An intermediate for the synthesis of chlorantraniliprole and cyantraniliprole and a process for its preparation

Abstract

The application provides an intermediate for synthesizing chlorantraniliprole and cyantraniliprole and a preparation method of the intermediate, and the structural formula of the intermediate is 2-amino-3-methylbenzoic acid. The intermediate is obtained by a -D-A reaction, aromatization and a Hoffmann elimination reaction from a cheap bio-based platform compound 2-methylfuran as a starting material. The whole process does not need a dangerous nitration process and a hydrogenation process, the process has mild reaction conditions, good operability, less wastewater and a high yield of the obtained intermediate, and is very suitable for industrialized preparation of an intermediate required by the high-efficiency insecticides chlorantraniliprole and cyantraniliprole.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical preparation technology, and more specifically, relates to an intermediate that can be used to synthesize the pesticides chlorantraniliprole and bromocyanamide, and a method for preparing the same. Background Technology

[0002] Chlorantraniliprole, developed by DuPont, is a highly effective insecticide. Since its launch in 2008, it has been sold in over 100 countries worldwide, covering almost all major markets. In 2024, its sales reached $2 billion, establishing and solidifying its leading position in the global insecticide market. Currently, several domestic companies are developing chlorantraniliprole technical and intermediate industrial chains. Once fully operational, these chains are expected to generate a production capacity of 57,000 tons of technical and 15,000 tons of intermediates, indicating a vast market potential and promising future.

[0003] Bromnipotent is a second-generation ryanodine receptor inhibitor insecticide developed by DuPont. It works by specifically activating ryanodine receptors in insects, leading to excessive release of intracellular calcium ions, causing sustained muscle contraction and nervous system dysfunction. This target differs from traditional insecticides; while it shares the same site of action as chlorantraniliprole, its binding mechanism differs, and it remains active against resistant pests.

[0004] Therefore, strengthening the development of synthetic process routes for chlorantraniliprole and bromocyanamide technical materials and their intermediates, so as to make them have greater advantages in terms of lower cost and green environmental protection, has significant economic and social benefits. It is a hot-fixing technology and product that many pesticide companies are competing to develop.

[0005] Currently, there are several main routes for synthesizing the intermediate 2-amino-3-methylbenzoic acid: one is to prepare 2-amino-3-methylbenzoic acid by oxidation with hydrogen peroxide using 7-methylindigo as a raw material (molecular Chemistry (2019), 17(20), 5099-5105); the second is to prepare 2-amino-3-methylbenzoic acid by hydrogenation using 2-nitro-3-methylbenzoic acid as a raw material (CN119500258 A); and the third is to prepare 2-amino-3-methylbenzoic acid by methylation and reduction with iron powder or tin dichloride using 2-nitro-3-methylbenzoic acid as a starting material (Tetrahedron (2008), 64(38), 9060-9072). However, the raw materials required for the above synthetic routes are not easy to obtain, and dangerous processes such as nitration or hydrogenation are required, or the cost of the required starting materials is high. Summary of the Invention

[0006] The technical problem this invention aims to solve is to address the current state of existing technologies by providing an intermediate—2-amino-3-methylbenzoic acid—that can be used in the synthesis of chlorantraniliprole and broflanilide technical materials, along with its preparation method. This method involves a strategy of constructing multi-substituted benzene rings using bio-based furans. The synthesis of this intermediate compound does not require nitration, offering advantages such as short process steps, low wastewater, and low cost, making it suitable for industrial production and enabling the large-scale preparation of the insecticides chlorantraniliprole and broflanilide.

[0007] K-amines are widely used in modern agriculture as a key intermediate in the highly effective insecticide chlorantraniliprole. In addition, they can also be used to prepare dyes and coatings. This invention uses bio-based 2-methylfuran as a starting material to construct a multi-substituted benzene ring to obtain 2-amino-3-methylbenzoic acid, which is a key raw material for the synthesis of the following K-amine derivatives.

