A process for the synthesis of halogenated pyridinyl pyrazole carboxylates

Abstract

The application discloses a kind of green synthesis process of halogenated pyridyl pyrazole dithiocarboxylate, it is related to compound synthesis technical field, including the following steps: S1, compound 1 is placed in polar solvent, and manganese dioxide, an oxidizing agent, is added to stir and heat reaction, with sulfuric acid as catalyst, to obtain compound 2 solution and suspension;S2, compound 2 solution and suspension are filtered, separated to obtain the filter cake of manganese dioxide and manganese sulfate and reaction filtrate, the filtrate is concentrated to recover polar solvent, and water is filtered to obtain compound 2;S3, filter cake is added to sodium hydroxide solution, to generate manganese hydroxide solution, and contain manganese dioxide solid, after filtration and separation, to obtain manganese dioxide solid and manganese hydroxide filtrate.The process is regenerated by the selection of potassium permanganate manganese dioxide oxidation system, realizes the efficient use of oxidizing agent, high conversion rate and high selectivity of reaction system and the reduction of process three wastes, and completes the green synthesis of halogenated pyridyl pyrazole dithiocarboxylate.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of compound synthesis, and particularly relates to a high-efficiency green synthesis process of halogenated pyridyl pyrazole alkane carboxylate. BACKGROUND

[0002] Chlorantraniliprole is the first insecticide in a new type, high-efficiency, low-toxicity ortho-formamido benzamide compound developed by DuPont (now Corteva) company; its domestic product is 20% chlorantraniliprole suspension concentrate, and the trade name is Kangkuan. Chlorantraniliprole is a fish netting receptor agent, and is a high-activity control agent for Lepidoptera (such as diamondback moth, corn earworm, tobacco budworm, beet armyworm, cabbage looper and the like) and Hemiptera (such as peach aphid, cotton aphid, potato leafhopper, silverleaf whitefly and the like) pests, and is mainly used for pest control on soybean, fruits and vegetables, rice, cotton, corn and the like. At present, chlorantraniliprole has been sold in more than 100 countries around the world, and almost covers all major markets. The insecticide has excellent stomach toxicity and certain contact activity, and has excellent systemicity and permeability; it has a wide insecticidal spectrum, high activity, low toxicity, is safe to environment and organisms, and has good adaptability to many major insecticides, and can be used for hundreds of crops to control pests. Compound 2 (halogenated pyridyl pyrazole alkane carboxylate) is one of key intermediates for synthesizing chlorantraniliprole, and its green synthesis has epoch-making significance.

[0003] The synthesis route is that compound 1 is subjected to oxidation reaction with an oxidizing agent to obtain compound 2. Compound 2 is a key intermediate for synthesizing chlorantraniliprole and its derivatives, and has important synthetic value. The traditional synthesis process needs to be reacted with an oxidizing agent such as sodium persulfate, potassium persulfate and the like in a polar solvent, and then water is added to crystallize to obtain compound 2. The reaction temperature in the synthesis process is generally 80-90 DEG C, the safety of the reaction process is very poor, and safety accidents such as material overflow and flash explosion are very easy to occur. At the same time, due to the excessively high reaction temperature, the reaction selectivity is poor, the content of the main product is generally less than 88% detected by HPLC, the molar yield is low, the synthesis cost is high, by-products such as sodium bisulfate and potassium bisulfate are generated in the reaction process, the by-products cannot be recycled for secondary utilization, the atomic utilization rate is low, the economy is poor, the mother liquor amount is large, and the mother liquor is high in ammonia nitrogen and salt, so that the sewage treatment is difficult, needs to be treated through processes such as evaporation crystallization and biodegradation, and can be discharged. In the production process, additional sewage treatment equipment needs to be added.

[0004] Therefore, the present application is proposed to solve the above technical problems. SUMMARY

[0005] The application aims to provide a synthesis process of halogenated pyridyl pyrazole dithiocarboxylate, so as to solve the technical problems of large amount of waste water, low utilization rate of raw materials and heavy environmental protection pressure in the synthesis scheme of halogenated pyridyl pyrazole dithiocarboxylate compound 2 in the prior art.

