A method for synthesizing pyriclor

Abstract

The application discloses a kind of synthesis methods of cyclofoprim, comprising the following steps: in organic solvent, 2-mercapto-4, 6-dimethoxy pyrimidine, 3-methyl-7-nitrophthalide, CuI, basic substance is added, vacuum nitrogen replacement is stirred after multiple times and heated to 100~110 DEG C and is reacted for 4~8h;Liquid chromatography tracks detection 3-methyl-7-nitrophthalide content is less than or equal to 0.2% to reaction completion, water is added to reactor and stirred after standing and is layered.Wherein, part of solvent is concentrated under reduced pressure after organic layer, and then cooled to 10~30 DEG C crystallization, suction filtration, with 10~20 DEG C's toluene rinsing filter cake, and filter cake is obtained by vacuum drying to obtain cyclofoprim.Compared with existing route, the application provides a new process with short synthesis route, safe process, green and environmental protection;Shorten the reaction step, improve production efficiency, reduce energy consumption and environmental pollution.

Description

Technical Field

[0001] This invention relates to the field of pesticide synthesis technology, specifically to a method for synthesizing cyclopropargyl ether. Background Technology

[0002] Pyriftalid is a pyrimidine salicylic acid herbicide for paddy fields developed by Syngenta, Switzerland. Its common name is Pyriftalid, and its IUPAC chemical name is (RS)-7-(4,6-dimethoxypyrimidin-2-ylthio)-3-methyl-2-benzofuran-1(3H)-one. Its molecular formula is C2. 15 H 14 N2O4S. Cyclopyralid is characterized by high efficiency, low toxicity, short retention time in soil, and safety for non-target plants and humans. Launched in 2002, it has received a positive market response and sales have increased annually, indicating broad application and market prospects.

[0003] Currently disclosed synthesis techniques for cyclopropane all involve the reaction of 3-methyl-7-mercaptophthalene with 4,6-dimethoxy-2-methanesulfonylpyrimidine to obtain cyclopropane.

[0004] The synthesis of 4,6-dimethoxy-2-methanesulfonylpyrimidine requires 4,6-dihydroxy-2-mercaptopyrimidine as a starting material and involves a four-step reaction. Specifically, 4,6-dihydroxy-2-mercaptopyrimidine (A) is thiol-methylated to obtain (B), then chlorinated to obtain (C), then methoxylated to obtain (D), and finally oxidized to obtain 4,6-dimethoxy-2-methanesulfonylpyrimidine (E). The synthetic route is as follows: Figure 1 As shown.

[0005] Among them, 3-methyl-7-mercaptophthalamide requires 3-methyl-7-nitrophthalamide as a raw material and is completed through a 3-step reaction. Specifically, 3-methyl-7-nitrophthalamide (1) is catalytically hydrogenated under high temperature and high pressure to obtain 3-methyl-7-aminophthalamide (2); compound (2) is subjected to a diazotization reaction to obtain the corresponding diazonium salt (3), and the diazonium salt is then reacted with potassium xanthate to obtain 3-methyl-7-mercaptophthalamide (4).

[0006] Finally, 3-methyl-7-mercaptophthalamide (4) reacts with 4,6-dimethoxy-2-methanesulfonylpyrimidine (E) to give cyclomethoxyphen ... Figure 2 As shown.

[0007] The existing synthesis process for cyclopyrazol requires 3-methyl-7-mercaptophthalamide and 4,6-dimethoxy-2-methanesulfonylpyrimidine as raw materials, involving eight steps and dangerous high-temperature, high-pressure reactions such as hydrogenation, diazotization, and chlorination. This process is cumbersome and generates a large amount of waste. There is an urgent need to address the problems of the existing process and develop a new, safe, and environmentally friendly one. Summary of the Invention

[0008] In view of this, the purpose of the present invention is to provide a method for synthesizing cyclopropionyl ether, thereby solving one or more of the above-mentioned problems in the prior art.

