-substituted), C1-C4 alkyl groups (C3-C4 cycloalkyl-substituted), etc. The C3 cycloalkyl group is cyclopropyl. Furthermore, "C3-C6 cycloalkyl-substituted C1-C4 alkyl" means that one or more hydrogen atoms in the C1-C4 alkyl group are replaced by one or more C3-C6 cycloalkyl groups. Specific examples of C3-C6 cycloalkyl groups in this invention include, but are not limited to: cyclopropylmethyl, cyclopropylethyl, cyclopropylmethyl, cyclopropylisopropyl, cyclopropylbutyl, cyclopropylisobutyl, cyclopropylpentyl, cyclopropylhexyl, cyclobutylmethyl, cyclobutylethyl, cyclobutylmethyl, cyclobutylisopropyl, cyclobutylbutyl, cyclobutylisobutyl, cyclobutylpentyl, cyclobutylhexyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylmethyl, cyclopentylisopropyl, cyclopentylbutyl, cyclopentylisobutyl, cyclopentylpentyl, cyclopentylhexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylmethyl, cyclohexylisopropyl, cyclohexylbutyl, cyclohexylisobutyl, cyclohexylpentyl, cyclohexylhexyl, etc.

[0051] “C6-C 14 "Aryl" indicates an aromatic group containing 6-14 carbon atoms, and specific examples include, but are not limited to, phenyl, biphenyl, naphthyl, anthracene, phenanthrene, etc.

[0052] “C6-C 14 "Aryl C1-C6 alkyl" indicates that one or more hydrogen atoms in the C1-C6 alkyl group are surrounded by one or more C6-C6 atoms. 14 The group substituted by the aryl group. "C6-C" 14 "C6-C" in "aryl" 14 "C1-C6 alkyl" is a limitation on the number of carbon atoms in the aryl group, and "C1-C6" in "C1-C6 alkyl" is a limitation on the alkyl group.

[0053] "C1~C6 alkylsulfonyl" indicates a "-S(O)2-C1~C6 alkyl" group, where "C1~C6" refers to the number of carbon atoms in the alkyl group being 1-6. Specific examples include, but are not limited to: methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, etc.

[0054] "Agriculturally acceptable salts" are salts formed by compounds of general formula (I) or (II) or their stereoisomers with organic or inorganic acids, representing those salts that retain the bioavailability and properties of the parent compound. These salts include, but are not limited to:

[0055] (1) It forms salts with acids by reacting the free base of the parent compound with inorganic or organic acids. Inorganic acids include (but are not limited to) hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, metaphosphoric acid, sulfuric acid, sulfurous acid and perchloric acid, etc., and organic acids include (but are not limited to) acetic acid, propionic acid, acrylic acid, oxalic acid, (D) or (L) malic acid, fumaric acid, maleic acid, hydroxybenzoic acid, γ-hydroxybutyric acid, methoxybenzoic acid, phthalic acid, methanesulfonic acid, ethanesulfonic acid, naphthalene-1-sulfonic acid, naphthalene-2-sulfonic acid, p-toluenesulfonic acid, salicylic acid, tartaric acid, citric acid, lactic acid, mandelic acid, succinic acid or malonic acid, etc.

[0056] (2) Salts formed by replacing acidic protons in the parent compound with metal ions or by coordination with organic bases. Metal ions include alkali metal ions, alkaline earth metal ions or aluminum ions, and organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucosamine, etc.

[0057] "Composition" refers to one or more compounds described herein, or their agriculturally acceptable salts, mixed with other chemical components, such as pesticide-acceptable carriers and excipients. The purpose of the composition is to facilitate the administration of the compound to an organism.

[0058] "Stereoisomers" refer to isomers in a chemical structural formula. They are isomers where the atoms in a molecule have the same bond order but different arrangements in three-dimensional space. They mainly include configurational isomers and conformational isomers. Configurational isomers, due to limitations imposed by double bonds, ring structures, etc., cannot freely convert between molecules and are further divided into cis-trans isomers (e.g., differences in the arrangement of groups on either side of a double bond) and enantiomers (mirrors that cannot be superimposed and exhibit chiral characteristics). Conformational isomers, on the other hand, are formed by rotation of single bonds and are usually discussed only for their lower-energy stable forms. Modern classification uses enantiomers and diastereomers (e.g., cis-trans isomers, meso compounds, etc.) as the main distinguishing dimension.

