Continuous purification method of pyroxasulfone intermediate

Abstract

The invention provides a continuous purification method of a pyroxasulfone intermediate, which comprises the following steps: a synthesized mixed solution containing 3-chloro-5, 5-dimethyl-4, 5-dihydroisoxazole of the pyroxasulfone intermediate enters a continuous extraction liquid separation device, the mixed solution is subjected to extraction separation to obtain an organic phase and a water phase, and the lower organic phase is extracted to a buffer tank; pumping the organic phase in the buffer tank into the middle section of a continuous distillation device, keeping the continuous distillation device at negative pressure, and obtaining a primary purified product at the bottom of the continuous distillation device; and pumping the primary purified product into the middle part of a continuous rectification device, and keeping the continuous rectification device at negative pressure, wherein the liquid extracted by a first-stage condenser is the pyroxasulfone intermediate. The reaction liquid is kept to be distilled, rectified and condensed at a specific temperature during post-treatment, so that the influence of high-temperature fractions (component 2) on the subsequent oxidation reaction is effectively removed, and the purity and yield of the final product pyroxasulfone are improved. And a high-purity product (the GC purity is 99% or above) is obtained, and the method has great significance in a full-continuous process.

Description

Technical Field

[0001] The invention aims to provide a method for purifying a sulfonepyraclostrobin intermediate, belonging to the technical field of post-processing. Background Art

[0002] Pyroxasulfone is an isoxazole herbicide with the chemical name of 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxazole, molecular formula of C12H14F5N3O4S, molecular weight of 391.32, and CAS registration number of 447399-55-5. Pyroxasulfone is mainly used as a pre-emergence blocking agent, mainly for killing broad-leaved grasses in the Gramineae family, and has many advantages: it is applicable to a wide range of crops, such as wheat, corn, peanuts, rice, soybeans, cotton, etc.; it is safe for the environment and for the current and next crops; and its effective period can reach about 28 days.

[0003] The current intermittent post-processing operation method is: after liquid separation, the solvent is evaporated by rotary evaporation for a long time, and then the product is purified by vacuum distillation. The high-temperature fractions produced during vacuum distillation in this method lead to reduced product purity and have a significant impact on the purity and yield of subsequent reactions; each batch of processed products will produce a lot of product loss when switching fractions, resulting in a reduction in yield. In addition, the intermittent post-processing method greatly reduces the efficiency of post-reaction processing, resulting in the post-processing speed not keeping up with the reaction speed. The actual purity is less than 95%. Summary of the invention

[0004] The object of the present invention is to provide a method for purifying a sulfonepyraclostrobin intermediate.

[0005] The method for purifying the sulfonepyraclostrobin intermediate comprises the following steps: S1: The synthesized mixed solution containing sulfonepyraclostrobin intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole enters a continuous extraction and liquid separation device, and the mixed solution is extracted and separated to obtain an organic phase and an aqueous phase, and the lower organic phase is extracted to a buffer tank; S2: The organic phase in the buffer tank is pumped into the middle section of the continuous distillation device to maintain the continuous distillation device at negative pressure. The bottom of the continuous distillation device is the primary purified product; S3: Pump the once purified product into the middle of the continuous distillation device, and keep the continuous distillation device at negative pressure. The liquid extracted from the primary condenser is the sulfonepyraclostrobin intermediate.

[0006] In the step S1, the mixed solution for synthesizing the sulfone-containing pyraclostrobin intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole contains organic solvents, 5,5-dimethyl-3-(2-methylprop-1-en-1-yl)-4,5-dihydroisoxazole, dichloroformaldehyde oxime dimer and other impurities, and the content of the impurities is approximately 60%.

[0007] During the process of the mixed solution entering the continuous extraction and liquid separation device, the gas generated by the reaction is discharged; the organic phase and the aqueous phase are separated, the upper aqueous phase is the waste liquid, the desired product is dissolved in the organic phase, and the organic phase is stored in a buffer tank; the upper aqueous phase liquid is extracted through overflow, and the lower liquid is extracted through a feed pump.