[0009] To achieve the above objectives, the present invention provides a method for synthesizing cyclopropionyl ether, comprising the following steps:

[0010] In an organic solvent, add 2-mercapto-4,6-dimethoxypyrimidine, 3-methyl-7-nitrophthalide, CuI, and an alkaline substance. After purging with nitrogen gas multiple times, stir and heat to 100-110℃ and react for 4-8 hours.

[0011] Liquid chromatography was used to monitor the 3-methyl-7-nitrophthalide content to ≤0.2% until the reaction was complete. Water was added to the reactor and stirred, and the mixture was allowed to stand and separate into layers. The organic layer was concentrated under reduced pressure to remove part of the solvent, then cooled to 10-30°C for crystallization, filtered, and the filter cake was washed with toluene at 10-20°C. The filter cake was then dried under vacuum to obtain the cyclopropane.

[0012] The above methods satisfy one or more of the following:

[0013] 1) The organic solvent is selected from any one or a combination of at least two of toluene, xylene, DMF, tetrahydrofuran, and 2-methyltetrahydrofuran;

[0014] 2) The alkaline substance is selected from any one of the following: potassium carbonate, sodium hydroxide, sodium bicarbonate, sodium carbonate, sodium ethoxide, sodium methoxide, and potassium hydroxide, which are inorganic bases or organic bases such as DBU, DMAP, and LDA.

[0015] 3) The molar ratio of 3-methyl-7-nitrophthalide to 2-mercapto-4,6-dimethoxypyrimidine is 1:2 to 3:2, the molar ratio of 3-methyl-7-nitrophthalide to CuI is 70:1 to 120:1, and the molar ratio of 3-methyl-7-nitrophthalide to the alkaline substance is 1:2 to 1:1.

[0016] In some embodiments, the 2-mercapto-4,6-dimethoxypyrimidine is obtained by reacting 1,2-bis(4,6-dimethoxypyrimidine) disulfide with a reducing agent;

[0017] The reducing agent is selected from any one of triphenylphosphine, sodium borohydride, potassium borohydride, lithium aluminum hydride, sodium dithionite, and sulfur dioxide.

[0018] In some embodiments, the reaction can be carried out in a one-pot process, in the presence of CuI and an alkaline substance and a reducing agent, 1,2-bis(4,6-dimethoxypyrimidine) disulfide reacts to give 2-mercapto-4,6-dimethoxypyrimidine, which then reacts with 3-methyl-7-nitrophthalide to give cyclomethoxypyrimidine.

[0019] In some embodiments, the 2-mercapto-4,6-dimethoxypyrimidine is prepared by the following steps:

[0020] In a reactor, 1,2-bis(4,6-dimethoxypyrimidine)disulfide, triphenylphosphine, tetrahydrofuran, and water are added, wherein the molar ratio of 1,2-bis(4,6-dimethoxypyrimidine)disulfide to triphenylphosphine is 1:2 to 1:1, the solid-liquid ratio of 1,2-bis(4,6-dimethoxypyrimidine)disulfide to tetrahydrofuran is 150-200 g / L, and the volume ratio of tetrahydrofuran to water is 10:1. After purging with nitrogen gas multiple times, the mixture is stirred and heated to 55-65°C for 2-4 hours.

[0021] Liquid chromatography was used to monitor the content of 1,2-bis(4,6-dimethoxypyrimidine) disulfide ≤0.2% until the reaction was complete. After most of the tetrahydrofuran was distilled off under reduced pressure at 45-55℃, toluene and water were added, stirred, and allowed to stand for separation.

[0022] The organic layer is concentrated and cooled to 20°C for crystallization. The filter cake is then washed with toluene at 10-20°C and the filter cake is dried under vacuum to obtain the 2-mercapto-4,6-dimethoxypyrimidine.

