Preparation method of N-isobutyl-4-chloropyrrolidone
By employing a three-step reaction route involving immobilized CAL-B enzyme-catalyzed Michael addition, amidation via a water/supercritical CO2 biphase reaction system, and Dieckmann condensation catalyzed by a hydrotalcite solid base, the atom economy and positional isomerism issues in the synthesis of N-alkylpyrrolidones in existing technologies have been resolved, enabling the industrial production of N-isobutyl-4-chloropyrrolidones with high selectivity and high efficiency.
Patent Information
- Application Number
- CN202511138222.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-14
- Publication Date
- 2025-11-28
AI Technical Summary
Existing methods for synthesizing N-alkylpyrrolidones suffer from poor atom economy and high positional isomerism, making it difficult to synthesize N-isobutyl-4-chloropyrrolidones efficiently.
A three-step reaction route was adopted, consisting of immobilized CAL-B enzyme-catalyzed Michael addition, amidation in a water/supercritical CO2 biphase reaction system, and Dieckmann condensation catalyzed by hydrotalcite solid base. This route directly introduces N-isobutyl and 4-chloro substituents during the cyclization process, thus avoiding the shortcomings of conventional methods.
The method achieves highly selective and efficient synthesis of N-isobutyl-4-chloropyrrolidone, with readily available raw materials, few reaction steps, and suitability for industrial production, thus reducing emissions of waste.
Smart Images
Figure BDA0005548794380000021 
Figure BDA0005548794380000031
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing N-isobutyl-4-chloropyrrolidone. Background Technology
[0002] N-Isobutyl-4-chloropyrrolidone is an important pyrrolidone derivative with potential applications in medicine, pesticides, and other fields. Its structure features an isobutyl substituted group at position 1 and a chlorine atom substituted at position 4, making its synthesis challenging.
[0003] In existing technologies, the synthesis of N-alkylpyrrolidones often involves the reaction of γ-butyrolactone with amine compounds, while 4-chlorosubstituted pyrrolidones are typically obtained through subsequent halogenation of N-alkylpyrrolidones. However, these conventional methods have significant drawbacks: the halogenation steps following the aminolysis of γ-butyrolactone are numerous and lack atom economy; direct halogenation of N-alkylpyrrolidones easily leads to positional isomerism, poor selectivity, and difficulty in efficiently obtaining the target product. Therefore, developing a novel method for the efficient synthesis of N-isobutyl-4-chloropyrrolidone that avoids conventional methods is of great significance. Summary of the Invention
[0004] The purpose of this invention is to provide a method for preparing N-isobutyl-4-chloropyrrolidone. This method achieves the synthesis of N-isobutyl-4-chloropyrrolidone through a three-step reaction, avoiding the defects of conventional methods. It has the advantages of readily available raw materials, fewer reaction steps, and high selectivity, making it suitable for industrial production.
[0005] To achieve the above objectives, the present invention provides a method for preparing N-isobutyl-4-chloropyrrolidone, comprising the following steps:
[0006] Step S1: Using isobutylamine and ethyl acrylate as raw materials, immobilized CAL-B enzyme is used as a catalyst to carry out Michael addition in an aqueous buffer system to synthesize N-isobutyl-β-alanine ethyl ester.
[0007] Reaction principle: Under the catalysis of immobilized CAL-B enzyme, isobutylamine (primary amine) and ethyl acrylate (α,β-unsaturated ester) undergo Michael addition to generate N-isobutyl-β-alanine ethyl ester (secondary amine ester).
[0008] Reaction formula:
[0009] (CH3)2CHCH2NH2+CH2=CHCOOEt→(CH3)2CHCH2NHCH2CH2COOEt;
[0010] Step S2: Using a water / supercritical CO2 two-phase reaction system, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is synthesized by amidation.
[0011] Reaction principle: N-isobutyl-β-alanine ethyl ester (secondary amine) undergoes an amidation reaction with chloroacetyl chloride (acylizer), introducing a chloroacetyl group (providing a chlorine source at the 4-position).
[0012] Reaction formula:
[0013]
[0014] Step S3: Using a hydrotalcite solid base catalyst, Dieckmann condensation was carried out in a supercritical CO2 / cosolvent system to synthesize N-isobutyl-4-chloropyrrolidone.
[0015] Reaction principle: Using hydrotalcite as a solid base catalyst, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester (containing amide and ester groups) undergoes Dieckmann condensation under alkaline conditions, forming a pyrrolidone ring, while retaining a chlorine atom at position 4.
[0016] Reaction formula:
[0017]
[0018] The reaction temperature of steps S1 to S3 is reduced by 20-30℃ compared with the prior art.
