Fludioxonil and synthesis method thereof
By synthesizing 3-methylsalicylaldehyde from o-cresol, oxidizing it to 3-methylcatechol, synthesizing methylpiperidine, chlorination, and electrocatalytic reaction, the problems of low yield and harsh reaction conditions in existing fludioxonil synthesis have been solved, and high-yield and high-purity fludioxonil synthesis has been achieved.
Patent Information
- Application Number
- CN202510826470.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-19
- Publication Date
- 2025-11-18
AI Technical Summary
Existing methods for synthesizing fludioxonil suffer from low yields, demanding reaction conditions, and are unsuitable for industrial production.
3-Methylsalicylaldehyde was synthesized from o-cresol, oxidized to 3-methylcatechol, and then methylpiperidine was synthesized. Chlorination and fluorine-chlorine exchange were carried out, followed by electrocatalytic reaction to synthesize cinnamate intermediate, which ultimately yielded fludioxonil.
This method achieves high-yield and high-purity synthesis of fludioxonil, avoids the use of butyllithium, and features mild and easily controllable reaction conditions, as well as a clean and safe process.
Abstract
Description
TECHNICAL FIELD
[0001] The present application belongs to the technical field of organic synthesis, and particularly relates to fludioxonil and a synthesis method thereof. BACKGROUND
[0002] Fludioxonil is a new type of contact-kill protective fungicide, and its mechanism of action is unique. It inhibits the growth of pathogenic fungal mycelium by inhibiting the transfer of glucose phosphorylation, and ultimately leads to the death of the pathogen. When applied to flowers, it mainly prevents and treats leaf wilt, leaf spot, partial stem rot, root rot and the like. It is convenient to use, and can be used for foliar spraying and root irrigation, and has the advantages of small dosage, low residue, obvious effect on pathogenic fungi resistant to other agents, no systemic action but strong penetration capacity. It has remarkable effects on the prevention and treatment of root rot, stem rot and botrytis.
[0003] At present, the synthesis methods of fludioxonil mainly include the following methods:
[0004] (1) 4-amino-2,2-difluoro-o-benzene dialdehyde formaldehyde is diazotized and reacted with acrylonitrile to obtain an unsaturated cinnamyl nitrile under alkaline conditions, and then Michael addition of the unsaturated bond and the isonitrile group connected with methylene occurs under alkaline conditions to obtain the required pyrrole ring, so as to generate the final product. This method has strong operability, but the yield is low, and the total yield is less than 40%;
[0005] (2) fluorinated cyclic ether or its derivative is used as a starting material, and is subjected to Heck reaction and acrylonitrile to finally close the ring to obtain the target product. This method has high yield, but the reaction uses n-butyl lithium, and needs to be carried out at very low temperature. In addition, the Heck reaction uses expensive catalyst palladium acetate, and the catalyst recovery is difficult, which are important factors restricting the industrial production.
[0006] (3) fluorinated cyclic ether is used as a starting material, and is reacted with butyl lithium to generate an organic metal compound, and then is reacted with acrylonitrile, and finally closed to obtain the target product. This synthesis method also has harsh reaction conditions, and needs to be carried out at very low temperature (below-60℃), which is not suitable for industrial production.
[0007] Therefore, the present application is proposed. SUMMARY
[0008] The present application aims to overcome the defects of the prior art, and provides fludioxonil and a synthesis method thereof. The synthesis method avoids using butyl lithium as a catalyst, has mild and easy-to-control synthesis conditions, has high product yield, and is clean and safe in the entire synthesis process.
