Method for synthesizing high-content clethodim and intermediate thereof

Abstract

The invention discloses a method for synthesizing high-content clethodim and an intermediate thereof, and particularly relates to the field of pesticide synthesis, and the method comprises the following steps: S1, taking a toluene solution of a rearrangement compound A, sequentially adding a certain amount of an alcohol proton solvent and a solid inorganic base, then adding a certain amount of sodium alkoxide, carrying out a heat preservation reaction until the reaction is complete, cooling and filtering to obtain a reaction solution; washing the filter cake with a certain amount of toluene to obtain a compound B; in the alkaline hydrolysis process of the rearrangement compound, the introduction of water is avoided through an alcohol protic solvent system, the solvent can be recycled, the generation of wastewater in the hydrolysis and decarboxylation process of the rearrangement compound is avoided, the purification process of the product is realized in a synchronous crystallization mode in the alkaline hydrolysis process, the purity of the obtained intermediate is up to 99% or above, and the product purity is up to 99% or above. According to the method, the subsequent purification process of propionyl triketone and clethodim is not needed, the yield loss caused by the processes of high-temperature distillation, acid-base extraction and the like is avoided, and the whole technological process is simple, conforms to the green and environment-friendly concept and is suitable for industrial production.

Description

Technical Field

[0001] The present invention relates to the field of pesticide synthesis, and more specifically, to a method for synthesizing high-content clethodim and its intermediates. Background Art

[0002] Clethodim, whose chemical name is 2-{1-[(3-chloro-2-allyl)oxy]iminopropyl}-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one, belongs to the cyclohexenone herbicide class and is an important class of active substances in the field of pesticides. It has many advantages such as high efficiency, broad-spectrum biological activity and environmental friendliness.

[0003] The industrial method for preparing clethodim generally uses crotonaldehyde, ethyl mercaptan, methyl acetoacetate, etc. as raw materials, first synthesizes 6-ethylthio-3-ene-2-heptanone, and then cyclizes with dimethyl malonate, and then obtains a rearranged compound through acylation and rearrangement. Thereafter, it is hydrolyzed with liquid alkali, and then decarboxylated with hydrochloric acid or sulfuric acid in an aqueous phase system to prepare propionyltrione. After propionyltrione is purified by distillation, it reacts with chloroallyloxyamine to synthesize clethodim. Because in the production process, the hydrolysis and decarboxylation process in the aqueous phase system requires a large amount of acid and alkali to react, and there are a large number of tar substances and inorganic salts in the wastewater, which makes the wastewater complex, high COD concentration, high salt content, difficult to biodegrade, and highly polluting. At the same time, since the content of clethodim produced by the conventional production process is generally only about 90%, in order to obtain a higher content of clethodim, a large amount of acid and alkali will be consumed in the process of purifying propionyltrione or clethodim by adjusting the base and acid, extraction and washing, and a large amount of wastewater will be generated; in the process of purifying and separating tar impurities by high-temperature and high-vacuum distillation of propionyltrione, 3%-5% of the material will also be decomposed, resulting in a decrease in the overall yield of clethodim. Therefore, the synthesis and purification process from rearranged compounds to clethodim is a key step in the generation of wastewater.

[0004] In the existing patent CN111233720A, propionyltrione is purified by acid-base salt formation and extraction and impurity removal, without high-temperature distillation, to obtain a 97% content of propionyltrione, and further synthesize a 94% content of clethodim, and the purification process produces a large amount of wastewater and salt; In the existing patents CN101575307A and CN106187841A, the synthesis temperature of clethodim is reduced and the content of clethodim is increased by using a ketone complex stabilizer or replacing the solvent, but the improvement effect is limited and the purity of propionyltrione is required to be high; In the existing patent CN107162945A, a green synthesis method of clethodim is reported, in which clethodim is obtained by oxime etherification reaction in the form of reactive distillation under the action of propionyltrione organic acid catalyst, without the need for water washing, stratification, dehydration and other processes. However, the yield of the oxime ether compound preparation is low, and clethodim is partially decomposed during high-temperature synthesis, resulting in a low yield. In the existing patent CN111960977A, an acid catalyst is used to directly hydrolyze and decarboxylate propionyltrione through a reactive distillation method, which reduces the amount of acid and alkali used, but the reaction is difficult to be thorough, and there are many by-products and tar impurities, and the yield of the intermediate is significantly reduced. Summary of the invention