[0008]

[0009] To achieve the above objectives, the present invention adopts the following technical solution: An intermediate that can be used to synthesize chlorantraniliprole and broflanilide is named 2-amino-3-methylbenzoic acid, and its structural formula is as follows:

[0010] A method for preparing intermediates that can be used to synthesize chlorantraniliprole and bromocyanamide, wherein the synthetic route can be selected from any of the following: Route 1:

[0011] Route 2:

[0012] For Route 1, the specific preparation steps of 2-amino-3-methylbenzoic acid, the intermediate for the synthesis of chlorantraniliprole and broflanilide, are as follows: Step 1: 2-Methylfuran and maleimide react directly in an organic solvent by heating or under the catalysis of a catalyst; alternatively, 2-methylfuran can be used as both a reactant and a solvent, reacting directly by heating or under the catalysis of a catalyst; after the reaction is complete, the solvent is removed by direct distillation to obtain the DA addition product; The organic solvents include, but are not limited to, toluene, benzene, (o-, m-, para)xylene, mesitylene, o-xylene, pseudo-xylene, chlorobenzene, (o-, m-, para)dichlorobenzene, alkanes with 5-10 carbon atoms, ethers with 4-16 carbon atoms, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, alcohols with 1-10 carbon atoms, acetone, butanone, DMF, DME, DMSO, NMP, or mixtures of two or more thereof. The catalysts include, but are not limited to, sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, polyphosphoric acid, AlCl3, anhydrous ZnCl2, anhydrous FeCl3, tin tetrachloride, yttrium trifluorosulfonate, scandium trifluorosulfonate, copper sulfate, copper trifluorosulfonate, boron trifluoride diethyl ether complex, and titanium tetrachloride, or mixtures of two or more thereof. The reaction time is 0.5-48 hours. The reaction temperature is from room temperature to the solvent boiling point. The molar ratio of 2-methylfuran to maleimide is 100:1 to 1:1. The molar ratio of 2-methylfuran to catalyst is 100:1 to 2:1.

[0013] Step 2: The DA addition product is dissolved in organic solvent 1, and the reaction occurs under the catalysis of a catalyst. After the reaction is complete, the reaction solution is poured into water and extracted with organic solvent 2. The dried organic layers are combined, and the mixed organic solvent is removed under reduced pressure to obtain compound 1. The organic solvent 1 and organic solvent 2 may be the same or different, including but not limited to toluene, benzene, (o-, m-, para-)toluene, mesitylene, o-trimethylbenzene, pseudotrimethylbenzene, chlorobenzene, (o-, m-, para-)dichlorobenzene, alkanes with 5-10 carbon atoms, ethers with 4-16 carbon atoms, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, alcohols with 1-10 carbon atoms, acetone, butanone (DMF), DME, DMSO, NMP, or mixtures of two or more thereof. The catalyst includes but is not limited to sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, phosphoric acid, AlCl3, anhydrous ZnCl2, anhydrous FeCl3, tin tetrachloride, yttrium trifluorosulfonate, scandium trifluorosulfonate, copper sulfate, copper trifluorosulfonate, boron trifluoride diethyl ether complex, and titanium tetrachloride, or mixtures of two or more thereof. The reaction time is 0.5-48 hours. The reaction temperature ranges from room temperature to the solvent boiling point. The molar ratio of 2-methylfuran to catalyst is 100:1 to 2:1.

[0014] Step 3: Compound 1 reacts with an aqueous solution of an oxidizing agent to give intermediate 2-amino-3-methylbenzoic acid (compound 2); The oxidant is one of sodium hypochlorite solution (mass fraction 8%~15%) or sodium hypobromite (prepared on-site from bromine and NaOH solution). The reaction time is 0.5~48 hours, and the reaction temperature is 0~80℃. The molar ratio of compound 1 to sodium hypochlorite is 1:1~1:50, and the molar ratio of compound 1 to sodium hypobromite is 1:1~1:10.