[0009] To achieve the above-mentioned purpose, the present application provides the following technical solutions:
[0010] This invention provides a method for synthesizing fludioxonil, the method comprising the following steps:
[0011] S1. Synthesize 3-methylsalicylaldehyde using o-cresol;
[0012] S2, Oxidize 3-methylsalicylaldehyde to 3-methylcatechol;
[0013] S3. Synthesize methylpiperidine ring using 3-methylcatechol;
[0014] S4. Chlorination of p-methylpiperidine ring yields the first intermediate;
[0015] S5. Perform fluorine-chlorine exchange on the first intermediate to obtain the second intermediate;
[0016] S6. Prepare a reaction solution using the second intermediate, and perform electrocatalysis on the reaction solution to obtain a third intermediate;
[0017] S7. Synthesize cinnamic ester intermediates using a third intermediate;
[0018] S8. Synthesize fludioxonil using cinnamic acid ester intermediates.
[0019] Specifically, in S1, the synthesis method of 3-methylsalicylaldehyde is as follows: 105-110 parts of o-phenol, 210-220 parts of toluene, and 95-105 parts of magnesium chloride are added to a reaction flask. The temperature is raised to 75-80°C, and 130-135 parts of triethylamine are added dropwise. The mixture is refluxed at 80-85°C for 1-1.5 hours. The temperature is lowered to 60-65°C, and 90-105 parts of paraformaldehyde are added. The mixture is reacted at 65-70°C for 4-4.5 hours. The temperature is lowered to 40-45°C, and 465-470 parts of 10wt.% hydrochloric acid are added dropwise. The mixture is stirred at 45-55°C for 1-1.5 hours. After standing for 30-60 seconds, the lower layer of water is removed to obtain 3-methylsalicylaldehyde. In this step, the parts are by mass.
[0020] Specifically, in S2, the preparation method of 3-methylcatechol is as follows: at room temperature, 95-105 parts of deionized water, 0.8-1.2 parts of tetrabutylammonium bromide, and 115-120 parts of 30wt.% hydrogen peroxide are added to the 3-methylsalicylaldehyde obtained in S1. The reaction is carried out for 6-8 hours, and the mixture is allowed to stand for 30-60 seconds. The lower layer of water is removed, and 180-220 parts of deionized water are added to wash the obtained upper organic phase once to obtain 3-methylcatechol. In this step, the parts are by mass.
[0021] Specifically, in step S3, the method for synthesizing the methylpiperidine ring is as follows: 3-methylcatechol obtained in step S2 is transferred to a high-pressure reactor, 80-90 parts of dichloromethane and 140-150 parts of potassium carbonate are added, the air in the high-pressure reactor is replaced with nitrogen, and then the nitrogen in the high-pressure reactor is replaced with hydrogen. The temperature is raised to 110-115℃ at a pressure of 0.2-0.25 MPa, and the reaction is carried out for 4-6 hours. The temperature is then lowered to room temperature, and the reaction system in the high-pressure reactor is transferred to a reaction flask. 300-350 parts of deionized water are added, and steam distillation is performed to obtain the methylpiperidine ring. In this step, the parts are by mass.
[0022] Specifically, in S4, the synthesis method of the first intermediate is as follows: 100-110 parts of phosphorus trichloride are added to the methyl pepper ring obtained in S3, the temperature is raised to 60-65°C, 65-75 parts of chlorine gas are introduced, the temperature is raised to 76-80°C, the reaction is refluxed for 2-4 hours, the temperature is lowered to 30-40°C, and phosphorus trichloride is recovered under vacuum to obtain the first intermediate. In this step, the parts are parts by mass.
[0023] Specifically, in S5, the synthesis method of the second intermediate is as follows: 45-55 parts of dimethyl sulfoxide, 125-135 parts of triethylamine trihydrofluoric acid, 240-245 parts of 30wt.% sodium hydroxide solution, and 200-250 parts of deionized water are added to the first intermediate obtained in S4. The mixture is extracted three times with dichloromethane, the organic phases are combined, and the dichloromethane is recovered using a rotary evaporator to obtain the second intermediate. During the extraction process, 200-220 parts of dichloromethane are added in the first extraction, and 100-120 parts of dichloromethane are added in the second and third extractions. In this step, the parts are by mass.
