Preparation method of (S)-2-methyl chloropropionate

Abstract

The invention belongs to the field of chemical engineering and pesticides, and particularly relates to a preparation method of (S)-2-methyl chloropropionate, which is characterized in that (R)-methyl lactate serving as a raw material and thionyl chloride are subjected to chlorination in the presence of a catalyst to generate the (S)-2-methyl chloropropionate. (S)-2-methyl chloropropionate is obtained with high yield and high ee value, and industrial popularization and application are facilitated.

Description

[0001] The present invention belongs to the fields of chemical engineering and pesticides, and relates to a preparation method of methyl ( S )-2-chloropropionate Background Art

[0002] Aryloxyphenoxypropionate herbicides are typical representatives of chiral pesticides with high efficacy of single isomers. Due to their characteristics such as high efficiency and low toxicity, broad herbicidal spectrum, long application window period, and safety for subsequent crops, their application proportion in the agricultural field has been continuously increasing in recent years, and the development and application research of related new compounds are active. Among them, methyl ( S )-2-chloropropionate, as a key chiral intermediate for synthesizing various aryloxyphenoxypropionate herbicides such as flumiclorac-pentyl, fenoxaprop-p-ethyl, haloxyfop-methyl, and cyhalofop-butyl, the optimization and innovation of its synthesis process are of great significance for improving the production efficiency and safety of such pesticides.

[0003] Currently, the synthesis methods of methyl ( S )-2-chloropropionate in the disclosed patents mainly include the following four categories: 1) Chiral hydrogen peroxide catalysis method (CN102381969), first preparing chiral hydrogen peroxide as a catalyst, and then using α -chloropropionic acid and methanol as raw materials to react to form the target product. The phosphoric acid used in the reaction has strong corrosiveness to equipment, and special material equipment is required, increasing production costs; hydrogen peroxide belongs to an easily explosive dangerous chemical, and there are safety hazards in storage and use, and the industrial operation risk is relatively high. 2) Vilsmeier reagent catalysis method (CN103232344), using Vilsmeier reagent (containing DMF) to catalyze the synthesis of the target product. In the reaction, DMF is easily hydrolyzed under strong acid conditions, and the hydrolysis products further decompose to release non-condensable gases, resulting in a low yield (only 88%); the reagent is easily hygroscopic and deliquescent, and the humidity of the experimental environment needs to be strictly controlled. The operation steps are cumbersome and the equipment sealing requirements are high; the treatment process of DMF wastewater generated by the reaction is complex and the environmental protection cost is relatively high. 3) D-lactic acid methyl ester thionyl chloride method (CN102775303), dropping D-lactic acid methyl ester into thionyl chloride, and standing and separating the layers after the reaction to obtain the product. The product is difficult to separate from the aqueous phase, which is easy to cause loss of the target substance, and a large amount of hydrogen chloride and sulfur dioxide remain in the oil phase; under strong acidic conditions ( S )-2-chloropropionate is easily hydrolyzed, resulting in a limited yield (only 90%); no treatment scheme for tail gases (HCl, SO2) is mentioned, and the environmental protection compliance is insufficient during industrial production. 4) Phase transfer catalysis method (CN116082151), using D-lactic acid methyl ester and thionyl chloride as raw materials, and pyridine as a phase transfer catalyst to synthesize the target product. Pyridine is toxic and irritating, and additional protective measures are required during the operation process. Summary of the Invention

[0004] The object of the present invention is to overcome the deficiencies in the prior art and provide a preparation method of methyl ( S )-2-chloropropionate, which has simple operation, low equipment requirements, easily available and safe raw materials, does not generate highly dangerous substances during the reaction process, has a high raw material conversion rate and a high ee value, and is conducive to industrial promotion and application.

[0005] To achieve the above object, the present invention is implemented by the following technical solutions: The present invention provides a preparation method of methyl ( S )-2-chloropropionate, comprising the following steps: Using methyl ( R )-lactate as a raw material, reacting with thionyl chloride in the presence of a catalyst to form methyl ( S )-2-chloropropionate The structural formula of the methyl ( S )-2-chloropropionate is as follows:

[0006] Further, the preparation route of the methyl ( S )-2-chloropropionate is as follows:

[0007] The catalyst in the reaction is any one or a combination of several of sodium bicarbonate, potassium phosphate, cesium carbonate, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, triethylamine, N , N -diisopropylethylamine, 2,6-dimethylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene; preferably, the catalyst is triethylamine.

