METHOD FOR PREPARING BISAMIDE INSECTICIDE AND AN INTERMEDIATE THEREOF

Description

1 / 30 METHOD FOR PREPARING BISAMIDE INSECTICIDE AND AN INTERMEDIATE THEREOF

[0001] This application is based on and claims priority over the Chinese application with application number CN 202310407854.0 and application date April 17, 2023, the content of which is incorporated herein by reference in its entirety. Technical Field

[0002] The present invention relates to the field of organic synthesis and, specifically, to a method for preparing a bisamide insecticide and an intermediate thereof. Background

[0003] 3-halogenated-l-(3-chloro-2-pyridyl)lH-pyrazol-5-benzoic acid and derivatives thereof (with structural formula as shown in Formula I) are important intermediates for the preparation of ortho-amido benzamide insecticides, such as chlorantraniliprole, cyantraniliprole, tetrachlorantraniliprole, cyclaniliprol, tetraniliprol, thiorantraniliprole, Fuyangchongxian'an (ZJ3757) and Saichongxian'an (JS9117). Formula 1

[0004] It is disclosed in CN101550130B that a carboxylic acid undergoes simultaneous halogenation and acyl oxidation reactions under the action of acyl halogenating agents such as oxalyl chloride, thionyl chloride, phosphorus tribromide, phosphorus trichloride, phosphorus pentabromide or phosphorus pentachloride to obtain the halide of Petition 870250092792, dated 10 / 10 / 2025, page 22 / 58 2 / 30 target acyl group. The method uses toluene and hexane as solvents with relatively good results, but the yield is not ideal (86%) and the solubility of the carboxylic acid in toluene or hexane is very low. Content of the present invention

[0005] In order to solve the problems existing in the prior art, the present invention provides a new method for the preparation of acyl halide. The method of the present invention can be used to obtain a target product with high purity and high yield, which can be used directly in subsequent reactions. The method is particularly suitable for the preparation of bisamide insecticides or their intermediates, and can bring greater economic benefits to the production of aquaculture chemicals.

[0006] Specifically, the present invention provides a method for preparing a compound represented by Formula I, comprising the following steps: The reaction of a carboxylic acid, represented by Formula 1-1, with a halogenating agent and an elemental halogen to obtain the compound represented by Formula 1: Formula 1-1 In Formula I and Formula 1-1, X is halogen; X' is halogen, C1-g alkyl, C1-g alkoxy or C1-g haloalkoxy; X'' is Petition 870250092792, dated 10 / 10 / 2025, p. 23 / 58 3 / 30 halogen; Y is H or halogen; X, X' and X'' are the same or different.

[0007] In some embodiments, X is Cl or Br; X' is Cl, Br, C1-2 alkyl, C1-2 alkoxy or C1-2 haloalkoxy; X'' is Cl or Br; Y is H, Cl or Br; X, X' and X'' are the same or different.

[0008] In some embodiments, X is Cl; X' is Cl or Br; X'' is Cl or Br; Y is H or Cl; X, X' and X'' are the same or different.

[0009] In some forms, X is Cl; X' is Br; X'' is Cl; Y is H.

[0010] In some embodiments, the halogenating agent is a chlorinating agent or a brominating agent.

[0011] In some embodiments, the chlorinating agent is selected from the group consisting of sulfinyl chlorides (e.g., thionyl chloride), sulfonyl chlorides (e.g., methanesulfonyl chloride or trichloromethanesulfonyl chloride), acyl chlorides (e.g., methoxyacetyl chloride, oxalyl chloride, phosgene or triphosgene) and phosphorus chlorides (e.g., phosphorus trichloride or phosphorus pentachloride).

[0012] In some embodiments, the brominating agent is selected from the group consisting of thionyl bromide and phosphorus tribromide.

[0013] In some embodiments, the molar ratio between the carboxylic acid and the halogenating agent (for a polymer such as triphosgene, the calculation is based on its monomeric unit) is 1:(1.0-3.0), preferably 1:(1.0-2.0). When the halogenating agent is a polymer, such as triphosgene, the molar ratio between the carboxylic acid and the halogenating agent refers to the molar ratio between the acid Petition 870250092792, dated 10 / 10 / 2025, page 24 / 58 4 / 30 carboxylic and all monomers that can be supplied by the polymer for the reaction.

[0014] In some forms, the elemental halogen is chlorine or bromine.

[0015] In some embodiments, the halogenating agent is thionyl chloride and the elemental halogen is chlorine.

[0016] In some embodiments, the reaction is carried out in a solvent.

[0017] In some embodiments, the solvent is one or more selected from the group consisting of acetonitrile, chlorobenzene, dioxane, tetrahydrofuran, dichloromethane, dichloroethane, chloroform and carbon tetrachloride.

[0018] In some embodiments, the solvent is acetonitrile.

[0019] In some modalities, the method comprises the following steps: Add the carboxylic acid, the halogenating agent (e.g., thionyl chloride), and the elemental halogen (e.g., chlorine) to the solvent, respectively, to obtain a solution containing the carboxylic acid, a solution containing the halogenating agent, and a solution containing the elemental halogen; Add the solution containing the carboxylic acid and the solution containing the halogenating agent obtained above to the solution containing the elemental halogen and react to obtain the compound represented by Formula I.

[0020] In some embodiments, the solution containing the carboxylic acid and the solution containing the halogenating agent are added to the solution containing the elemental halogen simultaneously. In some embodiments, the term Petition 870250092792, dated 10 / 10 / 2025, page 25 / 58 5 / 30 simultaneously refers to the fact that the operations of adding the solution containing the carboxylic acid and adding the solution containing the halogenating agent partially or completely overlap in time.