[0023] In some embodiments, the 2-mercapto-4,6-dimethoxypyrimidine is prepared by the following steps:

[0024] In a reactor, 1,2-bis(4,6-dimethoxypyrimidine) disulfide and tetrahydrofuran are added and stirred until dissolved. The solid-liquid ratio of 1,2-bis(4,6-dimethoxypyrimidine) disulfide to tetrahydrofuran is 150-200 g / L. The reactor is evacuated and purged with nitrogen multiple times. The temperature is controlled at 20-30°C. Sodium borohydride is added in batches over 1-2 hours. The molar ratio of 1,2-bis(4,6-dimethoxypyrimidine) disulfide to sodium borohydride is 1:2 to 1:1. After the addition is complete, the reactor is stirred and reacted for 2-6 hours.

[0025] Liquid chromatography was used to monitor the content of 1,2-bis(4,6-dimethoxypyrimidine) disulfide ≤0.2% until the reaction was complete. After most of the tetrahydrofuran was distilled off under reduced pressure, 300 mL of water was added, the pH was adjusted to 3-5 with hydrochloric acid, and then toluene was added and stirred before standing to separate the layers.

[0026] The organic layer is concentrated and cooled to 20°C for crystallization. The filter cake is then washed with toluene at 10-20°C and the filter cake is dried under vacuum to obtain the 2-mercapto-4,6-dimethoxypyrimidine.

[0027] In some embodiments, the 1,2-bis(4,6-dimethoxypyrimidine) disulfide is obtained by reacting 1,2-bis(4,6-dihydroxypyrimidine) disulfide with a methylating agent;

[0028] The methylating agent is selected from any one of dimethyl sulfate, iodomethane, bromomethane, and methyl trifluoromethanesulfonate.

[0029] In some embodiments, the 1,2-bis(4,6-dimethoxypyrimidine) disulfide is prepared by the following steps:

[0030] In a reactor, 1,2-bis(4,6-dihydroxypyrimidine) disulfide and toluene are added and stirred to dissolve. The solid-liquid ratio of the 1,2-bis(4,6-dihydroxypyrimidine) disulfide to the toluene is 100-150 g / L. Then, light K2CO3 is added. The ratio of the 1,2-bis(4,6-dihydroxypyrimidine) disulfide to K2CO3 is 1:10-1:5. Iodomethane is added dropwise to the above reaction system over 2-3 hours at a controlled temperature of 10-20°C. The molar ratio of the 1,2-bis(4,6-dihydroxypyrimidine) disulfide to iodomethane is 1:5-1:4.

[0031] Liquid chromatography was used to monitor the content of 1,2-bis(4,6-dihydroxypyrimidine) disulfide until the reaction was complete, with a concentration ≤0.2%.

[0032] The organic layer is washed and separated by water in the reactor. After concentration, the organic layer is cooled to 10-30°C for crystallization, filtered, and the filter cake is washed with toluene at 10-20°C. The filter cake is then dried under vacuum to obtain the 1,2-bis(4,6-dimethoxypyrimidine) disulfide.

[0033] In some embodiments, the 1,2-bis(4,6-dihydroxypyrimidine) disulfide is obtained by reacting sodium 4,6-dihydroxypyrimidine-2-thiol with an oxidant under acidic conditions. Further, sodium 4,6-dihydroxypyrimidine-2-thiol can be reacted under acidic conditions to generate 4,6-dihydroxypyrimidine-2-thiol, and 4,6-dihydroxypyrimidine-2-thiol can be reacted with oxygen under the action of a catalyst to obtain 1,2-bis(4,6-dihydroxypyrimidine) disulfide.

[0034] The catalyst is selected from any one or more of ferric ammonium sulfate dodecahydrate and ferrous chloride.

[0035] In some embodiments, the molar ratio of the sodium 4,6-dihydroxypyrimidine-2-thiolate to the catalyst is 50:1 to 100:1.