[0008] Further, the dosage of the catalyst is 5-15% of the mass of methyl ( R )-lactate; preferably, the dosage of the catalyst is 10% of the mass of methyl ( R )-lactate.

[0009] Further, the solvent is dimethyl sulfoxide, N , N -dimethylformamide, 1,4-dioxane, tetrahydrofuran, ethyl acetate, dichloromethane, 1,2-dichloroethane, toluene, ethylbenzene, or any combination thereof; preferably, the solvent is 1,4-dioxane, Further, the dosage of the solvent is 0.01-1 M (relative to methyl ( R )-lactate); preferably, the dosage of the solvent is 0.2 M (relative to methyl ( R )-lactate).

[0010] Further, the temperature is 0 to 100 °C, preferably 80 - 90 °C.

[0011] Further, in the synthesis reaction, the reaction time is 0.5 to 24 h, preferably 12 h.

[0012] Further, in the general formula, R the molar ratio of methyl ( R )-lactate to thionyl chloride is 1:1 - 2, preferably 1:1.5.

[0013] The present invention has the following beneficial effects: The present invention uses methyl ( R )-lactate and thionyl chloride as raw materials, triethylamine as a catalyst, and 1,4-dioxane as a solvent. The raw materials are easily obtained and have high safety. The reaction is carried out at an optimal temperature of 80 °C - 90 °C, the reaction temperature is relatively mild, there are fewer side reactions, it is easier to control, the raw material conversion rate can reach up to 100%, the yield can reach 99% when scaled up to the kilogram level, and the ee value reaches 98%. Specific Embodiments

[0014] Example 1: Add methyl ( R )-lactate (1.0 mmol, 1.0 equiv.) to a 25 mL reaction flask, then add toluene (5 mL) and stir evenly. Add triethylamine (10%) and cool to 5 o °C in an ice bath. Subsequently, slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) while maintaining the temperature at 15 - 20 o °C. After the addition is complete, stir and react for 1 h at 15 - 20 o °C, and finally stir and react at 70 o °C for 12 h. After the reaction is completed, cool to room temperature, then add ice water and ethyl acetate for extraction, add the internal standard dodecane, and measure the gas phase. The gas phase yield is detected to be 85%.

[0015] Example 2: Add methyl ( R )-lactate (1.0 mmol, 1.0 equiv.) to a 25 mL reaction flask, then add toluene (5 mL) and stir evenly. Add N,N-diisopropylethylamine (10%) and cool to 5 o °C in an ice bath. Subsequently, slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) while maintaining the temperature at 15 - 20 o °C. After the addition is complete, stir and react for 1 h at 15 - 20 o °C, and finally stir and react at 70 oStir the reaction at 12 h under C. After the reaction is completed, cool it to room temperature. Then add ice water and ethyl acetate for extraction, add dodecane as the internal standard, and measure the gas phase. The gas phase yield is detected to be 82%.

[0016] Example 3: Add methyl ( R )-lactate (1.0 mmol, 1.0 equiv.) to a 25 mL reaction flask, then add toluene (5 mL) and stir evenly. Add sodium carbonate (10%) and cool the temperature to 5 o C in an ice bath. Then slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) and maintain the temperature at 15 - 20 o C. After the addition is complete, stir the reaction at 15 - 20 o C for 1 h, and finally place it in 70 o C and stir the reaction for 12 h. After the reaction is completed, cool it to room temperature. Then add ice water and ethyl acetate for extraction, add dodecane as the internal standard, and measure the gas phase. The gas phase yield is detected to be 18%.

[0017] Example 4: Add methyl ( R )-lactate (1.0 mmol, 1.0 equiv.) to a 25 mL reaction flask, then add toluene (5 mL) and stir evenly. Add potassium phosphate (10%) and cool the temperature to 5 o C in an ice bath. Then slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) and maintain the temperature at 15 - 20 o C. After the addition is complete, stir the reaction at 15 - 20 o C for 1 h, and finally place it in 70 o C and stir the reaction for 12 h. After the reaction is completed, cool it to room temperature. Then add ice water and ethyl acetate for extraction, add dodecane as the internal standard, and measure the gas phase. The gas phase yield is detected to be 48%.