[0015] For Route 2, the specific preparation steps of 2-amino-3-methylbenzoic acid, the intermediate for the synthesis of chlorantraniliprole and broflanilide, are as follows: Step 1: 2-Methylfuran and maleic anhydride react directly in an organic solvent under heating or catalysis; alternatively, 2-methylfuran can be used as both reactant and solvent, reacting directly under heating or catalysis. After the reaction is complete, the solvent is removed by direct distillation to obtain the DA addition product (compound 3). The organic solvents include, but are not limited to, toluene, benzene, (o-, m-, para-)toluene, mesitylene, o-trimethylbenzene, pseudotrimethylbenzene, chlorobenzene, (o-, m-, para-)dichlorobenzene, alkanes with 5-10 carbon atoms, ethers with 4-16 carbon atoms, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, alcohols with 1-10 carbon atoms, acetone, butanone, DMF, DME, DMSO, NMP, or mixtures of two or more thereof. The catalysts include, but are not limited to, sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, polyphosphoric acid, AlCl3, anhydrous ZnCl2, anhydrous FeCl3, tin tetrachloride, yttrium trifluorosulfonate, scandium trifluorosulfonate, copper sulfate, copper trifluorosulfonate, boron trifluoride diethyl ether complex, and titanium tetrachloride, or mixtures of two or more thereof. The reaction time is 0.5-48 hours. The reaction temperature is from room temperature to the solvent boiling point. The molar ratio of 2-methylfuran to maleic anhydride is 100:1 to 1:1. The molar ratio of 2-methylfuran to the catalyst is 100:1 to 1:1.

[0016] Step 2: Compound 3 is reacted with organic solvent 1 under the catalysis of a catalyst. After the reaction is complete, the reaction solution is poured into water and extracted with organic solvent 2. The organic layer is dried, and the mixed organic solvent is removed under reduced pressure to obtain compound 4.

[0017] The organic solvent 1 and organic solvent 2 may be the same or different, including but not limited to toluene, benzene, (o-, m-, para)toluene, mesitylene, o-trimethylbenzene, pseudotrimethylbenzene, chlorobenzene, (o-, m-, para)dichlorobenzene, alkanes with 5-10 carbons, ethers with 4-16 carbons, dichloromethane, trichloromethane, carbon tetrachloride / 1,2-dichloroethane, 1,1-dichloroethane, alcohols with 1-10 carbons, acetone, butanone (DMF), DME, DMSO, NMP, or mixtures of two or more thereof. The catalyst includes but is not limited to sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, phosphoric acid, AlCl3, anhydrous ZnCl2, anhydrous FeCl3, tin tetrachloride, yttrium trifluorosulfonate, scandium trifluorosulfonate, copper sulfate, copper trifluorosulfonate, boron trifluoride diethyl ether complex, and titanium tetrachloride, or mixtures of two or more thereof. The reaction time is 0.5-48 hours. The reaction temperature ranges from room temperature to the solvent boiling point. The molar ratio of 2-methylfuran to catalyst is 100:1 to 1:1.

[0018] Step 3: Compound 3 is directly heated with ammonium salt in an organic solvent or directly heated with an aqueous ammonia solution to obtain compound 4.

[0019] The ammonium salt includes, but is not limited to, ammonium chloride, ammonium sulfate, ammonium bisulfate, ammonium acetate, ammonium monohydrogen phosphate, ammonium dihydrogen phosphate, ammonium phosphate, or one or more mixtures thereof. The organic solvent is an ether solvent with 4-16 carbon atoms, an alcohol with 1-10 carbon atoms, acetone, butanone, DMF, DME, DMSO, NMP, or a mixture of two or more thereof. The molar ratio of compound 3 to the ammonium salt or ammonia is 1:1 to 1:20. The reaction time is 0.5-48 hours. The reaction temperature is from room temperature to the solvent boiling point, and the pressure is 1-50 standard atmospheres.

[0020] Step 4: React compound 1 with an aqueous solution of an oxidizing agent to obtain intermediate 2-amino-3-methylbenzoic acid (compound 2).

[0021] The oxidant is either sodium hypochlorite solution (mass fraction 8%~15%) or sodium hypobromite (prepared on-site from bromine and NaOH solution). The reaction time is 0.5~48 hours. The reaction temperature is 0~80℃. The molar ratio of compound 1 to sodium hypochlorite is 1:1~1:50, and the molar ratio of compound 1 to sodium hypobromite is 1:1~1:10.