[0036] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0037] It provides a new process with a short synthesis route, safe process, and green environmental protection; it shortens the reaction steps, improves production efficiency, and reduces energy consumption and environmental pollution. Attached Figure Description

[0038] Figure 1 The above describes the synthetic route for 4,6-dimethoxy-2-methanesulfonylpyrimidine in the background art of this invention;

[0039] Figure 2 The background of this invention describes the synthetic route of cyclopropionyl ether.

[0040] Figure 3 This is a synthetic route for cyclopropionyl ether in one embodiment of the present invention;

[0041] Figure 4 This is an HNMR spectrum of cyclopropane in one embodiment of the present invention;

[0042] Figure 5 This is an HPLC spectrum of cyclopropane in one embodiment of the present invention; Detailed Implementation

[0043] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0044] Example 1: Using 2-mercapto-4,6-dimethoxypyrimidine as a raw material

[0045] In a 2000 mL reaction flask, 100.0 g (512.5 mmol) of 3-methyl-7-nitrophthalide solid, 93.6 g (538.2 mmol) of 2-mercapto-4,6-dimethoxypyrimidine solid, 1.0 g (5.2 mmol) of CuI powder, 89.0 g (640.7 mmol) of light K2CO3, and 1000 mL of toluene were added sequentially. After purging with nitrogen three times, the mixture was stirred and heated to 100–110 °C for 6 h. The 3-methyl-7-nitrophthalide content was monitored by liquid chromatography until the reaction was complete. 600 mL of water was added to the reaction flask and stirred for 30 minutes. After standing and separating the layers, the organic layer was concentrated under reduced pressure to remove part of the solvent. The mixture was then cooled to 20 °C to crystallize, filtered, and the filter cake was washed with 100 mL of toluene at 10–20 °C. The filter cake was then vacuum dried at 65 °C to obtain 152.0 g of pale yellow crystalline powder with an HPLC purity of 99.5% and a yield of 92.7%.

[0046] Example 2: Using 1,2-bis(4,6-dimethoxypyrimidine) disulfide as raw material

[0047] In a 1000 mL reaction flask, 100.0 g (289.2 mmol) of 1,2-bis(4,6-dimethoxypyrimidine) disulfide, 83.8 g (318.1 mmol) of triphenylphosphine, 600 mL of tetrahydrofuran, and 60 mL of water were added sequentially. After purging with nitrogen three times, the mixture was stirred and heated to 55–65 °C for 3 h. Liquid chromatography was used to monitor the reaction until the 1,2-bis(4,6-dimethoxypyrimidine) disulfide content was ≤0.2%. Once the reaction was complete, the reaction solution was transferred to a 2000 mL reaction flask. Most of the tetrahydrofuran was distilled off under reduced pressure at 45–55 °C. Then, 1000 mL of toluene and 300 mL of water were added, and the mixture was stirred for 30 minutes before being allowed to stand and separate into layers.

[0048] The organic layer was transferred to a 2000L reaction flask, and 118.5g (607.2mmol) of 3-methyl-7-nitrophthalide, 1.1g (5.78mmol) of CuI powder, and 100.4g (722.9mmol) of light K2CO3 were added. After purging with nitrogen three times, the mixture was stirred and heated to 100-110℃ for 6 hours. Liquid chromatography was used to monitor the reaction until the 3-methyl-7-nitrophthalide content was ≤0.5%. Once the reaction was complete, 600mL of water was added to the reaction flask, and the mixture was stirred for 30 minutes. After standing and separating the layers, the organic layer was concentrated under reduced pressure to remove some solvent, cooled to 20℃ for crystallization, filtered, and the filter cake was washed with 100mL of toluene at 10-20℃. The filter cake was then vacuum dried at 65℃ to obtain 165.0g of pale yellow crystalline powder with an HPLC purity of 99.2% and an overall yield of 88.9% based on 1,2-bis(4,6-dimethoxypyrimidine) disulfide.