[0021] In some embodiments, the temperature of the reaction system during the addition process is controlled. In some embodiments, the temperature of the reaction system during the addition process is controlled to be from 5 to 70 °C, for example, 5 to 45 °C, 5 to 40 °C, 5 to 30 °C, 5 to 20 °C or 10 to 15 °C.

[0022] In some embodiments, the reaction is carried out from -10 to 80 °C, preferably from 10 to 50 °C, more preferably from 10 to 45 °C, for example, from 10 to 40 °C, from 15 to 45 °C or from 30 to 45 °C.

[0023] In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of an acid-bonding agent.

[0024] In some embodiments, the acid linking agent is one or more selected from the group consisting of triethylamine, pyridine, 3-methylpyridine, and 2-methylpyridine. In some embodiments, the acid linking agent is triethylamine. In some embodiments, the acid linking agent is pyridine. In some embodiments, the acid linking agent is 3-methylpyridine.

[0025] In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of a catalyst.

[0026] In some embodiments, the catalyst is one or more selected from the group consisting of N,N-dimethylformamide, N,N-dimethylaniline, pyridine and Petition 870250092792, dated 10 / 10 / 2025, p. 26 / 58 6 / 30 triethylamine. In some embodiments, the catalyst is selected from N,N-dimethylformamide.

[0027] In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of an acidic bonding agent and a catalyst.

[0028] In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of one or more of the following substances: triethylamine, pyridine, 3-methylpyridine, 2-methylpyridine, N,N-dimethylformamide, and N,N-dimethylaniline. In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of N,N-dimethylformamide. In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of 3-methylpyridine. In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of pyridine. In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of triethylamine and N,N-dimethylformamide. In some embodiments, the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of 3-methylpyridine and N,N-dimethylformamide.

[0029] In some embodiments, the molar ratio between the acid-binding agent and the carboxylic acid is 0.05 to 0.5, such as 0.05 to 0.2 and, for another example, 0.1 to 0.2.

[0030] In some embodiments, the molar ratio of the catalyst to the carboxylic acid is from 0.05 to 0.5.

[0031] Using the above method of the present invention, the yield of the target product is greater than 80%, for example, greater than 85%, greater than 90%, greater than 91 Petition 870250092792, dated 10 / 10 / 2025, p. 27 / 58 7 / 30%, greater than 92%, greater than 93%, greater than 94%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 99%. Since the compound represented by Formula I prepared by the present invention has high activity, for convenience of calculation, in some cases, the yield of the compound represented by Formula I is calculated based on the carboxylic acid obtained by hydrolysis of the compound represented by Formula I. The purity of the corresponding carboxylic acid obtained is above 80%, for example, above 85%, above 90%, above 91%, above 92%, above 93%, above 94%, above 95%, above 96%, above 97%, above 98%, above 99%.

[0032] In another aspect, the present invention provides a method for preparing a compound represented by Formula II, which comprises the following steps: Use Formula 1-1 as raw material and perform the operation according to any of the methods described above to obtain the compound represented by Formula 1; hydrolyze the compound represented by Formula I to obtain the compound represented by Formula II, where the groups in Formula I, 1-1 and II are as defined above.

[0033] The compound represented by Formula I, as prepared above, can be used directly in Petition 870250092792, dated 10 / 10 / 2025, page 28 / 58 8 / 30 The next reaction, such as the amidation reaction, occurs after the removal of elemental halogen and low-boiling-point impurities from the solvent by vacuum distillation. In other embodiments, the compound represented by Formula I, as prepared above, can also be added to water (preferably adjusted to pH 2 to 3 with, for example, an aqueous solution of NaOH) and hydrolyzed to form a corresponding acid (for example, the carboxylic acid represented here by Formula II), which is then purified by extraction or crystallization to obtain a pure acid product, and the acid then reacts with an amino fragment to carry out the next step, such as the amidation reaction. Therefore, the compound represented by Formula I, as prepared by the present invention, can be used as an active intermediate for the preparation of various key chemical intermediates containing amide linkages, such as bisamide pesticides.

[0034] Therefore, in another aspect, the present invention provides a method for preparing a compound represented by Formula III, which comprises the following steps: A carboxylic acid represented by Formula I-1 is reacted with a halogenating agent and an elemental halogen according to the method described in any of the first aspects; The product obtained in the previous step is reacted with a compound represented by Formula IV to obtain a compound represented by Formula III; preferably, the reaction is carried out in the presence of an acidic linking agent (e.g., 3-methylpyridine); preferably, the reaction is Petition 870250092792, dated 10 / 10 / 2025, p. 29 / 58 9 / 30 performed at 10 to 60 °C (for example, 10 to 45 °C, 10 to 45 C, 10 to 30 °C, 15 to 25 °C or 20 to 25 °C); Halogenating agent, Xa Formula 1-1 Formula IV Amidation Formula III wherein, D is halogen or C1-6 alkyl, E is halogen or cyano; G is -C(O)NH-C1-6 alkyl, -C(S)NH-C1-6 alkyl, C(O)NH-C1-6 cycloalkyl, -C(S)NH-C1-6 cycloalkyl, or unsubstituted or halogen-substituted 5- to 6-membered heteroaryl or C1-6 alkyl; the remaining groups are as defined above.

