Preparation method of 2, 2-difluoroethyl pyrrolidone

Abstract

The invention provides a preparation method of 2, 2-difluoroethyl pyrrolidone, and the preparation method comprises the following steps: reacting difluoroethylamine with 4-chlorobutyryl chloride to obtain 4-chloro-N-(2, 2-difluoroethyl) butyramide; then, the 4-chloro-N-(2, 2-difluoroethyl) butyramide is subjected to a reaction in a sodium hydride dispersion solution, and 2, 2-difluoroethyl pyrrolidone is obtained; the preparation method is simple in reaction route, free of catalyst, mild in reaction condition and environmentally friendly, the obtained 2, 2-difluoroethyl pyrrolidone is high in purity and yield, the purity is larger than 90%, the yield is larger than 80%, and the 2, 2-difluoroethyl pyrrolidone can be used as an additive of lithium ion battery electrolyte.

Description

TECHNICAL FIELD

[0001] The application relates to a preparation method of 2,2-difluoroethyl pyrrolidone and belongs to the technical field of pyrrolidone preparation methods. BACKGROUND

[0002] 2,2-difluoroethyl pyrrolidone is a special cyclic fluorinated compound in the form of a colorless transparent liquid at room temperature and can be used as an additive of a lithium ion battery electrolyte. At present, the synthesis methods of pyrrolidone mainly include a gamma-butyrolactone amination method, which has been widely used in industry. The gamma-butyrolactone amination method uses gamma-butyrolactone and an amine compound as raw materials to generate pyrrolidone through an amination reaction. The gamma-butyrolactone amination method has the advantages of high yield and good purity, but the reaction time is relatively long, a relatively high pressure is required, and a relatively efficient catalyst is needed, and a large amount of solid waste and liquid waste is generated, which makes the gamma-butyrolactone amination method not meet the green and environmental protection concept. The synthesis method of pyrrolidone also includes a maleic anhydride hydrogenation amination method, which uses maleic anhydride as a raw material to generate pyrrolidone through two steps of hydrogenation and amination, and the process is mature and the cost is relatively low, but the raw material needs to be acidified with a strong acid, which does not meet the development of the green and environmental protection concept, and a noble metal catalyst is needed, and the cost is high. SUMMARY

[0003] The application aims to solve the problems of a complex reaction route, harsh reaction conditions, high cost of a catalyst and serious pollution in the production process in the prior art pyrrolidone preparation method, and provides a preparation method of 2,2-difluoroethyl pyrrolidone, which uses difluoroethylamine as a starting raw material to synthesize a 4-chloro-N-(2,2-difluoroethyl) butyramide intermediate; and then the 4-chloro-N-(2,2-difluoroethyl) butyramide intermediate is reacted to obtain 2,2-difluoroethyl pyrrolidone, the reaction route is simple, the conditions are mild, the safety risk is low, no catalyst is needed, the method meets the green and environmental protection requirements, and the obtained 2,2-difluoroethyl pyrrolidone has high purity and yield.

[0004] The above object of the application is achieved by the following technical scheme. The application provides a preparation method of 2,2-difluoroethyl pyrrolidone, which comprises the following steps. Step one: 4-chloro-N-(2,2-difluoroethyl) butyramide is obtained by adding a 4-chlorobutyryl chloride solution dropwise into a mixed solution of difluoroethylamine and an acid-binding agent, and stirring until the reaction is complete; and 4-chloro-N-(2,2-difluoroethyl) butyramide is obtained after purification; Step two: 2,2-difluoroethyl pyrrolidone is obtained by adding a 4-chloro-N-(2,2-difluoroethyl) butyramide solution dropwise into a sodium hydride dispersion solution, and stirring until the reaction is complete; and 2,2-difluoroethyl pyrrolidone is obtained after purification.

[0005] Specifically, the solvent of the mixed solution and the 4-chlorobutyryl chloride solution in step one is selected from at least one of dichloromethane, ethyl acetate or dimethyl carbonate; the acid binding agent is selected from at least one of N,N-diisopropylethylamine, triethylamine, pyridine.

[0006] Specifically, the molar ratio of the difluoroethylamine to the 4-chlorobutyryl chloride in step one ranges from 1:1 to 1.25; preferably from 1:1 to 1.2, and specifically can be 1:1, 1.1:1, 1.2:1, and further preferably 1.1:1.

