Synthesis process of halogenated pyridyl pyrazolidine carboxylate

Abstract

The invention discloses a high-efficiency green synthesis process of halogenated pyridyl pyrazolidine carboxylate, and relates to the technical field of compound synthesis, and the high-efficiency green synthesis process comprises the following steps: S1, putting a compound 1 into a polar solvent, adding an oxidant manganese dioxide, stirring, heating and reacting, and taking sulfuric acid as a catalyst to obtain a compound 2 solution and a suspended matter; s2, filtering and separating the compound 2 solution and the suspended matter 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, and filtering to obtain a compound 2; and S3, adding the filter cake into a sodium hydroxide solution to generate a manganese hydroxide solution containing a manganese dioxide solid, and filtering and separating to obtain the manganese dioxide solid and a manganese hydroxide filtrate. According to the technological process, through selection of a potassium permanganate regenerated manganese dioxide oxidation system, efficient utilization of an oxidizing agent, high conversion rate and high selectivity of a reaction system and reduction of three wastes in the process are achieved, and green synthesis of halogenated pyridyl pyrazolidine carboxylate is completed.

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 moth, etc.) and Hemiptera (such as peach aphid, cotton aphid, potato leafhopper, silver leaf whitefly, etc.) pests, and is mainly used for pest control on soybean, fruits and vegetables, rice, cotton, corn and other crops. 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 the environment, and has good adaptability to many major insecticides, and can be used for pest control on hundreds of crops. Compound 2 (halogenated pyridyl pyrazole alkane carboxylate) is one of the 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 other peroxides, in a polar solvent, and then water is added for crystallization 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 detected by HPLC is generally less than 88%, 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 amount of mother liquor obtained 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. 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; S2, compound 2 solution and suspension are obtained by filtering and separating 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 compound 2 is obtained by filtering after adding water; 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 filtering and separating; S4, the manganese dioxide crystal is continuously added to S1 for redox reaction; S5, a certain amount of potassium permanganate is added to the manganese hydroxide filtrate, manganese dioxide is obtained by reaction and precipitation, and the manganese dioxide is continuously added to S1 for redox reaction after filtering.

[0007] Further, the chemical formula of compound 1 is C9H6BrClN3O2R; The chemical formula of compound 2 is C9H4BrClN3O2R; R is one of methyl, ethyl, butyl, tert-butyl and isopropyl.

[0008] Further, the cycle equation of manganese dioxide is: ① ; ② ; ③ .

[0009] Further, the polar solvent is acetonitrile, N,N dimethylformamide, N,N dimethylacetamide, dimethyl sulfoxide, N-methyl pyrrolidone, methanol or ethanol.

[0010] Further, in step S1, the temperature of stirring and heating is 25-45 DEG C.

[0011] Further, in step S3, the concentration of the sodium hydroxide solution is 40-50%, the filter cake is added to the sodium hydroxide solution, heated to 60-90 DEG C, and stirred for 2-4 h, so that the PH value reaches 12-13.

[0012] Further, in step S5, after adding potassium permanganate, heating to 70-80℃ and keeping for 2-3h.

[0013] By adopting the technical scheme, the application has the following beneficial effects: Compared with the traditional synthesis process, the synthesis process of the embodiment 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 required for 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 by selecting the manganese dioxide oxidation system regenerated by potassium permanganate, and completes the green synthesis of halogenated pyridyl pyrazole alkylamine. DETAILED DESCRIPTION

[0014] The embodiment of the application provides a synthesis process of halogenated pyridyl pyrazole alkylamine, which comprises the following steps: 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; 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; 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; S4, continuously adding the manganese dioxide crystals to S1 to perform a redox reaction; S5, adding a certain amount of potassium permanganate to the manganese hydroxide filtrate to obtain manganese dioxide and precipitate, and filtering to continuously add to S1 to perform a redox reaction.

[0015] The process realizes efficient utilization of the oxidizing agent, high conversion rate and high selectivity of the reaction system by selecting the manganese dioxide oxidation system regenerated by potassium permanganate.

