Process for the preparation of chlorenvinphos

Abstract

The application relates to the technical field of pesticides and discloses a preparation method of chlobenzoic ring ester. The method comprises the following steps: adding chloroacetyl chloride into a mixed solution containing pleuromutilin, an acid binding agent and a solvent in a dropwise manner to generate a reaction to obtain chlobenzoic ring ester. The preparation method of chlobenzoic ring ester provided by the application has the advantages of reasonable design, mild reaction condition, easy-to-obtain raw materials, convenient operation, high product yield, suitability for large-scale production and good industrial replicability.

Description

Technical Field

[0001] This invention relates to the field of pesticide technology, specifically to a method for preparing chlorpyrifos. Background Technology

[0002] The control of bacterial diseases in crops has always been a global challenge. Due to their explosive outbreaks, rapid spread, difficulty in control, and limited availability of effective treatments, the severity of their damage has become increasingly apparent. Currently, thiamethoxam zinc and inorganic copper formulations are commonly used to control bacterial diseases. However, due to long-term use, pathogens have gradually developed resistance to these agents, leading to decreased control efficacy.

[0003] CN118878418A discloses an ester-containing truncated pleurotin derivative, its preparation method, and its uses. This is a novel bactericide independently developed by Guizhou University and possesses independent intellectual property rights. The structural formula of this ester-containing truncated pleurotin derivative is shown in Formula T: .

[0004] This bactericide is a highly effective and low-toxicity bactericide. When R is chloromethyl, the resulting structural formula is:

[0005] Its chemical name is (3aR,4R,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propionyl-cyclopentyl[8]cycloocten-5-yl-2-(2-chloroacetoxy)acetate, named chlorpyrifos, and has been approved by the National Pesticide Standardization Technical Committee (2024) Agricultural Standard No. 096.

[0006] Chloramphenicol is characterized by its outstanding efficacy in controlling bacterial plant diseases and its low cost, which can significantly promote increased production and income for farmers. Chloramphenicol exhibits excellent antibacterial activity against bacterial plant diseases, superior to truncated pleurotin, and can be used to prepare plant pathogen control agents. Moreover, its preparation method is simple and the production cost is low.

[0007] The patent document discloses a synthetic process for chlorpyrifos (see Example 2). However, the synthesis scale is only in the gram range with a low yield (only 80.5%), and the yield will further decrease upon scaling up. Furthermore, scaling up also presents issues related to reaction safety and environmental pollution.

[0008] For the reasons mentioned above, there is an urgent need to improve the synthesis process of chlorpyrifos to enable high-yield, safe, and environmentally friendly industrial production in tonnes and above. Summary of the Invention

[0009] The purpose of this invention is to overcome the problems existing in the prior art and provide a method for preparing chlorpyrifos.

[0010] To achieve the above objectives, the present invention provides a method for preparing chlorpyrifos, wherein the method comprises: adding chloroacetyl chloride dropwise to a mixed solution containing truncated pleurotin, an acid-binding agent and a solvent, and reacting to obtain chlorpyrifos.

[0011] The beneficial technical effects achieved by the present invention through the above technical solution are as follows: The preparation method of chlorpyrifos provided by this invention is reasonably designed, with mild reaction conditions, readily available raw materials, convenient operation, high product yield, and is suitable for large-scale production, with good industrial reproducibility. Detailed Implementation

[0012] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0013] This invention provides a method for preparing chlorpyrifos, wherein the method comprises: adding chloroacetyl chloride dropwise to a mixed solution containing truncated pleurotin, an acid-binding agent and a solvent, and reacting to obtain chlorpyrifos.

[0014] The dripping method used in this invention can specifically employ industrial methods such as constant pressure dripping or pump flow control dripping.

[0015] The reaction route of this invention is as follows:

[0016] Current synthetic processes involve directly mixing truncated pleurotin and chloroacetyl chloride in a solvent and reacting at room temperature. This process suffers from reduced selectivity in the primary alcohol reaction with chloroacetyl chloride and high selectivity in the secondary alcohol side reaction. The existing process is limited to gram-scale synthesis with a yield of only 80.5%. Scale-up further reduces the selectivity of the hydroxyl group reaction, generating numerous byproducts and leading to a further decrease in yield. The chemical equations for these byproducts are as follows:

[0017] The preparation process of chlorpyrifos provided by this invention is simpler, lower in cost, higher in reaction yield, and less environmentally impactful than existing processes, making it more suitable for industrial production.