[0007] Specifically, the solvent of the sodium hydride dispersion solution in step two is selected from at least one of ultradry tetrahydrofuran, ethyl acetate or 2-methyltetrahydrofuran, and preferably is ultradry tetrahydrofuran.

[0008] Specifically, the molar ratio of the 4-chloro-N-(2,2-difluoroethyl)butyramide to the sodium hydride in step two ranges from 0.6:1 to 1:1; preferably from 0.8:1 to 1:1, and specifically can be 0.8:1, 0.9:1, 1:1, and further preferably 0.9:1.

[0009] Specifically, the temperature of the dropping in step one is -10 to 60°C, and preferably is 0 to 20°C; the temperature of the stirring is -10 to 60°C, and preferably is 25°C (room temperature); and the time of the stirring is 1 to 3h, and preferably is 2h.

[0010] Specifically, the temperature of the dropping in step two is -10 to 20°C, and preferably is 0°C (ice bath condition); the temperature of the stirring is -10 to 90°C, and preferably is 25°C (room temperature); and the time of the stirring is 0.5 to 2h, and preferably is 1h.

[0011] Specifically, the reaction step after the dropping in step two is as follows: stirring and heating to 40 to 90°C for 8 to 48h until the sodium hydride reaction is complete; preferably, the heating temperature is 40°C; and the heating time is 8 to 24h.

[0012] Specifically, the purification of the 4-chloro-N-(2,2-difluoroethyl)butyramide intermediate crude product in step one specifically includes the following steps: rapid filtration of the crude product, water washing, extraction, drying, filtration, rotary evaporation concentration, and vacuum distillation after removal of dichloromethane; the purpose of the vacuum distillation is to remove residual low-boiling solvents, unreacted raw materials and trace amounts of high-boiling impurities that have not been analyzed.

[0013] Specifically, the purification of the 2,2-difluoroethyl pyrrolidinone crude product in step two includes the following steps: rapid filtration of the crude product, removal of tetrahydrofuran by rotary evaporation, water washing, extraction, drying, filtration, and vacuum distillation.

[0014] More specifically, the temperature of the reduced pressure distillation in step one is 120-160℃, preferably 140℃.

[0015] More specifically, the temperature of the reduced pressure distillation in step two is 60-100℃, preferably 80℃.

[0016] More specifically, the temperature of the reduced pressure distillation in step one is 85-95℃; the temperature of the reduced pressure distillation in step two is 58-65℃.

[0017] Compared with the prior art, the present application has the following advantages: The present application provides a preparation method of 2,2-difluoroethyl pyrrolidone, in which step one, difluoroethylamine reacts with 4-chlorobutyryl chloride to obtain 4-chloro-N-(2,2-difluoroethyl) butyramide intermediate; in step two, the 4-chloro-N-(2,2-difluoroethyl) butyramide intermediate undergoes condensation reaction to obtain 2,2-difluoroethyl pyrrolidone; in the present application, step one does not need to use any catalyst, but can directly obtain amide product by removing HCl, and the reaction condition is mild; after simple treatment, high-purity intermediate pure product is obtained by reduced pressure distillation, without further treatment; and the reaction condition of step two is mild; after simple treatment of the crude product, high-purity 2,2-difluoroethyl pyrrolidone can be obtained by reduced pressure distillation. In summary, the preparation method of the present application has a simple reaction route, mild conditions, does not need to use catalyst, and meets the concept of green and environmental protection; and the obtained 2,2-difluoroethyl pyrrolidone has high purity and yield, the purity is >90%, and the yield is >80%, which can be used as an additive of lithium ion battery electrolyte. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 NMR spectrum of 2,2-difluoroethyl pyrrolidone. DETAILED DESCRIPTION

[0019] The present application will be further described in conjunction with the specific embodiments, but the embodiments do not limit the present application in any form. Unless otherwise specified, the raw reagents used in the embodiments of the present application are conventionally purchased raw reagents.

