Synthesis method of N-(2-ethoxyl)-N-methyl-pyrrolidinium bromide
By adding 2-bromoethanol to the solution of N-methylpyrrolidine at room temperature and adding anti-solvent, the problem of high energy consumption and impurity of the preparation of N-(2-hydroxyethyl)-N-methyl-pyrrolidium bromide in the prior art was successfully solved, and high-efficiency, low-energy consumption synthesis and high-purity product acquisition were achieved.
Patent Information
- Application Number
- CN202311666149.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-06
- Publication Date
- 2025-06-06
AI Technical Summary
The preparation method of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide in the prior art consumes a lot of energy and has not been purified for product, which may affect the scientific research and industrial production for subsequent use.
2-bromoethanol was added dropwise to the solution containing N-methylpyrrolidine in an inactive atmosphere, and the anti-solvent was added after the reaction, and N-(2-hydroxyethyl)-N-methyl-pyrrolidium bromide was precipitated. The process is carried out at room temperature, avoiding heating, reducing energy consumption, and improving the purity of the product through steps such as anti-solvent and washing.
The high-purity and high yield of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide is achieved without heating, reducing energy consumption and simplifying the subsequent washing and purification process.
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Figure CN120097936A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to a method for synthesizing N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide, and belongs to the technical field of fine organic synthesis. Background Art
[0002] Quaternary ammonium salts are widely used in the development and application of zinc-bromine flow batteries as a bromine complexing agent because they can form quaternary ammonium polybromide oily ionic liquids with bromine, separate from aqueous solutions, and reduce the concentration of bromine in aqueous solutions. They are an important component of zinc-bromine flow battery electrolytes.
[0003] N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide is a new type of bromine complexing agent for zinc-bromine flow batteries. At present, there is no commercial product for this quaternary ammonium salt, so it needs to be synthesized by itself. The usual preparation method is: at room temperature, 2-bromoethanol, N-methylpyrrolidine and ultrapure water are mixed and heated to reflux for 0.5-10 days to obtain an aqueous solution of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide. When using this method for reaction, heating is required, which consumes a lot of energy; after the reaction is completed, the product is not purified, and the reactants that are not completely reacted may affect the subsequent use of the quaternary ammonium salt, causing uncertainty in scientific research or industrial production. Summary of the invention
[0004] According to one aspect of the present application, a method for synthesizing N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide is provided, which solves the problems of high energy consumption and impurities affecting the use of the preparation method in the prior art.
[0005] The structural formula of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide described in the present application is as follows:
[0006]
[0007] This application adopts the following technical solutions:
[0008] A method for synthesizing N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide comprises the following steps:
[0009] S1. In an inert atmosphere, 2-bromoethanol is added dropwise to a solution containing N-methylpyrrolidine in a reactor to react and obtain a raw material solution;
[0010] S2. Add an anti-solvent to the raw material solution obtained in step S1 to precipitate and obtain the N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide.
[0011] Optionally, the materials in the reactor are kept in a stirring state throughout the whole process of step S1.
[0012] Optionally, the synthesis method described in this application can be carried out at room temperature.
[0013] The room temperature refers to 20-35°C.
[0014] Optionally, the mixed solution is obtained by uniformly mixing N-methylpyrrolidine and an organic solvent under continuous stirring, and the stirring time of the process is 0.1 to 1 h, preferably 0.2 to 0.5 h.
[0015] Optionally, in step S1, the conditions for the dropwise addition include: the dropwise addition completion time is 0.1 to 3 hours.
[0016] Optionally, in step S1, the conditions for the dripping include: the dripping completion time is selected from any value of 0.1h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, or any range value therebetween.
[0017] Optionally, the conditions for the dropwise addition include: the dropwise addition completion time is 1 to 1.5 hours.
[0018] Optionally, in step S1, the solution further comprises an organic solvent.
[0019] Optionally, in step S1, the molar ratio of the N-methylpyrrolidine to the organic solvent is 1:0.01-2.
[0020] Optionally, in step S1, the molar ratio of the N-methylpyrrolidine to the organic solvent is selected from any value of 1:0.01, 1:0.05, 1:0.1, 1:0.5, 1:1, 1:1.5, 1:2, or any range therebetween.