[0022] This invention uses the inexpensive bio-based platform compound methylfuran as a starting material, and obtains the intermediate 2-amino-3-methylbenzoic acid through a -DA reaction, aromatization, and Hoffmann elimination reaction. The entire process does not require hazardous nitration or hydrogenation processes. The process features mild reaction conditions, good operability, low wastewater generation, and a high yield of the intermediate, making it highly suitable for the industrial production of the highly effective insecticides chlorantraniliprole and bromocyanamide.

[0023] Compared with the prior art, the present invention has the following advantages and beneficial effects: 1. The entire process does not require nitration or hydrogenation, ensuring good safety and low equipment investment costs.

[0024] 2. High product yield, high atom utilization rate, less waste, and low cost.

[0025] 3. The required raw materials and reagents are readily available and inexpensive. In particular, 2-methylfuran, maleimide, and maleic anhydride can all be prepared from furfural, a bio-based platform molecule, which has low-carbon advantages and is in line with the national "dual carbon" strategy. Attached Figure Description

[0026] Figure 1 This is a route diagram for the preparation of 2-amino-3-methylbenzoic acid according to the present invention.

[0027] Figure 2 The image shows the 1H NMR spectrum of the addition product of 2-methylfuran and maleimide in this invention.

[0028] Figure 3 This is the 1H NMR spectrum of compound 1 of the present invention.

[0029] Figure 4 This is the 1H NMR spectrum of compound 2 of the present invention. Detailed Implementation

[0030] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto. It should be noted that any processes not specifically described in detail below are those that can be implemented or understood by those skilled in the art by referring to existing technology. Reagents or instruments whose manufacturers are not specified are considered to be conventional products that can be purchased commercially.

[0031] Figure 1 This is a route diagram for the preparation of 2-amino-3-methylbenzoic acid according to the present invention.

[0032] The following Examples 1-6 describe the synthesis of 2-amino-3-methylbenzoic acid, an intermediate in the synthesis of chlorantraniliprole and broflanilide, according to Route 1: Example 1 Step 1: Maleimide (9.7 g, 0.1 mol), 2-methylfuran (16.4 g, 0.2 mol), and toluene (150 mL) were added sequentially to a 500 mL three-necked flask. The mixture was then reacted at 50 °C for 12 hours until the maleimide starting material was completely eliminated. Excess solvent toluene and the 2-methylfuran starting material were removed under reduced pressure to obtain 16.0 g of the DA addition product (yield 89%). The 1H NMR spectrum of this DA addition product is shown below. Figure 2 As shown.

[0033] Step 2: Dissolve 16.0 g of the DA addition product in 200 mL of chlorobenzene solution, then add methanesulfonic acid (960 mg), and react at 80 °C for 10 hours. After cooling the reaction solution to room temperature, pour it into water, filter the resulting solid, and dry it to obtain compound 1 (12.5 g, yield 86%). The 1H NMR spectrum of compound 1 is shown below. Figure 3 As shown.

[0034] Step 3: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, dissolve, and then add compound 2 (9.1 g) in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (7 g, yield 82%). The 1H NMR spectrum of compound 2 is shown below. Figure 4 As shown.

[0035] Example 2 Step 1: Maleimide (9.7 g, 0.1 mol) and 2-methylfuran (100 mL) were added sequentially to a 500 mL three-necked flask and reacted at 50 °C for 10 hours until the starting maleimide was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain the DA addition product (16.5 g, 92%).

[0036] Step 2: Dissolve 10 g of the DA addition product in 200 mL of chlorobenzene solution, then add methanesulfonic acid (500 mg), and react at 80 °C for 7 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it under vacuum to obtain compound 1 (8 g, yield 89%).

[0037] Step 3: In a 500 mL Erlenmeyer flask, add 95 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, dissolve, and then add compound 1 (8 g) in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (6.9 g, yield 92%).

[0038] Example 3 Step 1: Maleimide (9.7 g, 0.1 mol) and 2-methylfuran (100 mL) were added sequentially to a 500 mL three-necked flask and reacted at 50 °C for 10 hours until the starting maleimide was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain the DA addition product (17.5 g, 98%).

[0039] Step 2: Dissolve 8.25 g of the DA addition product in 200 mL of chlorobenzene solution, then add p-toluenesulfonic acid (1.72 g), and react at 80 °C for 10 hours. After cooling the reaction solution to room temperature, pour it into water, filter the resulting solid, and dry it under vacuum to obtain compound 1 (6.4 g, yield 86%).