[0019] Preferably, step S1 specifically involves:
[0020] Step S11: Using isobutylamine and ethyl acrylate as raw materials, a cosolvent is added to a phosphate buffer medium with a pH of 7.5, and immobilized CAL-B enzyme is used as a catalyst. The reaction is carried out at a temperature of 25-30°C for 3-4 hours.
[0021] Step S12: After the reaction is complete, the catalyst is recovered by magnetic separation, and then the solvent and ethyl acrylate are removed by vacuum distillation to obtain a colorless liquid product, namely N-isobutyl-β-alanine ethyl ester, with a yield >98%.
[0022] Preferably, in step S11, the co-solvent is tert-butanol, and the mass of the added co-solvent accounts for 10% of the total mass of isobutylamine and ethyl acrylate; the molar ratio of isobutylamine to ethyl acrylate is 1:1.1.
[0023] Among them, the immobilized CAL-B enzyme is loaded onto magnetic nanoparticles, and the immobilized CAL-B enzyme can be reused more than 10 times.
[0024] Preferably, in step S12, during the vacuum distillation process, the temperature of the bottom of the column is 60-65°C, the temperature of the top of the column is 35-40°C, and the pressure is -0.096 to -0.097 MPa.
[0025] Preferably, step S2 specifically involves:
[0026] Step S21: The N-isobutyl-β-alanine ethyl ester obtained in step S1 is reacted with chloroacetyl chloride in an aqueous medium and in the presence of an acid-binding agent at a temperature of 3-5°C for 1-1.5 hours.
[0027] Step S22: After the reaction is complete, supercritical CO2 is introduced to extract the product, which is then separated from the inorganic salts in the aqueous medium. After releasing CO2 under reduced pressure, a pale yellow liquid product is directly obtained, which is N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester, with a separation yield >95%.
[0028] Preferably, in step S2, the acid-binding agent is potassium carbonate, and the molar ratio of potassium carbonate to N-isobutyl-β-alanine ethyl ester is 1.2:1; the molar ratio of N-isobutyl-β-alanine ethyl ester to chloroacetyl chloride is 1:1.
[0029] The temperature at which supercritical CO2 is introduced to extract the product is 30–40°C, and the pressure is 10 MPa.
[0030] Preferably, step S3 specifically involves:
[0031] Step S31: Place the N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester obtained in step S2 and the solid base catalyst in a reaction vessel, introduce supercritical CO2 and add co-solvent ethanol, and react for 2-3 hours;
[0032] Step S32: After the reaction is complete, the product dissolves in the CO2 phase, and the solid base catalyst precipitates. Colorless crystals are obtained directly by vacuum crystallization, which is N-isobutyl-4-chloropyrrolidone, with a yield of >90%. The emissions of waste gas, wastewater, and solid waste are reduced by 80% compared with the existing technology.
[0033] Preferably, in step S31, the molar ratio of the solid base catalyst to N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is 1.5:1; the mass of the added co-solvent ethanol accounts for 5% of the total mass of N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester and the solid base catalyst.
[0034] The solid base catalyst is nano-Mg-Al hydrotalcite; the temperature for introducing supercritical CO2 is 60-70℃ and the pressure is 15MPa.
[0035] Preferably, in step S32, during the reduced pressure crystallization process, the temperature of the bottom of the column is 90-95℃, the temperature of the top of the column is 70-75℃, and the pressure is -0.097 to -0.098 MPa.
[0036] The present invention employs the above-mentioned method for preparing N-isobutyl-4-chloropyrrolidone, and the beneficial effects are as follows:
[0037] (1) Avoiding existing processes: This invention does not use the reaction of γ-butyrolactone with isobutylamine (a conventional method for synthesizing N-alkylpyrrolidone), nor does it use conventional methods such as subsequent halogenation of N-isobutylpyrrolidone (which easily leads to positional isomerism). This invention adopts a "linear precursor cyclization" strategy, which directly introduces N-isobutyl and 4-chloro substituents simultaneously during the cyclization process, and constructs the pyrrolidone ring through the cyclization reaction, thus avoiding the subsequent halogenation step, and is therefore an innovative route;
[0038] (2) Raw materials are readily available: Isobutylamine, ethyl acrylate and chloroacetyl chloride in this invention are all industrial-grade raw materials, which are low in cost and have a stable supply;
[0039] (3) Simplified steps: The preparation of N-isobutyl-4-chloropyrrolidone by the present invention requires only three reaction steps, and each reaction step is under mild conditions, without the need for special equipment such as high pressure and high temperature;
[0040] (4) High selectivity: This invention introduces isobutyl group through Michael addition and chloroacetyl group through amidation (providing chlorine source at 4 position). The Michael addition and amidation reactions have good selectivity and few by-products. Dieckmann condensation can accurately form a five-membered ring, thereby enabling controllable position of chlorine atom at 4 position.