[0006] The application aims to provide a synthesis process of halogenated pyridyl pyrazole dithiocarboxylate, so as to solve the technical problems of large amount of waste water, low utilization rate of raw materials and heavy environmental protection pressure in the synthesis scheme of halogenated pyridyl pyrazole dithiocarboxylate compound 2 in the prior art.

[0007] S1, compound 1 is put into a polar solvent, an oxidant manganese dioxide is added, stirring and heating reaction is carried out, sulfuric acid is used as a catalyst, and compound 2 solution and suspension are obtained;

[0008] S2, the compound 2 solution and the suspension are filtered and separated to obtain a filter cake of manganese dioxide and manganese sulfate and a reaction filtrate, the filtrate is concentrated to recover the polar solvent, and water is added to filter to obtain compound 2;

[0009] S3, the filter cake is added to a sodium hydroxide solution to generate a manganese hydroxide solution containing manganese dioxide solid, and the manganese dioxide solid and the manganese hydroxide filtrate are obtained after filtration and separation;

[0010] S4, the manganese dioxide crystal is continuously added to S1 for redox reaction;

[0011] S5, a certain amount of potassium permanganate is added to the manganese hydroxide filtrate, manganese dioxide is obtained by reaction and precipitation, and after filtration, the manganese dioxide is continuously added to S1 for redox reaction.

[0012] Further, the chemical general formula of compound 1 is C9H6BrClN3O2R;

[0013] The chemical general formula of compound 2 is C9H4BrClN3O2R;

[0014] R is one of methyl, ethyl, butyl, tert-butyl and isopropyl, and is preferably methyl.

[0015] Further, the cycle equation of manganese dioxide is:

[0016] ① ;

[0017] ② ;

[0018] ③ .

[0019] Further, the polar solvent is acetonitrile, N,N dimethylformamide, N,N dimethylacetamide, dimethyl sulfoxide, N-methyl pyrrolidone, methanol or ethanol.

[0020] Further, in step S1, the temperature of stirring and heating is 25-45 DEG C.

[0021] Further, in step S3, the concentration of the sodium hydroxide solution is 40-50%, the filter cake is added to the sodium hydroxide solution, and then heated to 60-90℃ and stirred for 2-4h, so that the PH reaches 12-13.

[0022] Further, in step S5, after adding potassium permanganate, heating to 70-80℃ and holding for 2-3h.

[0023] By adopting the technical scheme, the application has the following beneficial effects:

[0024] Compared with the traditional synthesis process, the synthesis process of the application has the advantages of green environmental protection, less waste, low energy consumption, recyclable raw and auxiliary materials, high utilization rate of raw materials, high atomic utilization rate and atomic economy, low cost of synthesis, high selectivity, high conversion rate, etc. The process realizes efficient utilization of the oxidizing agent, high conversion rate and high selectivity of the reaction system, and reduction of process waste, and completes the green synthesis of halogenated pyridyl pyrazole alkyl carboxylate. DETAILED DESCRIPTION

[0025] The application provides a synthesis process of halogenated pyridyl pyrazole alkyl carboxylate, including the following steps:

[0026] S1, putting compound 1 into a polar solvent, adding an oxidizing agent manganese dioxide, stirring and heating to react, taking sulfuric acid as a catalyst, to obtain a compound 2 solution and a suspension;

[0027] S2, filtering and separating the compound 2 solution and the suspension (manganese dioxide and manganese sulfate) to obtain a filter cake of manganese dioxide and manganese sulfate and a reaction filtrate, concentrating the filtrate to recover the polar solvent (for use in the next batch of reaction), and filtering to obtain compound 2 by adding water;

[0028] S3, adding the filter cake to a sodium hydroxide solution to generate a manganese hydroxide solution containing manganese dioxide solid, and filtering and separating to obtain manganese dioxide crystals and a manganese hydroxide filtrate;

[0029] S4, continuously adding the manganese dioxide crystals to S1 for redox reaction;

[0030] S5, adding a certain amount of potassium permanganate to the manganese hydroxide filtrate, to obtain manganese dioxide and precipitate, filtering and then continuously adding to S1 for redox reaction.