[0020] Example 1 2,2-difluoroethyl pyrrolidone is obtained by the following preparation method: Step one: under ice-bath condition, add 121.6 g (1.5 mol) of difluoroethylamine, 182.142 g (1.8 mol) of triethylamine, 400 mL of dichloromethane into a 2L three-necked flask, stir well; slowly drop a mixture of dichloromethane (200 mL) and 232.65 g (1.65 mol) of 4-chlorobutyryl chloride into the flask through a constant pressure dropping funnel, continue stirring at room temperature (25 °C) for 2 h after the dropping is completed, monitor the reaction by GC-MS, after the reaction is completed, quickly filter the crude product, wash with water, extract, dry, filter, concentrate by rotary evaporation, remove dichloromethane, perform vacuum distillation on the concentrated crude product at 140 °C using an oil pump, collect the fraction at 85-95 °C, and obtain the white solid compound as 4-chloro-N-(2,2-difluoroethyl)butyramide.

[0021] Step two: under ice-bath condition, add 1 L of ultradry tetrahydrofuran into a 2L three-necked flask, then add about 60 g of sodium hydride (1.1 eq.) into the flask; dissolve the white solid compound purified in step one in tetrahydrofuran, dilute, and place in a constant pressure dropping funnel, slowly drop into the flask under ice-bath condition; after the dropping is completed, stir at room temperature (25 °C) for 1 h, then warm to 40 °C, react for 18 h, and air cool using a condenser; after the reaction is completed, quickly filter the crude product, remove tetrahydrofuran by rotary evaporation, wash with water, extract, dry, filter, perform vacuum distillation on the concentrated crude product at 80 °C using an oil pump, collect the fraction at 58-65 °C, and obtain the colorless liquid compound, which is verified to be the target structure by nuclear magnetic hydrogen spectrum.

[0022] The synthesis route is as follows:

[0023] The purity of the 2,2-difluoroethyl pyrrolidinone obtained in this example is 99.82%, and the yield is 97.6%.

[0024] Example 2 Compared with Example 1, the only difference is that in step one, 121.6 g (1.5 mol) of difluoroethylamine, 151.179 g (1.5 mol) of triethylamine, and 400 mL of dichloromethane are added into a 2L three-necked flask under 20 °C condition, and the other steps are the same as in Example 1.

[0025] The purity of the 2,2-difluoroethyl pyrrolidinone obtained in this example is 98.63%, and the yield is 94.71%.

[0026] Example 3 The difference between the example 1 and the example 4 is that, in the step one, 121.6 g (1.5 mol) of difluoroethylamine, 232.63 g (1.8 mol) of N,N-diisopropyl ethylamine and 400 mL of dichloromethane were added into a 2L three-necked flask and stirred uniformly under the condition of 20°C.

[0027] The purity of 2,2-difluoroethyl pyrrolidinone obtained in the example 4 was 90.80% and the yield was 87.6%.

[0028] Example 4 The difference between the example 1 and the example 4 is that, in the step one, 121.6 g (1.5 mol) of difluoroethylamine, 232.63 g (1.8 mol) of N,N-diisopropyl ethylamine and 400 mL of dichloromethane were added into a 2L three-necked flask and stirred uniformly under the condition of 20°C. The purity of 2,2-difluoroethyl pyrrolidinone obtained in the example 4 was 90.80% and the yield was 87.6%.

[0029] Example 5 The difference between the example 1 and the example 5 is that, in the step two, after the dropwise addition was completed, the reaction was stirred for 1 h at room temperature, then the temperature was increased to 40°C, the reaction was carried out for 9 h and the air condensation was carried out in the condenser tube; and the other steps were the same as those in the example 1.

[0030] The purity of 2,2-difluoroethyl pyrrolidinone obtained in the example 5 was 99.62% and the yield was 81.2%.

[0031] Comparative Example 1 The difference between the example 1 and the comparative example 1 is that, in the step two, 1 L of anhydrous ethanol was added into a 2L three-necked flask under the condition of ice bath, then sodium methoxide (1.1 eq.) was added into the reaction flask, the white solid compound after purification in the step one was dissolved and diluted in THF, the THF solution was placed in a constant pressure dropping funnel and slowly added into the reaction flask under the condition of ice bath, after the dropwise addition was completed, the reaction was stirred for 1 h at room temperature, then the temperature was increased to 90°C, the reaction was carried out for 16 h and the condensation reflux was carried out; and the other steps were the same as those in the example 1.

[0032] The purity of 2,2-difluoroethyl pyrrolidinone obtained in the comparative example 1 was 94.16% and the yield was 49.7%.