[0018] Example 5: Add methyl ( R )-lactate (1.0 mmol, 1.0 equiv.) to a 25 mL reaction flask, then add tetrahydrofuran (5 mL) and stir evenly. Add triethylamine (10%) and cool the temperature to 5 o C in an ice bath. Then slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) and maintain the temperature at 15 - 20 o C. After the addition is complete, stir the reaction at 15 - 20 o C for 1 h, and finally place it in 70 o C and stir the reaction for 12 h. After the reaction is completed, cool it to room temperature. Then add ice water and ethyl acetate for extraction, add dodecane as the internal standard, and measure the gas phase. The gas phase yield is detected to be 82%.

[0019] Example 6: Add ( R )-methyl lactate (1.0 mmol, 1.0 equiv.) into a 25 mL reaction flask, then add 1,2-dichloroethane (5 mL) and stir evenly. Add triethylamine (10%) and cool down to 5 o °C in an ice bath. Subsequently, slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) while maintaining the temperature at 15 - 20 o °C. After the addition is complete, stir and react for 1 h at 15 - 20 o °C, and finally stir and react for 12 h at 70 o °C. After the reaction is completed, cool it down to room temperature, then add ice water and ethyl acetate for extraction, add the internal standard dodecane, and measure the gas phase. The gas phase yield is detected to be 73%.

[0020] Example 7: Add ( R )-methyl lactate (1.0 mmol, 1.0 equiv.) into a 25 mL reaction flask, then add dichloromethane (5 mL) and stir evenly. Add triethylamine (10%) and cool down to 5 o °C in an ice bath. Subsequently, slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) while maintaining the temperature at 15 - 20 o °C. After the addition is complete, stir and react for 1 h at 15 - 20 o °C, and finally stir and react for 12 h at 70 o °C. After the reaction is completed, cool it down to room temperature, then add ice water and ethyl acetate for extraction, add the internal standard dodecane, and measure the gas phase. The gas phase yield is detected to be 89%.

[0021] Example 8: Add ( R )-methyl lactate (1.0 mmol, 1.0 equiv.) into a 25 mL reaction flask, then add 1,4-dioxane (5 mL) and stir evenly. Add triethylamine (10%) and cool down to 5 o °C in an ice bath. Subsequently, slowly add thionyl chloride (1.2 mmol, 1.2 equiv.) while maintaining the temperature at 15 - 20 o °C. After the addition is complete, stir and react for 1 h at 15 - 20 o °C, and finally stir and react for 12 h at 70 o °C. After the reaction is completed, cool it down to room temperature, then add ice water and ethyl acetate for extraction, add the internal standard dodecane, and measure the gas phase. The gas phase yield is detected to be 91%.

[0022] Example 9: Add ( RMethyl (R)-lactate (1.0 mmol, 1.0 equiv.) was added to a 25 mL reaction flask, then 1,4-dioxane (5 mL) was added and stirred evenly. Triethylamine (10%) was added and the temperature was cooled to 5 o °C in an ice bath. Subsequently, thionyl chloride (1.2 mmol, 1.2 equiv.) was slowly added dropwise while maintaining the temperature at 15 - 20 o °C. After the addition was complete, the reaction was stirred at 15 - 20 o °C for 1 h, and finally stirred at 70 o °C for 18 h. After the reaction was completed, it was cooled to room temperature, then ice water and ethyl acetate were added for extraction. Dodecane as an internal standard was added, and the gas phase was measured. The gas phase yield was detected to be 90%.

[0023] Example 10: ( R Methyl (R)-lactate (1.0 mmol, 1.0 equiv.) was added to a 25 mL reaction flask, and triethylamine (10%) was added. The temperature was cooled to 5 o °C in an ice bath. Subsequently, thionyl chloride (1.5 mmol, 1.5 equiv.) was slowly added dropwise while maintaining the temperature at 5 - 10 o °C. After the addition was complete, the reaction was stirred at 15 - 20 o °C for 1 h, and finally stirred at 70 o °C for 18 h. After the reaction was completed, it was cooled to room temperature, then ice water and ethyl acetate were added for extraction. Dodecane as an internal standard was added, and the gas phase was measured. The gas phase yield was detected to be 90%.