[0041] (5) This invention can significantly enhance innovation by introducing novel catalysts and green process conditions.
[0042] The technical solution of the present invention will be further described in detail below through embodiments. Detailed Implementation
[0043] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.
[0044] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.
[0045] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.
[0046] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.
[0047] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.
[0048] Example 1
[0049] A method for preparing N-isobutyl-4-chloropyrrolidone includes the following steps:
[0050] Step S1: Using isobutylamine and ethyl acrylate as raw materials, immobilized CAL-B enzyme is used as a catalyst to carry out Michael addition in an aqueous buffer system to synthesize N-isobutyl-β-alanine ethyl ester.
[0051] Step S11: Weigh 7.31g of isobutylamine and 11.01g of ethyl acrylate as raw materials, add 1.83g of tert-butanol to phosphate buffer medium with pH 7.529.24mL, use immobilized CAL-B enzyme as catalyst, and react at 25℃ for 3 hours.
[0052] Step S12: After the reaction is complete, the catalyst is recovered by magnetic separation, and then the solvent and ethyl acrylate are removed by vacuum distillation to obtain a colorless liquid product, namely N-isobutyl-β-alanine ethyl ester, with a yield of 99%.
[0053] During the vacuum distillation process, the temperature at the bottom of the column is 65℃, the temperature at the top of the column is 35℃, and the pressure is -0.097MPa.
[0054] Step S2: Using a water / supercritical CO2 two-phase reaction system, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is synthesized by amidation.
[0055] Step S21: 173.29 g of N-isobutyl-β-alanine ethyl ester obtained in step S1 and 124.23 g of chloroacetyl chloride were reacted in an aqueous medium in the presence of 165.5 g of potassium carbonate at 3°C for 1 hour.
[0056] Step S22: After the reaction is complete, supercritical CO2 is introduced to extract the product at 30°C and 10 MPa. Separation from inorganic salts in the aqueous medium is achieved. After releasing CO2 under reduced pressure, a pale yellow liquid product, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester, is directly obtained with a separation yield of 96%.
[0057] Step S3: Using nano-Mg-Al hydrotalcite, Dieckmann condensation was carried out in a supercritical CO2 / cosolvent system to synthesize N-isobutyl-4-chloropyrrolidone.
[0058] Step S31: Place 263.5g of N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester obtained in step S2 and 24.15g of nano-Mg-Al hydrotalcite in a reaction vessel, introduce supercritical CO2, maintain the temperature at 65℃ and the pressure at 15MPa, and add 5.75g of the co-solvent ethanol. React for 2 hours.
[0059] Step S32: After the reaction is complete, the product dissolves in the CO2 phase, and nano-Mg-Al hydrotalcite precipitates. Colorless crystals are obtained directly by vacuum crystallization, which is N-isobutyl-4-chloropyrrolidone, with a yield of 95%.
[0060] During the reduced pressure crystallization process, the temperature at the bottom of the column is 90℃, the temperature at the top of the column is 75℃, and the pressure is -0.098MPa.
[0061] The N-isobutyl-4-chloropyrrolidone prepared in this example was tested, and the purity of the product was 96.8%. After recrystallization (solvent: ethanol / water = 1:1), the purity was 97.5%.
[0062] Example 2
[0063] A method for preparing N-isobutyl-4-chloropyrrolidone includes the following steps:
[0064] Step S1: Using isobutylamine and ethyl acrylate as raw materials, immobilized CAL-B enzyme is used as a catalyst to carry out Michael addition in an aqueous buffer system to synthesize N-isobutyl-β-alanine ethyl ester.
[0065] Step S11: Weigh 7.31g of isobutylamine and 11.01g of ethyl acrylate as raw materials, add 1.83g of tert-butanol to phosphate buffer medium with pH 7.529.24mL, use immobilized CAL-B enzyme as catalyst, and react at 25℃ for 4 hours.
[0066] Step S12: After the reaction is complete, the catalyst is recovered by magnetic separation, and then the solvent and ethyl acrylate are removed by vacuum distillation to obtain a colorless liquid product, namely N-isobutyl-β-alanine ethyl ester, with a yield of 99%.
[0067] During the vacuum distillation process, the temperature at the bottom of the column is 60℃, the temperature at the top of the column is 40℃, and the pressure is -0.096MPa.