[0016] The chemical general formula of compound 1 is C9H6BrClN3O2R; The chemical general formula of compound 2 is C9H4BrClN3O2R; R is one of methyl, ethyl, butyl, tert-butyl and isopropyl, and is preferably methyl.

[0017] The circulation equation of manganese dioxide is: ① ; ② ; ③ .

[0018] The polar solvent is acetonitrile, N,N dimethylformamide, N,N dimethylacetamide, dimethylsulfoxide, N-methylpyrrolidone, methanol or ethanol, preferably acetonitrile.

[0019] In step S1, the temperature of the stirring and heating is 25-45℃.

[0020] In step S3, the concentration of the sodium hydroxide solution is 40-50%, after the filter cake is added to the sodium hydroxide solution, heating to 60-90℃ and stirring for 2-4h, the PH reaches 12-13, the preferred conditions are 40% sodium hydroxide solution, the reaction temperature is 80℃, and the reaction time is 3h.

[0021] In step S5, after adding potassium permanganate, heating to 70-80℃ and keeping for 2-3h.

[0022] In reaction ①, under strong acidic conditions, manganese dioxide first shows strong oxidizing properties, converting compound 1 to compound 2, while the manganese ion in manganese dioxide is reduced from +4 to +2, generating a byproduct: manganese sulfate, which precipitates in the system. After the reaction is completed, the filtrate and filter cake are separated by filtration, the filtrate is an acetonitrile / compound 2 solution, and the filter cake is a mixture of manganese dioxide / manganese sulfate.

[0023] In reaction ②, the filter cake is added to the lye, at which time the manganese sulfate is first dissolved in water, then reacts with the base to form manganese hydroxide, which is dissolved in the lye, while the remaining manganese dioxide precipitates in the system. After filtration, high-purity manganese dioxide and manganese hydroxide / sodium hydroxide solution are obtained, and the manganese dioxide is dried and directly used in reaction ①.

[0024] In reaction ③, potassium permanganate is added to the manganese hydroxide / sodium hydroxide solution, and under alkaline conditions, potassium permanganate exhibits strong oxidizing properties, oxidizing the +2 manganese ion to +4 manganese dioxide, while the +7 manganese ion in potassium permanganate is reduced to +4 manganese dioxide. In the reaction process, manganese is recycled, improving atomic utilization and atomic economy.

[0025] Example 1 1.1. Preparation of compound 2, R is ethyl, the reaction formula is: ; Into a 500ml four-necked reaction flask, 50g of compound 1 is added, 50ml of acetonitrile is added, and the mixture is stirred and heated to 40℃, then 5g of manganese dioxide is added, and the mixture is heated to 60℃ and stirred for 2h, after the reaction is completed, the mixture is cooled to room temperature, and the filter cake is separated by filtration, the filtrate is acetonitrile / compound 2 solution, and the filter cake is manganese dioxide / manganese sulfate mixture. 11 H 11BrClN3O2, then 200 g of acetonitrile and 32 g of manganese dioxide (content > 60%) were added in turn, and stirred to warm to 25-30°C, 22.1 g of concentrated sulfuric acid was slowly added dropwise, and after dropping, the temperature was kept constant, thin layer chromatography was used to detect the disappearance of the raw material point, and the temperature was lowered to 15-20°C, and a mixture of manganese dioxide and manganese sulfate was obtained by filtration, the filtrate was recovered by reducing pressure, and after no distillate flowed out, 50 g of water was added dropwise, and compound 2 was obtained by stirring and crystallizing, and filtering, and drying at 70°C, with a yield of 95% and a purity of > 98%.

[0026] Compared with the traditional process, the wastewater is greatly reduced, only 10-20% of the traditional process, achieving the purpose of reducing the discharge of three wastes.