[0031] The chemical general formula of compound 1 is C9H6BrClN3O2R;

[0032] The chemical general formula of compound 2 is C9H4BrClN3O2R;

[0033] R is one of methyl, ethyl, butyl, tert-butyl and isopropyl, preferably methyl.

[0034] The circulation equation of manganese dioxide is:

[0035] 1 ;

[0036] 2 ;

[0037] 3 .

[0038] The process realizes efficient utilization of oxidant and high conversion rate and high selectivity of reaction system by selection of potassium permanganate for regeneration of manganese dioxide oxidation system.

[0039] The polar solvent is acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methyl pyrrolidone, methanol or ethanol, preferably acetonitrile.

[0040] In step S1, the temperature of stirring and heating is 25-45℃.

[0041] In step S3, the concentration of sodium hydroxide solution is 40-50%, and after the filter cake is added to the sodium hydroxide solution, heating is carried out to 60-90℃, and stirring is carried out for 2-4h, so that the PH reaches 12-13, and the preferred conditions are 40% sodium hydroxide solution, reaction temperature 80℃, and reaction time 3h.

[0042] In step S5, after adding potassium permanganate, heating is carried out to 70-80℃ and incubation is carried out for 2-3h.

[0043] In reaction 1, under strong acidic conditions, manganese dioxide first shows strong oxidizing property, converting compound 1 into compound 2, and at the same time, the manganese ion in manganese dioxide is reduced from +4 valence to +2 valence, generating by-product: manganese sulfate, which is precipitated in the system. After the reaction is completed, the filtrate and the filter cake are separated by filtration, the filtrate is acetonitrile / compound 2 solution, and the filter cake is a mixture of manganese dioxide / manganese sulfate.

[0044] In reaction 2, the filter cake is added to the lye, at this time the manganese sulfate is first dissolved in water, and then reacts with the base to generate manganese hydroxide, which is dissolved in the lye, while the remaining manganese dioxide is precipitated in the system. After filtration, high-content manganese dioxide and manganese hydroxide / sodium hydroxide solution are obtained, and the manganese dioxide is dried and directly used in reaction 1.

[0045] In reaction ③, potassium permanganate is added to the manganese hydroxide / sodium hydroxide solution. Under alkaline conditions, potassium permanganate exhibits strong oxidizing properties, oxidizing the +2 manganese ions to +4 manganese dioxide. The +7 manganese ions in potassium permanganate are reduced to +4 manganese dioxide. In the reaction process, manganese is recycled, and the atom utilization rate and atom economy are improved.

[0046] Example 1

[0047] 1.1. Preparation of compound 2, where R is an ethyl group, the reaction formula is:

[0048]

[0049] Add 50g of C to a 500ml four-necked reaction flask. 11 H 11 BrClN3O2 was added, followed by 200g acetonitrile and 32g manganese dioxide (content >60%). The mixture was stirred and heated to 25-30℃, and 22.1g concentrated sulfuric acid was slowly added dropwise. After the addition was complete, the mixture was kept at the same temperature. Thin-layer chromatography showed that the starting material spot disappeared. The mixture was then cooled to 15-20℃ and filtered to obtain a mixture of manganese dioxide and manganese sulfate. The filtrate was depressurized to recover acetonitrile. After no more distillate flowed out, 50g water was added dropwise, and the mixture was stirred to induce crystallization. The mixture was filtered to obtain compound 2, which was dried at 70℃ with a yield of 95% and a purity >98%.

[0050] Compared to traditional processes, the amount of wastewater is significantly reduced, to only 10-20% of that of traditional processes, thus achieving the goal of reducing the discharge of waste gas, wastewater, and solid waste.