[0035] In some embodiments, D is Cl, Br or C1-2 alkyl; E is Cl, Br or cyano; G is -C(O)NH-C1-4 alkyl, -C(S)NH-C1-4 alkyl, -C(O)NH-C1-2-cycloalkyl C3-6 alkylene, C(S)NH-C1-2-cycloalkyl C3-6 alkylene or unsubstituted or halogen-substituted 5-membered heteroaryl or C1-2 alkyl.

[0036] In some embodiments, D is Cl, Br, or methyl; E is Cl or cyano; G is selected from

[0037] The conditions for the amidation reaction described herein are known in the art and are not particularly limited. For more details, consult textbooks or literature. Petition 870250092792, dated 10 / 10 / 2025, page 30 / 58 10 / 30

[0038] In some embodiments, the compound represented by Formula III is a bisamide insecticide.

[0039] In some embodiments, the compound represented by Formula III is an ortho-amidobenzamide insecticide.

[0040] In some embodiments, the orthoamido benzamide insecticide is selected from the group consisting of chlorantraniliprole, cyantraniliprole, tetrachlorantraniliprole, cyclaniliprol, tetraniliprol, thiorantraniliprole, Fuyangchongxian'an (ZJ3757) and Saichongxian'an (JS9117).

[0041] In another aspect, the present invention provides the use of the method described in any of the above aspects in the manufacture of a bisamide insecticide.

[0042] In some embodiments, the bisamide insecticide is an ortho-amidobenzamide insecticide.

[0043] In some embodiments, the benzamide orthoamido insecticide is selected from the group consisting of chlorantraniliprole, cyantraniliprole, tetrachlorantraniliprole, cyclaniliprol, tetraniliprol, thiorantraniliprole, Fuyangchongxian'an (ZJ3757) and Saichongxian'an (JS9117). Definition of terms

[0044] As used herein, unless otherwise specified, the scientific and technical terms used have the meanings commonly understood by those skilled in the art. At the same time, for a better understanding of the present invention, definitions and explanations of the relevant terms are provided below.

[0045] As used in this document, the singular forms a, an and the are also intended to include plural forms, unless the context clearly indicates otherwise. In addition, the terms include, comprise, Petition 870250092792, dated 10 / 10 / 2025, p. 31 / 58 11 / 30 have, contain, or their variations are open-ended and not exclusive or exhaustive. Furthermore, the terms herein, preamble, and hereafter, or words of similar meaning, shall refer to the entire application, and not to any specific part thereof.

[0046] The term halogen is defined to include F, Cl, Br and I.

[0047] The term alkyl is defined as a saturated aliphatic hydrocarbon group with a linear or branched chain. For example, the term C1-6 alkyl refers to an alkyl with 1 to 6 carbon atoms, and for other examples, C1-5 alkyl, C1-4 alkyl, C1-3 alkyl, or C1-2 alkyl. Common examples of alkyl include (but are not limited to) methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, and n-hexyl. When a hydrogen atom is removed from the alkyl, the resulting group is the alkylene, as described herein, as C1-6 alkylene, C1-5 alkylene, C1-4 alkylene, C1-3 alkylene, or C1-2 alkylene.

[0048] The term alkoxy refers to a group with an alkyl-O- structure, wherein the alkyl is defined as described above. For example, C1-6 alkoxy, C1-5 alkoxy, C1-4 alkoxy, C1-3 alkoxy or C1-2 alkoxy, etc. Common examples of alkoxy include (but are not limited to) methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, hexyloxy, etc.

[0049] The term haloalkyl refers to an alkyl substituted with one or more (e.g., 1, 2, or 3) identical or different halogen atoms, where the alkyl is defined as described above. For example, the term C1-6 haloalkyl refers to a haloalkyl with 1 to 6 Petition 870250092792, dated 10 / 10 / 2025, p. 32 / 58 12 / 30 carbon atoms. Common examples of haloalkyl include (but are not limited to) -CH2F, -CHF2, -CF3, -CH2CF3, CF2CF3, -CH2CH2CF3, -CH2Cl, etc.

[0050] The term haloalkoxy refers to an alkoxy substituted with one or more (e.g., 1, 2, or 3) identical or different halogen atoms, where the alkoxy is defined as above. For example, the term C1-6 haloalkoxy refers to a haloalkoxy with 1 to 6 carbon atoms. Common examples of haloalkoxy include (but are not limited to) -OCH2F, OCHF2, -OCF3, -OCH2CF3, -OCF2CF3, -OCH2CH2CF3, -OCH2Cl, etc.

[0051] The term cycloalkyl refers to a saturated cyclic hydrocarbon group. For example, the term C3-6 cycloalkyl refers to a cycloalkyl with 3 to 6 carbon atoms in the ring. Common examples of cycloalkyl include (but are not limited to) cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0052] The term heteroaryl refers to an aromatic ring group containing at least one ring member selected from the group consisting of N, O, and S. For example, 5-6 membered heteroaryl, 5-6 membered nitrogen-containing heteroaryl, 5-6 membered oxygen-containing heteroaryl, etc. Common examples of heteroaryl compounds include (but are not limited to) furanyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, 1,2,4,5-tetrazinyl, etc.

[0053] The term substitution refers to the replacement of one or more hydrogen atoms (for example, Petition 870250092792, dated 10 / 10 / 2025, p. 33 / 58 13 / 30 one, two, three or four) by a designated atom. Unless otherwise indicated, the substituent attachment point may be at any suitable position in the substituted structure.