[0027] 1.2. Recovery of manganese salt A mixture of manganese dioxide and manganese sulfate obtained by filtering in the previous step was added to a 500 ml four-necked reaction flask, 80 g of 50% concentrated lye was added, and the temperature was raised to 60°C, and stirred for 2 h, and the system PH was detected to be 12-13, and filtered while hot, and the filter cake was recovered manganese dioxide (content > 50%), which could be directly used in the preparation of compound 3, 10 g of potassium permanganate was added to the filtrate, the temperature was raised to 80°C, and the system was kept constant for 2 h, and the oxidation of the system was continuously detected during the constant temperature period, the excess potassium permanganate was dissolved in the lye, and the product manganese dioxide was precipitated, which was filtered and recovered to be used in the preparation of compound 2, and the filtrate was titrated with free base, and sodium hydroxide was added to make the concentration about 50%, which was directly used in the recovery of manganese salt in the next batch.

[0028] In the recovery process of manganese salt, the lye can be repeatedly used by adding sodium hydroxide, which can be used for about 10 times, and the wastewater can be directly treated in a three-effect evaporator after pretreatment, which is a high-salt wastewater, achieving the purpose of reducing the discharge of three wastes.

[0029] 1.3. Use of recovered manganese dioxide A 500 ml four-necked reaction flask was charged with 50 g of C 11 H 11 BrClN3O2, then 200 g of acetonitrile and 32 g of manganese dioxide (content > 60%) were added in turn, and stirred to warm to 25-30°C, 22.1 g of concentrated sulfuric acid was slowly added dropwise, and after dropping, the temperature was kept constant, thin layer chromatography was used to detect the disappearance of the raw material point, and the temperature was lowered to 15-20°C, and a mixture of manganese dioxide and manganese sulfate was obtained by filtration, the filtrate was recovered by reducing pressure, and after no distillate flowed out, 50 g of water was added dropwise, and compound 2 was obtained by stirring and crystallizing, and filtering, and drying at 70°C, with a yield of 95% and a purity of > 98%.

[0030] The effective content of recovered manganese dioxide was detected by titration, which was > 50% and could be directly used in the reaction, improving the atomic economy and atomic utilization, and reducing the synthesis cost of compound 2.

[0031] Example 2 2.1 Preparation of compound 2, where R is butyl, the reaction formula is: ; Add 50g of C to a 500ml four-necked reaction flask. 13 H 13 BrClN3O2 was added, followed by 200g acetonitrile and 31g manganese dioxide (content >60%). 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%.

[0032] 2.2 Recovery of manganese salts 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 4. 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 with the filtrate, add sodium hydroxide to the concentration to about 50%, and directly reuse it in the next batch of manganese salt recovery.

[0033] 2.3 Recycling and reuse of manganese dioxide: 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%.

[0034] Example 3 3.1 Preparation of Compound 2, where R is a methyl group, the reaction formula is: ; Add 50g of C to a 500ml four-necked reaction flask. 10H9BrClN3O2, then 200 g acetonitrile and 29.5 g manganese dioxide (content > 60%) were added in turn, and stirred to warm to 40-45°C, 20.4 g concentrated sulfuric acid was slowly added dropwise, and after dropping, the temperature was kept constant, thin layer chromatography was used to detect the disappearance of the raw material point, and the temperature was lowered to 15-20°C, and the mixture of manganese dioxide and manganese sulfate was obtained by filtration, the filtrate was recovered by reducing pressure, and after no distillate was obtained, 50 g of water was added dropwise, and the product was obtained by stirring and crystallization, and compound 2 was obtained by filtration, and dried at 70°C, with a yield of 95% and a purity of > 98%.

[0035] 3.2 Recovery of manganese salt: The mixture of manganese dioxide and manganese sulfate obtained by filtration in the previous step was added to a 500 ml four-necked reaction flask, 93 g of 50% concentrated lye was added, and the temperature was raised to 60°C, and stirred for 2 h, and the system PH was detected to be 12-13, and then filtered while hot, and the filter cake was recovered manganese dioxide (content > 50%), which could be directly used in the preparation of compound 5, 12 g of potassium permanganate was added to the filtrate, the temperature was raised to 80°C, and the system was kept constant for 2 h, and the oxidation of the system was continuously detected during the constant temperature period, the excess potassium permanganate was dissolved in the lye, and the product manganese dioxide was precipitated, which was filtered and recovered to be used in the preparation of compound 2, and the filtrate was titrated with free base, and sodium hydroxide was added to make the concentration about 50%, which was directly used in the recovery of manganese salt in the next batch.