[0021] Optionally, in step S1, the molar ratio of the N-methylpyrrolidine to the organic solvent is 1:0.8-1.5.
[0022] Optionally, in step S1, the molar ratio of N-methylpyrrolidine to 2-bromoethanol is 1:0.5-2.0.
[0023] Optionally, in step S1, the molar ratio of N-methylpyrrolidine to 2-bromoethanol is 1:0.8-1.2.
[0024] Optionally, in step S1, the organic solvent is selected from at least one of acetonitrile, ethanol, methanol, and N-N-dimethylamide.
[0025] Optionally, in step S1, the organic solvent is preferably acetonitrile.
[0026] The present application, the solvent described in step S1 and N-methylpyrrolidine have good mutual solubility, and its mutual solubility does not change significantly with the change of temperature or concentration. Meanwhile, in the process of the reaction, until the reaction is terminated, the precipitation of the product should not occur, because the reaction rate of the two reactants in the solution is the largest, and the reaction is the most complete. The reactant is dissolved in the anti-solvent, and the product is insoluble in the anti-solvent, and a pure product can be obtained at room temperature, which is conducive to reducing the difficulty and cost of washing and purification of the product.
[0027] Optionally, in step S1, the reaction conditions include: stirring for 24 to 72 hours.
[0028] Optionally, in step S1, the reaction conditions include: stirring for 36 to 48 hours.
[0029] Optionally, in step S2, the anti-solvent is selected from at least one of ethyl acetate, dichloromethane, acetone, and diethyl ether.
[0030] Optionally, in step S2, the anti-solvent is preferably diethyl ether.
[0031] Anti-solvent was added and a large amount of solid material precipitated.
[0032] Optionally, in step S1, a condensation reflux circulation state is maintained during the dropwise addition process.
[0033] Optionally, in step S1, the conditions of the condensation reflux circulation state include: the condensation reflux time is 0.1 to 48 hours, preferably 2 to 4 hours.
[0034] Optionally, in step S2, the precipitation further comprises filtering, washing, rotary evaporation, and drying;
[0035] The washing is performed using an anti-solvent.
[0036] Optionally, the washing condition is washing 0 to 5 times.
[0037] Optionally, the rotary evaporation is performed by using a vacuum rotary evaporator to remove most of the anti-solvent.
[0038] Optionally, the drying is to use a vacuum oven to dry the solid, the drying temperature is 25 to 120° C., preferably the drying temperature is 40 to 50° C., and the oven drying time is 1 to 48 hours, preferably 8 to 20 hours.
[0039] The yield of the product obtained by the above operation in the present application is greater than 90%. If the operation is proper, the yield of the product obtained can be greater than 95%, and the purity of the product is high.
[0040] The synthesis method adopted in the present application does not require heating, saves energy, and the obtained product is easy to separate from the solvent. The obtained product particles are small, which is very conducive to subsequent washing, filtering and other operations.
[0041] In order to obtain a higher product purity, the precipitated product in step S2 may be recrystallized.
[0042] Optionally, the rotary evaporation further comprises recrystallization using a good solvent, and then repeating the steps of washing, rotary evaporation and drying.
[0043] Optionally, the good solvent is acetonitrile.
[0044] Optionally, the washing condition is washing 0 to 5 times.
[0045] Optionally, the rotary evaporation is performed by using a vacuum rotary evaporator to remove most of the anti-solvent.
[0046] Optionally, the drying is to use a vacuum oven to dry the solid, the drying temperature is 25 to 120° C., preferably the drying temperature is 40 to 50° C., and the oven drying time is 1 to 48 hours, preferably 20 to 30 hours.
[0047] The beneficial effects of this application include:
[0048] The synthesis method of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide provided by the present application, by using a high concentration reaction, synthesizes a high purity, high yield, and easy-to-separate N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid without heating. Compared with the aqueous synthesis method, the non-aqueous synthesis method used in the present invention can obtain a pure N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid instead of an aqueous solution that is difficult to remove impurities; N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide can be purified by washing, recrystallization, etc., which is helpful to cope with the scene where a higher purity N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid is needed in scientific research or industrial production; heating can be avoided during the reaction process, saving energy consumption in large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS
[0049] Figure 1 The hydrogen nuclear magnetic resonance spectrum of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide prepared in Example 1 of the present application is shown in D 2 O is a solvent. DETAILED DESCRIPTION
[0050] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.