[0054] The term one or more refers to one or more atoms under reasonable conditions, such as 2, 3, 4, 5 or more. Detailed Description of the Modalities

[0055] The embodiments of the present invention will be described in detail below, together with examples, but those skilled in the art will understand that the following examples are used only to illustrate the present invention and should not be considered as limiting the scope of the present invention. If no specific condition was specified in the examples, they were carried out in accordance with conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without indication from the manufacturer were all conventional, commercially available products. Example 1: Preparation of raw material KA-1

[0056] 7.2 g of sodium hydroxide and 250 g of water were added to a conical flask to prepare an alkaline solution. 50 g (0.150 mol) of KB-1 were added to a three-necked flask, followed by the addition of 50 g of ethanol. The resulting mixture was stirred at 10 °C, and then the previously prepared alkaline solution was added slowly, drop by drop. After HPLC detection indicated the Petition 870250092792, dated 10 / 10 / 2025, page 34 / 58 14 / 30 disappearance of the raw material, diluted hydrochloric acid was added to adjust the pH from 1 to 2, and then ethyl acetate was added twice for extraction. The organic phases were combined and 45.7 g of a viscous liquid were obtained by rotary evaporation, with a yield of 95.1% and HPLC purity of 97.5%. Example 2

[0057] 25.0 g (0.0821 mol) of KA-1, 0.830 g (0.00821 mol) of triethylamine and 100 g of acetonitrile were added to a single-necked flask to prepare a mixed solution for later use.

[0058] 14.7 g of thionyl chloride, 50.0 g of acetonitrile, and 0.3 g of N,N-dimethylformamide were added to a four-necked flask, stirred at 45 °C, purged with nitrogen gas for about 5 minutes, purged with chlorine gas, and slowly added to the prepared mixed solution using a booster pump, and the reaction was maintained at 45 °C. After HPLC detection indicated the disappearance of the raw material, the reaction was stopped. A 20% sodium hydroxide solution was added to adjust the pH to 2-3, the phases were separated, and then ethyl acetate was added for extraction. The organic phases were combined and rotatably evaporated to obtain 23.9 g of product KA, with a yield of 96.2% and a purity of 96.9% by HPLC. Example 3-1 Petition 870250092792, dated 10 / 10 / 2025, page 35 / 58 15 / 30 KA-1 KA-2 KA

[0059] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. First, nitrogen gas was introduced into a four-necked flask containing 25 g of acetonitrile for approximately 5 minutes. Then, chlorine gas was introduced, stirred at 15 °C, and then added along with the KA-1 solution prepared in single-necked flask #1 using a booster pump #1, followed by the addition of thionyl chloride solution prepared in single-necked flask #2 using a booster pump #2. After the introduction of KA-1 and thionyl chloride was complete, the reaction system was heated to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was terminated.A 20% sodium hydroxide solution was added to adjust the pH to 2-3, the layers were separated, and then ethyl acetate was added for extraction. The organic layers were combined and rotary evaporated to obtain 23.8 g of the KA product, with a yield of 96.1% and an HPLC purity of 95.6%. Example 3-2

[0060] According to the method of Example 3-1, after the introduction of KA-1 and thionyl chloride, the reaction was Petition 870250092792, dated 10 / 10 / 2025, page 36 / 58 A 16 / 30 assay was performed at 10 °C to obtain 23.5 g of product KA, with a yield of 94.8% and a purity by HPLC of 94.6%. Example 3-3

[0061] According to the method of Example 3-1, after the introduction of KA-1 and thionyl chloride, the reaction was carried out at 50 °C to obtain 23.2 g of the product KA, with a yield of 93.5 % and a purity by HPLC of 94.1 %. Example 3-4

[0062] 25.0 g (0.0821 mol) of KA-1, 1.5 g (0.0164 mol) of 3-methylpyridine, and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride, 50 g of acetonitrile, and 3.0 g of DMF were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 3-1 to obtain 24.0 g of the KA product, with a yield of 96.5% and an HPLC purity of 97.5%. Example 3-5

[0063] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride, 50 g of acetonitrile, and 3.0 g of DMF were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 3-1 to obtain 23.9 g of the product KA, with a yield of 96.4% and a purity of HPLC of 97.3%. Example 3-6

[0064] 25.0 g (0.0821 mol) of KA-1, 1.5 g (0.0164 mol) of 3-methylpyridine and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare Petition 870250092792, dated 10 / 10 / 2025, page 37 / 58 17 / 30 a solution for later use. 14.7 g (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 3-1 to obtain 23.8 g of product KA, with a yield of 96.1% and an HPLC purity of 95.8%. Example 3-7

[0065] 25.0 g (0.0821 mol) of KA-1, 1.3 g (0.0164 mol) of pyridine, and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 31 to obtain 23.7 g of the KA product, with a yield of 95.6% and an HPLC purity of 95.6%. Example 3-8

[0066] 25.0 g (0.0821 mol) of KA-1, 1.5 g (0.0164 mol) of 3-methylpyridine, and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.108 mol) of phosphorus trichloride and 75 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 3-1, yielding 24.1 g of a viscous liquid with a purity of 86.8% by HPLC. Example 3-9

[0067] 25.0 g (0.0821 mol) of KA-1, 1.5 g (0.0164 mol) of 3-methylpyridine, and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 22.5 g (0.108 mol) of Petition 870250092792, dated 10 / 10 / 2025, page 38 / 58 18 / 30 g of phosphorus pentachloride and 100 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 3-1 to obtain 25.1 g of a viscous liquid, with a purity of 82.8% by HPLC. Example 3-10

[0068] According to the method of Example 3-1, only thionyl chloride was replaced by oxalyl chloride to obtain 23.4 g of product KA with a yield of 94.2% and an HPLC purity of 94.7%. Example 3-11

[0069] According to the method of Example 3-1, only thionyl chloride was replaced by 14.6 g (0.0493 mol) of triphosgene to obtain 23.1 g of product KA with a yield of 93.2% and an HPLC purity of 94.0%. Example 3-12

[0070] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 25.6 g (0.123 mol) of thionyl bromide and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use.