[0005] Aiming at the problems of large amount of wastewater generated by alkaline decarboxylation in the production process of clethodim and yield loss and wastewater generation caused by the process of purifying clethodim and propionyltrione, the inventors propose a method for synthesizing high-content clethodim and its intermediates. The inventors find that most of the impurities affecting the content of clethodim are introduced by rearrangement compounds, and the subsequent extraction and distillation processes cannot achieve good separation of impurities; the rearrangement compounds are introduced into an anhydrous mixed solvent system through an alcohol proton solvent, and the alkaline hydrolysis process can be successfully completed. The addition of sodium alcohol can make the generated alkaline hydrolysis compound crystallize smoothly, while tar impurities and other impurities are left in the organic layer mother liquor, and high-purity alkaline hydrolysis compound sodium salt solid can be obtained with high yield after solid-liquid separation; the alkaline hydrolysis compound sodium salt is directly decarboxylated by the addition of anhydrous acid in an organic solvent system, and a high-content by-product salt can be obtained by filtration, and the obtained filtrate is a propionyltrione solution, and the propionyltrione solution is directly reacted with chloroallyloxyamine to obtain a high-content clethodim. The whole process can avoid the large amount of wastewater generated by the alkaline decarboxylation and purification of clethodim and propionyltrione, directly obtain a high-content by-product salt, save the high-temperature distillation purification process of propionyltrione, avoid the high-temperature decomposition loss of materials, the process is green and environmentally friendly, and is suitable for industrial production.

[0006] To achieve the above object, the present invention provides the following technical solutions: A method for synthesizing high-content clethodim and its intermediates comprises the following steps: Step S1, taking a toluene solution of the rearranged compound A, adding a certain amount of an alcohol protic solvent and a solid inorganic base in sequence, and then adding a certain amount of sodium alcoholate, keeping the temperature to react until complete, cooling and filtering, and washing the filter cake with a certain amount of toluene to obtain a compound B; Step S2, adding a certain amount of sulfuric acid to the obtained compound B in an organic solvent to neutralize it, cooling and filtering to obtain a by-product salt, and washing the filtrate with a small amount of water to obtain a propionyltrione solution; Step S3, reacting the obtained propionyltrione solution with chloroallyloxyamine to synthesize clethodim.

[0007] In a preferred embodiment, in step S1, the protic solvent is any one of methanol, ethanol and isopropanol, preferably methanol, and the amount of the protic solvent is 1%-10% by weight of the toluene solution.

[0008] In a preferred embodiment, in step S1, the solid inorganic base is one or more of sodium hydroxide and potassium hydroxide, preferably sodium hydroxide, and the amount of the solid inorganic base is 2.0-2.3 times the molar amount of the rearrangement compound A.

[0009] In a preferred embodiment, in step S1, the sodium alkoxide is any one of sodium methoxide and sodium ethoxide, preferably sodium methoxide. The sodium alkoxide may be a sodium alkoxide solid or an alcohol solution of sodium alkoxide. The amount of sodium alkoxide used is 0.1-0.4 times the molar amount of compound A.

[0010] In a preferred embodiment, in step S1, the reaction temperature is set to 60-80°C, preferably a reflux reaction, and the alkaline hydrolysis time is set to 3-10h.

[0011] In a preferred embodiment, in step S2, the organic solvent is any one of petroleum ether, toluene, xylene and cyclohexane, preferably petroleum ether, and the amount of the organic solvent is 0.5-3 times that of compound B.

[0012] In a preferred embodiment, in step S2, the sulfuric acid is concentrated sulfuric acid with a content of 98%.