[0024] Specifically, in S6, the synthesis method of the third intermediate is as follows: 5.5-6 parts of sodium methylbenzenesulfonate, 2.8-3.2 parts of pyridine, 0.3-0.8 parts of sodium carbonate, 14.2-15 parts of the second intermediate, and 2.4-4 parts of anhydrous methanol are uniformly mixed to obtain a reaction solution. The reaction solution is added to an electrolytic cell, heated to 30-45°C, and reacted for 6-8 hours to obtain the third intermediate. In this step, the parts are by mass.
[0025] Specifically, in S7, the synthesis method of the cinnamic acid ester intermediate is as follows: 12-15 parts of deionized water and 8-10 parts of methyl cyanoacetate are added to the third intermediate obtained in S6, the mixture is stirred and reacted at room temperature for 8-10 hours, filtered, and the filtrate is dried at 50-60°C for 6-8 hours to obtain the cinnamic acid ester intermediate. In this step, the parts are by mass.
[0026] Specifically, in S8, the synthesis method of fludioxonil is as follows: 85-90 parts of cinnamic acid ester intermediate, 250-270 parts of anhydrous methanol, and 60-70 parts of 98 wt.% TOSMIC are uniformly mixed, cooled to 5-8℃, and 145-155 parts of 30 wt.% potassium methoxide methanol solution are added dropwise. The reaction is carried out at 3-15℃ for 2-4 hours. The anhydrous methanol is recovered at (-0.095)-(-0.09) MPa. 300-400 parts of deionized water and 50... 0–550 parts of ethyl acetate were stirred at 40–45°C for 30–60 min, allowed to stand for 30–60 s, and the lower layer of water was removed. 8–12 parts of decolorizing activated carbon were added to the resulting upper organic phase, the temperature was raised to 75–80°C, and the mixture was refluxed for 1–1.5 h. The mixture was filtered, and 350–400 parts of deionized water were added to the filtrate to recover the ethyl acetate. The temperature was lowered to 20–30°C, and the mixture was filtered under vacuum. The filtrate was dried at 60–65°C for 2–3 h to obtain fludioxonil. In this step, the parts are by weight.
[0027] The present invention also provides a fludioxonil, which is obtained by the above-described synthesis method.
[0028] Compared with the prior art, the technical solution provided by the present invention has the following beneficial effects:
[0029] (1) The present invention is highly operable, with each step closely linked to the next, and the product yield and purity are both high. The total yield of fludioxonil is over 65%, and the purity can reach over 98%.
[0030] (2) This invention does not require butyllithium to participate in the reaction, and the reaction conditions are mild and easy to control. In S6, the methyl group on the second intermediate in the reaction solution can be oxidized to an aldehyde group by electrocatalysis using a safe voltage (4.1~4.5V).
[0031] (3) The synthesis method proposed in this invention is clean and safe, with no discharges during the entire reaction process, and some of the chemical substances can be recovered and recycled. Detailed Implementation
[0032] Exemplary embodiments will be described in detail below. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Rather, they are merely examples consistent with some aspects of the invention as detailed in the appended claims.
