Preparation method of 4-acryloylmorpholine

Abstract

The invention relates to the technical field of chemical synthesis, and provides a preparation method of 4-acryloylmorpholine, which comprises the following steps: S1, reacting morpholine with 3-chloropropionyl chloride, and adding a basic catalyst and a solvent to obtain a reaction solution; s2, the reaction liquid is treated, and an organic phase solution with 3-chloropropionyl morpholine and 4-acryloyl morpholine is obtained; s3, adding the basic catalyst and the polymerization inhibitor into the organic phase solution with the 3-chloropropionyl morpholine and the 4-acryloyl morpholine again, and converting to obtain an organic phase solution with the 4-acryloyl morpholine; s4, the organic phase solution with the 4-acryloyl morpholine is treated, and the 4-acryloyl morpholine is obtained. The method has high chemical selectivity, ensures that 3-chloropropionyl chloride is mainly converted into 4-acryloylmorpholine, reduces the generation of byproducts, improves the reaction rate and yield, and enables the preparation process to be more efficient, mild in reaction condition, simple to operate, appropriate in raw material price, high in product yield and high in purity.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis technology, and more specifically to a preparation method of 4-acryloylmorpholine. Background Art

[0002] 4-Acryloylmorpholine is an unsaturated organic small molecule compound containing double bonds and is an important raw material for synthesizing high molecular polymers. 4-Acryloylmorpholine is an effective modifier for acrylate resins and gelatin. The polymer products synthesized with it as raw material are often used in oilfield additives, ink additives, papermaking additives and adhesives. Since the molecular structure of 4-acryloylmorpholine contains both hydrophilic morpholine groups and hydrophobic carbon chain structures, it is soluble in both water and most organic solvents, so it is widely used in chemical, pharmaceutical and other fields. Due to its low viscosity, fast curing speed and miscibility with water, it is often used as a reactive diluent for water-based UV resins, making the resin have good acid resistance, alkali resistance and solvent resistance, and improving the hardness, toughness and adhesion of the resin. Because it has the advantages of non-toxicity, low irritation and good biocompatibility, it can replace acrylamide and its polymers in the field of wastewater treatment. Because it has the advantages of good adhesion and good air permeability, it is also often used in the field of medical gels. Therefore, it is of great significance to develop a simple and efficient synthesis process for 4-acryloylmorpholine.

[0003] At present, the methods for synthesizing 4-acryloylmorpholine at home and abroad include the following:

[0004] (1) Condensation method of acetylmorpholine and formaldehyde. Acetic acid and morpholine are premixed to form acetic acid-morpholine salt, which is heated and dehydrated to obtain acetylmorpholine. Acetylmorpholine reacts with formaldehyde to produce crude acryloylmorpholine product, which is then extracted with dichloromethane to obtain acryloylmorpholine.

[0005] (2) Acryloyl chloride method. The chlorine atom of phosphorus trichloride reacts with the hydroxyl group of acrylic acid to form acryloyl chloride. Acryloyl chloride reacts with morpholine to form 4-acryloylmorpholine. Acryloyl chloride has the problems of easy hydrolysis, volatility, polymerization, high toxicity, and difficulty in storage and transportation.

[0006] (3) Thermal cracking method. Using methyl acrylate and morpholine as raw materials, the carbon-carbon double bond on methyl acrylate is first protected by an addition reaction, then acylated with morpholine, and finally cracked at high temperature under the action of a catalyst to obtain 4-acryloylmorpholine.

[0007] Alternatively, methanol is used as a double bond protecting agent. First, methyl acrylate is added to methanol under the catalytic action of sodium methoxide to protect the carbon-carbon double bond and generate 3-methoxypropionic acid methyl ester. Then, ester aminolysis occurs with morpholine to generate 3-methoxypropionyl morpholine. Finally, pyrolysis is performed at high temperature under the action of a catalyst to obtain 4-acryloyl morpholine.

[0008] Alternatively, diethylamine is used as a double bond protecting agent. First, methyl acrylate and diethylamine are reacted by Michael addition to protect the double bond to generate an intermediate product, which is then subjected to an amidation reaction, and finally, is subjected to high temperature cracking under the action of a catalyst to obtain 4-acryloylmorpholine.

[0009] The above high-temperature cracking methods all have problems such as high reaction temperature, high energy consumption, difficulty in reaction control, and easy aggregation of products, which seriously affect production efficiency and product quality.