[0049] Example 3: Using 1,2-bis(4,6-dihydroxypyrimidine) disulfide as raw material

[0050] In a 2000L reaction flask, 100g (345.8mmol) of 1,2-bis(4,6-dihydroxypyrimidine) disulfide and 1000mL of toluene were added and stirred until dissolved. Then, 250g (1.79mol) of light K₂CO₃ was added. 236.8g (1.66mol) of iodomethane was added dropwise to the reaction system over 2–3 hours at a controlled temperature of 10–20℃. Liquid chromatography was used to monitor the 1,2-bis(4,6-dihydroxypyrimidine) disulfide content until the reaction was complete, ensuring it was ≤0.2%. The reaction flask was washed with water to separate the layers. The organic layer was concentrated, cooled to 20℃ for crystallization, filtered, washed with toluene, and the filter cake was dried under vacuum at 50℃ to obtain 225.0g of 1,2-bis(4,6-dimethoxypyrimidine) disulfide, a pale yellow solid with an HPLC purity of 99.0% and a yield of 94.0%.

[0051] In a 1000 mL reaction flask, 100.0 g (289.2 mmol) of 1,2-bis(4,6-dimethoxypyrimidine) disulfide and 600 mL of tetrahydrofuran were added and stirred to dissolve. The mixture was purged with nitrogen three times under vacuum and the temperature was controlled at 20–30 °C for 1–2 hours. 22.3 g (578.3 mmol) of sodium borohydride was added in portions, and the reaction was continued with stirring for 4 hours after the addition was complete. Liquid chromatography was used to monitor the 1,2-bis(4,6-dimethoxypyrimidine) disulfide content until it was ≤0.2% until the reaction was complete. After most of the tetrahydrofuran was distilled off under reduced pressure, 300 mL of water was added, and the pH was adjusted to 3–5 with hydrochloric acid. Then, 1000 mL of toluene was added, and the mixture was stirred for 30 minutes before allowing it to stand and separate into layers. After the organic layer was concentrated, it was cooled to 20°C for crystallization, filtered, washed with toluene, and the filter cake was dried under vacuum at 50°C to obtain 88.2 g of 2-mercapto-4,6-dimethoxypyrimidine with an HPLC purity of 99.5% and a yield of 88.1%.

[0052] In a 2000 mL reaction flask, 75.0 g (384.4 mmol) of 3-methyl-7-nitrophthalide solid, 70.0 g (403.6 mmol) of 2-mercapto-4,6-dimethoxypyrimidine solid, 1.0 g (5.2 mmol) of CuI powder, 66.7 g (480.5 mmol) of light K₂CO₃, and 800 mL of toluene were added sequentially. After purging with nitrogen three times under vacuum, the mixture was stirred and heated to 100–110 °C for 6 h. Liquid chromatography was used to monitor the reaction until the 3-methyl-7-nitrophthalide content was ≤0.2%. Once the reaction was complete, 500 mL of water was added to the reaction flask, and the mixture was stirred for 30 minutes. After standing and separating the layers, the organic layer was concentrated under reduced pressure to remove some solvent, cooled to 20 °C for crystallization, filtered, and the filter cake was washed with toluene. The filter cake was then dried under vacuum at 50–60 °C to obtain 114.3 g of pale yellow crystalline powder with an HPLC purity of 99.4% and a yield of 92.8%. The overall yield was 76.8% based on 1,2-bis(4,6-dihydroxypyrimidine) disulfide.