[0059] The dithiobenzoylpyrazole compounds disclosed in this invention, namely the compounds of formula (I) or their stereoisomers, or agriculturally acceptable salts of the compounds of formula (I) or their stereoisomers, especially the compounds of formula (II) or their stereoisomers, or agriculturally acceptable salts of the compounds of formula (II) or their stereoisomers, can be used in agriculture for weed control, particularly in rice.

[0060] The weeds referred to in this invention include, but are not limited to, weeds of the genera *Barnyardgrass*, *Gnaphalium*, *Gnaphalium*, *Digitaria*, *Sorghum*, *Gnaphalium*, *Amaranthus*, *Polygonum*, *Xanthium*, and *Cyperus*, especially common grass weeds in paddy fields, such as barnyardgrass, *Digitaria*, and *Echinochloa crus-galli*.

[0061] The present invention discloses a herbicidal composition containing a dithiobenzoylpyrazole compound of the present invention, namely, the compound of formula (I) or its stereoisomer, or an agriculturally acceptable salt of the compound of formula (I) or its stereoisomer, particularly the compound of formula (II) or its stereoisomer, or an agriculturally acceptable salt of the compound of formula (II) or its stereoisomer, wherein the weight percentage of the dithiobenzoylpyrazole compound is 1-99%.

[0062] This invention discloses a safe broad-spectrum herbicide for rice, characterized in that the herbicide comprises an active ingredient and an adjuvant, wherein the active ingredient is a dithiobenzoylpyrazole compound provided by this invention, and the active ingredient accounts for 1-99% of the weight percentage of the herbicide.

[0063] In the herbicidal composition or safe broad-spectrum herbicide of the present invention, the weight percentage of dithiobenzoylpyrazole compounds is 1-99%, or may be 2-98%, 3-97%, 4-96%, 5-95%, 6-94%, 10-90%, 15-85%, 20-80%, 25-75%, 30-70%, 35-65%, 40-60%, etc.

[0064] The herbicidal compositions or safe, broad-spectrum herbicides of the present invention can be applied in various formulations. Typically, the compounds of the present invention are dissolved or dispersed in a carrier to formulate a formulation that facilitates dispersion when used as a herbicide. For example, these chemical formulations can be formulated as wettable powders or emulsifiable concentrates. Therefore, at least one oily liquid or solid carrier is added to these compositions, and a suitable surfactant is usually required.

[0065] The present invention also provides a method for controlling weeds, comprising applying an effective amount of the herbicidal composition of the present invention to the surface of the weeds, the site of weed growth, or the growth medium thereof. A suitable effective dosage is 1 to 1000 grams per hectare, preferably 10 to 500 grams per hectare. For certain applications, one or more other herbicides may be added to the herbicidal composition of the present invention, thereby producing additional advantages and effects.

[0066] The dithiobenzoylpyrazole compounds provided by this invention overcome the problem that these compounds containing methylsulfonyl groups also have a killing effect on rice. The compounds of this invention have high selectivity for rice and can be safely applied to weed control in rice fields. These compounds have excellent herbicidal activity and have practical application value.

[0067] The dithiobenzoylpyrazole compounds of this invention not only exhibit excellent herbicidal activity, but also demonstrate superior control of weeds resistant to ALS and ACCase inhibitors in rice paddies (such as barnyardgrass in Northeast China, Rhizophora oryzae in Southern China, and Echinochloa crus-galli). More importantly, these compounds show extremely high safety for crops, being harmless to rice at normal herbicidal dosages; even at a 5-fold increase in dosage, no significant phytotoxicity was observed.

[0068] It is this high selectivity and safety that ensures the wide applicability of the compounds of this invention in practical applications. They can provide reliable weed control solutions for both japonica and indica rice varieties, while ensuring the healthy growth of crops. Detailed Implementation

[0069] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0070] It should be clearly stated that various modifications and alterations can be made within the scope defined by the claims of this invention.

[0071] Synthesis Examples

[0072] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available products or can be prepared by known methods.

[0073] 1. Synthesis of intermediate benzylthiourea bromate

[0074] Methyl 3-bromomethyl-2-chloro-4-methanesulfonylbenzoate (20.0 g, 58.6 mmol) was dissolved in 35 mL of ethanol. Thiourea (4.5 g, 58.6 mmol) was added with stirring, and the mixture was refluxed for 2 h. After the reaction was complete, the solvent was evaporated to dryness, yielding benzylthiourea bromate as 24.4 g of white solid, in 99.8% yield.