[0040] Step 3: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, and after dissolving, add compound 1 (10.4 g) in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (8.2 g, yield 84%).

[0041] Example 4 Step 1: Maleimide (9.7 g, 0.1 mol), 2-methylfuran (16.4 g, 0.2 mol), and p-xylene (150 mL) were added sequentially to a 500 mL three-necked flask. The mixture was then reacted at 50 °C for 12 hours until the maleimide starting material was completely eliminated. Excess solvent toluene and the 2-methylfuran starting material were removed under reduced pressure to obtain 16.4 g of the DA addition product (92% yield).

[0042] Step 2: Dissolve the above DA addition product (8.4 g) in 200 mL of chlorobenzene solution, then add trifluoromethanesulfonic acid (1.49 g), and react at 80 °C for 16 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it under vacuum to obtain compound 1 (6.35 g, yield 84%).

[0043] Step 3: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, dissolve, and then add compound 1 (12.4 g) obtained in Step 2 in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (9.1 g, yield 78%).

[0044] Example 5 Step 1: Maleimide (9.7 g, 0.1 mol) and 2-methylfuran (100 mL) were added sequentially to a 500 mL three-necked flask and reacted at 40 °C for 10 hours until the starting maleimide was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain the DA addition product (17.9 g, 100%).

[0045] Step 2: Dissolve 10 g of the above DA addition product in 200 mL of chlorobenzene solution, then add concentrated sulfuric acid (98% by mass, 10 mL), and react at 50 °C for 14 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it to obtain compound 1 (8.4 g, yield 93%).

[0046] Step 3: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypobromite solution (10% by mass, prepared on-site from bromine and sodium hydroxide solution), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, and after dissolving, add compound 1 (12.4 g) obtained in Step 2 in 6 batches at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (8.8 g, yield 76%).

[0047] Example 6 Step 1: Maleimide (9.7 g, 0.1 mol) and 2-methylfuran (100 mL) were added sequentially to a 500 mL three-necked flask and reacted at 55 °C for 10 hours until the starting maleimide was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain the DA addition product (17.0 g, 95%).

[0048] Step 2: Dissolve 14 g of the above DA addition product in 200 mL of chlorobenzene solution, then add 5 mL of boron trifluoride diethyl ether, and react at 40 °C for 12 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it under vacuum to obtain compound 1 (11.7 g, yield 93%).

[0049] Step 3: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, and after dissolving, add compound 1 (11.7 g) obtained in Step 2 in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and dry to obtain the target compound (9.9 g, yield 90%).

[0050] The following Examples 7-9, which synthesize the intermediate 2-amino-3-methylbenzoic acid for chlorantraniliprole and broflanilide, are synthesized according to Route 2: Example 7 Step 1: Maleic anhydride (9.8 g, 0.1 mol) and 2-methylfuran (24.6 g, 0.3 mol) were added sequentially to a 500 mL three-necked flask and reacted at 50 °C for 10 hours until the maleic anhydride was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain 16.8 g of the DA addition product (yield 93%).

[0051] Step 2: Dissolve 15 g of the above DA addition product in 200 mL of chlorobenzene solution, then add 5 mL of boron trifluoride diethyl ether, and react at 40 °C for 12 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it to obtain compound 1 (12.4 g, yield 93%).

[0052] Step 3: Dissolve the crude product 12.4 in 200 mL of ammonia water and heat at 80°C for 24 hours under 5 atmospheres. Cool the reaction solution, pour it into an ice-water bath, filter under reduced pressure to obtain a solid, and dry the solid to obtain compound 1 (11.9 g, yield 96%).

[0053] Step 4: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, and after dissolving, add compound 1 (12.4 g) obtained in Step 3 in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (9.5 g, yield 82%).

[0054] Example 8 Step 1: Maleic anhydride (9.8 g), 2-methylfuran (16.4 g), and 100 mL of ethyl acetate were added sequentially to a 500 mL three-necked flask. The mixture was reacted at 50 °C for 10 hours until the maleic anhydride was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain 15.9 g of the DA addition product (yield 88%).