[0018] In some embodiments of the present invention, the acid-binding agent is selected from at least one of triethylamine, pyridine, potassium carbonate, potassium bicarbonate and potassium hydroxide, preferably selected from at least one of triethylamine, pyridine and potassium carbonate.

[0019] In some embodiments of the present invention, the solvent is selected from at least one of benzene, toluene, xylene, acetonitrile, and dichloroethane, preferably at least one of toluene and acetonitrile. Existing synthesis processes use DMF as a solvent, which has a high boiling point, is miscible with water, and is difficult to separate, resulting in difficulties in recovery and the generation of large amounts of DMF wastewater. The solvent used in the present invention is immiscible with water, and the azeotropic distillation principle allows for direct separation of the solvent and water during the distillation process, enabling the recovery and reuse of both.

[0020] In some embodiments of the present invention, the mass ratio of truncated pleurotin to chloroacetyl chloride is 1-1.1:0.25-0.40, preferably 1-1.05:0.28-0.36.

[0021] In some embodiments of the present invention, the mass ratio of truncated pleurotin to solvent in the mixed solution is 1-1.1:2-5, preferably 1-1.05:2.5-4.

[0022] In some embodiments of the present invention, the mass ratio of truncated pleurotin to acid-binding agent in the mixed solution is 1-1.1:0.2-0.5.

[0023] In some embodiments of the present invention, the temperature of the reaction is -10 to 15°C, for example -10°C, -5°C, 0°C, 5°C, 10°C, 15°C, etc., and any value within the range of any two of the above values, preferably -5 to 10°C, and more preferably 0-5°C.

[0024] The reaction of truncated pleurotin with chloroacetyl chloride is a violently exothermic reaction. Existing synthetic processes involve the reaction at room temperature; however, scaling up to a 5L scale results in abnormally significant temperature rises and runaway reactions. This application addresses this issue by controlling the reaction temperature to avoid the risks of runaway reactions or temperature instability during scale-up, thereby improving safety, reducing byproducts, and increasing yield and selectivity.

[0025] In some embodiments of the present invention, the reaction time is 15-40h, such as 15h, 18h, 20h, 24h, 28h, 32h, 34h, etc., and any value within the range of any two of the above values, preferably 18-32h, preferably 24-28h.

[0026] In some embodiments of the present invention, the method further includes: washing and extracting the reaction solution obtained after the reaction with water to obtain an organic phase, and then performing azeotropic distillation to separate and obtain chlorpyrifos.

[0027] Existing synthesis processes show reduced yields and high byproduct production when scaled up to 1L and 5L, rendering conventional separation processes infeasible and necessitating column chromatography for purification. While this method is easy to operate in laboratory synthesis, industrial-scale production requires large quantities of low-boiling-point, volatile solvents such as ethyl acetate and petroleum ether. These solvents produce strong odors, significantly impacting the environment, and workers must wear special protective masks during production.

[0028] This invention optimizes and improves the post-processing technology by employing azeotropic crystallization. Compared to existing post-processing methods (adding the reaction solution to water, extracting with ethyl acetate, drying, removing ethyl acetate by rotary evaporation, and separating the final product by column chromatography), this method reduces the use of ethyl acetate in the extraction step. In existing synthesis processes, the "drying" step involves drying the ethyl acetate organic phase with a desiccant (anhydrous magnesium sulfate / anhydrous sodium sulfate). After drying, filtration and separation of the desiccant are necessary, followed by concentration and crystallization of the dried ethyl acetate, and then purification by column chromatography. This invention, through process improvement, increases the yield and reaction selectivity, allowing chlorpyrifos to crystallize directly in an aqueous system, thus reducing the steps of drying the ethyl acetate organic phase and column chromatography separation.

[0029] In some embodiments of the invention, the water washing extraction is carried out at room temperature. For example, tap water can be used.

[0030] In some embodiments of the present invention, the mass ratio of water to truncated pleurotin used in the water washing extraction process is 2-6:1-1.1, preferably 2.5-4.5:1-1.05.

[0031] In some embodiments of the present invention, the temperature of the azeotropic distillation is 45-120°C, preferably 50-70°C.

[0032] In some embodiments of the present invention, the method is carried out entirely within the same reaction vessel.

