Synthesis method of N-(2-ethoxyl)-N-methylmorpholinium bromide

Abstract

The invention discloses a synthesis method of N-(2-ethoxyl)-N-methylmorpholinium bromide, which comprises the following steps: S1, in an inactive atmosphere, dropwise adding 2-bromoethanol into a constant-temperature solution containing N-methylmorpholine in a reactor, heating for reaction, and cooling to obtain a constant-temperature raw material solution; and S2, adding an anti-solvent into the constant-temperature raw material solution obtained in the step S1, and separating out to obtain the N-(2-ethoxyl)-N-methylmorpholinium bromide. According to the method, the reaction can be carried out under normal pressure, the quaternary ammonium salt generated by the reaction can be separated out by adding an anti-solvent, and the anti-solvent is used for washing and filtering. The quaternary ammonium salt obtained by the method is high in yield, purity and selectivity; intermediate steps are few, and separation and purification are simple.

Description

Technical Field

[0001] The present application relates to a method for synthesizing N-(2-hydroxyethyl)-N-methylmorpholinium 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-methylmorpholinium 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: react methyl bromide acetonitrile solution and morpholine in a reaction solvent at 30-100°C for 1-24 hours to obtain a tertiary amine salt reaction solution; add 2-bromoethanol and an inorganic base to the tertiary amine salt reaction solution, react at 30100°C for 124 hours to obtain a quaternary ammonium salt reaction solution; purify the quaternary ammonium salt reaction solution to obtain N-(2-hydroxyethyl)-N-methylmorpholinium bromide. This method has a long reaction step, a yield of about 85%, and a complicated impurity removal process. Summary of the invention

[0004] According to one aspect of the present application, a method for synthesizing N-(2-hydroxyethyl)-N-methylmorpholinium bromide is provided, which solves the problems of complicated preparation steps and impurities affecting the use of the prior art.

[0005] The structural formula of N-(2-hydroxyethyl)-N-methylmorpholinium bromide described in this application is as follows:

[0006]

[0007] This application adopts the following technical solutions:

[0008] A method for synthesizing N-(2-hydroxyethyl)-N-methylmorpholinium bromide comprises the following steps:

[0009] S1. In an inactive atmosphere, 2-bromoethanol is added dropwise to a constant temperature solution containing N-methylmorpholine in a reactor, heated for reaction, and cooled to obtain a constant temperature raw material solution;

[0010] S2. Add an anti-solvent to the constant temperature raw material solution obtained in step S1 to precipitate and obtain the N-(2-hydroxyethyl)-N-methylmorpholinium bromide.

[0011] Optionally, the materials in the reactor are kept in a stirring state throughout the whole process of step S1.

[0012] Optionally, the mixed solution is obtained by uniformly mixing N-methylmorpholine and an organic solvent under continuous stirring, and the stirring time of the process is 0.1 to 1 h, preferably 0.1 to 0.5 h.

[0013] Optionally, in step S1, the mixed liquid is kept in a condensation reflux circulation state during the mixing process.

[0014] Optionally, in step S1, the temperature of the constant temperature mixed liquid is 50-130°C.

[0015] Optionally, in step S1, the temperature of the constant temperature mixed liquid is selected from any value of 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, 130°C, or any range therebetween.

[0016] Optionally, in step S1, the conditions for the dropwise addition include: the dropwise addition completion time is 0.1 to 3 hours.

[0017] 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.

[0018] Optionally, the conditions for the dropwise addition include: the dropwise addition completion time is 1 to 1.5 hours.

[0019] Optionally, in step S1, the constant temperature solution further comprises an organic solvent.

[0020] Optionally, in step S1, the molar ratio of N-methylmorpholine to the organic solvent is 1:0.01-2.

[0021] Optionally, in step S1, the molar ratio of N-methylmorpholine 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.

[0022] Optionally, in step S1, the molar ratio of the N-methylpyrrolidine to the organic solvent is 1:1 to 1.5.

[0023] Optionally, in step S1, the molar ratio of N-methylmorpholine to 2-bromoethanol is 1:0.5-2.

[0024] Optionally, in step S1, the molar ratio of N-methylpyrrolidine to 2-bromoethanol is 1:0.8-1.2.

[0025] Optionally, in step S1, the organic solvent is selected from at least one of acetonitrile, ethanol, methanol, and N-N-dimethylamide.

[0026] Optionally, in step S1, the organic solvent is preferably acetonitrile.

[0027] The present application, the organic solvent described in step S1 and N-methylmorpholine 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 described in step (3), until the reaction is completed, the precipitation of the product should not occur, because the reaction rate of the two reactants in the solution is the maximum, 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.

[0028] Optionally, in step S1, the reaction conditions include: reaction temperature of 50 to 130° C., and stirring for 24 to 72 hours.

[0029] Optionally, in step S1, the reaction conditions include: stirring for 36 to 48 hours.

[0030] A homogeneous solution can be obtained after the reaction described in this application.

[0031] Optionally, the temperature of the constant temperature raw material liquid is less than or equal to 40°C.

[0032] Optionally, in step S2, the anti-solvent is selected from at least one of ethyl acetate, acetone, and diethyl ether.