[0068] Step S2: Using a water / supercritical CO2 two-phase reaction system, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is synthesized by amidation.
[0069] Step S21: 17.33 g of N-isobutyl-β-alanine ethyl ester obtained in step S1 and 11.30 g of chloroacetyl chloride were reacted in an aqueous medium in the presence of 16.58 g of potassium carbonate at 4 °C for 1.5 hours.
[0070] Step S22: After the reaction is complete, supercritical CO2 is introduced to extract the product at 35°C and 10 MPa. Separation from inorganic salts in the aqueous medium is achieved. After releasing CO2 under reduced pressure, a pale yellow liquid product, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester, is directly obtained with a separation yield of 98%.
[0071] Step S3: Using nano-Mg-Al hydrotalcite, Dieckmann condensation was carried out in a supercritical CO2 / cosolvent system to synthesize N-isobutyl-4-chloropyrrolidone.
[0072] Step S31: Place 24.78 g of N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester obtained in step S2 and 30.15 g of nano-Mg-Al hydrotalcite in a reaction vessel, introduce supercritical CO2, maintain the temperature at 65℃ and the pressure at 15 MPa, and add 5.75 g of the co-solvent ethanol. React for 2 hours.
[0073] Step S32: After the reaction is complete, the product dissolves in the CO2 phase, and nano-Mg-Al hydrotalcite precipitates. Colorless crystals are obtained directly by vacuum crystallization, which is N-isobutyl-4-chloropyrrolidone, with a yield of 97%.
[0074] During the reduced pressure crystallization process, the temperature at the bottom of the column is 95℃, the temperature at the top of the column is 70℃, and the pressure is -0.098MPa.
[0075] The N-isobutyl-4-chloropyrrolidone prepared in this embodiment was tested, and the purity of the product was 97.9%. After recrystallization (solvent: ethanol / water = 1:1), the purity was 99.5%.
[0076] Example 3
[0077] A method for preparing N-isobutyl-4-chloropyrrolidone includes the following steps:
[0078] Step S1: Using isobutylamine and ethyl acrylate as raw materials, immobilized CAL-B enzyme is used as a catalyst to carry out Michael addition in an aqueous buffer system to synthesize N-isobutyl-β-alanine ethyl ester.
[0079] Step S11: Weigh 7.31g of isobutylamine and 11.01g of ethyl acrylate as raw materials, add 1.83g of tert-butanol to phosphate buffer medium with pH 7.529.24mL, use immobilized CAL-B enzyme as catalyst, and react at 25℃ for 3 hours.
[0080] Step S12: After the reaction is complete, the catalyst is recovered by magnetic separation, and then the solvent and ethyl acrylate are removed by vacuum distillation to obtain a colorless liquid product, namely N-isobutyl-β-alanine ethyl ester, with a yield of 99%.
[0081] During the vacuum distillation process, the temperature at the bottom of the column is 65℃, the temperature at the top of the column is 35℃, and the pressure is -0.097MPa.
[0082] Step S2: Using a water / supercritical CO2 two-phase reaction system, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is synthesized by amidation.
[0083] Step S21: 173.29 g of N-isobutyl-β-alanine ethyl ester obtained in step S1 and 124.23 g of chloroacetyl chloride were reacted in an aqueous medium in the presence of 179.67 g of potassium carbonate at 3°C for 1 hour.
[0084] Step S22: After the reaction is complete, supercritical CO2 is introduced to extract the product at 30°C and 10 MPa. Separation from inorganic salts in the aqueous medium is achieved. After releasing CO2 under reduced pressure, a pale yellow liquid product, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester, is directly obtained with a separation yield of 97%.
[0085] Step S3: Using nano-Mg-Al hydrotalcite, Dieckmann condensation was carried out in a supercritical CO2 / cosolvent system to synthesize N-isobutyl-4-chloropyrrolidone.
[0086] Step S31: Place 263.5 g of N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester obtained in step S2 and 36.23 g of nano-Mg-Al hydrotalcite in a reaction vessel, introduce supercritical CO2, maintain the temperature at 65℃ and the pressure at 15 MPa, and add 15.0 g of the co-solvent ethanol. React for 2 hours.
[0087] Step S32: After the reaction is complete, the product dissolves in the CO2 phase, and nano-Mg-Al hydrotalcite precipitates. Colorless crystals are obtained directly by vacuum crystallization, which is N-isobutyl-4-chloropyrrolidone, with a yield of 96%.
[0088] During the reduced pressure crystallization process, the temperature at the bottom of the column is 90℃, the temperature at the top of the column is 75℃, and the pressure is -0.098MPa.