[0033] Example 1 This embodiment proposes a method for synthesizing fludioxonil, which is performed according to the following steps: S1. Add 105g of o-phenol, 210g of toluene, and 95g of magnesium chloride to a reaction flask. Heat to 75℃, add 130g of triethylamine dropwise, reflux at 80℃ for 1.5h, cool to 60℃, add 90g of paraformaldehyde, react at 65℃ for 4.5h, cool to 40℃, add 465g of 10wt.% hydrochloric acid dropwise, stir at 45℃ for 1.5h, let stand for 30s, separate the lower layer of water, and obtain 3-methylsalicylaldehyde. The route for synthesizing 3-methylsalicylaldehyde from o-cresol is as follows: ; S2. At room temperature, 95g of deionized water, 0.8g of tetrabutylammonium bromide, and 115g of 30wt.% hydrogen peroxide were added to the 3-methylsalicylaldehyde obtained in S1. The reaction was carried out for 6 hours, allowed to stand for 30 seconds, the lower layer of water was separated, and the upper organic phase was washed once with 180g of deionized water to obtain 3-methylcatechol. The route for obtaining 3-methylcatechol from 3-methylsalicylaldehyde is as follows: ; S3. The 3-methylcatechol obtained in S2 was transferred to a high-pressure reactor. 80g of dichloromethane and 140g of potassium carbonate were added. The air in the high-pressure reactor was replaced with nitrogen, and then the nitrogen was replaced with hydrogen. The reactor was heated to 110℃ at a pressure of 0.2MPa and reacted for 6 hours. After cooling to room temperature, the reaction system in the high-pressure reactor was transferred to a reaction flask. 300g of deionized water was added, and steam distillation was performed to obtain 106g of methylpiperidine with a purity of 99.8%. The route for synthesizing methylpiperidine from 3-methylcatechol is as follows: ; S4. Add 100g of phosphorus trichloride to the methyl piperine ring obtained in S3, heat to 60℃, introduce 65g of chlorine gas, then heat to 76℃, reflux for 4 hours, cool to 30℃, and recover phosphorus trichloride under vacuum to obtain 160g of the first intermediate with a purity of 99.4%. The route for obtaining the first intermediate through the methyl piperine ring is as follows: ; S5. Add 45g of dimethyl sulfoxide, 125g of triethylamine trihydrofluoric acid, 240g of 30wt.% sodium hydroxide solution, and 200g of deionized water to the first intermediate obtained in S4. Extract three times with dichloromethane, combine the organic phases, and recover the dichloromethane using a rotary evaporator to obtain 131g of the second intermediate with a purity of 98.5%. During the extraction process, 200g of dichloromethane was added in the first extraction, and 100g of dichloromethane was added in both the second and third extractions. The route for synthesizing the second intermediate from the first intermediate is as follows: ; S6. Mix 5.5g sodium toluenesulfonate, 2.8g pyridine, 0.3g sodium carbonate, 14.2g the second intermediate, and 2.4g anhydrous methanol evenly to obtain a reaction solution. Add the reaction solution to an electrolytic cell, heat to 30℃, and react for 8 hours to obtain the third intermediate. The route for synthesizing the third intermediate from the second intermediate is as follows: ; S7. Add 12g of deionized water and 8g of methyl cyanoacetate to the third intermediate obtained in S6, stir the reaction at room temperature for 8 hours, filter, and dry the filtrate at 50℃ for 8 hours to obtain 21g of cinnamic acid ester intermediate with a purity of 99.2%; the route for synthesizing the cinnamic acid ester intermediate through the third intermediate is as follows: ; S8. 85g of cinnamic acid ester intermediate, 250g of anhydrous methanol, and 60g of 98wt.% TOSMIC were uniformly mixed, cooled to 5℃, and 145g of 30wt.% potassium methoxide methanol solution was added dropwise. The mixture was reacted at 3℃ for 4h, and the anhydrous methanol was recovered at -0.095MPa. 300g of deionized water and 500g of ethyl acetate were added to the obtained solid, and the mixture was stirred at 40℃ for 60min, allowed to stand for 60s, and the lower water layer was separated. 8g of decolorizing activated carbon was added to the obtained upper organic phase, the temperature was raised to 75℃, and the mixture was refluxed for 1h. The mixture was filtered, and 350g of deionized water was added to the filtrate to recover ethyl acetate. The mixture was cooled to 20℃, filtered under vacuum, and the filtrate was dried at 60℃ for 2h to obtain 75g of fludioxonil with a purity of 98.2%. The route for synthesizing fludioxonil from the cinnamic acid ester intermediate is as follows: .