[0051] 1.2. Recovery of manganese salts

[0052] Add the mixture of manganese dioxide and manganese sulfate obtained from the previous filtration step to a 500ml four-necked reaction flask, add 80g of 50% concentrated alkali solution, heat to 60℃, stir for 2h, and check the pH of the system to be 12~13. Filter while hot, and the filter cake is the recovered manganese dioxide (content >50%), which can be directly reused in the preparation of compound 3. Add 10g of potassium permanganate to the filtrate, heat to 80℃ and keep warm for 2h. During the holding period, continuously check the oxidizing property of the system. Excess potassium permanganate dissolves in the alkali solution, and the product manganese dioxide will precipitate out. Filter, combine and reuse the recovered manganese dioxide in the preparation of compound 2. Titrate the free alkali in the filtrate, add sodium hydroxide to the concentration to about 50%, and directly reuse it in the next batch of manganese salt recovery.

[0053] During the recovery of manganese salts, the alkaline solution can be reused by adding sodium hydroxide, and can be reused about 10 times. After pretreatment, the wastewater has a relatively simple composition and is high-salt wastewater, which can be directly treated in a triple-effect evaporator, thus achieving the goal of reducing the discharge of waste gas, wastewater, and solid waste.

[0054] 1.3. Reuse of manganese dioxide

[0055] Into a 500ml four-necked flask, 50g of compound 1 was added, followed by 200g of acetonitrile and 38g of recovered manganese dioxide (content > 60%), and the mixture was stirred and heated to 25-30°C. Then 22.1g of concentrated sulfuric acid was slowly added dropwise. After the addition was completed, the mixture was kept warm until the raw material point disappeared on TLC. The mixture was then cooled to 15-20°C, and the manganese dioxide and manganese sulfate mixture was filtered. The acetonitrile in the filtrate was recovered under reduced pressure. When no distillate was obtained, 50g of water was added, and the mixture was stirred to crystallize. The compound 2 was filtered and dried at 70°C. The yield was 95%, and the purity was > 98%. 11 H 11 BrClN3O2, followed by 200g of acetonitrile and 38g of recovered manganese dioxide (content > 60%), and the mixture was stirred and heated to 25-30°C. Then 22.1g of concentrated sulfuric acid was slowly added dropwise. After the addition was completed, the mixture was kept warm until the raw material point disappeared on TLC. The mixture was then cooled to 15-20°C, and the manganese dioxide and manganese sulfate mixture was filtered. The acetonitrile in the filtrate was recovered under reduced pressure. When no distillate was obtained, 50g of water was added, and the mixture was stirred to crystallize. The compound 2 was filtered and dried at 70°C. The yield was 95%, and the purity was > 98%.

[0056] The effective content of the recovered manganese dioxide was determined by titration, and > 50% could be directly used in the reaction, improving the atomic economy and atomic utilization, and reducing the synthesis cost of compound 2.

[0057] Example 2

[0058] 2.1 Preparation of compound 2, R is butyl, and the reaction formula is as follows:

[0059]

[0060] Into a 500ml four-necked flask, 50g of compound 1 was added, followed by 200g of acetonitrile and 38g of recovered manganese dioxide (content > 60%), and the mixture was stirred and heated to 25-30°C. Then 22.1g of concentrated sulfuric acid was slowly added dropwise. After the addition was completed, the mixture was kept warm until the raw material point disappeared on TLC. The mixture was then cooled to 15-20°C, and the manganese dioxide and manganese sulfate mixture was filtered. The acetonitrile in the filtrate was recovered under reduced pressure. When no distillate was obtained, 50g of water was added, and the mixture was stirred to crystallize. The compound 2 was filtered and dried at 70°C. The yield was 95%, and the purity was > 98%. 13 H 13 BrClN3O2, followed by 200g of acetonitrile and 38g of recovered manganese dioxide (content > 60%), and the mixture was stirred and heated to 25-30°C. Then 22.1g of concentrated sulfuric acid was slowly added dropwise. After the addition was completed, the mixture was kept warm until the raw material point disappeared on TLC. The mixture was then cooled to 15-20°C, and the manganese dioxide and manganese sulfate mixture was filtered. The acetonitrile in the filtrate was recovered under reduced pressure. When no distillate was obtained, 50g of water was added, and the mixture was stirred to crystallize. The compound 2 was filtered and dried at 70°C. The yield was 95%, and the purity was > 98%.