[0051] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.
[0052] Unless otherwise specified, conventional methods were used for testing and instrument settings were those recommended by the manufacturer.
[0053] Example 1
[0054] At room temperature, mix 1 mol of N-methylpyrrolidine and 60 mL of acetonitrile in a three-necked flask with a reflux device under nitrogen protection, and use a magnetic stirrer to mix thoroughly. Slowly drip 1 mol of 2-bromoethanol into the three-necked flask using a constant pressure dropping funnel, and complete the addition within 1 hour. Stir thoroughly while adding, so that the reactants are fully mixed and contacted. Stop the addition of 2-bromoethanol 2 hours after the end of the addition. 2 Protect and reflux the condensed water to keep the solution in a stirring state. 48 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, and the three-necked flask was still a uniform solution. While using mechanical stirring, 150 mL of ether was added to the three-necked flask at one time, and a large amount of solid precipitated. The solid was separated by filtration. The solid product was washed with 100 mL of ether at room temperature, washed 5 times, and then dried in a vacuum oven at 40°C for 8 hours to obtain a beige N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid powder with a yield of 95.0% of the theoretical yield.
[0055] Example 2
[0056] At room temperature, mix 1 mol of N-methylpyrrolidine and 60 mL of acetonitrile in a three-necked flask with a reflux device under nitrogen protection, and use a magnetic stirrer to mix thoroughly. Slowly drip 1 mol of 2-bromoethanol into the three-necked flask using a constant pressure dropping funnel, and complete the addition within 1 hour. Stir thoroughly while adding, so that the reactants are fully mixed and contacted. Stop the addition of 2-bromoethanol 2 hours after the end of the addition. 2 Protect and reflux the condensed water to keep the solution in a stirring state. 24 hours after the addition of 2-bromoethanol was completed, stop the magnetic stirring, and the three-necked flask was still a uniform solution. While using mechanical stirring, add 150mL of ether to the three-necked flask at one time, and a large amount of solid precipitates. Use filtration to separate the solid matter. Wash the solid product with 100mL of ether at room temperature, wash 5 times, and then dry it in a vacuum oven at 40°C for 8 hours to finally obtain a beige N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid powder with a yield of 91.4% of the theoretical yield.
[0057] Example 3 (without organic solvent)
[0058] At room temperature, mix 1 mol of N-methylpyrrolidine in a three-necked flask with a reflux device under nitrogen protection, and use a magnetic stirrer to mix thoroughly. Slowly drip 1 mol of 2-bromoethanol into the three-necked flask using a constant pressure dropping funnel, and complete the addition within 1 hour. Stir thoroughly while adding, so that the reactants are fully mixed and contacted. Stop the addition of 2-bromoethanol 2 hours after the end of the addition. 2 Protect and reflux the condensed water to keep the solution in a stirring state. 48 hours after the addition of 2-bromoethanol is completed, stop the magnetic stirring, and the three-necked flask is in a viscous solid state. While using mechanical stirring, add 150mL of ether to the three-necked flask at one time. Use filtration to separate the solid matter. Wash the solid product with 100mL of ether at room temperature, wash 5 times, and then dry it in a vacuum oven at 40°C for 8 hours to finally obtain a beige N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid powder with a yield of 79.0% of the theoretical yield.
[0059] Comparative Example 1
[0060] Mix 1 mol of N-methylpyrrolidine and 60 mL of ultrapure water in a three-necked flask with a reflux device under nitrogen protection, and mix thoroughly with magnetic stirring. The three-necked flask is heated in an oil bath to maintain a constant temperature of 80°C. Use a constant pressure dropping funnel to slowly drip 1 mol of 2-bromoethanol into the three-necked flask, and complete the addition within 1 hour. Stir thoroughly while adding, so that the reactants are fully mixed and contacted completely. Four days after the addition of 2-bromoethanol is completed, stop heating and magnetic stirring to obtain an aqueous solution of N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide. The obtained N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide aqueous solution. Compared with the method described in the present invention, the final product obtained is an aqueous solution mixture, and the application scenario is limited; the product is not purified, and there is a possibility of side reactions in the unreacted reactants; the reaction requires continuous heating, which consumes high energy.