[0008] In the extraction and separation process, the extraction solvent is selected from C1-C3 halogenated hydrocarbons selected from methyl halogenated hydrocarbons, ethyl halogenated hydrocarbons, and propyl halogenated hydrocarbons; the halogen substitution is monohalogen substitution or polyhalogen substitution; the halogen is selected from any one of F, Cl, and Br. The C1-C3 halogenated hydrocarbon is selected from any one of CH3X, CH2X2, CHX3, CX4, CH3CH2X, CH3CHX2, CH3CX3, CH2CH2X2, CH1CH1X4, CX3CX3, CH3CH2CH2X, CH3CH2CHX2, CH3CH2CX3, CH3CHX1CH3, CH3CX2CH3, CH2XCH2CH2X, CH2XCHXCH2, CHX2CH2CHX2, CX3CH2CX3, CX3CHXCH3, (CH3)2CHX, (CH3)3CX, wherein X is selected from any one of F, Cl, and Br.

[0009] The C1-C3 alcohol is selected from any one of CH3OH, CH3CH2OH, OHCH2CH2OH, (CH3)2CHOH, and (CH3)3COH.

[0010] The C2-C6 ether is selected from any one of CH3OCH3, CH3CH2OCH3, CH3CH2OCH2CH3, CH3CH2CH2OCH3, CH3CH2CH2OCH2CH3, and CH3CH2CH2OCH3CH2CH2.

[0011] The C2-C6 esters are selected from any one of methyl formate, ethyl formate, propyl formate, methyl acetate, ethyl acetate, propyl acetate, methyl propionate, ethyl propionate and propyl propionate.

[0012] In the step S1, the mixed solution containing the sulfonepyraclostrobin intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole enters the continuous extraction and separation device, and the lower layer is extracted into the buffer tank so that the separation surface of the organic phase and the aqueous phase is always kept in the middle position of the extraction and separation device.

[0013] In the step S2, the organic phase in the buffer tank enters the middle section of the continuous distillation device through a feed pump, and the used solvent is removed by continuous distillation. The vaporized solvent enters the condenser through the upper outlet of the device and is condensed, and collected for reuse. The tail of the condenser is connected to a vacuum pump to maintain a negative pressure in the continuous distillation device. The collection tank at the bottom of the device collects the purified product once.

[0014] The vacuum degree range of the continuous distillation apparatus in S2 is -0.01 to -0.1 Mpa; the temperature range of the continuous distillation apparatus is 30 to 60° C. The organic phase is pumped into the 1 / 3 to 2 / 3 position of the continuous distillation apparatus.

[0015] The condenser temperature range described in S2 is 0 ~ -10 ℃.

[0016] In the step S3, the liquid in the primary purification product collection tank is pumped into the middle of the continuous distillation device through a feed pump, and the trace light components and all heavy components are distilled and removed. The liquid after the primary condenser is controlled to flow back to the continuous distillation device, and the rear of the secondary condenser is connected to a vacuum pump to maintain the continuous distillation device at a negative pressure. The liquid extracted from the primary condenser is the desired product.

[0017] The vacuum degree range of the continuous distillation device in S3 is -0.01 ~ -0.5 Mpa; the temperature range of the continuous distillation device is 130 ~ 200 ° C. The liquid inlet position of the once purified product is at the 1 / 3 ~ 2 / 3 position of the continuous distillation device.

[0018] The once purified product in S3 begins to reflux 10 to 30 minutes after entering the continuous distillation device, and the reflux ratio ranges from 0.1 to 0.3.

[0019] The temperature range of the first condenser in S3 is 30-60°C. The temperature range of the second condenser is 0 ~ -20°C.

[0020] The feed pump is a self-feeding pressure feeder for a horizontal flow pump. The continuous purification device is made of glass, PTFE, and Hastelloy. The continuous distillation device and the continuous rectification device are spherical heat exchange tubes and thorn-shaped heat exchange tubes. The condenser is a serpentine condenser and a spherical condenser. The connecting pipe used is a PTE hose or a PEEK tube.

[0021] Technical Effects The present invention is of great significance in order to overcome the shortcomings of the prior art, including low product purity, low yield, significant waste of cold and heat sources during the reaction process, long processing time, complicated steps, etc.