[0033] According to a particularly preferred embodiment of the present invention, a method for preparing chlorpyrifos includes the following steps: (1) Add the prescribed amount of pleurotin, acid-binding agent and solvent into the reaction vessel, stir and cool to the required reaction temperature; add the prescribed amount of chloroacetyl chloride into the dropping tank and cool to the reaction temperature; slowly add chloroacetyl chloride into the reaction vessel and start timing, control the reaction temperature to -10 to 15℃, and the reaction time to 15-40h to generate a reaction solution containing chloramphenicol; (2) Add water to the reactor, stir for 15 min and let stand for 20 min to separate the layers. Separate the lower aqueous phase and the upper organic phase. Add water to the reactor again and heat to 50-70℃. Separate the solvent by azeotropic distillation for about 3 h. Finally, centrifuge and filter the mixture of water and chlorpyrifos to obtain chlorpyrifos wet powder. Dry in a hot air oven for 4 h to obtain chlorpyrifos technical.

[0034] To make the technical solution and beneficial effects of the present invention more apparent and understandable, a detailed description is provided below by listing specific embodiments. It should be understood that these embodiments are for illustrative purposes only and not for limiting the scope of the invention. Experimental methods in the following embodiments without specific conditions are generally performed under conventional experimental conditions. Unless otherwise specified, all reagents and raw materials used in the present invention are commercially available. The pesticide technicals, solvents, surfactants, stabilizers, dispersants, catalysts, and carriers used in the present invention are all purchased from domestic and international chemical and agricultural raw material companies and can be used directly. Unless otherwise specified, all percentages in the following embodiments are mass percentages.

[0035] Example 1 This example illustrates the preparation of chlorpyrifos.

[0036] (1) Add 10.0 kg of 93% pleurotin, 2.7 kg of 98% pyridine and 25 kg of acetonitrile to a 100 L glass reactor and keep stirring; add 2.8 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to -5 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to -5 °C, and after 18 h of reaction, obtain a reaction solution containing chloramphenicol.

[0037] (2) Add 25 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 25 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 10.9 kg of chlorpyrifos technical material is obtained with a content of 90.91% and a yield of 88.45%.

[0038] Example 2 This example illustrates the preparation of chlorpyrifos.

[0039] (1) Add 10.0 kg of 93% pleurotin, 3.5 kg of 98% triethylamine and 25 kg of acetonitrile to a 100 L glass reactor and keep stirring; add 2.8 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to -5 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to -5 °C, and after 24 h of reaction, obtain the reaction solution containing chloramphenicol.

[0040] (2) Add 30 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 30 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 11.2 kg of chlorpyrifos technical material is obtained with a content of 86.41% and a yield of 86.56%.

[0041] Example 3 This example illustrates the preparation of chlorpyrifos.

[0042] (1) Add 10.0 kg of 93% pleurotin, 4.8 kg of 98% potassium carbonate and 25 kg of acetonitrile to a 100 L glass reactor and keep stirring; add 2.8 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to -5 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to -5 °C, and after 32 h of reaction, obtain a reaction solution containing chloramphenicol.

[0043] (2) Add 35 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 35 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 11.0 kg of chlorpyrifos technical material is obtained with a content of 87.47% and a yield of 86.24%.

[0044] Example 4 This example illustrates the preparation of chlorpyrifos.

[0045] (1) Add 10.0 kg of 93% pleurotin, 2.7 kg of 98% pyridine and 35 kg of toluene to a 100 L glass reactor and keep stirring; add 3.0 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 0 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to 0 °C, and after 18 h of reaction, obtain the reaction solution containing chloramphenicol.

[0046] (2) Add 25 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 25 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 11.0 kg of chlorpyrifos technical material is obtained with a content of 91.33% and a yield of 89.64%.

[0047] Example 5 This example illustrates the preparation of chlorpyrifos.

[0048] (1) Add 10.0 kg of 93% pleurotin, 3.5 kg of 98% triethylamine and 35 kg of toluene to a 100 L glass reactor and keep stirring; add 3.0 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 0 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to 0 °C, and after 24 h of reaction, obtain a reaction solution containing chloramphenicol.

[0049] (2) Add 30 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 30 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; after drying, 11.6 kg of chlorpyrifos technical material with a content of 86.77% and a yield of 90.04% is obtained.

[0050] Example 6 This example illustrates the preparation of chlorpyrifos.

[0051] (1) Add 10.0 kg of 93% pleurotin, 4.8 kg of 98% potassium carbonate and 35 kg of toluene to a 100 L glass reactor and keep stirring; add 3.0 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 0 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to 0 °C, and after 32 h of reaction, obtain a reaction solution containing chloramphenicol.

[0052] (2) Add 35 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 35 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 11.4 kg of chlorpyrifos technical material is obtained with a content of 86.16% and a yield of 88.17%.

[0053] Example 7 This example illustrates the preparation of chlorpyrifos.