[0010] In summary, the condensation method of acetylmorpholine and formaldehyde has problems such as difficult product purification and low yield; the raw material acryloyl chloride used in the acryloyl chloride method has problems such as easy hydrolysis, easy volatility, easy polymerization, high toxicity, and difficult storage and transportation. The high-temperature pyrolysis method has problems such as high reaction temperature, high energy consumption, difficult reaction control, and easy product polymerization, which seriously affects production efficiency and product quality. Summary of the invention

[0011] The invention provides a method for preparing 4-acryloylmorpholine. 3-chloropropionyl chloride reacts with morpholine under the action of an alkaline catalyst to generate 3-chloropropionylmorpholine and part of 4-acryloylmorpholine. Then, by increasing the temperature and adding a sufficient amount of alkali, the unconverted 3-chloropropionylmorpholine is further converted into 4-acryloylmorpholine. Finally, high-quality 4-acryloylmorpholine can be obtained by distillation technology. The scheme has mild reaction conditions, low energy consumption, and is suitable for industrial production.

[0012] Based on the above purpose, the present invention provides a method for preparing 4-acryloylmorpholine, comprising the following steps:

[0013] S1, reacting morpholine with 3-chloropropionyl chloride, adding a basic catalyst and a solvent to obtain a reaction solution;

[0014] S2, treating the reaction solution to obtain an organic phase solution having 3-chloropropionylmorpholine and 4-acryloylmorpholine;

[0015] S3, adding the alkaline catalyst and the polymerization inhibitor again to the organic phase solution containing 3-chloropropionylmorpholine and 4-acryloylmorpholine to convert the organic phase solution containing 4-acryloylmorpholine;

[0016] S4, treating the organic phase solution containing 4-acryloylmorpholine to obtain 4-acryloylmorpholine.

[0017] In some embodiments, the basic catalyst includes one or more of sodium carbonate, triethylamine, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate, calcium carbonate, magnesium oxide, sodium bicarbonate, potassium bicarbonate, pyridine and its derivatives, imidazole and its derivatives, and trimethylamine.

[0018] In some embodiments, the solvent includes one or more mixed solvents of anhydrous ethanol, methanol, isopropanol, 1,4-dioxane, ethyl acetate, isopropyl acetate, toluene and n-heptane.

[0019] In some embodiments, the polymerization inhibitor includes one or more of 4-methoxyphenol, hydroquinone, and phenothiazine.

[0020] In some embodiments, the molar ratio of morpholine to 3-chloropropionyl chloride ranges from 1:0.1 to 1:10.

[0021] In some embodiments, the molar ratio of the basic catalyst to morpholine is in the range of 1:1-1:10.

[0022] In some embodiments, in step S1 and step S3, the reaction temperature ranges from -10 to 100°C.

[0023] In some embodiments, the step of treating the organic phase solution having 4-acryloylmorpholine to obtain 4-acryloylmorpholine comprises:

[0024] filtering the organic phase solution containing 4-acryloylmorpholine, and adding a neutralizing agent to the filtrate for neutralization to obtain a neutralized solution;

[0025] The neutralized solution is subjected to reduced pressure distillation to remove the solvent to obtain a neutralized solution after desolventization;

[0026] The neutralized solution after desolventizing is distilled and purified to obtain 4-acryloylmorpholine.

[0027] The invention provides 4-acryloylmorpholine, which is prepared by the preparation method of 4-acryloylmorpholine.

[0028] The invention provides an application of 4-acryloylmorpholine, such as the application of 4-acryloylmorpholine prepared by the preparation method of 4-acryloylmorpholine.

[0029] The present invention has at least the following beneficial technical effects:

[0030] The present invention proposes a method for preparing 4-acryloylmorpholine, which comprises: S1, reacting morpholine with 3-chloropropionyl chloride, adding an alkaline catalyst and a solvent, and obtaining a reaction solution; S2, treating the reaction solution to obtain an organic phase solution having 3-chloropropionylmorpholine and 4-acryloylmorpholine; S3, adding the alkaline catalyst and the inhibitor again to the organic phase solution having 3-chloropropionylmorpholine and 4-acryloylmorpholine, and converting to obtain an organic phase solution having 4-acryloylmorpholine; S4, treating the organic phase solution having 4-acryloylmorpholine to obtain 4-acryloylmorpholine. The present invention has a high degree of chemical selectivity, ensures that 3-chloropropionyl chloride is mainly converted into 4-acryloylmorpholine, reduces the generation of by-products, improves the reaction rate and yield, and makes the preparation process more efficient.