[0075] 2. Synthesis of intermediate A

[0076] Benzylthiourea bromate (20 g, 47.9 mmol) was dissolved in 300 mL of acetonitrile, followed by the addition of bromopropane (5.9 g, 47.9 mmol). After stirring for 10 min, 26.4 mL of 2N sodium hydroxide was added, and the reaction was allowed to proceed at room temperature for 4 h. After the reaction was complete, the solvent was evaporated, and 200 mL of water was added. 10% dilute hydrochloric acid was added dropwise with stirring to adjust the pH to 6–7. The filter cake was dried to give intermediate A, 15.1 g of white solid, with a yield of 93.6%.

[0077] 3. Synthesis of intermediate B

[0078] Intermediate A (14.0 g, 41.6 mmol) was dissolved in 200 mL of methanol and 200 mL of water, followed by the addition of sodium hydroxide (5.0 g, 124.7 mmol). The reaction was carried out at room temperature for 4 h. After the reaction was complete, the solvent was evaporated to dryness, 300 mL of water was added, and 10% dilute hydrochloric acid was added dropwise with stirring to adjust the pH to 1–2. The solid was filtered, dried, and yielded 12.5 g of a white solid, with a yield of 93.2%.

[0079] The benzoic acid (10.0 g, 31.0 mmol) generated in the previous step was dissolved in 200 mL of dichloromethane, and oxaloyl chloride (11.8 g, 93.0 mmol) was slowly added dropwise with stirring. After stirring for 5 min, 2 mL of DMF catalyst was added, and the reaction was refluxed for 2.5 h. After the reaction was completed, the solvent was evaporated and used directly in the next step.

[0080] 1,3-Dimethyl-5-hydroxypyrazole (3.6 g, 32.5 mmol) was dissolved in 200 mL of dichloromethane, followed by the addition of triethylamine (3.4 g, 40.2 mmol). After stirring for 10 min, 100 mL of the dichloromethane solution of benzoyl chloride generated in the previous step was added, and the reaction was allowed to proceed at room temperature for 1 h. After the reaction was complete, the solvent was evaporated to dryness, and the mixture was extracted with 200 mL of water and 200 mL of ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and subjected to column chromatography (ethyl acetate: petroleum ether = 1:1) to give 11.1 g of a yellow solid, in 86.0% yield.

[0081] The ester obtained in the previous step (10.0 g, 24.0 mmol) was dissolved in 150 mL of dichloromethane, followed by the addition of triethylamine (3.2 g, 31.2 mmol). After stirring for 10 min, 5 drops of acetone cyanohydrin were added, and the reaction was allowed to proceed at room temperature for 12 h. After the reaction was complete, the solvent was evaporated to dryness, and the mixture was extracted with 200 mL of water and 200 mL of ethyl acetate. The aqueous phase was retained, and 10% dilute hydrochloric acid was added dropwise with stirring to adjust the pH to 1–2. The solid was filtered, washed with 50 mL of methanol, filtered, and dried to obtain intermediate B, yielding 8.9 g of a yellow solid, with a yield of 89.0%.

[0082] 4. Synthesis of compound D10

[0083] Intermediate B (8.0 g, 19.2 mmol) was dissolved in 200 mL of 1,2-dichloroethane, followed by the addition of triethylamine (2.9 g, 21.1 mmol). After stirring for 10 min, diethylcarbamoyl chloride (2.3 g, 23.0 mmol) was added, followed by 50 mg of DMAP catalyst. The mixture was refluxed for 6 h. After the reaction was complete, 200 mL of water was added for extraction. The organic phase was dried over anhydrous sodium sulfate and subjected to column chromatography (ethyl acetate: petroleum ether = 1:1) to give compound D10 as 8.5 g of yellow solid, in 85.8% yield.

[0084] 5. Synthesis of compound D11

[0085] Compound D10 (5.0 g, 9.7 mmol) was dissolved in 100 mL of dichloromethane, followed by the addition of m-chloroperoxybenzoic acid (1.7 g, 9.7 mmol), and the reaction was carried out at room temperature for 3 h. After the reaction was complete, extraction was performed by adding 50 mL of saturated sodium thiosulfate solution and 50 mL of saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate and subjected to column chromatography (ethyl acetate: petroleum ether = 2:1) to give compound D11 as 3.7 g of white solid, in 71.8% yield.

[0086] 6. Synthesis of Compound 2

[0087] Compound D10 (5.0 g, 9.7 mmol) was dissolved in 100 mL of dichloromethane, followed by the addition of m-chloroperoxybenzoic acid (4.2 g, 24.2 mmol), and the reaction was carried out at room temperature for 3 h. After the reaction was complete, extraction was performed by adding 50 mL of saturated sodium thiosulfate solution and 50 mL of saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate and subjected to column chromatography (ethyl acetate:petroleum ether = 2:1) to give compound 2 as 4.9 g of white solid, in 92.3% yield.