[0061] 2.2 Recovery of manganese salt

[0062] Into a 500ml four-necked flask, 50g of compound 1 was added, followed by 200g of acetonitrile and 38g of recovered manganese dioxide (content > 60%), and the mixture was stirred and heated to 25-30°C. Then 22.1g of concentrated sulfuric acid was slowly added dropwise. After the addition was completed, the mixture was kept warm until the raw material point disappeared on TLC. The mixture was then cooled to 15-20°C, and the manganese dioxide and manganese sulfate mixture was filtered. The acetonitrile in the filtrate was recovered under reduced pressure. When no distillate was obtained, 50g of water was added, and the mixture was stirred to crystallize. The compound 2 was filtered and dried at 70°C. The yield was 95%, and the purity was > 98%.

[0063] 2.3 Use of recovered manganese dioxide:

[0064] Add 50g of C to a 500ml four-necked reaction flask. 13 H 13 BrClN3O2 was added, followed by 200g acetonitrile and 36g manganese dioxide (content >50%). The mixture was stirred and heated to 40-45℃, and 21.5g concentrated sulfuric acid was slowly added dropwise. After the addition was complete, the mixture was kept at the same temperature. Thin-layer chromatography showed that the starting material spot disappeared. The mixture was then cooled to 15-20℃ and filtered to obtain a mixture of manganese dioxide and manganese sulfate. The filtrate was depressurized to recover acetonitrile. After no more distillate flowed out, 50g water was added dropwise, and the mixture was stirred to induce crystallization. The mixture was then filtered to obtain compound 2, which was dried at 70℃ with a yield of 95% and a purity >98%.

[0065] Example 3

[0066] 3.1 Preparation of Compound 2, where R is a methyl group, the reaction formula is:

[0067]

[0068] Add 50g of C to a 500ml four-necked reaction flask. 10 H9BrClN3O2 was added sequentially with 200g acetonitrile and 29.5g manganese dioxide (content >60%). The mixture was stirred and heated to 40-45℃, and 20.4g concentrated sulfuric acid was slowly added dropwise. After the addition was complete, the mixture was kept at the same temperature. Thin-layer chromatography showed that the starting material spot disappeared. The mixture was then cooled to 15-20℃ and filtered to obtain a mixture of manganese dioxide and manganese sulfate. The filtrate was depressurized to recover acetonitrile. After no more distillate flowed out, 50g water was added dropwise, and the mixture was stirred to induce crystallization. The mixture was filtered to obtain compound 2, which was dried at 70℃ with a yield of 95% and a purity >98%.

[0069] 3.2 Recovery of manganese salts:

[0070] Add the mixture of manganese dioxide and manganese sulfate obtained from the previous filtration to a 500ml four-necked reaction flask, add 93g of 50% concentrated alkali solution, heat to 60℃, stir for 2h, and check the pH of the system to be 12~13. Filter while hot, and the filter cake is the recovered manganese dioxide (content >50%), which can be directly reused in the preparation of compound 5. Add 12g of potassium permanganate to the filtrate, heat to 80℃ and keep warm for 2h. During the holding period, continuously check the oxidizing property of the system. Excess potassium permanganate dissolves in the alkali solution, and the product manganese dioxide will precipitate out. Filter, combine and reuse the recovered manganese dioxide in the preparation of compound 2. Titrate the free alkali in the filtrate, add sodium hydroxide to the concentration to about 50%, and directly reuse it in the next batch of manganese salt recovery.

[0071] 3.3 Recycling and reuse of manganese dioxide:

[0072] Add 50g of C to a 500ml four-necked reaction flask. 10H9BrClN3O2, then 200 g acetonitrile and 35.4 g manganese dioxide (content > 50%) were added in sequence, and stirred to warm to 40-45°C, 23.5 g concentrated sulfuric acid was slowly added dropwise, and after the dropwise addition was completed, the temperature was maintained, thin layer chromatography was used to detect the disappearance of the raw material point, the temperature was lowered to 15-20°C, and a mixture of manganese dioxide and manganese sulfate was obtained by filtration. The acetonitrile in the filtrate was recovered under reduced pressure, and after no distillate was obtained, 50 g of water was added dropwise, and compound 2 was obtained by stirring and crystallization, and was dried at 70°C, with a yield of 94.6% and a purity of > 98.5%.