[0036] 3.3 Recovery of manganese dioxide: Into a 500 ml four-necked reaction flask, 50 g of C 10 H9BrClN3O2, then 200 g acetonitrile and 29.5 g manganese dioxide (content > 60%) were added in turn, and stirred to warm to 40-45°C, 20.4 g concentrated sulfuric acid was slowly added dropwise, and after dropping, the temperature was kept constant, thin layer chromatography was used to detect the disappearance of the raw material point, and the temperature was lowered to 15-20°C, and the mixture of manganese dioxide and manganese sulfate was obtained by filtration, the filtrate was recovered by reducing pressure, and after no distillate was obtained, 50 g of water was added dropwise, and the product was obtained by stirring and crystallization, and compound 2 was obtained by filtration, and dried at 70°C, with a yield of 95% and a purity of > 98%.

[0037] Traditional synthesis process and data comparison (1) Traditional synthesis process Into a 500 ml four-necked reaction flask, 50 g of C 11 H 11 BrClN3O2, then 150 g of DMF was added in turn, and stirred to warm to 80-90°C, then solid oxidizing agent (sodium persulfate, ammonium persulfate, or potassium persulfate) was slowly added in batches, and after adding, the temperature was kept constant, thin layer chromatography was used to detect the disappearance of the raw material point, and 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 dried at 70°C, with a yield of 82%-85% and a purity of 96%, and the product of this process still needs to be further refined.

[0038] Table 1 is the reaction condition of different oxidation systems ; From Table 1, it can be seen that when different oxidation systems are used to prepare the target compound, the required reaction conditions are different. The activation energy required by the traditional process is relatively high, and a higher reaction temperature is required, which has reached 80-90℃. In the process of feeding peroxide, a large amount of heat is released from the system, and the reaction temperature is difficult to control. The system is easy to be out of temperature, and accidents such as out of material may occur. At the same time, when the feeding speed of peroxide is too fast, there may be excess peroxide accumulated in the system. When the personnel operation is improper, there may be a risk of safety accidents such as flash explosion. The process using manganese dioxide oxidation in the embodiments of the present application has a relatively low activation energy required for reaction, which can react below 45℃. At the same time, the reaction is mild, and the risk of safety accidents is smaller. At the same time, manganese dioxide can be recycled, which improves the atomic utilization rate.

[0039] The specific embodiments are only an explanation of the invention, and are not a limitation of the invention. Those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, as long as the modifications are within the protection scope of the invention, and are protected by the patent law.

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 reaction filtrate to recover the polar solvent, adding water to the reaction filtrate to obtain compound 2 by filtration; S3, adding the filter cake into a sodium hydroxide solution to generate a manganese hydroxide solution and contain manganese dioxide solid, and obtaining manganese dioxide crystals and a manganese hydroxide filtrate by filtering and separating the manganese dioxide solution; S4, continuously adding the manganese dioxide crystals into S1 to perform a redox reaction; S5, adding a quantitative 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 filtering.

2. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 1, wherein, The chemical general formula of the compound 1 is C9H6BrClN3O2R. The chemical general formula of the compound 2 is C9H4BrClN3O2R. R is one of a methyl group, an ethyl group, a butyl group, a tert-butyl group and an isopropyl group.

3. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 2, wherein, The regeneration cycle equation of the manganese dioxide is: ① ； ② ； ③ 。 4. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 3, wherein, The polar solvent is acetonitrile, N,N dimethylformamide, N,N dimethylacetamide, dimethyl sulfoxide, N-methyl pyrrolidone, methanol or ethanol.

5. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 4, wherein, In the step S1, the temperature of the stirring and heating is 25-45 DEG C.

6. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 5, wherein, In the step 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.

7. The process for the synthesis of halogenated pyridinyl pyrazole dithiocarboxylate according to claim 6, wherein, In the step S5, the potassium permanganate is added and heated to 70-80 DEG C and kept for 2-3 h.

Images