[0055] Step 2: Dissolve 15 g of the above DA addition product in 200 mL of chlorobenzene solution, then add copper trifluoromethanesulfonate (2.4 g), and react at 40 °C for 12 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it under vacuum to obtain compound 1 (11.5 g, yield 85%).

[0056] Step 3: Dissolve 11.5 g of the crude product in 200 mL of ammonia water and heat at 80 °C for 24 hours under 5 atm. Cool the reaction solution, pour it into an ice-water bath, filter under reduced pressure to obtain a solid, and dry the solid to obtain compound 1 (11.0 g, yield 96%).

[0057] Step 4: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypobromite solution (10% by mass, prepared on-site from bromine and sodium hydroxide solution), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, and after dissolving, add compound 1 (11.0 g) obtained in Step 3 in 6 batches at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (9.8 g, yield 95%).

[0058] Example 9 Step 1: Maleic anhydride (9.8 g), 2-methylfuran (16.4 g), and THF (100 mL) were added sequentially to a 500 mL three-necked flask and reacted at 50 °C for 10 hours until the maleic anhydride was completely eliminated. Excess 2-methylfuran was removed under reduced pressure to obtain 16.6 g of the DA addition product (yield 92%).

[0059] Step 2: Dissolve 16.6 g of the above DA addition product in 200 mL of dichloromethane solution, then add 2 mL of TiCl4 in dichloromethane solution (1 M), and react at 0 °C for 2 hours. After cooling the reaction solution to room temperature, pour it into water, filter the obtained solid, and dry it under vacuum to obtain compound 1 (12.6 g, yield 85%).

[0060] Step 3: Dissolve 12.6 g of the crude product and 15 g of ammonium acetate in 200 mL of acetonitrile, heat at 80 °C for 24 hours under 5 atm pressure. Cool the reaction solution, pour it into an ice-water bath, filter under reduced pressure to obtain a solid, and dry the solid to obtain compound 1 (10.5 g, yield 83%).

[0061] Step 4: In a 500 mL Erlenmeyer flask, add 100 g of sodium hypochlorite solution (10% by mass), cool to 0°C in an ice-water bath, add 10 mL of 30% sodium hydroxide solution, dissolve, and then add compound 1 (10.5 g) obtained in Step 3 in 6 portions at room temperature while stirring. Then heat to 80°C and maintain for 30 min. Cool to room temperature, add 100 mL of saturated sodium bisulfite solution, stir, cool, and filter. Acidify the filtrate with concentrated hydrochloric acid to neutralize, filter, wash the solid with cold water, and air dry to obtain the target compound (8.7 g, yield 88%).

[0062] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. An intermediate for the synthesis of chlorantraniliprole and bromocyanamide, characterized in that, The structural formula of the intermediate is: Its name is 2-amino-3-methylbenzoic acid.

2. The method for preparing the intermediate for synthesizing chlorantraniliprole and bromocyanamide according to claim 1, characterized in that, The synthetic route can be selected from any of the following: Route 1: Route 2: 。 3. The preparation method according to claim 2, characterized in that, Route 1 includes the following steps: Step 1: 2-Methylfuran and maleimide react directly in an organic solvent under heating or catalysis to give the DA addition product; Step 2: Dissolve the DA addition product in organic solvent 1 and react under the catalysis of the catalyst. Pour the reaction solution into water, extract with organic solvent 2, combine and dry the organic layers, and remove the mixed organic solvent under reduced pressure to obtain compound 1. Step 3: Compound 1 reacts with an aqueous solution of an oxidizing agent to obtain intermediate 2-amino-3-methylbenzoic acid.

4. The preparation method according to claim 2, characterized in that, Route 2 includes the following steps: Step 1: 2-Methylfuran and maleic anhydride react in an organic solvent by direct heating or under the catalysis of a catalyst to obtain compound 3; Step 2: Dissolve compound 3 in organic solvent 1 and react under the catalysis of the catalyst. Pour the reaction solution into water and extract with organic solvent 2. Combine the dried organic layers and remove the mixed organic solvent under reduced pressure to obtain compound 4. Step 3: Heat compound 4 directly with ammonium salt in an organic solvent, or heat directly with an aqueous ammonia solution to obtain compound 1; Step 4: React compound 1 with an aqueous solution of an oxidizing agent to obtain intermediate 2-amino-3-methylbenzoic acid.