[0088] By using the above method and changing the raw materials, different compounds can be prepared. Table 1 lists the structures and physicochemical properties of the specific compounds.

[0089] Table 1. Structure and physicochemical properties of some compounds

[0090] Following the method described above, by changing the raw materials containing different substituents, the compounds shown in Table 2 can also be prepared (the synthesis of D10 and D11 has been provided). The compounds in Table 2 are used as some reference samples in subsequent examples.

[0091] Table 2. Structure and physicochemical properties of reference compounds

[0092] Some compounds 1 The H NMR data are as follows:

[0093] Compound 1 (400 MHz, Chloroform-d): 8.13 (d, 1H), 7.54 (s, 1H), 7.58 (d, 1H), 4.03–3.99 (m, 2H), 3.41 (s, 3H), 3.33–3.30 (m, 4H), 3.22–3.18 (m, 2H), 1.48–1.44 (m, 6H), 1.22–1.08 (m, 8H).

[0094] Compound 2 (400 MHz, Chloroform-d): 8.09 (d, 1H), 7.51 (d, 1H), 5.44 (d, 2H), 3.60 (s, 3H), 3.40 (s, 3H), 3.27–3.11 (m, 4H), 3.02–2.85 (m, 2H), 2.35 (s, 3H), 2.00–1.93 (m, 2H), 1.15–1.03 (m, 9H).

[0095] Compound 3 (400 MHz, Chloroform-d): 8.09 (d, 1H), 7.65 (s, 1H), 7.42 (d, 1H), 4.61 (s, 2H), 4.02–3.98 (m, 2H), 3.41 (s, 3H), 3.36–3.22 (m, 4H), 2.67 (d, 2H), 1.46 (t, 3H), 1.35–1.15 (m, 6H), 1.10–1.06 (m, 1H), 0.61–0.58 (m, 2H), 0.29–0.21 (m, 2H).

[0096] Compound 4 (400 MHz, Chloroform-d): 7.85–7.72 (m, 2H), 7.60 (s, 1H), 4.97 (s, 2H), 4.26–4.03 (m, 4H), 3.36–3.20 (m, 4H), 3.08 (s, 3H), 1.57–1.52 (m, 2H), 1.42–1.12 (m, 7H), 0.91 (t, 3H), 0.45–0.30 (m, 2H).

[0097] Compound 5 (400 MHz, Chloroform-d): 8.09 (d, 1H), 7.51 (d, 1H), 5.54 (s, 2H), 3.60 (s, 3H), 3.41 (s, 3H), 3.22 (d, 2H), 3.13 (d, 2H), 2.96 (d, 2H), 2.34 (s, 3H), 1.10–1.06 (m, 6H), 0.85–0.81 (m, 3H), 0.49–0.45 (m, 2H).

[0098] Compound 6 (400 MHz, Chloroform-d): 7.86–7.73 (m, 2H), 7.60 (s, 1H), 4.77 (s, 2H), 4.21–4.18 (m, 2H), 3.47 (d, 2H), 3.39–3.25 (m, 4H), 3.10 (s, 3H), 1.66–1.44 (m, 3H), 1.42–1.15 (m, 6H), 0.91 (t, 3H), 0.50–0.32 (m, 2H).

[0099] Compound D1 (400 MHz, Chloroform-d): 8.18 (d, 1H), 7.79 (d, 1H), 7.38 (s, 1H), 5.38 (s, 2H), 4.11 (s, 3H), 4.02–3.98 (m, 2H), 3.46 (s, 3H), 3.32 (d, 2H), 1.31–1.26 (m, 6H).

[0100] Compound D2 (400MHz, Chloroform-d): 7.92–7.90 (m, 2H), 7.78 (d, 1H), 7.76 (d, 1H), 7.36 (d, 2H), 7.17–7.14 (m, 2H), 4.76 (s, 2H), 4.64 (s, 2H), 3.73 (s, 3H), 3.47–3.42 (m, 2H), 3.10 (s, 3H), 2.33 (t, 2H), 1.39 (t, 3H).

[0101] Compound D3 (400 MHz, Chloroform-d): 8.13 (d, 1H), 7.71 (s, 1H), 7.57 (d, 1H), 5.46 (d, 2H), 4.02–3.98 (m, 2H), 3.43 (s, 3H), 3.22–2.98 (m, 2H), 2.95 (s, 6H), 1.50 (t, 3H), 1.45 (t, 3H).