[0061] Comparative Example 2
[0062] At room temperature, 1 mol of N-methylpyrrolidine and 60 mL of acetonitrile were mixed in a three-necked flask with a reflux device under nitrogen protection, and magnetic stirring was used to mix thoroughly. 1 mol of 2-bromoethanol was directly poured into the three-necked flask and stirred thoroughly. After stirring for a period of time, the reaction boiled violently, and some reactants rushed out of the condenser tube. 48 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, and the three-necked flask was still a uniform solution. Under mechanical stirring, 150 mL of ether was added to the three-necked flask at one time, and a large amount of solid precipitated. The solid was separated by filtration. The solid product was washed with 100 mL of ether at room temperature, washed 5 times, and dried in a vacuum oven at 40 ° C for 8 hours, and finally a beige N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid powder was obtained, and the yield was 68.7% of the theoretical yield. The reaction is exothermic, so the reactants need to be added slowly to prevent the reaction from boiling violently and causing product loss.
[0063] Comparative Example 3
[0064] Mix 1 mol of N-methylpyrrolidine and 60 mL of acetonitrile in a three-necked flask with a reflux device under nitrogen protection, and mix thoroughly with magnetic stirring. The three-necked flask is heated in an oil bath to maintain a constant temperature of 80°C. Use a constant pressure dropping funnel to slowly drip 1.2 mol of 2-bromoethanol into the three-necked flask, and complete the addition within 1.2 hours. Stir thoroughly while adding, so that the reactants are fully mixed and contacted completely. 48 hours after the addition of 2-bromoethanol is completed, stop magnetic stirring, and the three-necked flask is still a uniform solution. When the solution is cooled to room temperature, 150 mL of ether is added to the three-necked flask at one time under mechanical stirring, and a large amount of solid precipitates. Use filtration to separate the solid matter. Wash the obtained solid product with 100 mL of ether at room temperature, wash 5 times, and dry it in a vacuum oven at 40°C for 8 hours, and finally obtain a beige N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide solid powder, with a yield of 97.2% of the theoretical yield. Compared with Example 1, although the yield is high, the economic benefit gained by the increased yield due to heating is not obvious, and it brings about a greater energy consumption cost.
[0065] The above are only a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.
Claims
1. A method for synthesizing N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide, It is characterized in that The steps include: S1. In an inert atmosphere, 2-bromoethanol is added dropwise to a solution containing N-methylpyrrolidine in a reactor to react and obtain a raw material solution; S2. Add an anti-solvent to the raw material solution obtained in step S1 to precipitate and obtain the N-(2-hydroxyethyl)-N-methyl-pyrrolidinium bromide.
2. The synthesis method according to claim 1, It is characterized in that In step S1, the conditions for the dropwise addition include: the dropwise addition completion time is 0.1 to 3 hours.
3. The synthesis method according to claim 1, It is characterized in that In step S1, the solution further comprises an organic solvent; Preferably, in step S1, the molar ratio of N-methylpyrrolidine to the organic solvent is 1:0.01-2.
4. The synthesis method according to claim 1, It is characterized in that In step S1, the molar ratio of N-methylpyrrolidine to 2-bromoethanol is 1:0.5-2.
0.
5. The synthesis method according to claim 1, It is characterized in that In step S1, the organic solvent is selected from at least one of acetonitrile, ethanol, methanol, and N-N-dimethylamide.
6. The synthesis method according to claim 1, It is characterized in that In step S1, the reaction conditions include: stirring for 24 to 72 hours.
7. The synthesis method according to claim 1, It is characterized in that In step S2, the anti-solvent is selected from at least one of ethyl acetate, dichloromethane, acetone, and diethyl ether.
8. The synthesis method according to claim 1, It is characterized in that In step S1, the condensation reflux circulation state is maintained during the dropwise addition process.
9. The synthesis method according to claim 1, It is characterized in that In step S2, the precipitation further includes filtering, washing, rotary evaporation, and drying; The washing is performed using an anti-solvent.
10. The synthesis method according to claim 9, It is characterized in that The rotary evaporation further includes recrystallization using a good solvent, and then repeating the steps of washing, rotary evaporation and drying.