[0071] First, gaseous nitrogen was introduced into a four-necked flask with 25 g of acetonitrile for approximately 5 minutes, then gaseous chlorine was introduced, under stirring at 10 °C. Next, the KA-1 solution prepared in single-necked flask No. 1 was added using a pump No. 1, and the thionyl bromide solution prepared in single-necked flask No. 2 was added using a pump No. 2. After the introduction of KA-1 and thionyl bromide, the Petition 870250092792, dated 10 / 10 / 2025, page 39 / 58 The reaction system was continuously stirred at 10 °C. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped. A 20% sodium hydroxide solution was added to adjust the pH from 2 to 3, the phases were separated, and then ethyl acetate was added for extraction. The organic phases were combined and rotary evaporated to obtain 23.5 g of product KA, with a yield of 94.6% and HPLC purity of 97.1%. Example 3-13

[0072] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 25.6 g (0.123 mol) of thionyl bromide and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use, and 15.7 g of bromine and 50 g of acetonitrile were added to a No. 3 single-neck flask to prepare a solution for later use.

[0073] Nitrogen gas was introduced into a four-necked flask containing 25 g of acetonitrile. Then, the KA-1 solution prepared in single-necked flask #1 was added using a booster pump #1. The thionyl bromide solution prepared in single-necked flask #2 was added using a booster pump #2, and the bromine solution prepared in single-necked flask #3 was added using a booster pump #3. The three material flows were maintained at a constant rate, and their introduction was stopped simultaneously. The temperature during introduction was 5 ± 2 °C. After the introduction was complete, the reaction system was continuously stirred at 5 °C. After HPLC detection indicated the disappearance of Petition 870250092792, dated 10 / 10 / 2025, pp. 40 / 58 After 20 / 30 of the raw materials, the reaction was stopped. A 20% sodium hydroxide solution was added to adjust the pH to 2-3, the phases were separated, and then ethyl acetate was added for extraction. The organic phases were combined and rotatably evaporated to obtain 23.8 g of the KA product, with a yield of 94.4% and HPLC purity of 93.2%. Example 4-1

[0074] 25.0 g (0.0738 mol) of KD-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 13.2 g (0.111 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. First, nitrogen gas was introduced into a four-necked flask containing 25 g of acetonitrile for approximately 5 minutes. Then, chlorine gas was introduced and stirred at 15 °C. Next, the KD-1 solution prepared in single-necked flask #1 was slowly added using a booster pump #1, and the thionyl chloride solution prepared in single-necked flask #2 was slowly added using a booster pump #2. After the introduction of KD-1 and thionyl chloride was complete, the reaction system was heated to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was terminated.A 20% sodium hydroxide solution was added to. Petition 870250092792, dated 10 / 10 / 2025, page 41 / 58 21 / 30 adjust the pH to 2-3, the phases were separated, and then ethyl acetate was added for extraction. The organic phases were combined and rotatably evaporated to obtain 23.0 g of the KD-3 product, with a yield of 92.3% and HPLC purity of 91.8%. Example 4-2

[0075] 25.0 g (0.0738 mol) of KD-1 and 125 g of dioxane were added to a No. 1 single-neck flask to prepare a solution for later use. 13.2 g (0.111 mol) of thionyl chloride and 50 g of dioxane were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 4-1 to obtain 23.4 g of the product KD-3, with a yield of 94.0% and HPLC purity of 91.2%. Example 4-3

[0076] 25.0 g (0.0738 mol) of KD-1 and 125 g of tetrahydrofuran were added to a No. 1 single-neck flask to prepare a solution for later use. 13.2 g (0.111 mol) of thionyl chloride and 50 g of tetrahydrofuran were added to a No. 2 single-neck flask to prepare a solution for later use. The remaining operations were the same as in Example 4-1 to obtain 23.0 g of the product KD-3, with a yield of 92.3% and an HPLC purity of 91.8%. Example 4-4

[0077] 25.0 g (0.0738 mol) of KD-1 and 125 g of tetrahydrofuran were added to a No. 1 single-neck flask to prepare a solution for later use. 13.2 g (0.111 mol) of thionyl chloride and 50 g of tetrahydrofuran were added to a No. 2 single-neck flask to prepare a solution for later use. Petition 870250092792, dated 10 / 10 / 2025, page 42 / 58 22 / 30

[0078] First, gaseous nitrogen was introduced into a four-necked flask containing 25 g of tetrahydrofuran for approximately 5 minutes, followed by gaseous chlorine, under stirring at 50 °C. Then, the KD-1 solution prepared in single-necked flask No. 1 was added slowly using a booster pump No. 1, and the thionyl chloride solution prepared in single-necked flask No. 2 was added slowly using a booster pump No. 2. After the introduction of KD-1 and thionyl chloride, the reaction system was heated to 50 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped. 20% sodium hydroxide solution was added to adjust the pH to 2-3, the phases were separated, and ethyl acetate was added for extraction. The organic phases were combined and rotatably evaporated to obtain 23.7 g of the KD-3 product, with a yield of 95.2% and a purity of 95.8% by HPLC. Example 5 KC-1 KC-2

[0079] 30.0 g (0.115 mol) of KCl and 120 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 20.6 g (0.173 mol) of thionyl chloride and 60 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use.