[0031] Compared with the acryloyl chloride method, the 3-chloropropionyl chloride used in the present invention is easy to obtain, easy to store, and will not have polymerization problems, and is easy to store and transport. At the same time, the reaction conditions are mild, the operation is simple, the raw material price is appropriate, and the product yield is high and the purity is high. As an important organic compound, 4-acryloylmorpholine has significant economic value and practical significance. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the following specific embodiments, they are used to explain the present invention but do not constitute a limitation of the present invention. In the accompanying drawings:

[0033] Figure 1 The figure shows a flow chart of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention.

[0034] Figure 2 A schematic diagram of the reaction process of 4-acryloylmorpholine is shown in a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention.

[0035] Figure 3 A gas chromatogram of the first step reaction of Example 1 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0036] Figure 4 A gas chromatogram of the second step reaction of Example 1 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0037] Figure 5 A gas chromatogram of the first step reaction of Example 2 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0038] Figure 6A gas chromatogram of the second step reaction of Example 2 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0039] Figure 7 A gas chromatogram of the first step reaction of Example 3 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0040] Figure 8 A gas chromatogram of the second step reaction of Example 3 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0041] Fig. 9 A gas chromatogram of the first step reaction of Example 4 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0042] Fig.10 A gas chromatogram of the second step reaction of Example 4 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0043] Fig.11 A gas chromatogram of the first step reaction of Example 5 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0044] Fig.12 A gas chromatogram of the second step reaction of Example 5 of a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown.

[0045] Fig.13 The gas chromatogram of the product 4-acryloylmorpholine obtained by distilling the reaction liquid in a method for preparing 4-acryloylmorpholine according to an embodiment of the present invention is shown. DETAILED DESCRIPTION

[0046] The specific implementation of the present disclosure is described in detail below in conjunction with the accompanying drawings. It should be understood that the specific implementation described herein is only used to illustrate and explain the present disclosure, and is not used to limit the present disclosure.

[0047] In addition, reference to "embodiments" herein means that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present invention. The appearance of the phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0048] It will be understood by those skilled in the art that, unless otherwise defined, all terms (including technical terms and scientific terms) used herein have the same meaning as the general understanding of those skilled in the art to which this application belongs. It should also be understood that terms such as those defined in general dictionaries should be understood to have the same meaning as in the context of the prior art, and will not be interpreted with an idealized or overly formal meaning unless specifically defined as in the embodiments of this application.

[0049] The present invention provides a method for preparing 4-acryloylmorpholine. Figure 1 and Figure 2 , including the following steps:

[0050] S1, reacting morpholine with 3-chloropropionyl chloride, adding a basic catalyst and a solvent to obtain a reaction solution;

[0051] S2, treating the reaction solution to obtain an organic phase solution having 3-chloropropionylmorpholine and 4-acryloylmorpholine;

[0052] S3, adding the alkaline catalyst and the polymerization inhibitor again to the organic phase solution containing 3-chloropropionylmorpholine and 4-acryloylmorpholine to convert the organic phase solution containing 4-acryloylmorpholine;

[0053] S4, treating the organic phase solution containing 4-acryloylmorpholine to obtain 4-acryloylmorpholine.

[0054] The preparation process of the invention comprises the following steps: 3-chloropropionyl chloride reacts with morpholine under the action of an alkaline catalyst to generate a part of the intermediate product 3-chloropropionyl morpholine and the final product 4-acryloyl morpholine, and solid salt is removed by filtration to obtain an organic phase. An alkaline catalyst is added to the organic phase to convert the remaining 3-chloropropionyl morpholine into 4-acryloyl morpholine. The hydrochloride generated by the reaction is filtered, neutralized and removed, the solvent is removed, and the product is purified by rectification.

[0055] The invention has high chemical selectivity, ensures that 3-chloropropionyl chloride is mainly converted into 4-acryloylmorpholine, reduces the generation of by-products, improves the reaction rate and yield, and makes the preparation process more efficient.

[0056] Compared with the acryloyl chloride method, the 3-chloropropionyl chloride used in the present invention is easy to obtain, easy to store, and will not have polymerization problems, and is easy to store and transport. At the same time, the reaction conditions are mild, the operation is simple, the raw material price is appropriate, and the product yield is high and the purity is high. As an important organic compound, 4-acryloylmorpholine has significant economic value and practical significance.

[0057] In some embodiments, see Figure 1 and Figure 2The alkaline catalyst includes one or more of sodium carbonate, triethylamine, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate, calcium carbonate, magnesium oxide, sodium bicarbonate, potassium bicarbonate, pyridine and its derivatives, imidazole and its derivatives, and trimethylamine.