[0033] Optionally, in step S2, the anti-solvent is preferably ethyl acetate.

[0034] Anti-solvent was added and a large amount of solid material precipitated.

[0035] Optionally, in step S1, a condensation reflux circulation state is maintained during the dropwise addition process.

[0036] Optionally, in step S2, the process of adding the anti-solvent maintains a condensation reflux circulation state.

[0037] Optionally, the conditions of the condensation reflux circulation state include: the condensation reflux time is 0.1 to 48 hours, preferably 2 to 4 hours.

[0038] Optionally, in step S2, the precipitation further comprises filtering, washing, rotary evaporation, and drying;

[0039] The washing is performed using an anti-solvent.

[0040] The washing is performed using an anti-solvent.

[0041] Optionally, the washing condition is washing 0 to 5 times.

[0042] Optionally, the rotary evaporation is performed by using a vacuum rotary evaporator to remove most of the anti-solvent.

[0043] 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.

[0044] The yield of the product obtained by the above operation in the present application is greater than 95%, and the purity of the product is high.

[0045] In order to obtain a higher product purity, the precipitated product in step S2 may be recrystallized.

[0046] Optionally, the rotary evaporation further comprises recrystallization using a good solvent, and then repeating the steps of washing, rotary evaporation and drying.

[0047] Optionally, the good solvent is acetonitrile.

[0048] Optionally, the washing condition is washing 0 to 5 times.

[0049] Optionally, the rotary evaporation is performed by using a vacuum rotary evaporator to remove most of the anti-solvent.

[0050] 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.

[0051] The beneficial effects of this application include:

[0052] The synthetic method of N-(2-hydroxyethyl)-N-methylmorpholinium bromide provided by the present application, by using a one-step reaction, avoids the yield decline and additional impurity removal problems introduced by the two-step reaction, and the method is easy to separate N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid from the solvent, and the obtained product has small particles, which is very conducive to subsequent washing, filtering and other operations, and the synthesis purity is high and the yield is high. The synthetic method used in the present application has simple reaction steps and easy impurity removal. Compared with the synthetic method using inorganic alkali, the intermediate process of the reaction is reduced, and the process of reaction impurity removal is greatly simplified. After the synthetic method obtained product used in the present application is washed many times, the product has almost no impurities. Without recrystallization operation, the yield of the product can still be greater than 93%. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 The hydrogen nuclear magnetic resonance spectrum of N-(2-hydroxyethyl)-N-methylmorpholinium bromide prepared in Example 1 of the present application is shown in D 2 O is a solvent. DETAILED DESCRIPTION

[0054] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0055] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0056] Unless otherwise specified, conventional methods were used for testing and instrument settings were those recommended by the manufacturer.

[0057] Example 1

[0058] Keep the oil bath at a constant temperature of 90°C, mix 1 mol of N-methylmorpholine 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. After the addition of 2-bromoethanol is completed, stop N 2 For protection, it is necessary to keep the condensed water refluxed and keep the solution stirred. 48 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, the oil bath heating was stopped, and the three-necked flask was still a uniform solution. When the solution was cooled to 40°C, ethyl acetate was slowly poured into the three-necked flask while using mechanical stirring, and a large amount of solid precipitated. The solid was separated by filtration. The solid product was washed with 100mL of ethyl acetate at room temperature, washed 5 times, and dried in a vacuum oven at 40°C for 8 hours to finally obtain a white N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid powder with a yield of 94.2% of the theoretical yield.

[0059] Example 2

[0060] Keep the oil bath at a constant temperature of 90°C, mix 1 mol of N-methylmorpholine 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. After the addition of 2-bromoethanol is completed, stop N 2 For protection, it is necessary to keep the condensed water refluxed and keep the solution stirred. 72 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, the oil bath heating was stopped, and the three-necked flask was still a uniform solution. When the solution was cooled to 40°C, ethyl acetate was slowly poured into the three-necked flask while using mechanical stirring, and a large amount of solid precipitated. The solid was separated by filtration. The solid product was washed with 100mL of ethyl acetate at room temperature, washed 5 times, and dried in a vacuum oven at 40°C for 8 hours to finally obtain a white N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid powder with a yield of 95.1% of the theoretical yield.

[0061] Example 3

[0062] Keep the oil bath at a constant temperature of 110°C, mix 1 mol of N-methylmorpholine and 60 mL of acetonitrile in a three-necked flask with a reflux device under nitrogen protection, and stir thoroughly with a magnetic stirrer. 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. After the addition of 2-bromoethanol is completed, stop N 2 For protection, it is necessary to keep the condensed water refluxed and keep the solution stirred. 72 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, the oil bath heating was stopped, and the three-necked flask was still a uniform solution. When the solution was cooled to 40°C, ethyl acetate was slowly poured into the three-necked flask while using mechanical stirring, and a large amount of solid precipitated. The solid was separated by filtration. The solid product was washed with 100mL of ethyl acetate at room temperature, washed 5 times, and dried in a vacuum oven at 40°C for 8 hours to finally obtain a white N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid powder with a yield of 94.5% of the theoretical yield.