[0022] The innovation of the present invention is to use continuous flow technology to perform post-processing purification in the synthesis of sulfonepyraclostrobin, which reduces the difficulty of post-processing of the amplified reaction compared to the intermittent reaction post-processing. This technology adopts a continuous operation method, which can be well connected with the previous continuous flow reaction process; the organic solvent removed by distillation can be reused; the time required for purification is greatly reduced, and the purification operation steps are simplified. This technology can keep the reaction solution distilled, rectified and condensed at a specific temperature during post-processing, effectively remove the influence of the high-temperature fraction (component 2) on the subsequent oxidation reaction, so that the purity and yield of the final product sulfonepyraclostrobin are improved. And a high-purity product (GC purity is 99% and above) is obtained, which is of great significance to the full continuous process. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a process flow chart of the present invention. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is directed to the continuous flow synthesis method of the intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole described in detail in patent CN117486821A. However, although the purity of the unpurified product is relatively high, a certain amount of impurities still exist in the product. The impurities will reduce the yield and purity of subsequent reactions to a certain extent.

[0025] In this patent, taking Example 1 as an example, the product obtained has a yield of 85% and a purity of 96.9%, wherein impurities include 5,5-dimethyl-3-(2-methylprop-1-en-1-yl)-4,5-dihydroisoxazole, dimer of dichloroformaldehyde oxime and other impurities.

[0026] Example 1 A method for continuous purification using 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole, The following steps are involved: Preheat the continuous distillation device and the continuous rectification device to 35°C and 180°C respectively. Set the temperature of condenser 6 to -10°C, the temperature of the first condenser 12 to 35°C, and the temperature of the second condenser to -10°C. Control the vacuum degree of the continuous distillation device 5 to -0.1 Mpa, and the vacuum degree of the continuous rectification device 11 to -0.1 Mpa.

[0027] The mixed solution of the synthesized sulfone-containing pyrazoline intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole was fed into the continuous extraction and liquid separation device at 20 ml / min. The organic solvent was dichloromethane. The upper aqueous phase waste liquid and the waste gas CO2 generated in the reaction were separated. The lower layer was a dichloromethane organic phase. The dichloromethane organic phase was extracted to the buffer tank 3 by the extraction pump 2 at a flow rate of 8 ml / min to control the liquid-liquid interface to be located in the middle of the liquid separation device. The flow rate of the inlet pump 4 was controlled to be 10 ml / min to continuously send the organic phase in the buffer tank to the 1 / 2 position of the continuous distillation device. The organic solvent was condensed by the condenser and reused, and the once purified product entered the collection tank 9. The flow rate of the inlet pump 10 was controlled to be 3 ml / min to continuously send the once purified product in the buffer tank to the 1 / 2 position of the continuous distillation device. The lower heavy component waste liquid flowed into the collection tank 16 and was continuously extracted by the extraction pump 17. The upper light component enters the primary condenser and the secondary condenser in turn. The primary condenser 12 produces the desired product, and the reflux ratio is controlled to be 0.1. The secondary condenser 13 produces the dichloromethane solvent and trace reaction by-products that have not been completely evaporated in the previous step of continuous distillation, and the product purity is 99.95%. The solvent recovered by distillation can reach a purity of more than 99.9% when it is reused in the next batch.

[0028] Example 2 This example is the same as Example 1, except that the organic phase solvent in this example is ethyl acetate, the temperature of the continuous distillation apparatus is 50° C., and the temperature of the primary condenser is 50° C. The purity of the obtained product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is 99.97%.

[0029] Example 3 This example is the same as Example 1, except that the organic phase solvent in this example is ethylene glycol, the temperature of the continuous distillation device is 50° C., and the temperature of the primary condenser is 50° C. The purity of the obtained product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is 98.70%.

[0030] Example 4 This example is the same as Example 1, except that the continuous distillation feed position in this example is 2 / 3 of the distance from the top of the device, and the continuous rectification feed position is 2 / 3 of the distance from the top of the device. The purity of the obtained product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is 99.83%.