[0102] Compound D4 (400 MHz, Chloroform-d): 8.10 (d, 1H), 7.75 (s, 1H), 7.60 (d, 1H), 5.29 (s, 2H), 3.99–3.95 (m, 2H), 3.41 (s, 2H), 3.34 (s, 3H), 3.25–3.14 (m, 6H), 1.49–1.44 (m, 6H).

[0103] Compound D5 (400 MHz, Chloroform-d): 8.18 (d, 1H), 7.86 (d, 1H), 7.69–7.64 (m, 1H), 5.39 (s, 2H), 3.96–3.92 (m, 2H), 3.48 (d, 3H), 3.39–3.30 (m, 3H), 3.20–3.08 (m, 2H), 2.75 (d, 2H), 1.35–1.27 (m, 6H), 1.05–1.01 (m, 3H).

[0104] Compound D6 (400 MHz, Chloroform-d): 8.15 (d, 1H), 7.60–7.55 (m, 2H), 4.07–4.03 (m, 2H), 3.81 (s, 4H), 3.76 (d, 4H), 3.71–3.60 (m, 2H), 3.41 (s, 3H), 3.23–3.20 (m, 2H), 1.48–1.43 (m, 6H).

[0105] Compound D7 (400 MHz, Chloroform-d): 8.13 (d, 1H), 7.65 (s, 1H), 7.57 (d, 1H), 6.30–4.58 (m, 2H), 4.03–4.00 (m, 2H), 3.45 (s, 4H), 3.42 (s, 3H), 3.22–2.98 (m, 2H), 1.67–1.62 (m, 6H), 1.48–1.45 (m, 6H).

[0106] Compound D8 (400 MHz, Chloroform-d): 8.19 (d, 1H), 7.86 (s, 1H), 7.69 (d, 1H), 5.39 (s, 2H), 4.00–3.98 (m, 2H), 3.62–3.54 (m, 6H), 3.48 (s, 3H), 3.38–3.31 (m, 4H), 1.32–1.28 (m, 6H).

[0107] Compound D9 (400 MHz, Chloroform-d): 7.99–7.94 (m, 2H), 7.77 (s, 1H), 7.48 (d, 1H), 3.97–3.93 (m, 2H), 3.86 (d, 2H), 3.82 (s, 3H), 3.23–3.20 (m, 2H), 3.15 (s, 3H), 2.47 (d, 2H), 2.40 (s, 3H), 1.51 (t, 3H), 1.43 (t, 3H).

[0108] Compound D10 (400 MHz, Chloroform-d): 7.90–7.70 (m, 2H), 4.05 (s, 2H), 3.75 (s, 3H), 3.36–3.20 (m, 4H), 3.07 (s, 3H), 2.65 (t, 2H), 2.29 (s, 3H), 1.37–1.45 (m, 4H), 1.23 (t, 3H), 1.10–0.88 (m, 2H).

[0109] Compound D11 (400MHz, Chloroform-d): 8.09(d, 1H), 7.68(d, 2H), 7.49(d, 1H), 7.38(d, 2H), 5.86(s, 2H), 3.53(s, 3H), 3.40(s, 3H), 3.23–3.12(m, 2H), 2.47(s, 3H), 2.27(s, 3H), 2.03–1.91(m, 2H), 1.11(t, 3H).

[0110] Compound D12 (400MHz, Chloroform-d): 8.08 (d, 1H), 7.44 (d, 1H), 5.87 (s, 2H), 3.69–3.51 (m, 9H), 3.33 (s, 5H), 3.16–3.08 (m, 2H), 2.17 (s, 3H), 1.97–1.85 (m, 2H), 1.06 (t, 3H).

[0111] Compound D13 (400MHz, Chloroform-d): 8.11 (d, 1H), 7.51 (d, 1H), 5.88 (s, 2H), 5.78–5.65 (m, 2H), 5.29–5.10 (m, 4H), 3.88–3.70 (m, 2H), 3.61–3.53 (m, 5H), 3.40 (s, 3H), 3.21–3.11 (m, 2H), 2.30 (s, 3H), 2.06–1.90 (m, 2H), 1.12 (t, 3H).

[0112] Compound D14 (400 MHz, Chloroform-d): 7.85–7.71 (m, 2H), 4.77 (s, 2H), 3.75 (s, 3H), 3.50–3.27 (m, 6H), 3.10 (s, 3H), 2.29 (s, 3H), 1.97–1.93 (m, 2H), 1.63–1.36 (m, 6H), 0.90 (t, 3H).