[0063] Example 4

[0064] Keep the oil bath at 90°C, mix 1 mol of N-methylmorpholine in a three-necked flask with a reflux device under nitrogen protection, and use a magnetic stirrer to mix thoroughly. 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. After the addition of 2-bromoethanol is completed, stop N 2 For protection, it is necessary to keep the condensed water refluxed and keep the solution stirred. 48 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, the oil bath heating was stopped, and there was a viscous solid in the three-necked flask. When the solution was cooled to 40°C, ethyl acetate was slowly poured into the three-necked flask to wash the product while using mechanical stirring. The solid was separated by filtration. The solid product was washed with 100mL of ethyl acetate at room temperature, washed 5 times, and dried in a vacuum oven at 40°C for 8 hours to finally obtain a white N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid powder with a yield of 67.0% of the theoretical yield.

[0065] Comparative Example 1

[0066] At room temperature, 0.1 mol of morpholine is uniformly mixed in 20 mL of acetonitrile, and an acetonitrile solution containing 0.1 mol of methyl bromide is slowly dripped into the acetonitrile solution of morpholine, and reacted at 25°C for 2 hours to obtain a tertiary amine salt reaction solution; 0.1 mol of 2-bromoethanol is uniformly mixed in 20 mL of acetonitrile, and the acetonitrile solution of 2-bromoethanol is slowly dripped into the tertiary amine salt reaction solution, 10 g of sodium hydroxide is weighed and added to a three-necked flask, and the oil bath is kept at a constant temperature of 80°C, and the reaction is refluxed for 8 hours. After the system is cooled to room temperature, the solvent is evaporated to dryness to obtain a solid, 100 mL of dichloromethane is added to dissolve the solid, the insoluble matter is filtered, the filtrate is collected, and the filtrate is evaporated to dryness again to obtain a crude product. Use 100 mL of ethanol to dissolve the crude product, heat to help dissolve, wait for the solution to become clear, and slowly cool to -5°C. A large amount of product is recrystallized and precipitated. Quickly filter and collect the solid. After recrystallization three times, the target product is obtained. Finally, the product is dried in a vacuum oven at 65°C for 24 hours to obtain the target product. The yield is 80.4% of the theoretical yield. This method has a long reaction process and a complicated impurity removal process.

[0067] Comparative Example 2

[0068] At room temperature, mix 1 mol of N-methylmorpholine 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. After the addition of 2-bromoethanol is completed, stop N 2 Protect, keep the condensed water reflux, and keep the solution in a stirring state. 24 hours after the addition of 2-bromoethanol is completed, stop the magnetic stirring. The three-necked flask is still a uniform solution. When using mechanical stirring, slowly pour ethyl acetate into the three-necked flask, and a small amount of solid precipitates. Use filtration to separate the solid matter. Wash the solid product obtained with 100mL of ethyl acetate at room temperature, wash 5 times, and then dry it in a vacuum oven at 40°C for 8 hours to finally obtain a white N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid powder. The yield is only 13% of the theoretical yield, indicating that heating can promote the full reaction.

[0069] Comparative Example 3

[0070] Keep the oil bath at a constant temperature of 90°C, mix 1 mol of N-methylmorpholine 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. After the addition of 2-bromoethanol is completed, stop N 2Protection, it is necessary to keep the condensed water refluxed and keep the solution stirred. 72 hours after the addition of 2-bromoethanol was completed, the magnetic stirring was stopped, the oil bath heating was stopped, and the three-necked flask was still a uniform solution. When the solution was cooled to 40°C, dichloromethane was slowly poured into the three-necked flask under mechanical stirring, and no solid was precipitated. Ethyl acetate was then poured into it, and the solid was separated by filtration. The solid product was washed with 100mL of ethyl acetate at room temperature, washed 5 times, and dried in a vacuum oven at 40°C for 8 hours to finally obtain a white N-(2-hydroxyethyl)-N-methylmorpholinium bromide solid powder with a yield of 49.2% of the theoretical yield. This shows that dichloromethane cannot be used as an anti-solvent.

[0071] 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-methylmorpholinium bromide, It is characterized in that The steps include: S1. In an inactive atmosphere, 2-bromoethanol is added dropwise to a constant temperature solution containing N-methylmorpholine in a reactor, heated for reaction, and cooled to obtain a constant temperature raw material solution; S2. Add an anti-solvent to the constant temperature raw material solution obtained in step S1 to precipitate and obtain the N-(2-hydroxyethyl)-N-methylmorpholinium bromide.

2. The synthesis method according to claim 1, It is characterized in that In step S1, the temperature of the constant temperature mixed liquid is 50-130°C; Preferably, 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 constant temperature solution further comprises an organic solvent; Preferably, in step S1, the molar ratio of N-methylmorpholine 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-methylmorpholine to 2-bromoethanol is 1:0.5-2.

5. The synthesis method according to claim 3, 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: reaction temperature of 50 to 130° C., stirring for 24 to 72 hours; Preferably, the temperature of the constant temperature raw material liquid is less than or equal to 40°C.

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, 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.

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