[0054] (1) Add 10.0 kg of 93% pleurotin, 2.7 kg of 98% pyridine and 40 kg of toluene to a 100 L glass reactor and keep stirring; add 3.2 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 5 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature at 5 °C, and after 28 h of reaction, obtain a reaction solution containing chloramphenicol.

[0055] (2) Add 30 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 30 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 10.9 kg of chlorpyrifos technical material is obtained with a content of 89.95% and a yield of 87.69%.

[0056] Example 8 This example illustrates the preparation of chlorpyrifos.

[0057] (1) Add 10.0 kg of 93% pleurotin, 3.5 kg of 98% triethylamine and 30 kg of acetonitrile to a 100 L glass reactor and keep stirring; add 3.4 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 5 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature to 5 °C, and after 32 h of reaction, obtain a reaction solution containing chloramphenicol.

[0058] (2) Add 35 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 35 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 11.1 kg of chlorpyrifos technical material is obtained with a content of 90.63% and a yield of 89.61%.

[0059] Example 9 This example illustrates the preparation of chlorpyrifos.

[0060] (1) Add 10.0 kg of 93% pleurotin, 4.8 kg of 98% potassium carbonate and 30 kg of acetonitrile to a 100 L glass reactor and keep stirring; add 3.6 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 5 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature at 5 °C, and after 24 h of reaction, obtain a reaction solution containing chloramphenicol.

[0061] (2) Add 40 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 40 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 11.5 kg of chlorpyrifos technical material is obtained with a content of 88.58% and a yield of 91.41%.

[0062] Example 10 This example illustrates the preparation of chlorpyrifos.

[0063] (1) Add 10.0 kg of 93% pleurotin, 2.7 kg of 98% pyridine and 30 kg of acetonitrile to a 100 L glass reactor and keep stirring; add 3.0 kg of 98% chloroacetyl chloride to a dropping tank and cool the reactor to 10 °C; slowly add chloroacetyl chloride to the reactor and start timing, control the reaction temperature at 10 °C, and after 24 h of reaction, obtain the reaction solution containing chloramphenicol.

[0064] (2) Add 40 kg of water to the reactor, stir evenly, let stand and separate into layers, separate the lower aqueous phase and obtain the upper organic phase; add 40 kg of water to the reactor again, heat to 50-70℃, and separate the solvent by azeotropic distillation; finally, centrifuge and filter the mixture of the separated water and chlorpyrifos to obtain chlorpyrifos wet powder; the post-treatment (add water for azeotropic crystallization / centrifuge and filter to obtain chlorpyrifos wet powder after the reaction) takes about 6-7 hours. After drying, 10.8 kg of chlorpyrifos technical material is obtained with a content of 89.48% and a yield of 86.82%.

[0065] Comparative Example 1 Example 2 in CN118878418A is used as Comparative Example 1.

[0066] Comparative Example 2 The small-scale process of Example 2 in patent CN118878418A was verified as follows: Pleurotus ostreatus (0.50 g, 1.29 mmol) and chloroacetyl chloride (0.175 g, 1.55 mmol) were dissolved in DMF with stirring. Triethylamine (0.16 g, 1.55 mmol) was slowly added and the reaction was carried out at room temperature. The developing solvent was ethyl acetate (v): petroleum ether (v) = 3:2. Potassium permanganate was used for color development. After the reaction was completed, the reaction solution was added to water and extracted with ethyl acetate. The solution was dried with anhydrous magnesium sulfate, filtered, and the filter cake was washed with ethyl acetate. The ethyl acetate was removed by rotary evaporation. The post-processing (from the end of the reaction to column chromatography separation) took about 1-2 days. The wet powder of chlorpyrifos was separated by column chromatography to obtain 0.45 g of the compound chlorpyrifos, with a yield of 76.7%.

[0067] Comparative Example 3 The process of Example 2 in patent CN118878418A was scaled up to 1L (100-fold increase): Pleurotin (50g, 129mmol) and chloroacetyl chloride (17.5g, 155mmol) were dissolved in DMF with stirring, and triethylamine (16g, 155mmol) was slowly added. The reaction was carried out at room temperature with ethyl acetate (v): petroleum ether (v) = 3:2 as the developing solvent. Potassium permanganate was used for color development. After the reaction was complete, the reaction solution was added to water and extracted with ethyl acetate. The solution was dried with anhydrous magnesium sulfate, filtered, and the filter cake was washed with ethyl acetate. The ethyl acetate was removed by rotary evaporation. The post-treatment (from the end of the reaction to column chromatography) took about 3-4 days. Column chromatography yielded 39.2g of the compound chloramphenicol, with a yield of 65.5%.