[0013] The technical effects and advantages of the method for synthesizing high-content clethodim and its intermediates of the present invention are as follows: 1. The alkaline hydrolysis process of the rearranged compound avoids the introduction of water through the alcohol proton solvent system, and the solvent can be recycled, avoiding the generation of wastewater in the hydrolysis and decarboxylation process of the rearranged compound; 2. The alkaline hydrolysis process realizes the purification process of the product by means of synchronous crystallization. The purity of the intermediate obtained is as high as over 99%. There is no need for subsequent purification of propionyltrione and clethodim, thus avoiding the yield loss caused by high-temperature distillation and acid-base extraction processes; 3. The clethodim prepared by this process has a high content and light color, which is significantly better than the traditional purification process; 4. Direct filtration during the process obtains a high content of anhydrous sodium sulfate as a by-product, which directly meets the by-product sales standards; 5. The whole process is simple, in line with the concept of green environmental protection, and suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The synthetic route of the present invention is shown in FIG. DETAILED DESCRIPTION

[0015] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Example

[0016] The present invention provides a method for synthesizing a high-content clethodim and an intermediate thereof, which specifically comprises the following steps: To 300 g of toluene solution of rearranged compound A synthesized by normal process (containing 0.218 mol of rearranged compound A), 9 g of methanol, 19.2 g of sodium hydroxide (0.48 mol), and 2.4 g of sodium methoxide solid (0.04 mol) were added in sequence under stirring; the temperature was raised to 68°C and refluxed for 4 h until the reaction was complete, the temperature was lowered and filtered, the filter cake was washed with a small amount of toluene, and dried to obtain 77.67 g of white granular alkaline hydrolysis compound B sodium salt, which was analyzed by high performance liquid chromatography (HPLC) with a purity of 99.0%; The above compound B was added with 60g of petroleum ether solvent, and concentrated sulfuric acid was added dropwise at 30°C to adjust the pH of the reaction solution to neutral. The reaction was refluxed for 2h, the temperature was lowered and filtered, and the filter cake was washed with petroleum ether. The filter cake was dried to obtain 32.5g of white crystalline sodium sulfate (dry basis content 99.2%). 25.3g of chloroallyloxyamine was added to the filtrate. After the reaction was completed, 77.1g of clethodim was obtained after acid washing, water washing and desolventizing according to the conventional process, with a content of 96.7%, and a total yield of 95.0% based on compound A.

[0017] Embodiment 2:

[0018] The present invention provides a method for synthesizing a high-content clethodim and an intermediate thereof, which specifically comprises the following steps: To 300 g of toluene solution of rearranged compound A synthesized by normal process (containing 0.218 mol of rearranged compound A), 9 g of ethanol, 18.4 g (0.46 mol) of sodium hydroxide, and 14.8 g (0.04 mol) of 20% sodium ethoxide solution were added in sequence under stirring; the temperature was raised to 78°C and refluxed for 3 h until the reaction was complete, the temperature was lowered and filtered, and the filter cake was washed with a small amount of toluene. The wet product was tested for HPLC purity of 98.8%; The above compound B was directly added to 60g of toluene solvent without drying, and concentrated sulfuric acid was added dropwise at 30°C to adjust the pH of the reaction solution to neutral. The temperature was raised to 68°C for reaction for 2h, the temperature was lowered and filtered, and the filter cake was washed with a small amount of toluene. The filter cake was dried to obtain 31.2g of white crystalline sodium sulfate (dry basis content 99.4%). 25.3g of chloroallyloxyamine was added to the filtrate for reaction. After the reaction was completed, 77.4g of clethodim was obtained after acid washing, water washing, and desolventizing, with a content of 96.5%, and the total yield was 95.2% based on compound A.

[0019] Embodiment 3:

[0020] The present invention provides a method for synthesizing a high-content clethodim and an intermediate thereof, which specifically comprises the following steps: To 300 g of toluene solution of rearranged compound A synthesized by normal process (containing 0.218 mol of rearranged compound A), 9 g of isopropanol, 17.6 g (0.44 mol) of sodium hydroxide and 4.7 g (0.09 mol) of sodium methoxide were added in sequence under stirring; the temperature was raised to 80°C and refluxed for 5 h until the reaction was complete, the temperature was lowered and filtered, and the filter cake was washed with a small amount of toluene. The wet product was tested for HPLC purity of 98.8%; The wet product of compound B was directly added with 60 g of cyclohexane solvent, and concentrated sulfuric acid was added dropwise at 35 ° C to adjust the pH of the reaction solution to neutral. The temperature was raised and refluxed for 2 h, the temperature was lowered and filtered, and the filter cake was washed with a small amount of cyclohexane. The filter cake was dried to obtain 32.8 g of white crystalline sodium sulfate (dry basis content 99.0%). The filtrate was directly added with 25.3 g of chloroallyloxyamine to react. After the reaction was completed, 76.7 g of clethodim was obtained after acid washing, water washing, and desolventizing, with a content of 96.7%, and the total yield was 94.5% based on compound A.