[0053] Example 4: Using 4,6-dihydroxy-2-mercaptopyrimidine as a raw material

[0054] In a 1000 mL reaction flask, 100 g (686.8 mmol) of 4,6-dihydroxy-2-mercaptopyrimidine and 500 mL of methanol were added and stirred to dissolve. Then, 3.35 g (6.87 mmol) of ferric ammonium sulfate dodecahydrate was added to the system. The mixture was stirred and purged with oxygen at 20–30 °C for 6 h. Liquid chromatography was used to monitor the reaction until the 4,6-dihydroxy-2-mercaptopyrimidine content was ≤0.2% until the reaction was complete. The reaction solution was concentrated under reduced pressure at 45–55 °C until thick. 600 g of dichloroethane and 300 g of water were added, and the mixture was stirred to extract and separate the layers. The organic layer was concentrated, cooled to crystallize, filtered, and washed to obtain a pale yellow filter cake. The filter cake was dried under reduced pressure at 45–55 °C to obtain 182.0 g of pale yellow powdered 1,2-bis(4,6-dihydroxypyrimidine) disulfide, with an HPLC purity of 99.0% and a yield of 91.6%.

[0055] In a 2000L reaction flask, 100g (345.8mmol) of 1,2-bis(4,6-dihydroxypyrimidine) disulfide and 1000mL of toluene were added and stirred until dissolved. Then, 250g (1.79mol) of light K₂CO₃ was added. 236.8g (1.66mol) of iodomethane was added dropwise to the reaction system over 2–3 hours at a controlled temperature of 10–20℃. Liquid chromatography was used to monitor the 1,2-bis(4,6-dihydroxypyrimidine) disulfide content until the reaction was complete, ensuring it was ≤0.2%. The reaction flask was washed with water to separate the layers. The organic layer was concentrated, cooled to 20℃ for crystallization, filtered, washed with toluene, and the filter cake was dried under vacuum at 50℃ to obtain 225.0g of 1,2-bis(4,6-dimethoxypyrimidine) disulfide, a pale yellow solid with an HPLC purity of 99.0% and a yield of 94.0%.

[0056] In a 1000 mL reaction flask, 100.0 g (289.2 mmol) of 1,2-bis(4,6-dimethoxypyrimidine) disulfide and 600 mL of tetrahydrofuran were added and stirred to dissolve. The mixture was purged with nitrogen three times under vacuum and the temperature was controlled at 20–30 °C for 1–2 hours. 22.3 g (578.3 mmol) of sodium borohydride was added in portions, and the reaction was continued with stirring for 4 hours after the addition was complete. Liquid chromatography was used to monitor the 1,2-bis(4,6-dimethoxypyrimidine) disulfide content until it was ≤0.2% until the reaction was complete. After most of the tetrahydrofuran was distilled off under reduced pressure, 300 mL of water was added, and the pH was adjusted to 3–5 with hydrochloric acid. Then, 1000 mL of toluene was added, and the mixture was stirred for 30 minutes before allowing it to stand and separate into layers.

[0057] The organic layer was transferred to a 2000L reaction flask, and 118.5g (607.2mmol) of 3-methyl-7-nitrophthalide, 1.1g (5.78mmol) of CuI powder, and 100.4g (722.9mmol) of light K2CO3 were added. After purging with nitrogen three times, the mixture was stirred and heated to 100-110℃ and kept at that temperature for 6 hours. Liquid chromatography was used to monitor the reaction until the 3-methyl-7-nitrophthalide content was ≤0.5%. Once the reaction was complete, 600mL of water was added to the reaction flask, and the mixture was stirred for 30 minutes. After standing and separating the layers, the organic layer was concentrated, cooled to 20℃ for crystallization, filtered, and the filter cake was washed with 100mL of toluene at 10-20℃. The filter cake was then vacuum dried at 65℃ to obtain 168.0g of pale yellow crystalline powder with an HPLC purity of 99.5% and a total yield of 76.5% based on 4,6-dihydroxy-2-mercaptopyrimidine.

[0058] 1 HNMR(CDCl3;)δ:7.82(dxd,1H),7.67(t,1H),7.44(dxd,1H),5.73(s,1H),5.52(q,1H),3.72(s,6H),1.63(d,3H).

[0059] The specific synthetic route is as follows Figure 3 As shown.