[0051] Example 2
[0052] This embodiment proposes a method for synthesizing fludioxonil, which is performed according to the following steps:
[0053] S1. Add 108g of o-phenol, 215g of toluene, and 100g of magnesium chloride to a reaction flask, heat to 77℃, add 133g of triethylamine dropwise, reflux at 83℃ for 1.3h, cool to 62℃, add 97g of paraformaldehyde, react at 68℃ for 4.3h, cool to 42℃, add 467g of 10wt.% hydrochloric acid dropwise, stir at 50℃ for 1.3h, let stand for 45s, separate the lower layer of water to obtain 3-methylsalicylaldehyde;
[0054] S2. At room temperature, add 100g of deionized water, 1.0g of tetrabutylammonium bromide, and 118g of 30wt.% hydrogen peroxide to the 3-methylsalicylaldehyde obtained in S1. React for 7h, let stand for 45s, separate the lower layer of water, add 200g of deionized water to wash the obtained upper organic phase once to obtain 3-methylcatechol.
[0055] S3. The 3-methylcatechol obtained in S2 was transferred to a high-pressure reactor. 85g of dichloromethane and 145g of potassium carbonate were added. The air in the high-pressure reactor was replaced with nitrogen, followed by hydrogen. The reactor was heated to 113℃ at a pressure of 0.23MPa and reacted for 5 hours. The mixture was then cooled to room temperature. The reaction system was transferred to a reaction flask, and 325g of deionized water was added. Steam distillation was performed to obtain 111g of methylpiperidine with a purity of 99.8%.
[0056] S4. Add 105g of phosphorus trichloride to the methyl pepper ring obtained in S3, heat to 62°C, introduce 70g of chlorine gas, heat to 78°C, reflux for 3 hours, cool to 35°C, and recover phosphorus trichloride under vacuum to obtain 165g of the first intermediate with a purity of 99.5%.
[0057] S5. Add 50g of dimethyl sulfoxide, 130g of triethylamine trihydrofluoric acid, 243g of 30wt.% sodium hydroxide solution, and 230g of deionized water to the first intermediate obtained in S4. Extract with dichloromethane three times, combine the organic phases, and recover the dichloromethane using a rotary evaporator to obtain 132g of the second intermediate with a purity of 98.7%. During the extraction process, 210g of dichloromethane was added in the first extraction, and 110g of dichloromethane was added in the second and third extractions.
[0058] S6. Mix 5.8g sodium methylbenzenesulfonate, 3.0g pyridine, 0.5g sodium carbonate, 14.6g second intermediate, and 3.5g anhydrous methanol evenly to obtain a reaction solution. Add the reaction solution to an electrolytic cell, heat to 37℃, and react for 7h to obtain the third intermediate.
[0059] S7. Add 13g of deionized water and 9g of methyl cyanoacetate to the third intermediate obtained in S6, stir and react at room temperature for 9h, filter, and dry the filtrate at 55℃ for 7h to obtain 23g of cinnamic acid ester intermediate with a purity of 99.5%.
[0060] S8. Mix 87g of cinnamic acid ester intermediate, 260g of anhydrous methanol, and 65g of 98wt.% TOSMIC evenly. Cool to 7℃, add 150g of 30wt.% potassium methoxide methanol solution dropwise, react at 9℃ for 3h, recover anhydrous methanol at -0.093MPa, add 350g of deionized water and 520g of ethyl acetate to the obtained solid, stir at 43℃ for 45min, let stand for 45s, separate the lower water layer, add 10g of decolorizing activated carbon to the obtained upper organic phase, heat to 78℃, reflux for 1.3h, filter, add 380g of deionized water to the obtained filtrate, recover ethyl acetate, cool to 25℃, filter by suction, and dry the filtrate at 62℃ for 2.5h to obtain 75.5g of fludioxonil with a purity of 98.5%.