[0068] Comparative Example 4 The process of Example 2 in patent CN118878418A was scaled up to 5L: 250g (645mmol) of truncated pleurotin and chloroacetyl chloride (87.53g, 775mmol) were dissolved in DMF with stirring. Triethylamine (80g, 775mmol) was slowly added and the reaction was carried out at room temperature. The developing solvent was ethyl acetate (v): petroleum ether (v) = 3:2. Potassium permanganate was used for color development. After the reaction was complete, the reaction solution was added to water and extracted with ethyl acetate. The solution was dried with anhydrous magnesium sulfate, filtered, and the filter cake was washed with ethyl acetate. The ethyl acetate was removed by rotary evaporation. The post-treatment (from the end of the reaction to column chromatography) took about 6-7 days. Column chromatography yielded 177.3g of the compound chloramphenicol, with a yield of 59.2%.

[0069] The yields of Examples 1-10 and Comparative Examples 1-4 are summarized in Table 1 below.

[0070] Table 1

[0071] As can be seen from Table 1, the chlorpyrifos prepared in Examples 1-10 of the present invention has a high yield, with an average yield of 88.46%; while the yield of chlorpyrifos prepared in Example 2 of CN118878418A is 80.5%, and the yield of the present invention is 7.96% higher.

[0072] As can be seen from Comparative Examples 2-4, the yield is 65.5% when the process in patent CN118878418A is scaled up to a 1L scale and 59.2% when scaled up to a 5L scale. The existing process has poor selectivity for the alcohol hydroxyl reaction after scale-up, produces a large number of byproducts, and has a significant scale-up effect; at the same time, the process description in patent CN118878418A is too simple and general, without specific operational details, and does not meet the requirements for industrial scale-up production.

[0073] The method for preparing chlorpyrifos provided by this invention greatly improves the yield, and by continuously scaling up to 1L, 5L and 100L, the scale-up effect in the process has been solved, so that the production output, content and yield can be kept stable, making it suitable for direct industrial production.

[0074] In addition, by scaling up the process operation flow in CN118878418A to the scale of the embodiments of this invention to calculate the cost, the cost of raw and auxiliary materials in this invention is reduced by about 18%, and the cost of raw and auxiliary materials per ton of product is reduced by about 74,000 yuan; the total production time of a single batch is reduced from 4 days to 2 days, which reduces labor intensity, shortens the production cycle, and increases production efficiency by more than double.

[0075] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A method for preparing chlorpyrifos, characterized in that, The method includes: adding chloroacetyl chloride dropwise to a mixed solution containing truncated pleurotin, an acid-binding agent, and a solvent, and reacting to obtain chlorpyrifos.

2. The method according to claim 1, wherein, The acid-binding agent is selected from at least one of triethylamine, pyridine, potassium carbonate, potassium bicarbonate and potassium hydroxide, preferably selected from at least one of triethylamine, pyridine and potassium carbonate.

3. The method according to claim 1 or 2, wherein, The solvent is selected from at least one of benzene, toluene, xylene, acetonitrile and dichloroethane, preferably at least one of toluene and acetonitrile.

4. The method according to any one of claims 1-3, wherein, The mass ratio of truncated pleurotin to chloroacetyl chloride is 1-1.1:0.25-0.40, preferably 1-1.05:0.28-0.

36.

5. The method according to any one of claims 1-4, wherein, In the mixed solution, the mass ratio of truncated pleurotin to solvent is 1-1.1:2-5, preferably 1-1.05:2.5-4; Preferably, in the mixed solution, the mass ratio of truncated pleurotin to acid-binding agent is 1-1.1:0.2-0.

5.

6. The method according to any one of claims 1-5, wherein, The reaction temperature is -10 to 15°C, preferably -5 to 10°C, and more preferably 0 to 5°C; Preferably, the reaction time is 15-40 hours, more preferably 18-32 hours, and even more preferably 24-28 hours.

7. The method according to any one of claims 1-6, wherein, The method further includes: washing and extracting the reaction solution obtained after the reaction with water to obtain an organic phase, and then performing azeotropic distillation to separate and obtain chlorpyrifos.

8. The method according to claim 7, wherein, The water washing extraction was carried out at room temperature; Preferably, the mass ratio of water to truncated pleurotin used in the water washing extraction process is 2-6:1-1.1, more preferably 2.5-4.5:1-1.

05.

9. The method according to claim 7 or 8, wherein, The temperature of the azeotropic distillation is 45-120℃, preferably 50-70℃.

10. The method according to any one of claims 1-9, wherein, The entire process is carried out in the same reactor.

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