[0024] Example 11: ( R Methyl (R)-lactate (100 mmol, 1.0 equiv.) was added to a 150 mL reaction flask, then 1,4-dioxane (50 mL) was added and stirred evenly. Triethylamine (10%) was added and the temperature was cooled to 15 o °C in an ice bath. Subsequently, thionyl chloride (150 mmol, 1.5 equiv.) was slowly added dropwise while maintaining the temperature at 5 - 10 o °C. After the addition was complete, the reaction was stirred at 15 - 20 o °C for 1 h, and finally stirred at 80 o °C for 12 h. After the reaction was completed, it was cooled to room temperature, then ice water and ethyl acetate were added for extraction. Dodecane as an internal standard was added, and the gas phase was measured. The gas phase yield was detected to be 93%.

[0025] Example 12: ( RMethyl (R)-lactate (1000 mmol, 1.0 equiv.) was added to a 2000 mL reaction flask, and then 1,4-dioxane (500 mL) was added and stirred evenly. Triethylamine (10%) was added, and the temperature was cooled to 15 o °C in an ice bath. Subsequently, thionyl chloride (1500 mmol, 1.5 equiv.) was slowly added dropwise while maintaining the temperature at 15 - 20 o °C. After the addition was complete, the reaction was stirred at 15 - 25 o °C for 1 h, and finally stirred at 80 o °C for 12 h. After the reaction was completed, it was cooled to room temperature, and then ice water and ethyl acetate were added for extraction. Dodecane as the internal standard was added, and gas chromatography was measured. The gas-phase yield was detected to be 99%, and the ee value was 98%.

[0026] Gas chromatography was used to determine methyl ( R R S )-lactate and methyl ( R S S )-lactate, and methyl ( R S S )-lactate and methyl ( R R S )-lactate were used as controls.

[0027] ( S )-Methyl 2-chloropropionate chiral test conditions: Gas chromatograph: Shimadzu gas chromatograph; Detector: Flame ionization detector (FID); Chromatographic column: CYCLOSIL-B 30 m × 0.32 mm × 0.25 um; Chromatographic conditions: Column flow rate 1 mL / min; Purge flow rate 1.5 mL / min; Split ratio 40 : 1; Injector and detector temperature 200 °C; Column temperature 80 °C; Hydrogen 55 mL / min; Air 400 mL / min; Tail gas blow 30 mL / min; Results: Retention time: S configuration 5.6 min, R configuration 6.2 min.

[0028] As can be seen from the above examples, the yield of the preparation method of the present application can reach 99%, and the ee value is 98%.

[0029] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. Any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A method for preparing methyl ( S )-2-chloropropionate, characterized in that, Including the following steps: Using ( R )-methyl lactate as a raw material, reacting with thionyl chloride in the presence of a catalyst to form ( S )-methyl 2-chloropropionate The said ( S ) methyl (±)-2-chloropropionate has the following structural formula:

2. The preparation method of a kind of ( S )-methyl 2-chloropropionate according to claim 1, characterized in that The synthetic route is as follows:

3. The preparation method of a kind of ( S )-methyl 2-chloropropionate as claimed in claim 2, characterized in that In the synthesis reaction, the catalyst is any one or a combination of several of sodium bicarbonate, potassium phosphate, cesium carbonate, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, triethylamine, N , N -diisopropylethylamine, 2,6-dimethylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene; preferably, the catalyst is triethylamine, and the dosage is ( R ) - 5-15% of the mass of methyl lactate.

4. The preparation method of a ( S )-methyl 2-chloropropionate according to claim 2, characterized in that In the synthesis reaction, the solvent is dimethyl sulfoxide, N , N N,N-dimethylformamide, 1,4-dioxane, tetrahydrofuran, ethyl acetate, dichloromethane, 1,2-dichloroethane, toluene, ethylbenzene, or any combination thereof; preferably, the solvent is 1,4-dioxane, and the amount used is 0.01-1 M (relative to ( R -methyl lactate).

5. The preparation method of a methyl ( S )-2-chloropropionate as claimed in claim 2, characterized in that The reaction temperature in the synthesis reaction is 0 to 100 °C.

6. The preparation method of a certain ( S ) - methyl 2 - chloropropionate according to claim 2, characterized in that The reaction time in the synthesis reaction is 0.5 to 24 h.

7. The preparation method of methyl ( S )-2-chloropropionate as claimed in claim 2, characterized in that The molar ratio of methyl ( R )-lactate shown by the general formula to thionyl dichloride is 1:1-2.

Images