[0021] Embodiment 4:

[0022] The present invention provides a method for synthesizing a high-content clethodim and an intermediate thereof, which specifically comprises the following steps: To 300 g of toluene solution of rearranged compound A synthesized by normal process (containing 0.218 mol of rearranged compound A), 15 g of methanol, 19.2 g (0.48 mol) of sodium hydroxide, and 7.85 g (0.04 mol) of 30% sodium methoxide solution were added in sequence under stirring; the temperature was raised and refluxed for 3 h until the reaction was complete, the temperature was lowered and filtered, and the filter cake was washed with a small amount of toluene. The wet product was tested for HPLC purity of 99.1%; The above compound B was directly added with 60 g of cyclohexane without drying, and concentrated sulfuric acid was added dropwise at a temperature of 40 ° C to adjust the pH of the reaction solution to neutral. The temperature was raised to reflux for 2 h, the temperature was lowered and filtered, and the filter cake was washed with a small amount of cyclohexane. The filter cake was dried to obtain white crystalline sodium sulfate. 25.3 g of chloroallyloxyamine was added to the filtrate to react. After the reaction was completed, 76.5 g of clethodim was obtained after acid washing, water washing, and desolventizing, with a content of 96.8%, and a total yield of 94.4% based on compound A.

[0023] Embodiment 5:

[0024] The present invention provides a method for synthesizing a high-content clethodim and an intermediate thereof, which specifically comprises the following steps: To 300 g of toluene solution of rearranged compound A synthesized by normal process (containing 0.218 mol of rearranged compound A), 30 g of methanol, 19.2 g of sodium hydroxide (0.48 mol), and 1.2 g of sodium methoxide (0.02 mol) were added in sequence under stirring; the temperature was raised and refluxed for 3 h until the reaction was complete, the temperature was lowered and filtered, and the filter cake was washed with a small amount of toluene. The wet product was tested for HPLC purity of 99.4%; The above compound B was directly added with 60 g of petroleum ether without drying, and concentrated sulfuric acid was added dropwise at a temperature of 35 ° C to adjust the pH of the reaction solution to neutral. The temperature was raised to reflux for 2 h, the temperature was lowered and filtered, and the filter cake was washed with a small amount of petroleum ether. The filter cake was dried to obtain white crystalline sodium sulfate. 25.3 g of chloroallyloxyamine was added to the filtrate to react. After the reaction was completed, 75.9 g of clethodim was obtained after acid washing, water washing, and desolventizing, with a content of 97.1%, and the total yield was 93.9% based on compound A.

[0025] Comparative Example 1 Take 300g of compound A toluene solution (containing 0.218mol of compound A), add 66.83g of 30% liquid alkali and 50g of water in sequence under stirring, heat to 68℃ and reflux for 3h, cool and separate, extract the toluene layer with a small amount of water, combine the aqueous phases, add 75g of concentrated hydrochloric acid dropwise, decarboxylate at 65℃ for 2h, cool and add 80g of petroleum ether for extraction, wash the petroleum ether layer with alkali and water, and then desolventize to obtain 65.31g of crude propionyltrione with a content of 88.5%. , with a yield of 98.2%; the crude propionyltrione was purified by high-temperature reduced-pressure distillation to obtain 60.16g of fine propionyltrione, with a content of 93.2% and a high-temperature distillation purification yield of 97.0%; the obtained fine propionyltrione was diluted with 60g of petroleum ether, and 26.8g of chloroallyloxyamine was added to react. After acid washing and water washing, the petroleum ether was distilled off to obtain 79.72g of clethodim, with a content of 91.0%, and the total yield based on compound A was 92.46%.