[0080] First, nitrogen gas was introduced into a four-necked flask containing 25 g of acetonitrile by Petition 870250092792, dated 10 / 10 / 2025, pp. 43 / 58 23 / 30 for approximately 5 minutes, then chlorine gas was introduced, stirred at 5 °C, and then the KC-1 solution prepared in single-neck flask No. 1 was slowly added using a No. 1 booster pump, and the thionyl chloride solution prepared in single-neck flask No. 2 was slowly added using a No. 2 booster pump. After the introduction of KC-1 and thionyl chloride was complete, the reaction system was heated to 15 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped. 20% sodium hydroxide solution was added to adjust the pH to 2-3, the phases were separated, and then ethyl acetate was added for extraction. The organic phases were combined and rotatably evaporated to obtain 27.9 g of the KC-3 product, with a yield of 94.1% and HPLC purity of 94.3%. Example 6 KA-1

[0081] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. First, nitrogen gas was introduced into a four-neck flask containing 25 g of acetonitrile for approximately 5 minutes. Then, chlorine gas was introduced. Petition 870250092792, dated 10 / 10 / 2025, pp. 44 / 58 24 / 30 slowly, under stirring at 15 °C. Then, the KA-1 solution prepared in single-neck flask No. 1 was added slowly with a pump No. 1, and the thionyl chloride solution prepared in single-neck flask No. 2 was added slowly with a pump No. 2. After the introduction of KA-1 and thionyl chloride, the reaction system was heated to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped.

[0082] The reaction solution was subjected to distillation under reduced pressure at a distillation temperature not exceeding 45 °C to obtain 185 g of a mixed liquid. 16.3 g of 2-amino-5-chloro-N,3-dimethylbenzamide were added to the mixed liquid in batches, stirred at 15 °C for about 0.5 hours, heated to 40 °C and stirred for 2 hours. After HPLC detection, it was shown that about 8% of the KA-2 did not react completely. Most of the hydrogen chloride was removed by vacuum distillation, and then 1.6 g (0.0164 mol) of 3-methylpyridine and 0.9 g (0.00821 mol) of methylsulfonyl chloride were added and stirred at 15 °C. After HPLC detection indicated the disappearance of the raw materials, the reaction was terminated. 75 g of water were added slowly, drop by drop, and the mixture was stirred at room temperature for crystallization.After filtration, the filter cake was dried to obtain 36.5 g of the whitish solid product KK, with a yield of 92.1%. Example 6-1

[0083] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g Petition 870250092792, dated 10 / 10 / 2025, pp. 45 / 58 25 / 30 (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use.

[0084] First, gaseous nitrogen was introduced into a four-necked flask with 25 g of acetonitrile for approximately 5 minutes. Then, gaseous chlorine was slowly introduced under stirring at 30 °C. Next, the KA-1 solution prepared in single-necked flask No. 1 was slowly added using a booster pump No. 1, and the thionyl chloride solution prepared in single-necked flask No. 2 was slowly added using a booster pump No. 2. After the introduction of KA-1 and thionyl chloride, the reaction system was heated to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped.

[0085] The reaction solution was subjected to distillation under reduced pressure at a distillation temperature not exceeding 45 °C to obtain 185 g of a mixed liquid. 16.3 g of 2-amino-5-chloro-N,3-dimethylbenzamide, 32.6 g of acetonitrile, and 16.8 g of 3-methylpyridine were added to another three-necked flask, shaken at 20 °C for 10 minutes. Then, 185 g of the mixed liquid prepared above were added slowly, dropwise, to the three-necked flask, maintaining the internal temperature between 20 and 25 °C during the reaction. After the dropwise addition, the temperature was maintained for the continuation of the reaction. After HPLC detection indicated the end of the reaction, 68.6 g of hydrochloric acid diluted to 7.2% were added dropwise to the three-necked flask, which was shaken at 20 °C for 90 minutes. After filtration, the filter cake was dried. Petition 870250092792, dated 10 / 10 / 2025, pp. 46 / 58 26 / 30 yielding 37.0 g of a whitish solid, with a yield of 93.3%. Example 7

[0086] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use.

[0087] First, gaseous nitrogen was introduced into a four-necked flask with 25 g of acetonitrile for about 5 minutes. Then, gaseous chlorine was introduced, under stirring at 15 °C. Next, the KA-1 solution prepared in single-necked flask No. 1 was added slowly using Propel pump No. 1, and the thionyl chloride solution prepared in single-necked flask No. 1 was added slowly using Propel pump No. 2. After the introduction of KA-1 and thionyl chloride, the reaction was heated to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped.

[0088] The reaction solution was subjected to distillation under reduced pressure at a distillation temperature not exceeding 45 °C to obtain 185 g of a mixed liquid. 15.5 g of 2-amino-5-cyano-N,3-dimethylbenzamide were added to the mixed liquid in batches, stirred at 15 °C for approximately Petition 870250092792, dated 10 / 10 / 2025, pp. 47 / 58 27 / 30 0.5 hours, then heated to 40 °C and stirred for 2 hours. After HPLC detection indicated that approximately 6% of the KA-2 was not fully reacted, most of the hydrogen chloride was removed by vacuum distillation, and then 1.6 g (0.0164 mol) of 3-methylpyridine and 0.9 g (0.00821 mol) of methylsulfonyl chloride were added and stirred at 15 °C. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped. 100 g of water were added slowly, dropwise, and stirred at room temperature for crystallization. After filtration, the filter cake was dried to obtain 36.3 g of the whitish solid product CYTR, with a yield of 93.4%. Example 8: Preparation of tetrachlorantraniliprole