[0058] 3-Chloropropionyl chloride reacts with morpholine to generate hydrogen chloride. The alkaline catalyst is also an acid binding agent and reacts with hydrogen chloride to generate hydrochloride. The alkaline catalyst is one or more of sodium carbonate, triethylamine, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate, calcium carbonate, magnesium oxide, sodium bicarbonate, potassium bicarbonate, pyridine and its derivatives, imidazole and its derivatives, and trimethylamine.

[0059] In the reaction of 3-chloropropionyl chloride and morpholine, hydrogen chloride is generated. In order to promote the reaction and control the pH value of the reaction system, an alkaline catalyst is usually added as an acid binding agent to react with the generated hydrogen chloride to form hydrochloride. One of sodium carbonate, triethylamine, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate, calcium carbonate, magnesium oxide, sodium bicarbonate, potassium bicarbonate, pyridine and its derivatives, imidazole and its derivatives, and trimethylamine can effectively neutralize hydrogen chloride, thereby promoting the forward progress of the reaction.

[0060] Sodium carbonate is a relatively environmentally friendly catalyst, and its reaction products are easy to handle and have little environmental pollution. Sodium carbonate is relatively stable under reaction conditions and is not easy to decompose or produce harmful byproducts. Compared with triethylamine and sodium hydroxide, the cost of sodium carbonate is generally lower, which is conducive to reducing production costs.

[0061] Triethylamine is a strong alkaline organic amine that has a good catalytic effect on many chemical reactions, including esterification, acylation and other reactions. Triethylamine is a liquid at room temperature and is easy to measure and add to the reaction system. Triethylamine is not only suitable for reactions under acidic conditions, but also can play a catalytic role under neutral or weak alkaline conditions.

[0062] Sodium hydroxide is a strong base that can quickly neutralize the hydrogen chloride generated in the reaction, thereby promoting the forward reaction. Due to its strong alkalinity, sodium hydroxide can usually provide a faster reaction rate and higher yield. Sodium hydroxide is a commonly used chemical raw material and is easily available on the market.

[0063] For the reaction of 3-chloropropionyl chloride with morpholine, sodium carbonate may be a better choice due to its environmental friendliness and cost-effectiveness; triethylamine is favored due to its good catalytic effect and easy operation; sodium hydroxide may be more suitable in some cases due to its strong alkalinity and high efficiency.

[0064] In some embodiments, see Figure 1 and Figure 2The solvent includes one or more mixed solvents selected from anhydrous ethanol, methanol, isopropanol, 1,4-dioxane, ethyl acetate, isopropyl acetate, toluene and n-heptane.

[0065] Ethanol has good solubility for some substances that are difficult to dissolve in water, which can enhance the mixing effect of reactants and promote the reaction. Ethanol can reduce the surface tension of water, make the reaction system more uniform, and facilitate the full contact and reaction of reactants. Ethanol has a certain effect on the pH value of water and can change the pH value of the solution.

[0066] 1,4-dioxane can dissolve a variety of organic and inorganic substances, providing a good solvent environment for the reaction. Its miscibility with water and a variety of organic solvents makes it suitable for use in a variety of reaction systems, especially in reactions that require consideration of both aqueous and organic phases. 1,4-dioxane is relatively chemically stable at room temperature and is not prone to react with other substances, ensuring the smooth progress of the reaction.

[0067] Ethyl acetate can dissolve many organic substances and help the reactants to be evenly distributed in the solvent. Ethyl acetate has the characteristics of rapid volatilization, which is conducive to the rapid removal of solvents during the reaction and improves the reaction efficiency. Compared with other organic solvents, ethyl acetate has lower toxicity and is relatively safe for the human body and the environment.

[0068] Toluene can dissolve many organic compounds and provide the necessary solvent environment for the reaction. Toluene has a high evaporation rate and can quickly remove volatile substances produced in the reaction. Toluene can also be used as a catalyst or reaction medium to promote the reaction.

[0069] n-heptane has good cleaning ability and is particularly suitable for removing impurities such as oil and fat, which helps keep the reaction system clean. n-heptane can evaporate quickly, allowing the reaction system to be dried quickly when needed. n-heptane has a high ignition point and flash point, is not flammable or explosive, and improves the safety of the reaction process.

[0070] In some embodiments, see Figure 1 and Figure 2 , the inhibitor includes one or more of 4-methoxyphenol, hydroquinone and phenothiazine.

[0071] 4-Acryloylmorpholine has the possibility of polymerization under alkaline conditions. 4-Methoxyphenol (MEHQ) is selected as an inhibitor. MEHQ can only play an inhibitory effect under the action of oxygen. When it comes to unsaturated compounds such as 4-acryloylmorpholine, it is easy to undergo polymerization under alkaline conditions, which may lead to impure products or loss of control of the reaction process. Therefore, it is particularly important to select a suitable inhibitor to control this polymerization reaction. 4-Methoxyphenol (MEHQ) is an effective inhibitor and can play an excellent inhibitory effect under the action of oxygen.