[0073] Traditional synthesis process and data comparison

[0074] (1) Traditional synthesis process

[0075] Into a 500 ml four-necked reaction flask, 50 g of C 11 H 11 BrClN3O2, then 150 g of DMF was added in sequence, and stirred to warm to 80-90°C, a solid oxidizing agent (sodium persulfate, ammonium persulfate, or potassium persulfate) was slowly added in batches, and after the addition was completed, the temperature was maintained, thin layer chromatography was used to detect the disappearance of the raw material point, the temperature was lowered to 60°C, and a certain amount of water was added to precipitate the product, and compound 2 was obtained by filtration, and was dried at 70°C, with a yield of 82%-85% and a purity of 96%. The product of this process needs to be further refined.

[0076] Table 1 shows the reaction conditions of different oxidation systems

[0077]

[0078] As can be seen from Table 1, when preparing the target compound using different oxidation systems, the required reaction conditions are different. The traditional process requires a higher activation energy, and a higher reaction temperature of 80-90°C. During the addition of the peroxide, a large amount of heat is released, and it is difficult to control the reaction temperature. The system is prone to temperature overshoot, and accidents such as overflow may occur. At the same time, if the addition of the peroxide is too fast, excess peroxide may accumulate in the system, and if the operation is not proper, there is a risk of a flash explosion. The manganese dioxide oxidation process used in the present application has a relatively low activation energy, and the reaction can be carried out at a temperature of 45°C or lower. The reaction is mild, and the risk of safety accidents is smaller. In addition, manganese dioxide can be recycled, and the atomic utilization rate is improved.

[0079] The specific embodiments are merely an explanation of the application, and are not a limitation of the application. Those skilled in the art can make modifications to the embodiments without creative contribution, as long as the modifications are within the scope of the application.

Claims

1. A process for the synthesis of halogenated pyridyl pyrazole dithiocarboxylate characterized in that, The method comprises the following steps: S1, putting compound 1 into a polar solvent, adding an oxidant manganese dioxide, stirring, heating and reacting, taking sulfuric acid as a catalyst to obtain a compound 2 solution and a suspension; S2, filtering and separating the compound 2 solution and the suspension to obtain a filter cake of manganese dioxide and manganese sulfate and a reaction filtrate, concentrating the filtrate to recover the polar solvent, adding water to the filtrate to obtain compound 2 through filtration; S3, adding the filter cake into a sodium hydroxide solution to generate a manganese hydroxide solution containing manganese dioxide solid, and obtaining manganese dioxide crystals and a manganese hydroxide filtrate through filtration and separation; S4, continuously adding the manganese dioxide crystals into S1 to perform a redox reaction; S5, adding a certain amount of potassium permanganate into the manganese hydroxide filtrate to obtain manganese dioxide and precipitate, and continuously adding the manganese dioxide into S1 to perform a redox reaction after filtration. wherein Compound 1 is , Compound 2 is , and R is one of methyl, ethyl, butyl, t-butyl and isopropyl.

2. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 1, wherein, The polar solvent is acetonitrile, N, N dimethylformamide, N, N dimethylacetamide, dimethyl sulfoxide, N-methyl pyrrolidone, methanol or ethanol.

3. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 2, wherein, In S1, the temperature of stirring and heating is 25-45 DEG C.

4. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 3, wherein, In S3, the concentration of the sodium hydroxide solution is 40-50%, the filter cake is added into the sodium hydroxide solution, heated to 60-90 DEG C, and stirred for 2-4 h to make the PH reach 12-13.

5. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 4, wherein, In S5, the potassium permanganate is heated to 70-80 DEG C after being added and kept for 2-3 h.

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