[0033] Comparative Example 2 Compared with Example 1, the only difference is that in step two: 1L anhydrous ethanol is added into a 2L three-necked bottle under ice bath condition, and then potassium hydroxide (1.1 eq.) is added into the reaction bottle; the white solid compound purified in step one is dissolved and diluted in THF, and is placed in a constant pressure dropping funnel, and is slowly added into the reaction bottle under ice bath condition; after the addition is completed, stirring is carried out at room temperature for 1h, and then the temperature is increased to 90℃, and the reaction is carried out for 16h, and the condensation reflux is carried out; and other steps are the same as in Example 1.

[0034] The purity of 2,2-difluoroethyl pyrrolidone obtained in the present comparative example is 87.70%, and the yield is 35.60%.

[0035] The purity of the target product 2,2-difluoroethyl pyrrolidone in Examples 1-5 is 90.80-99.82%, and the yield is as high as 81.2-97.6%, the reaction route of the preparation method is simple, no catalyst is needed, the conditions are mild, the safety risk is low, and the concept of green environmental protection is met; the base reagent used in step two of the examples is sodium hydride, sodium hydride has strong hydrogen abstraction ability, can efficiently activate the active hydrogen in the reaction substrate, promote the directional progress of the target reaction, and after simple treatment, vacuum distillation is carried out, the fraction at a specific temperature is collected, and high yield and high purity of the target product 2,2-difluoroethyl pyrrolidone are realized. The base reagent in step two of Comparative Examples 1-2 is replaced by sodium methoxide or potassium hydroxide, compared with sodium hydride, the hydrogen abstraction ability of sodium methoxide is weaker, and is restricted by the principle of imbalance between nucleophilicity and basicity, resulting in reduced reaction activation efficiency, and finally causing the yield of the target product to decrease significantly, so the yield of 2,2-difluoroethyl pyrrolidone in Comparative Examples 1-2 is only 35.60% and 49.7%.

[0036] Obviously, the above examples of the present application are only examples for clearly illustrating the present application, and are not a limitation on the embodiments of the present application. Based on the above description, other different forms of changes or variations can be made by those skilled in the art. Here, all the embodiments are not required to be exhausted, and any modification, equivalent replacement and improvement made within the spirit and principle of the present application should be included in the protection scope of the claims of the present application.

Claims

1. A method for preparing 2,2-difluoroethylpyrrolidone, characterized in that, Includes the following steps: Step 1: Add 4-chlorobutyryl chloride solution dropwise to a mixed solution containing difluoroethylamine and an acid-binding agent. After the addition is complete, stir until the reaction is complete to obtain crude 4-chloro-N-(2,2-difluoroethyl)butyramide. After purification, 4-chloro-N-(2,2-difluoroethyl)butyramide is obtained. Step 2: Add 4-chloro-N-(2,2-difluoroethyl)butyramide solution dropwise to the sodium hydride dispersion solution. After the addition is complete, stir until the reaction is complete to obtain crude 2,2-difluoroethylpyrrolidone. After purification, 2,2-difluoroethylpyrrolidone is obtained.

2. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The molar ratio of difluoroethylamine to 4-chlorobutyryl chloride is in the range of 1:1 to 1.

25.

3. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The molar ratio of 4-chloro-N-(2,2-difluoroethyl)butyramide to sodium hydride is in the range of 0.6 to 1:

1.

4. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The temperature at which the drop is added in step one is -10~60℃.

5. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The temperature at which the drop is added in step two is -10 to 20°C.

6. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The reaction steps following the addition of sodium hydride in step two are as follows: stir, then heat to 40~90℃, react for 8~48h until the sodium hydride reacts completely.

7. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The specific purification steps described in Step 1 are as follows: After removing the solvent and inorganic salts from the crude 4-chloro-N-(2,2-difluoroethyl)butyramide product, vacuum distillation is performed.

8. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 1, characterized in that, The specific purification steps in step two are as follows: after removing the solvent and inorganic salts from the crude 2,2-difluoroethylpyrrolidone product, vacuum distillation is performed.

9. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 7, characterized in that, The temperature for vacuum distillation in step one is 120~160℃.

10. The method for preparing 2,2-difluoroethylpyrrolidone according to claim 8, characterized in that, The temperature for vacuum distillation in step two is 60~100℃.

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