[0072] MEHQ can significantly inhibit the free radical polymerization of unsaturated compounds such as 4-acryloylmorpholine in the presence of oxygen. This inhibitory effect helps maintain the stability of the reaction system and prevents product quality degradation or reaction runaway caused by too fast polymerization. The inhibitory effect of MEHQ depends on the presence of oxygen. This feature makes MEHQ more flexible and controllable in reaction systems that require control of oxygen concentration. By adjusting the oxygen content in the reaction system, the inhibitory effect of MEHQ can be precisely controlled to meet different reaction requirements. MEHQ is not only suitable for the polymerization of 4-acryloylmorpholine, but also widely used in the inhibition process of other vinyl plastic monomers. Its wide applicability makes MEHQ an important chemical raw material and reaction aid. MEHQ is relatively stable under normal conditions of use and is not easy to decompose and produce harmful substances. At the same time, its use as an inhibitor is relatively small, which helps to reduce the generation of waste and environmental pollution. In addition, the toxicity of MEHQ is relatively low, and it is less harmful to the human body and the environment.

[0073] In some embodiments, see Figure 1 and Figure 2 The molar ratio of morpholine to 3-chloropropionyl chloride is in the range of 1:0.1-1:10.

[0074] The amount of morpholine is enough to fully react with 3-chloropropionyl chloride, thereby ensuring the efficient conduct of the reaction. When the amount of morpholine is slightly lower than or slightly higher than the stoichiometric ratio, the reaction can still maintain a higher efficiency, which helps to reduce the reaction time and improve production efficiency. The generation of by-products can be minimized to the greatest extent, thereby improving the yield and purity of 4-acryloylmorpholine. This ratio range is obtained after multiple experiments and optimizations, and can balance the relationship between reaction rate, yield and purity. Excessive morpholine may increase the cost of raw materials, while too little may cause incomplete reaction and reduce yield. Therefore, being set in the range of 1:0.1 to 1:10, it is possible to reduce production costs while ensuring the reaction effect.

[0075] In some embodiments, see Figure 1 and Figure 2, the molar ratio of the basic catalyst to morpholine is in the range of 1:1-1:10.

[0076] Alkaline catalysts can effectively reduce the activation energy of the reaction and make the reaction easier to carry out. When the molar ratio of the alkaline catalyst to morpholine is controlled within this range, the activity of the alkaline catalyst is fully utilized, thereby increasing the rate of the reaction. Alkaline catalysts can effectively reduce the activation energy of the reaction and make the reaction easier to carry out. An appropriate amount of alkaline catalyst helps to reduce the formation of by-products, thereby improving the purity of 4-acryloylmorpholine. When the molar ratio of the catalyst to morpholine is properly controlled, unnecessary side reactions can be minimized to make the product purer. The cost of the alkaline catalyst is also one of the factors that need to be considered. Excessive alkaline catalysts not only increase costs, but may also bring difficulties in handling. Selecting the amount of alkaline catalyst within this ratio range can reduce production costs while ensuring the reaction effect. Setting a clear molar ratio of the alkaline catalyst to the reactant can make the experimental operation simpler and more standardized. This not only improves the repeatability of the experiment, but also reduces the error rate during the operation.

[0077] In some embodiments, see Figure 1 and Figure 2 In step S1 and step S3, the reaction temperature ranges from -10 to 100°C.

[0078] Within this temperature range, the reactant molecules can obtain enough energy to overcome the activation energy of the reaction, thereby accelerating the reaction. Although higher temperatures can generally further increase the reaction rate, too high a temperature may lead to an increase in side reactions and reduce the yield of 4-acryloylmorpholine. The appropriate temperature helps to control the reaction path so that the formation of 4-acryloylmorpholine is dominant. In the range of -10-100°C, unnecessary side reactions can be minimized and the selectivity of 4-acryloylmorpholine can be improved. Lower reaction temperatures help to reduce the energy level of the reaction system and reduce safety accidents that may be caused by high temperatures. In addition, lower temperatures also help to control the reaction rate and avoid reactions that are too violent and difficult to control.