[0089] The N-isobutyl-4-chloropyrrolidone prepared in this example was tested, and the purity of the product was 97.6%. After recrystallization (solvent: ethanol / water = 1:1), the purity was 98.7%.
[0090] Therefore, the present invention adopts the above-mentioned method for preparing N-isobutyl-4-chloropyrrolidone. This method achieves the synthesis of N-isobutyl-4-chloropyrrolidone through a three-step reaction, avoiding the defects of conventional methods. It has the advantages of readily available raw materials, fewer reaction steps, and high selectivity, and is suitable for industrial production.
[0091] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.
Claims
1. A method for preparing N-isobutyl-4-chloropyrrolidone, characterized in that, Includes the following steps: Step S1: Using isobutylamine and ethyl acrylate as raw materials, immobilized CAL-B enzyme is used as a catalyst to carry out Michael addition in an aqueous buffer system to synthesize N-isobutyl-β-alanine ethyl ester. Step S2: Using a water / supercritical CO2 two-phase reaction system, N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is synthesized by amidation. Step S3: Using a hydrotalcite solid base catalyst, Dieckmann condensation is carried out in a supercritical CO2 / cosolvent system to synthesize N-isobutyl-4-chloropyrrolidone.
2. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 1, characterized in that: Step S1 specifically involves: Step S11: Using isobutylamine and ethyl acrylate as raw materials, a cosolvent is added to a phosphate buffer medium with a pH of 7.5, and immobilized CAL-B enzyme is used as a catalyst. The reaction is carried out at a temperature of 25-30°C for 3-4 hours. Step S12: After the reaction is complete, the catalyst is recovered by magnetic separation, and then the solvent and ethyl acrylate are removed by vacuum distillation to obtain a colorless liquid product, namely N-isobutyl-β-alanine ethyl ester.
3. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 2, characterized in that: In step S11, the co-solvent is tert-butanol, and the mass of the added co-solvent accounts for 10% of the total mass of isobutylamine and ethyl acrylate; the molar ratio of isobutylamine to ethyl acrylate is 1:1.
1. Among them, the immobilized CAL-B enzyme is loaded onto magnetic nanoparticles, and the immobilized CAL-B enzyme can be reused more than 10 times.
4. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 2, characterized in that: In step S12, during the vacuum distillation process, the temperature of the bottom of the column is 60-65℃, the temperature of the top of the column is 35-40℃, and the pressure is -0.096 to -0.097 MPa.
5. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 1, characterized in that: Step S2 specifically involves: Step S21: The N-isobutyl-β-alanine ethyl ester obtained in step S1 is reacted with chloroacetyl chloride in an aqueous medium and in the presence of an acid-binding agent at a temperature of 3-5°C for 1-1.5 hours. Step S22: After the reaction is complete, supercritical CO2 is introduced to extract the product, which is then separated from the inorganic salts in the aqueous medium. After releasing CO2 under reduced pressure, a pale yellow liquid product is directly obtained, which is N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester.
6. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 5, characterized in that: In step S2, the acid-binding agent is potassium carbonate, and the molar ratio of potassium carbonate to N-isobutyl-β-alanine ethyl ester is (1.1~1.3):1; the molar ratio of N-isobutyl-β-alanine ethyl ester to chloroacetyl chloride is 1:
1. The temperature at which supercritical CO2 is introduced to extract the product is 30–40°C, and the pressure is 10 MPa.
7. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 1, characterized in that: Step S3 specifically involves: Step S31: Place the N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester obtained in step S2 and the solid base catalyst in a reaction vessel, introduce supercritical CO2 and add co-solvent ethanol, and react for 2-3 hours; Step S32: After the reaction is complete, the product dissolves in the CO2 phase, precipitates with a solid base catalyst, and is directly obtained as colorless crystals by vacuum crystallization, which is N-isobutyl-4-chloropyrrolidone.
8. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 7, characterized in that: In step S31, the molar ratio of the solid base catalyst to N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester is (0.04~0.06):1; the mass of the added co-solvent ethanol accounts for 5% of the total mass of N-isobutyl-N-(chloroacetyl)-β-alanine ethyl ester and the solid base catalyst. The solid base catalyst is nano-Mg-Al hydrotalcite; the temperature for introducing supercritical CO2 is 60-70℃ and the pressure is 15MPa.
9. The method for preparing N-isobutyl-4-chloropyrrolidone according to claim 7, characterized in that: In step S32, during the reduced pressure crystallization process, the temperature of the bottom of the column is 90-95℃, the temperature of the top of the column is 70-75℃, and the pressure is -0.097 to -0.098 MPa.