[0113] Compound D15 (400 MHz, Chloroform-d): 7.83–7.70 (m, 2H), 4.77 (s, 2H), 3.75 (s, 3H), 3.69–3.51 (m, 8H), 3.44 (t, 2H), 3.10 (s, 3H), 2.29 (s, 3H), 1.97–1.91 (m, 2H), 0.90 (t, 3H).

[0114] Compound D16 (400 MHz, Chloroform-d): 7.85–7.71 (m, 2H), 4.77 (s, 2H), 3.75 (s, 3H), 3.64–3.37 (m, 6H), 3.10 (s, 3H), 2.56–2.50 (m, 4H), 2.40 (s, 3H), 2.29 (s, 3H), 1.97–1.91 (m, 2H), 0.90 (t, 3H).

[0115] Compound D17 (400 MHz, Chloroform-d): 8.08 (d, 1H), 7.64 (s, 1H), 7.41 (d, 1H), 4.59 (s, 2H), 3.71 (s, 3H), 3.40 (s, 3H), 3.39–3.19 (m, 4H), 2.66 (d, 2H), 1.19–1.14 (m, 6H), 1.09–1.03 (m, 1H), 0.67–0.48 (m, 2H), 0.24–0.20 (m, 2H).

[0116] Compound D18 (400 MHz, Chloroform-d): 8.07 (d, 1H), 7.36 (d, 1H), 4.60 (s, 2H), 3.58 (s, 3H), 3.43 (s, 3H), 2.78 (s, 3H), 2.66 (d, 2H), 2.60 (s, 3H), 2.43 (s, 3H), 1.06 (m, 1H), 0.69–0.55 (m, 2H), 0.25–0.21 (m, 2H).

[0117] Compound D19 (400 MHz, Chloroform-d): 8.09 (d, 1H), 7.71 (s, 1H), 7.41 (d, 1H), 4.61 (s, 2H), 4.00–3.96 (m, 2H), 3.42 (s, 3H), 2.90 (d, 6H), 2.66 (d, 2H), 1.44 (t, 3H), 1.06–1.02 (m, 1H), 0.65–0.58 (m, 2H), 0.25–0.21 (m, 2H).

[0118] Compound D20 (400MHz, Chloroform-d): 8.12 (d, 1H), 7.70 (s, 1H), 7.56 (d, 1H), 5.31 (s, 2H), 4.01–3.98 (m, 2H), 3.42 (s, 3H), 3.13 (d, 2H), 2.95 (d, 6H), 1.44 (t, 3H), 1.33–1.27 (m, 1H), 0.91–0.74 (m, 2H), 0.53–0.44 (m, 2H).

[0119] Compound D21 (400MHz, Chloroform-d): 8.05(d, 1H), 7.35(d, 1H), 4.49(s, 2H), 3.58(s, 3H), 3.38(s, 3H), 3.17–3.13(m, 2H), 2.89–2.85(m, 2H), 2.78(d, 2H), 2.58–2.54(m, 1H), 2.37(s, 3H), 2.18–2.06(m, 2H), 1.94–1.80(m, 2H), 1.77–1.65(m, 2H), 1.08–1.02(m, 6H).

[0120] Compound D22 (400MHz, Chloroform-d): 7.84–7.70 (m, 2H), 4.78 (s, 2H), 3.75 (s, 3H), 3.44–3.22 (m, 6H), 3.10 (s, 3H), 2.34–2.10 (m, 4H), 1.61–1.16 (m, 16H).

[0121] Biological test examples

[0122] Bioactivity evaluation:

[0123] The activity level standards for plant damage (i.e., growth control rate) are as follows:

[0124] Level 9: Complete death;

[0125] Level 8: Growth control rate is greater than or equal to 90% and less than 100%;

[0126] Level 7: Growth control rate is greater than or equal to 80% and less than 90%;

[0127] Level 6: Growth control rate is greater than or equal to 70% and less than 80%;

[0128] Level 5: Growth control rate is greater than or equal to 50% and less than 70%;

[0129] Level 4: Growth control rate is greater than or equal to 30% and less than 50%;

[0130] Level 3: Growth control rate greater than or equal to 20% and less than 30%;

[0131] Level 2: Growth control rate greater than or equal to 10% and less than 20%;

[0132] Level 1: Growth control rate less than 10%;

[0133] Level 0: No effect.