[0079] In some embodiments, see Figure 1 and Figure 2 The step of treating the organic phase solution containing 4-acryloylmorpholine to obtain 4-acryloylmorpholine comprises:

[0080] filtering the organic phase solution containing 4-acryloylmorpholine, and adding a neutralizing agent to the filtrate for neutralization to obtain a neutralized solution;

[0081] The neutralized solution is distilled under reduced pressure to remove the solvent;

[0082] The desolvated neutralized solution is distilled and purified to obtain 4-acryloylmorpholine.

[0083] By filtering step, insoluble impurities and particulate matter in the organic phase solution with 4-acryloylmorpholine can be removed, reducing the impact of these impurities on product purity. Neutralization step can adjust the pH value of the solution to make it closer to the stable existence range of 4-acryloylmorpholine, avoiding side reactions or degradation caused by inappropriate acid-base in subsequent steps. Desolventization is to separate the solvent used in the reaction from the system, further reduce the impurity content, and improve the purity of the product. The final rectification and purification step is based on the difference in boiling points of different substances, and the target product 4-acryloylmorpholine is separated from the mixture to obtain a high-purity product.

[0084] The invention provides 4-acryloylmorpholine, which is prepared by any one of the methods for preparing 4-acryloylmorpholine.

[0085] The invention adopts 3-chloropropionyl chloride to undergo substitution reaction with morpholine under the action of an alkaline catalyst to generate an intermediate product 3-chloropropionyl morpholine and a final product 4-acryloyl morpholine, and then filters and removes solid salt to obtain an organic phase. An alkaline catalyst is added to the organic phase to convert the remaining 3-chloropropionyl morpholine into 4-acryloyl morpholine. The hydrochloride generated by the reaction is filtered, neutralized and removed, the solvent is removed, and the product is purified by rectification to obtain a high-purity product.

[0086] In some embodiments, see Figure 3 , Figure 4 , Figure 5 , Figure 6 , Figure 7 , Figure 8 , Fig. 9 , Fig.10 , Fig.11 , Fig.12 and Fig.13 , and conduct multiple experiments. The process is as follows:

[0087] Example 1:

[0088] Step 1: Add 87.1g (1mol) of morpholine and 200g of ethyl acetate to a reaction bottle to form a mixed solution, and place it in a 5°C water bath. Dissolve 127.2g (1.2mol) of sodium carbonate in 400g of water to form an aqueous sodium carbonate solution. Add the aqueous sodium carbonate solution to the mixed solution formed by morpholine and ethyl acetate at one time under stirring. Then add dropwise a mixed solution formed by 139.7g (1.1mol) of 3-chloropropionyl chloride and 100g of ethyl acetate. During the dropwise addition, the temperature of the reaction liquid is kept below 10°C by controlling the dropwise addition rate. After the dropwise addition is completed, maintain a 5°C water bath condition and continue stirring the reaction for 2 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to the peak area ratio of 3-chloropropionylmorpholine (retention time 16min) is 5.6:100. For details, please refer to the following: Figure 3 Gas chromatogram of the reaction shown.

[0089] The gas chromatograph used was a GC-4000A gas chromatograph produced by Dongxi Analytical Technology Instrument Co., Ltd. The chromatographic column was a KB-624 capillary column produced by Kromat, with a length, inner diameter, and film thickness of 30 m, 0.53 mm, and 3.00 μm, respectively. The column temperature was 120°C, the vaporization chamber temperature was 240°C, the detector was a FID detector, and the hydrogen flame temperature was 240°C. The reaction liquid in the second step of this example and the reaction liquids in other examples were analyzed using this method.

[0090] Step 2: Filter to remove solid salts, remove the lower aqueous phase, and obtain an organic phase solution. Add 0.4g MEHQ to the organic phase solution, introduce air, heat to 70°C, slowly drop 161.9g (1.6mol) triethylamine, and control the temperature of the reaction solution to be below 80°C. After the addition is completed, heat the reaction solution to 80°C and react for 6 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to 3-chloropropionylmorpholine (retention time 16min) is 100:8.8. For details, please refer to Figure 4 Gas chromatogram of the reaction shown.

[0091] Example 2:

[0092] Step 1: Add 87.1g (1mol) of morpholine and 200g of ethyl acetate to a reaction bottle to form a mixed solution, and place it in a 5°C water bath. Add sodium carbonate powder to the mixed solution formed by morpholine and ethyl acetate at one time under stirring. Then add dropwise a mixed solution formed by 139.7g (1.1mol) of 3-chloropropionyl chloride and 100g of ethyl acetate. During the dropwise addition, the temperature of the reaction liquid is kept below 10°C by controlling the dropwise addition rate. After the dropwise addition is completed, maintain the 5°C water bath condition and continue stirring the reaction for 2 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to the peak area ratio of 3-chloropropionylmorpholine (retention time 16min) is 8.7:100. For details, please refer to the following. Figure 5 Gas chromatogram of the reaction shown.