[0061] Example 3
[0062] This embodiment proposes a method for synthesizing fludioxonil, which is performed according to the following steps:
[0063] S1. Add 110g of o-phenol, 220g of toluene, and 105g of magnesium chloride to a reaction flask. Heat to 80℃, add 135g of triethylamine dropwise, reflux at 85℃ for 1 hour, cool to 65℃, add 105g of paraformaldehyde, react at 70℃ for 4 hours, cool to 45℃, add 470g of 10wt.% hydrochloric acid dropwise, stir at 55℃ for 1 hour, let stand for 60 seconds, separate the lower layer of water, and obtain 3-methylsalicylaldehyde. The route for synthesizing 3-methylsalicylaldehyde from o-cresol is as follows:
[0064] S2. At room temperature, add 105g of deionized water, 1.2g of tetrabutylammonium bromide, and 120g of 30wt.% hydrogen peroxide to the 3-methylsalicylaldehyde obtained in S1. React for 8 hours, let stand for 60 seconds, remove the lower layer of water, add 220g of deionized water to wash the obtained upper organic phase once to obtain 3-methylcatechol.
[0065] S3. The 3-methylcatechol obtained in S2 was transferred to a high-pressure reactor. 90g of dichloromethane and 150g of potassium carbonate were added. The air in the high-pressure reactor was replaced with nitrogen, followed by hydrogen. The reactor was heated to 115℃ at a pressure of 0.25MPa and reacted for 4 hours. The mixture was then cooled to room temperature. The reaction system was transferred to a reaction flask, and 350g of deionized water was added. Steam distillation was performed to obtain 115g of methylpiperidine with a purity of 99.7%.
[0066] S4. Add 110g of phosphorus trichloride to the methyl pepper ring obtained in S3, heat to 65℃, introduce 75g of chlorine gas, heat to 80℃, reflux for 2h, cool to 40℃, and recover phosphorus trichloride under vacuum to obtain 173g of the first intermediate with a purity of 99.6%.
[0067] S5. Add 55g of dimethyl sulfoxide, 135g of triethylamine trihydrofluoric acid, 245g of 30wt.% sodium hydroxide solution, and 250g of deionized water to the first intermediate obtained in S4. Extract with dichloromethane three times, combine the organic phases, and recover the dichloromethane using a rotary evaporator to obtain 144g of the second intermediate with a purity of 98.6%. During the extraction process, 220g of dichloromethane was added in the first extraction, and 120g of dichloromethane was added in the second and third extractions.
[0068] S6. Mix 6g sodium methylbenzenesulfonate, 3.2g pyridine, 0.8g sodium carbonate, 15g second intermediate, and 4g anhydrous methanol evenly to obtain a reaction solution. Add the reaction solution to an electrolytic cell, heat to 45℃, and react for 6 hours to obtain the third intermediate.
[0069] S7. Add 15g of deionized water and 10g of methyl cyanoacetate to the third intermediate obtained in S6, stir and react at room temperature for 10h, filter, and dry the filtrate at 60℃ for 6h to obtain 25g of cinnamic acid ester intermediate with a purity of 99.6%.
[0070] S8. Mix 90g of cinnamic acid ester intermediate, 270g of anhydrous methanol, and 70g of 98wt.% TOSMIC evenly. Cool to 8℃ and add 155g of 30wt.% potassium methoxide methanol solution dropwise. React at 15℃ for 2h. Recover anhydrous methanol at -0.09MPa. Add 400g of deionized water and 550g of ethyl acetate to the obtained solid. Stir at 45℃ for 30min, let stand for 30s, and remove the lower water layer. Add 12g of decolorizing activated carbon to the obtained upper organic phase. Heat to 80℃ and reflux for 1.5h. Filter. Add 400g of deionized water to the obtained filtrate to recover ethyl acetate. Cool to 30℃ and filter under vacuum. Dry the filtrate at 65℃ for 3h to obtain 80g of fludioxonil with a purity of 98.3%.