[0089] 25.0 g (0.0738 mol) of KD-1, 125 g of acetonitrile, and 1.5 g (0.0164 mol) of 3-methylpyridine were added to a No. 1 single-neck flask to prepare a solution for later use. 13.2 g (0.111 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. First, nitrogen gas was introduced into a four-neck flask with 25 g of acetonitrile for approximately 5 minutes, then chlorine gas was introduced, under stirring at 15 °C. Then, the KA-1 solution prepared in the No. 1 single-neck flask was added slowly using a pump. Petition 870250092792, dated 10 / 10 / 2025, pages 48 / 58 28 / 30 propellant pump #1, and the thionyl chloride solution prepared in single-neck flask #2 was added slowly using a propellant pump #2. After the introduction of KA-1 and thionyl chloride, the reaction system was heated to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw material, the reaction was terminated.

[0090] The reaction solution was distilled under reduced pressure at a distillation temperature not exceeding 45 °C to obtain 190 g of a mixed liquid. 15.4 g (0.0701 mol) of 2-amino-3,5-dichlorobenzamide were added to the mixed liquid in batches, stirred at 15 °C for about 0.5 hours, and then heated to 40 °C and stirred for 2 hours. After HPLC detection indicated that approximately 5% of the KA-2 did not react completely; most of the hydrogen chloride was removed by vacuum distillation, and then 1.6 g (0.0164 mol) of 3-methylpyridine and 0.9 g (0.00821 mol) of methylsulfonyl chloride were added and stirred at 15 °C. After HPLC detection indicated the disappearance of the raw material, the reaction was stopped. 100 g of water were added slowly, dropwise, and the mixture was stirred to crystallize at room temperature. After filtration, the filter cake was dried to obtain 34.0 g of solid SD product with a yield of 85.7%. Comparative Example 1

[0091] 25.0 g (0.0821 mol) of KA-1 and 125 g of acetonitrile were added to a No. 1 single-neck flask to prepare a solution for later use. 14.7 g (0.123 mol) of thionyl chloride and 50 g of acetonitrile were added to a No. 2 single-neck flask to prepare a solution for later use. Petition 870250092792, dated 10 / 10 / 2025, pp. 49 / 58 29 / 30

[0092] First, gaseous nitrogen was introduced into a four-necked flask with 25 g of acetonitrile for about 5 minutes and stirred at 15 °C. Then, the KA-1 solution prepared in single-necked flask No. 1 was added slowly using a booster pump No. 1, and the thionyl chloride solution prepared in single-necked flask No. 2 was added slowly using a booster pump No. 2. After the introduction of KA-1 and thionyl chloride, the reaction system was heated slowly to 30 °C and stirred. After HPLC detection indicated the disappearance of the raw materials, the reaction was stopped. 20% sodium hydroxide solution was added to adjust the pH to 2-3, the phases were separated, and then ethyl acetate was added for extraction. The organic phases were combined and rotatably evaporated to obtain 23.7 g of residue.HPLC showed that the KA product represented only 49% (with a yield of 46%), the KA-1 raw material remained at 28%, and the rest were impurities. Comparative Example 2

[0093] 25.0 g (0.0821 mol) of KA-1, 0.2 g of N,N-dimethylformamide, and 125 g of dichloromethane were added to a three-necked flask. 24.4 g (0.205 mol) of thionyl chloride and 24 g of dichloromethane were added to an addition funnel and then slowly added dropwise to the reaction flask. The temperature was controlled between 35 and 40 °C, and the reaction was carried out for 2 to 3 hours. HPLC showed that the product KA represented 77%, with the remainder being impurities. Petition 870250092792, dated 10 / 10 / 2025, pages 50 / 58 30 / 30

[0094] Although the specific embodiments of the present invention have been described in detail, those skilled in the art should understand that various modifications and substitutions may be made to these details based on all disclosed teachings, and such changes are within the scope of protection of the present invention. The full scope of the present invention is provided by the appended claims and any equivalents thereof. Petition 870250092792, dated 10 / 10 / 2025, pp. 51 / 58

Claims

1 / 6 CLAIMS 1. Method for preparing a compound represented by Formula I characterized in that it comprises the following steps: reaction of a carboxylic acid represented by Formula 1-1 with a halogenating agent and an elemental halogen to obtain the compound represented by Formula I: Formula 1-1 Formula I in Formula I and Formula 1-1, X is halogen; X' is halogen, C1-6 alkyl, C1-6 alkoxy or C1-6 haloalkoxy; X'' is a halogen; Y is H or halogen; X, X' and X'' are the same or different; preferably, X is Cl or Br; X' is Cl, Br, C1-2 alkyl, C1-2 alkoxy or C1-2 haloalkoxy; X'' is Cl or Br; Y is H, Cl or Br; X, X' and X'' are the same or different; preferably, X is Cl; X' is Cl or Br; X'1 is Cl or Br; Y is H or Cl; X, X', and X'' are the same or different; preferably, X is Cl; X' is Br; X'' is Cl; Y is H.

2. Method according to claim 1, characterized in that the halogenating agent is a chlorinating agent or a brominating agent; preferably, the chlorinating agent is selected from the group consisting of sulfinyl chlorides (e.g., thionyl chloride), sulfonyl chlorides (e.g., methanesulfonyl chloride or trichloromethanesulfonyl chloride), acyl chlorides (e.g., methoxyacetyl chloride, oxalyl chloride, phosgene or triphosgene) and phosphorus chlorides (e.g., phosphorus trichloride or phosphorus pentachloride); preferably, the brominating agent is selected from the group consisting of thionyl bromide and phosphorus tribromide.