[0093] Step 2: Filter to remove solid salts and excess sodium carbonate, remove the lower aqueous phase, and obtain an organic phase solution. Add 0.4g MEHQ to the organic phase solution, introduce air, heat to 70°C, slowly add 48g (1.2mol) of flaky sodium hydroxide, and control the temperature of the reaction solution to be below 80°C. After the addition is completed, the reaction solution is heated to 80°C and reacted for 6 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to 3-chloropropionylmorpholine (retention time 16min) is 100:25.5. For details, please refer to the following: Figure 6 Gas chromatogram of the reaction shown.

[0094] Example 3:

[0095] Step 1: Add 87.1g (1mol) of morpholine and 200g of ethyl acetate to the reaction flask to form a mixed solution. Place the reaction flask in a 5°C water bath and add 151.8g (1.5mol) of triethylamine at one time while stirring. Then add dropwise a mixed solution formed by 139.7g (1.1mol) of 3-chloropropionyl chloride and 160g of ethyl acetate. During the dropwise addition, the temperature of the reaction liquid is kept below 10°C by controlling the dropwise addition rate. After the dropwise addition is completed, maintain the 5°C water bath condition and continue stirring the reaction for 2 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to the peak area ratio of 3-chloropropionylmorpholine (retention time 16min) is 33.8:100. For details, please refer to the following: Figure 7 Gas chromatogram of the reaction shown.

[0096] Step 2: Filter to remove solid salts and obtain an organic phase solution. Add 0.4g MEHQ to the organic phase solution, introduce air, heat to 70°C, slowly drop 131.5g (1.3mol) triethylamine, and control the temperature of the reaction solution to be below 80°C. After the addition is completed, heat the reaction solution to 80°C and react for 6 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to 3-chloropropionylmorpholine (retention time 16min) is 100:41.4. For details, please refer to Figure 8 Gas chromatogram of the reaction shown.

[0097] Example 4

[0098] Step 1: Add 87.1g (1mol) of morpholine and 200g of ethyl acetate to the reaction bottle to form a mixed solution. Place the reaction bottle in a 5°C water bath, and add 151.8g (1.5mol) of triethylamine at one time under stirring. Then add dropwise a mixed solution formed by 139.7g (1.1mol) of 3-chloropropionyl chloride and 160g of ethyl acetate. During the dropwise addition, the temperature of the reaction liquid is kept below 10°C by controlling the dropwise addition rate. After the dropwise addition is completed, maintain the 5°C water bath condition and continue stirring the reaction for 2 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to the peak area ratio of 3-chloropropionylmorpholine (retention time 16min) is 78.9:100. For details, please refer to the following: Fig. 9 Gas chromatogram of the reaction shown.

[0099] Step 2: Filter to remove solid salts and obtain an organic phase solution. Remove ethyl acetate from the organic phase solution by vacuum distillation. Then add 0.4g MEHQ and 400g ethanol, let in air, heat to 70°C, slowly drop 101.2g (1mol) triethylamine, and control the temperature of the reaction solution to be below 80°C. After the addition is completed, heat the reaction solution to 80°C and react for 6 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to 3-chloropropionylmorpholine (retention time 16min) is 100:4.3. For details, please refer to the following: Fig.10 Gas chromatogram of the reaction shown.

[0100] Example 5

[0101] Step 1: Add 87.1g (1mol) of morpholine and 200g of ethyl acetate to a reaction flask to form a mixed solution. Place the reaction flask in a water bath at room temperature, and add 127.2g (1.2mol) of sodium carbonate at one time under stirring. Then add dropwise a mixed solution formed by 139.7g (1.1mol) of 3-chloropropionyl chloride and 160g of ethyl acetate. During the dropwise addition, the temperature of the reaction liquid is kept below 40°C by controlling the dropwise addition rate. After the dropwise addition is completed, maintain a 40°C water bath condition and continue stirring the reaction for 2 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to the peak area ratio of 3-chloropropionylmorpholine (retention time 16min) is 91.6:100. For details, please refer to the following: Fig.11 Gas chromatogram of the reaction shown.

[0102] Step 2: Filter to remove solid salts and obtain an organic phase solution. Add 0.4g MEHQ to the organic phase solution, introduce air, heat to 70°C, slowly add 148g (1.2mol) of flaky sodium hydroxide, and control the temperature of the reaction solution to be below 80°C. After the addition is completed, heat the reaction solution to 80°C and react for 6 hours. Gas chromatography analysis shows that the peak area ratio of 4-acryloylmorpholine (retention time 12min) to 3-chloropropionylmorpholine (retention time 16min) is 100:7.6. For details, refer to Fig.12 Gas chromatogram of the reaction shown.