5. The preparation method according to claim 2, characterized in that, In step one of routes one and two, The organic solvents include toluene, benzene, (o-, m-, para)toluene, mesitylene, o-trimethylbenzene, pseudotrimethylbenzene, chlorobenzene, (o-, m-, para)dichlorobenzene, alkanes with 5-10 carbons, ether solvents with 4-16 carbons, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, alcohols with 1-10 carbons, acetone, butanone, DMF, DME, DMSO, NMP, or mixtures of two or more thereof; The catalyst comprises two or more of the following: sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, polyphosphoric acid, AlCl3, anhydrous ZnCl2, anhydrous FeCl3, tin tetrachloride, yttrium trifluorosulfonate, scandium trifluorosulfonate, copper sulfate, copper trifluorosulfonate, boron trifluoride diethyl ether complex, and titanium tetrachloride. The reaction time is 0.5 to 48 hours, and the reaction temperature is from room temperature to the solvent boiling point. The molar ratio of 2-methylfuran to maleimide or maleic anhydride is 100:1 to 1:1; the molar ratio of 2-methylfuran to catalyst is 100:1 to 1:

1.

6. The preparation method according to claim 2, characterized in that, In step two of both route one and route two, The organic solvent 1 and organic solvent 2 may be the same or different, including toluene, benzene, (o-, m-, para)toluene, mesitylene, o-trimethylbenzene, pseudotrimethylbenzene, chlorobenzene, (o-, m-, para)dichlorobenzene, alkanes with 5 to 10 carbons, ether solvents with 4 to 16 carbons, dichloromethane, trichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane, alcohols with 1 to 10 carbons, acetone, butanone, DMF, DME, DMSO, NMP, or mixtures of two or more of them; The catalyst comprises two or more of the following: sulfuric acid, p-toluenesulfonic acid, camphorsulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, phosphoric acid, AlCl3, anhydrous ZnCl2, anhydrous FeCl3, tin tetrachloride, yttrium trifluorosulfonate, scandium trifluorosulfonate, copper sulfate, copper trifluorosulfonate, boron trifluoride diethyl ether complex, and titanium tetrachloride. The reaction time is 0.5 to 48 hours, and the reaction temperature is from room temperature to the solvent boiling point. The molar ratio of 2-methylfuran to the catalyst is 100:1 to 2:

1.

7. The preparation method according to claim 2, characterized in that, In step three of route one, The oxidant is one of sodium hypochlorite solution and sodium hypobromite; The molar ratio of compound 1 to sodium hypochlorite is 1:1 to 1:50, and the molar ratio of compound 1 to sodium hypobromite is 1:1 to 1:

10. The reaction time is 0.5 to 48 hours, and the reaction temperature is 0 to 80℃.

8. The preparation method according to claim 2, characterized in that, In step three of route two, The ammonium salt includes ammonium chloride, ammonium sulfate, ammonium bisulfate, ammonium acetate, ammonium monohydrogen phosphate, ammonium dihydrogen phosphate, ammonium phosphate, or one or more mixtures thereof; The organic solvent is an ether solvent with 4 to 16 carbons, an alcohol with 1 to 10 carbons, acetone, butanone, DMF, DME, DMSO, NMP, or a mixture of two or more thereof; The molar ratio of compound 3 to ammonium salt or ammonia water is 1:1 to 1:20; The reaction time is 0.5 to 48 hours, the reaction temperature is from room temperature to the solvent boiling point, and the pressure is 1 to 50 standard atmospheres.

9. The preparation method according to claim 2, characterized in that, In step three of route two, The oxidant is one of sodium hypochlorite solution and sodium hypobromite; The molar ratio of compound 1 to sodium hypochlorite is 1:1 to 1:50, and the molar ratio of compound 1 to sodium hypobromite is 1:1 to 1:

10. The reaction time is 0.5 to 48 hours, and the reaction temperature is 0 to 80℃.

10. The use of the intermediate described in claim 1 as a raw material in the synthesis of chlorantraniliprole and bromocyanamide.

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