[0031] Comparative Example 1 This example is the same as Example 1, except that the continuous distillation temperature in this example is 50°C and the continuous rectification temperature is 140°C. The purity of the obtained product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is 99.32%. Although the yield is high, the purity of the organic solvent obtained by distillation decreases and cannot be reused; the yield of the obtained product decreases by 5% compared with the previous example. Incompletely purified product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole was detected in the heavy component waste liquid.

[0032] Comparative Example 2 This example is the same as Example 1, except that the continuous distillation temperature in this example is 200° C. The purity of the obtained product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is 98.55%. Due to the high distillation temperature, the dimer content of the by-product 5,5-dimethyl-3-(2-methylprop-1-en-1-yl)-4,5-dihydroisoxazole and dichloroformaldehyde oxime increases.

[0033] Comparative Example 3 This embodiment is the same as 1, except that the vacuum degree of the continuous distillation device 5 is -0.05 Mpa, and the vacuum degree of the continuous rectification device 11 is -0.05 Mpa. The purity of the obtained product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole is 98.75%. If the distillation vacuum degree is too small, the organic solvent will not be completely evaporated, which will affect the temperature of the subsequent continuous distillation and may be dangerous.

[0034] Comparative Example 4 This comparative example adopts intermittent post-treatment, the organic solvent is dichloromethane, the continuous flow reaction is continuously operated for five hours, and about 6 L of the reaction liquid is collected. The liquid is separated twice using a 5 L separatory funnel to obtain an organic phase. The organic phase is rotary evaporated for about 3 hours to obtain a concentrated product. The concentrated product is subjected to vacuum distillation for about 5 hours to obtain the product 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole with a purity of 98.87%. The intermittent purification takes longer time than the continuous purification, and the process is cumbersome.

Claims

1. A continuous purification method for a sulfonepyraclostrobin intermediate, characterized in that: The steps include: S1: The synthesized mixed solution containing sulfonepyraclostrobin intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole enters a continuous extraction and liquid separation device, and the mixed solution is extracted and separated to obtain an organic phase and an aqueous phase, and the lower organic phase is extracted to a buffer tank; S2: The organic phase in the buffer tank is pumped into the middle section of the continuous distillation device to maintain the continuous distillation device at negative pressure. The bottom of the continuous distillation device is the primary purified product; S3: Pump the once purified product into the middle of the continuous distillation device, and keep the continuous distillation device at negative pressure. The liquid extracted from the primary condenser is the sulfonepyraclostrobin intermediate.

2. The purification method according to claim 1, characterized in that During the extraction and separation process, the extraction solvent is selected from an organic solvent such as any one of C1-C3 halogenated hydrocarbons, C1-C3 alcohols, C2-C6 ethers, and C2-C6 esters.

3. The purification method according to claim 1, characterized in that The mixed solution containing the sulfonepyraclostrobin intermediate 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole enters the continuous extraction and separation device, and the lower organic phase is extracted into the buffer tank so that the separation surface of the organic phase and the aqueous phase is always kept in the middle position of the extraction and separation device.

4. The purification method according to claim 1, characterized in that The vacuum degree range of the continuous distillation apparatus in S2 is -0.01 ~ -0.1 Mpa; the temperature range of the continuous distillation apparatus is 30 ~ 60 ° C.

5. The purification method according to claim 4, characterized in that The organic phase is pumped into the continuous distillation apparatus at the 1 / 3 to 2 / 3 position.

6. The purification method according to claim 1, characterized in that The vacuum degree range in the continuous distillation device described in S3 is -0.01 ~ -0.5 Mpa; the temperature range in the continuous distillation device is 130 ~ 200 °C.

7. The purification method according to claim 6, characterized in that The liquid inlet position of the once purified product is at the 1 / 3 to 2 / 3 position of the continuous distillation device.

8. The purification method according to claim 1, characterized in that The once purified product in S3 begins to reflux 10 to 30 minutes after entering the continuous distillation device, and the reflux ratio ranges from 0.1 to 0.

3.

9. The purification method according to claim 1, characterized in that The continuous purification device is made of glass, PTFE, and Hastelloy; the continuous distillation device and the continuous rectification device are spherical heat exchange tubes and thorn-shaped heat exchange tubes.

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