3. Method according to claim 1 or 2, characterized in that the molar ratio of the carboxylic acid to the halogenating agent (for a polymer such as triphosgene, the calculation is based on its monomeric unit) is 1:(1.0-3.0), preferably 1:(1.0-2.0), for example, 1:(1.0-1.5).

4. A method according to any one of claims 1 to 3, characterized in that the elemental halogen is chlorine or bromine.

5. A method according to any one of claims 1 to 4, characterized in that the halogenating agent is thionyl chloride and the elemental halogen is chlorine.

6. A method according to any one of claims 1 to 5, characterized in that the reaction is carried out in a solvent; preferably, the solvent is selected from the group consisting of acetonitrile, chlorobenzene, dioxane, tetrahydrofuran, dichloromethane, dichloroethane, chloroform and carbon tetrachloride; preferably, the solvent is acetonitrile.

7. Method according to claim 6, characterized in that it comprises the following steps: adding the carboxylic acid, the halogenating agent (e.g., thionyl chloride) and the elemental halogen. Petition 870250092792, dated 10 / 10 / 2025, p.53 / 58 3 / 6 (for example, chlorine) to the solvent, respectively, to obtain a solution containing the carboxylic acid, the halogenating agent or the elemental halogen; add (for example, add simultaneously) the solution containing the carboxylic acid and the solution containing the halogenating agent obtained above to the solution containing the elemental halogen and react to obtain the compound represented by Formula I; preferably, the temperature of the reaction system during the addition process is controlled; preferably, the temperature of the reaction system during the addition process is controlled to be from 5 to 70 °C, preferably from 5 to 20 °C, for example, from 10 to 15 °C; Preferably, the reaction is carried out from -10 to 80 °C, preferably from 10 to 50 °C, more preferably from 10 to 45 °C, for example, from 10 to 40 °C, from 15 to 45 °C or from 30 to 45 °C.

8. A method according to any one of claims 1 to 7, characterized in that the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of an acidic binding agent; preferably, the acid-binding agent is one or more selected from the group consisting of triethylamine, pyridine, 3-methylpyridine and 2-methylpyridine.

9. Method according to any one of claims 1 to 7, characterized in that the carboxylic acid reacts with the halogenating agent and the elemental halogen in the presence of a catalyst; Petition 870250092792, dated 10 / 10 / 2025, page 54 / 58 4 / 6 preferably, the catalyst is one or more selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, pyridine and triethylamine.

10. Method for preparing a compound represented by Formula II, characterized in that it comprises the following steps: using Formula 1-1 as a raw material to obtain the compound represented by Formula I according to the steps defined in the method as defined in any one of claims 1 to 9; hydrolysis of the compound represented by Formula I to obtain the compound represented by Formula II, wherein the groups in Formulas I, 1-1 and II are as defined in claim 1.

11. Method for preparing a compound represented by Formula III characterized in that it comprises the following steps: reacting a carboxylic acid represented by Formula 1-1 with a halogenating agent and an elemental halogen, according to the method as defined in any one of claims 1 to 10; further reaction of the product obtained in the previous step with a compound represented by Formula IV to obtain a compound represented by Formula III; Petition 870250092792, dated 10 / 10 / 2025, p. 55 / 58 5 / 6 Halogenating agent, X2 Formula 1-1 Formula IV An.Formula III, wherein D is a halogen or Cl-6 alkyl; E is a halogen or cyano; G is -C(O)NH-C1-6 alkyl, -C(S)NH-C1-6 alkyl, C(O)NH-C1-6 cycloalkyl C3-6 alkylene, -C(S)NH-C1-6 cycloalkyl C3-6 alkylene, or a 5- to 6-membered heteroaryl unsubstituted or substituted with halogen or C1-6 alkyl; the remaining groups are as defined in claim 1; preferably, D is Cl, Br or C1-2 alkyl; E is Cl, Br or cyano; G is -C(O)NH-C1-4 alkyl, -C(S)NH-C1-4 alkyl, C(O)NH-C1-2 cycloalkyl C3-6 alkylene, -C(S)NH-C1-2 cycloalkyl C3-6 alkylene, or unsubstituted or halogen-substituted 5-membered heteroaryl or C1-2 alkyl; preferably, D is Cl, Br or methyl; E is Cl or cyano; G is selected from.

12. Method according to claim 11, characterized in that the compound represented by Formula III is a bisamide insecticide; preferably, the compound represented by Formula III is an ortho-amido benzamide insecticide; preferably, the ortho-amido benzamide insecticide is selected from the group consisting of chlorantraniliprole, cyantraniliprole, tetrachlorantraniliprole, cyclaniliprol, tetraniliprol, thiorantraniliprole, Fuyangchongxian'an (ZJ3757).

13. Use of the method, as defined in any one of claims 1 to 12, characterized in that it is in the manufacture of a bisamide insecticide; preferably, the bisamide insecticide is an ortho-amidobenzamide insecticide; preferably, the ortho-amidobenzamide insecticide is selected from the group consisting of chlorantraniliprole, cyantraniliprole, tetrachlorantraniliprole, cyclaniliprol, tetraniliprol, thioantraniliprole, Fuyangchongxian'an (ZJ3757) and Saichongxian'an (JS9117). Petition 870250092792, dated 10 / 10 / 2025, pp. 57 / 58