[0134] Post-emergence testing experiment:

[0135] The technical grade compounds obtained in the above synthetic examples were dissolved in acetone or DMF and then prepared into test solutions of the required concentrations using a 1‰ (wt) Tween 80 aqueous solution according to experimental requirements. Common paddy field grass weeds (barnyard grass, crabgrass, and Echinochloa crus-galli) and rice seeds were sown separately in paper cups with a diameter of 7 cm containing nutrient soil. After sowing, the seeds were covered with 1 cm of soil, compacted, and watered. The plants were then cultivated in a greenhouse using conventional methods. After the weeds reached the 2-3 leaf stage, post-emergence foliar spraying was performed. The treated plants and controls were cultured in a greenhouse for 20 days, and the experimental results were statistically analyzed. Table 3 shows the indoor biological test results for some compounds.

[0136] Test Example 1: Post-emergence Compound Activity Test in Greenhouse

[0137] Table 3. Results of post-emergence compound activity testing in greenhouses (effective dose: 150 g ai / ha) Note: Barnyard grass a Collected from Yuanjiang, Hunan Province, barnyard grass b Collected from Wuxi, Jiangsu Province, barnyard grass cThe seeds were collected from Wuchang, Heilongjiang Province, and the *Qianjinzi* variety from Wuwei, Anhui Province. Testing showed that these seeds exhibited resistance to conventional doses of penoxsulam and oxazolidinone. The rice seeds were purchased from the market and are varieties widely cultivated throughout the country.

[0138] Table 4. Results of initial activity tests of post-emergence compounds in greenhouse

[0139] According to the data in Table 3, the compounds of this invention generally exhibit high control efficacy against a variety of weeds. When applied post-emergence at a dosage of 150 g ai / ha, they showed excellent control effects against resistant barnyard grass, Echinochloa crus-galli, and Digitaria sanguinalis in rice paddies, effectively addressing the increasingly serious problem of resistance. Furthermore, the compounds of this invention not only maintain highly efficient herbicidal activity but also exhibit extremely high selectivity and safety for rice (both indica and japonica varieties). In contrast, while the controls KC-1, KC-2, and KC-3 have herbicidal effects, they show extremely low selectivity and safety for crops and are harmful to rice.

[0140] According to the data in Tables 3 and 4, compounds 1–6 showed significant selectivity against multiple rice varieties, and their control efficacy against weeds such as barnyard grass, Echinochloa crus-galli, and Digitaria sanguinalis was superior to that of compounds D1–D22. Especially under reduced dosage conditions, the representative compound 2 not only showed better safety in rice but also demonstrated superior weed control efficacy compared to the control compounds D5, D9, D17, and D18.

[0141] It is noteworthy that, at the same dosage, these compounds exhibited significantly better overall weed control than traditional pyrazole herbicides (such as pyrazosulfuron, bensulfuron-methyl, and pyrazosulfuron). Furthermore, they not only maintained excellent selectivity but also demonstrated herbicidal activity exceeding or at least comparable to existing control compounds against most resistant weeds, showing superior application potential. Test Example 2: Post-emergence Compound Re-screening Activity Test in Greenhouse

[0142] The compounds of this invention were selected for further screening tests on major weeds and various types of rice in paddy fields.

[0143] Table 5. Results of post-emergence compound re-screening activity test in greenhouse Note: The recommended field dose of penoxsulam is 30 g ai / ha. Currently, there are reports that several barnyardgrass populations have developed high levels of resistance to penoxsulam (Zhang Liya et al., Resistance mechanism of penoxsulam in paddy fields and screening of control agents, Chinese Agricultural Science, 2023, 56(14):2713-2723).

[0144] As shown in Table 5, the compounds of this invention exhibit excellent effects in weed control in paddy fields, especially showing extremely high activity against barnyard grass and Echinochloa crus-galli resistant to ALS herbicides (such as penflusulfonamide) and ACCase herbicides (such as oxazolidinamide). This provides a new solution to the problem of resistant weeds.

[0145] It is noteworthy that these compounds exhibited higher safety for the "Daohuaxiang No. 2" rice variety, which is widely cultivated in Northeast China. Compound 2, in particular, did not cause phytotoxicity to rice even at high doses. In contrast, traditional HPPD herbicides such as mesotrione easily caused phytotoxicity problems in "Daohuaxiang No. 2". Furthermore, the compounds of this invention are not only safe for japonica rice but also suitable for indica rice, maintaining high selectivity and safety even at five times the normal application dose.

[0146] Test Example 3: Field Trial

[0147] Meanwhile, compound 2 was also subjected to field trials.

[0148] Test method: Each plot is 24m2, and each treatment is repeated 3 times. The treatment is applied as a foliar spray 12 days after direct seeding of rice. Water is added 48 hours after application and kept moist for 5-7 days.

[0149] Twenty days after treatment, the treated and control areas were observed, and the weed control efficacy and crop safety were statistically analyzed by visual inspection.