[0026] Comparison of the effect of the present invention and comparative example 1 Product Purity Comparison The content of clethodim finally obtained in Comparative Example 1 is only 91.0%, which is significantly lower than the content of clethodim in the embodiments of the present invention (mostly above 96.5%); the content of the crude propionyltrione obtained in Comparative Example 1 after a series of complex treatments is 88.5%, and even after high-temperature reduced pressure distillation and purification, the content of the fine propionyltrione obtained is only 93.2%, which is also lower than the purity level of the corresponding intermediates and final products in the embodiments of the present invention. This fully demonstrates that the method of the present invention has significant advantages over the traditional method (the conventional method represented by Comparative Example 1) in improving product purity.

[0027] Comparison of total yield The total yield of the comparative example 1 based on compound A is 92.46%, while the total yield of each embodiment of the present invention is basically 93.9% or above, indicating that the synthesis method of the present invention is also superior to the conventional synthesis process adopted in the comparative example 1 in terms of overall yield, and can more efficiently utilize the raw materials to synthesize the target product clethodim.

[0028] Comparison of process complexity and environmental performance The process of Comparative Example 1 involves the use of a large amount of water (such as 50 g of water and subsequent water operations such as washing and stripping), acid and alkali (liquid alkali, concentrated hydrochloric acid), and also requires a high-temperature reduced-pressure distillation purification step. Not only is the operation relatively cumbersome and complicated, but there are also many problems in terms of wastewater generation, energy consumption, and material loss due to high-temperature decomposition. In the embodiments of the present invention, through a specific anhydrous mixed solvent system and avoiding high-temperature distillation, the generation of wastewater and the high-temperature decomposition loss of materials are effectively reduced, the process is more green, environmentally friendly, simple and efficient, and the advantages of the method of the present invention are further highlighted from the perspective of the overall process.

[0029] By comparing the above embodiments with Comparative Example 1, it can be seen that the method for synthesizing high-content sethoxydim and its intermediates proposed in the present invention has obvious advantages over traditional synthesis processes in terms of improved product purity, improved total raw material yield, and green environmental protection and simplicity of the process. It can well solve the problems of large amount of wastewater, yield loss and difficulty in increasing product content in the production process of sethoxydim mentioned in the background technology, and has good application prospects and industrial promotion value.

[0030] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art who is familiar with the present technical field can easily think of changes or substitutions within the technical scope disclosed in the present application, which should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

[0031] Finally: The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for synthesizing high-content clethodim and its intermediates, characterized in that: The steps include: Step S1, taking a toluene solution of the rearranged compound A, adding a certain amount of an alcohol protic solvent and a solid inorganic base in sequence, and then adding a certain amount of sodium alcoholate, keeping the temperature to react until complete, cooling and filtering, and washing the filter cake with a certain amount of toluene to obtain a compound B; Step S2, adding a certain amount of sulfuric acid to the obtained compound B in an organic solvent to neutralize it, cooling and filtering to obtain a by-product salt, and washing the filtrate with a small amount of water to obtain a propionyltrione solution; Step S3, reacting the obtained propionyltrione solution with chloroallyloxyamine to synthesize clethodim.

2. A method for synthesizing high-content clethodim and its intermediates according to claim 1, characterized in that: In the step S1, the protic solvent is any one of methanol, ethanol and isopropanol, and the amount of the protic solvent is 1%-10% of the weight of the toluene solution.

3. A method for synthesizing high-content clethodim and its intermediates according to claim 1, characterized in that: In step S1, the solid inorganic base is one or more of sodium hydroxide and potassium hydroxide, and the amount of the solid inorganic base is 2.0-2.3 times the molar amount of the rearrangement compound A.

4. A method for synthesizing high-content clethodim and its intermediates according to claim 1, characterized in that: In the step S1, the sodium alkoxide is any one of sodium methoxide and sodium ethoxide, and the amount of the sodium alkoxide is 0.1-0.4 times the molar amount of compound A.

5. The method for synthesizing high-content clethodim and its intermediates according to claim 1, characterized in that: In the step S1, the reaction temperature is set to 60-80° C., and the alkaline hydrolysis time is set to 3-10 h.

6. A method for synthesizing high-content clethodim and its intermediates according to claim 1, characterized in that: In step S2, the organic solvent is any one of petroleum ether, toluene, xylene and cyclohexane, and the amount of the organic solvent is 0.5-3 times that of compound B.

7. A method for synthesizing high-content clethodim and its intermediates according to claim 1, characterized in that: In step S2, the sulfuric acid is concentrated sulfuric acid with a content of 98%.

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