[0071] In the above embodiment, in S6, an anode vertical graphite plate (2.5cm high, 8cm wide, and 0.4cm thick) and two cathode vertical graphite plates (2cm high, 8cm wide, and 0.4cm thick) are provided in the electrolytic cell, with an electrode spacing of 1mm. Electrocatalysis of the reaction solution in the electrolytic cell is performed under the conditions of 4.1~4.5V and 0.22A~0.23A.
[0072] As can be seen from the above embodiments, the method for synthesizing fludioxonil proposed in this invention does not require the participation of butyllithium in the reaction, the reaction conditions are easy to control, the whole process is clean and safe, and the total yield and purity of the synthesized fludioxonil are both high.
[0073] The above description is merely a specific embodiment of the present invention, enabling those skilled in the art to understand or implement the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention.
[0074] It should be understood that the present invention is not limited to the content already described above, and various modifications and changes can be made without departing from its scope. The scope of the present invention is limited only by the appended claims.
Claims
1. A method for synthesizing fludioxonil, characterized in that, The method includes the following steps: S1. Synthesize 3-methylsalicylaldehyde using o-cresol; S2, Oxidize 3-methylsalicylaldehyde to 3-methylcatechol; S3. Synthesize methylpiperidine ring using 3-methylcatechol; S4. Chlorination of p-methylpiperidine ring yields the first intermediate; S5. Perform fluorine-chlorine exchange on the first intermediate to obtain the second intermediate; S6. Prepare a reaction solution using the second intermediate, and perform electrocatalysis on the reaction solution to obtain a third intermediate; S7. Synthesize cinnamic ester intermediates using a third intermediate; S8. Synthesize fludioxonil using cinnamic acid ester intermediates.
2. The method for synthesizing fludioxonil according to claim 1, characterized in that, In S1, the synthesis method of 3-methylsalicylaldehyde is as follows: 105-110 parts of o-phenol, 210-220 parts of toluene, and 95-105 parts of magnesium chloride are added to a reaction flask. The temperature is raised to 75-80°C, and 130-135 parts of triethylamine are added dropwise. The mixture is refluxed at 80-85°C for 1-1.5 hours. The temperature is lowered to 60-65°C, and 90-105 parts of paraformaldehyde are added. The mixture is reacted at 65-70°C for 4-4.5 hours. The temperature is lowered to 40-45°C, and 465-470 parts of 10wt.% hydrochloric acid are added dropwise. The mixture is stirred at 45-55°C for 1-1.5 hours. After standing for 30-60 seconds, the lower layer of water is separated to obtain 3-methylsalicylaldehyde. In this step, the parts are by mass.
3. The method for synthesizing fludioxonil according to claim 1, characterized in that, In S2, the preparation method of 3-methylcatechol is as follows: at room temperature, 95-105 parts of deionized water, 0.8-1.2 parts of tetrabutylammonium bromide, and 115-120 parts of 30wt.% hydrogen peroxide are added to 3-methylsalicylaldehyde obtained in S1. The reaction is carried out for 6-8 hours, and the mixture is allowed to stand for 30-60 seconds. The lower layer of water is removed, and 180-220 parts of deionized water are added to wash the upper organic phase once to obtain 3-methylcatechol. In this step, the parts are by mass.
4. The method for synthesizing fludioxonil according to claim 1, characterized in that, In step S3, the method for synthesizing the methylpiperidine ring is as follows: 3-methylcatechol obtained in step S2 is transferred to a high-pressure reactor, 80-90 parts of dichloromethane and 140-150 parts of potassium carbonate are added, the air in the high-pressure reactor is replaced with nitrogen, and then the nitrogen in the high-pressure reactor is replaced with hydrogen. The temperature is raised to 110-115℃ at a pressure of 0.2-0.25 MPa, and the reaction is carried out for 4-6 hours. The temperature is then lowered to room temperature, and the reaction system in the high-pressure reactor is transferred to a reaction flask. 300-350 parts of deionized water are added, and steam distillation is performed to obtain the methylpiperidine ring. In this step, the parts are by mass.