[0150] Experimental locations: Dandong, Liaoning and Changsha, Hunan.

[0151] Table 6. Field trial results of compound 2 (Dandong, Liaoning)

[0152] Table 7. Field trial results of compound 2 (Changsha, Hunan)

[0153] The results of the above two trials show that, at all the dosages, compound 2 caused significant whitening of barnyard grass in different regions after 4 days. Even at a low dose of 150 g ai / ha, it had excellent control effects on barnyard grass and also had excellent control effects on Echinochloa crus-galli.

[0154] Under the same conditions, for the eight tested rice varieties (three leaves and one heart): when compound 2 of the present invention was applied, the rice did not exhibit obvious biological whitening and there was no phytotoxicity.

[0155] Therefore, the compounds of this invention not only exhibit excellent herbicidal activity but also significantly improve crop safety, meeting the requirements for field application and providing an ideal tool for weed management and crop protection in agricultural practice.

[0156] In summary, the compounds of this invention not only possess highly efficient weed-control performance, but also exhibit high selectivity and safety for rice, and have significant commercial value.

[0157] The above description provides an exemplary account of the implementation methods of the technical solutions disclosed in this application. It should be understood that the scope of protection of this disclosure is not limited to the above-described implementation methods. Any modifications, equivalent substitutions, or improvements made by those skilled in the art within the spirit and principles of this application should be included within the scope of protection of the claims of this application.

Claims

1. A bis-thiobenzoyl pyrazole compound, characterized by, It is a compound represented by Formula (I) or a stereoisomer thereof, or an agriculturally acceptable salt of the compound represented by Formula (I) or a stereoisomer thereof, In formula (I), X1 is selected from halogens; X2is selected from C1to C6alkyl, C3to C6cycloalkylalkyl or C6to C10aryl; 14 aryl C1to C6alkyl; X3 is selected from C1-C6 alkylsulfonyl groups; R1 is selected from C1-C6 alkyl groups; R2 is selected from hydrogen or C1-C6 alkyl groups; Q is selected from -C(O)NR3R4; R3 and R4 may be the same or different, and are independently selected from C1-C6 alkyl groups; n is selected from 0, 1, or 2.

2. The dithiobenzoyl pyrazole compound according to claim 1, wherein It is a compound represented by Formula (II) or a stereoisomer thereof, or an agriculturally acceptable salt of the compound represented by Formula (II) or a stereoisomer thereof, in, X2 is selected from one of C1-C6 alkyl, C3-C6 cycloalkyl-substituted C1-C4 alkyl; n is selected from 0, 1, or 2; R1 is selected from C1-C6 alkyl groups; R2 is selected from hydrogen or C1-C6 alkyl groups.

3. The dithiobenzoylpyrazole compound according to claim 2, characterized in that, X2 is selected from one of C1-C3 alkyl groups substituted with C2-C4 alkyl or C3-C5 cycloalkyl; n is selected from 0, 1, or 2; R1 is selected from C1 to C4 alkyl groups; R2 is selected from hydrogen or C1-C4 alkyl groups.

4. The dithiobenzoylpyrazole compound according to claim 3, characterized in that, X2 is selected from one of C1-C3 alkyl groups substituted with C2-C3 alkyl or C3 cycloalkyl; n is selected from 0, 1, or 2; R1 is selected from C1 to C3 alkyl groups; R2 is selected from hydrogen or C1-C3 alkyl groups.

5. The dithiobenzoylpyrazole compound according to claim 4, characterized in that, X2 is selected from one of ethyl, n-propyl, isopropyl, and cyclopropylmethyl; n is selected from 0, 1, or 2; R1 is selected from methyl or ethyl; R2 is selected from hydrogen or methyl.

6. The dithiobenzoyl pyrazole compound according to claim 1, wherein The compound is selected from:

7. A process for the preparation of the bis-phenylthiobenzoyl pyrazoles of claim 1, characterized by, The preparation of the compound of formula (I) comprises the following steps:

8. The use of the dithiobenzoylpyrazole compound according to any one of claims 1 to 6 in the agricultural control of weeds, particularly in the control of weeds in rice.

9. A herbicidal composition, characterized by It contains a dithiobenzoylpyrazole compound as described in any one of claims 1 to 6, wherein the weight percentage of the dithiobenzoylpyrazole compound is 1-99%.

10. A safe broad-spectrum herbicide against rice, characterized by The herbicide comprises an active ingredient and an adjuvant, wherein the active ingredient is a dithiobenzoylpyrazole compound as described in any one of claims 1 to 6, and the active ingredient accounts for 1-99% of the weight of the herbicide.

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