[0060] in, Figure 4 The HNMR spectrum of cyclopropane; Figure 5 The HPLC spectrum of cyclopropane;

[0061] The liquid chromatography analysis method for cyclopropane is as follows:

[0062] 1. Instruments and chromatographic conditions

[0063] High-performance liquid chromatograph: Agilent 1260 / Shimadzu LC-20A;

[0064] Chromatographic column: 250mm×4.0mm (id) stainless steel column, packed with NUCLEOSIL C18 packing material with a particle size of 5μm.

[0065] Flow rate: 1.0 mL / min;

[0066] Column temperature: 25℃;

[0067] Detection wavelength: 240nm;

[0068] Injection volume: 5 μL;

[0069] Running time: 38 minutes.

[0070] Solvent: Acetonitrile / 5% phosphoric acid aqueous solution;

[0071] 2. Measurement Procedure

[0072] Standard solution: Weigh 50.0 mg of cyclohexane standard, place it in a 100 mL volumetric flask, add 90 mL of solvent and sonicate to dissolve, return to room temperature, dilute to the mark with solvent and shake well.

[0073] Sample solution: Weigh 50.0 mg of the sample to be tested, place it in a 100 mL volumetric flask, add 90 mL of solvent and sonicate to dissolve, restore to room temperature, dilute to the mark with solvent and shake well.

[0074] Under the above operating conditions, once the instrument is stable, inject one blank solution and three standard solutions. The RSD of the peak area of ​​the three main peaks should not exceed 2.0%. The measurements should be performed in the order of standard solution, sample solution, sample solution, and standard solution.

[0075] 3. Calculation

[0076] The content of cyclopropane is calculated using the following formula:

[0077]

[0078] In the formula:

[0079] Cu and Cs represent the concentrations (mg / mL) of the sample solution and standard solution, respectively.

[0080] rs — the main peak response value corresponding to the standard solution;

[0081] ru — the main peak response value corresponding to the sample solution;

[0082] P – Content of cyclohexane standard, %.

[0083] When testing for cyclohexane content, the absolute value of the difference between two parallel determinations should not exceed 0.5%, and the arithmetic mean should be taken as the final determination result.

[0084] Compared with the existing process of cyclopyralid, the optimal embodiment of the present invention avoids dangerous high-temperature and high-pressure reactions such as hydrogenation, diazotization, and chlorination. The optimal embodiment of the present invention shortens the original 8-step reaction to 4 steps, which is simple and produces less waste, improves production efficiency, reduces energy consumption and environmental pollution, and solves the problems existing in the existing process. It is a new process that is safe, green and environmentally friendly.

[0085] Finally, it should be noted that those skilled in the art should understand that this invention is not limited to the above-described embodiments. The above embodiments and descriptions are merely illustrative of the principles of this invention. Various changes and modifications can be made to this invention without departing from its spirit and scope, and all such changes and modifications should fall within the scope of the invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing cyclopyralid, characterized in that, Specifically, 100.0 g of 3-methyl-7-nitrophthalide solid, 93.6 g of 2-mercapto-4,6-dimethoxypyrimidine solid, 1.0 g of CuI powder, 89.0 g of light K2CO3, and 1000 mL of toluene were added sequentially to a reaction flask. After purging with nitrogen three times, the mixture was stirred and heated to 100-110 °C for 6 hours. The 3-methyl-7-nitrophthalide content was monitored by liquid chromatography until the reaction was complete, at which point 600 mL of water was added to the reaction flask and stirred for 30 minutes. The mixture was then allowed to stand and separate into layers. The organic layer was concentrated under reduced pressure to remove some solvent, cooled to 20 °C, and crystallized. The crystals were filtered, and the filter cake was washed with 100 mL of toluene at 10-20 °C. The filter cake was then dried under vacuum at 65 °C to obtain 152.0 g of pale yellow crystalline powder with an HPLC purity of 99.5% and a yield of 92.7%.

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