5. The method for synthesizing fludioxonil according to claim 1, characterized in that, In step S4, the synthesis method of the first intermediate is as follows: 100-110 parts of phosphorus trichloride are added to the methyl pepper ring obtained in step S3, the temperature is raised to 60-65°C, 65-75 parts of chlorine gas are introduced, the temperature is raised to 76-80°C, the reaction is refluxed for 2-4 hours, the temperature is lowered to 30-40°C, and phosphorus trichloride is recovered under vacuum to obtain the first intermediate. In this step, the parts are parts by mass.
6. The method for synthesizing fludioxonil according to claim 1, characterized in that, In step S5, the synthesis method of the second intermediate is as follows: 45-55 parts of dimethyl sulfoxide, 125-135 parts of triethylamine trihydrofluoric acid, 240-245 parts of 30wt.% sodium hydroxide solution, and 200-250 parts of deionized water are added to the first intermediate obtained in step S4. The mixture is extracted three times with dichloromethane, the organic phases are combined, and the dichloromethane is recovered using a rotary evaporator to obtain the second intermediate. During the extraction process, 200-220 parts of dichloromethane are added in the first extraction, and 100-120 parts of dichloromethane are added in the second and third extractions. In this step, the parts are by mass.
7. The method for synthesizing fludioxonil according to claim 1, characterized in that, In S6, the synthesis method of the third intermediate is as follows: 5.5-6 parts of sodium methylbenzenesulfonate, 2.8-3.2 parts of pyridine, 0.3-0.8 parts of sodium carbonate, 14.2-15 parts of the second intermediate, and 2.4-4 parts of anhydrous methanol are uniformly mixed to obtain a reaction solution. The reaction solution is added to an electrolytic cell, heated to 30-45°C, and reacted for 6-8 hours to obtain the third intermediate. In this step, the parts are by mass.
8. The method for synthesizing fludioxonil according to claim 1, characterized in that, In S7, the synthesis method of the cinnamic acid ester intermediate is as follows: 12-15 parts of deionized water and 8-10 parts of methyl cyanoacetate are added to the third intermediate obtained in S6, the mixture is stirred and reacted at room temperature for 8-10 hours, filtered, and the filtrate is dried at 50-60°C for 6-8 hours to obtain the cinnamic acid ester intermediate. In this step, the parts are by mass.
9. The method for synthesizing fludioxonil according to claim 1, characterized in that, In S8, the synthesis method of fludioxonil is as follows: 85-90 parts of cinnamic acid ester intermediate, 250-270 parts of anhydrous methanol, and 60-70 parts of 98 wt.% TOSMIC are uniformly mixed, cooled to 5-8℃, and 145-155 parts of 30 wt.% potassium methoxide methanol solution are added dropwise. The mixture is reacted at 3-15℃ for 2-4 hours. The anhydrous methanol is recovered at (-0.095)-(-0.09) MPa. 300-400 parts of deionized water and 500- 550 parts of ethyl acetate were stirred at 40–45°C for 30–60 min, allowed to stand for 30–60 s, and the lower layer of water was removed. 8–12 parts of decolorizing activated carbon were added to the resulting upper organic phase, the temperature was raised to 75–80°C, and the mixture was refluxed for 1–1.5 h. The mixture was filtered, and 350–400 parts of deionized water were added to the filtrate to recover the ethyl acetate. The temperature was lowered to 20–30°C, and the mixture was filtered under vacuum. The filtrate was dried at 60–65°C for 2–3 h to obtain fludioxonil. In this step, the parts are by weight.
10. A fludioxonil, characterized in that, The fludioxonil is obtained by the synthesis method described in any one of claims 1 to 9.