[0103] The post-processing method of the above examples 1-5 is shown in Example 6:

[0104] Example 6

[0105] For the crude 4-acryloylmorpholine solution obtained in Example 1-5, solid salts were first filtered to obtain a uniform organic phase solution. The residual alkaline substances in the organic phase solution were then neutralized with a saturated sodium bisulfate aqueous solution until the solution pH was 7. Since 4-acryloylmorpholine has good water solubility, a saturated sodium bisulfate aqueous solution must be used in the neutralization process, thereby reducing the solubility of 4-acryloylmorpholine in the sodium bisulfate aqueous solution, reducing losses, and improving product yield.

[0106] After that, the solvent was removed by distillation under reduced pressure. Finally, high-quality 4-acryloylmorpholine was obtained by rectification with a yield of 82%. Gas chromatography analysis showed that the purity of 4-acryloylmorpholine (retention time 12 min) was 99.3% (see Fig.13 ). The distillation process uses a glass spring with a diameter of 3mm as filler, the effective height of the distillation column is 750mm, the reflux ratio is 8:3, the vacuum degree is 5mmHg, and the distillation process uses gas chromatography to monitor the fraction content. For details, please refer to Fig.13 The gas chromatogram shown is that of 4-acryloylmorpholine after distillation.

[0107] In summary, 3-chloropropionyl chloride undergoes a substitution reaction with morpholine under the action of an alkaline catalyst to generate an intermediate product, 3-chloropropionyl morpholine, and a final product, 4-acryloyl morpholine, and the solid salt is filtered to remove the organic phase. An alkaline catalyst is added to the organic phase to convert the remaining 3-chloropropionyl morpholine into 4-acryloyl morpholine. The hydrochloride generated by the reaction is filtered, neutralized and removed, the solvent is removed, and the product is purified by distillation to obtain a high-purity product.

[0108] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0109] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0110] In addition, various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A method for preparing 4-acryloylmorpholine, characterized in that: The following steps are involved: S1, reacting morpholine with 3-chloropropionyl chloride, adding a basic catalyst and a solvent to obtain a reaction solution; S2, treating the reaction solution to obtain an organic phase solution having 3-chloropropionylmorpholine and 4-acryloylmorpholine; S3, adding the alkaline catalyst and the polymerization inhibitor again to the organic phase solution containing 3-chloropropionylmorpholine and 4-acryloylmorpholine to convert the organic phase solution containing 4-acryloylmorpholine; S4, treating the organic phase solution containing 4-acryloylmorpholine to obtain 4-acryloylmorpholine.

2. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: The alkaline catalyst includes one or more of sodium carbonate, triethylamine, sodium hydroxide, potassium hydroxide, calcium hydroxide, potassium carbonate, calcium carbonate, magnesium oxide, sodium bicarbonate, potassium bicarbonate, pyridine and its derivatives, imidazole and its derivatives, and trimethylamine.

3. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: The solvent includes one or more mixed solvents selected from anhydrous ethanol, methanol, isopropanol, 1,4-dioxane, ethyl acetate, isopropyl acetate, toluene and n-heptane.

4. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: The polymerization inhibitor includes one or more of 4-methoxyphenol, hydroquinone and phenothiazine.

5. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: The molar ratio of morpholine to 3-chloropropionyl chloride is in the range of 1:0.1-1:

10.

6. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: The molar ratio of the basic catalyst to morpholine is in the range of 1:1-1:

10.

7. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: In step S1 and step S3, the reaction temperature ranges from -10 to 100°C.

8. The method for preparing 4-acryloylmorpholine according to claim 1, characterized in that: The step of treating the organic phase solution containing 4-acryloylmorpholine to obtain 4-acryloylmorpholine comprises: filtering the organic phase solution containing 4-acryloylmorpholine, and adding a neutralizing agent to the filtrate for neutralization to obtain a neutralized solution; The neutralized solution is subjected to reduced pressure distillation to remove the solvent to obtain a desolvated neutralized solution; The neutralized solution after desolventizing is distilled and purified to obtain 4-acryloylmorpholine.

9. A 4-acryloylmorpholine, characterized in that The 4-acryloylmorpholine is prepared by the preparation method of any one of claims 1 to 8.

10. An application of 4-acryloylmorpholine, characterized in that: 4-Acryloylmorpholine prepared by the preparation method of 4-acryloylmorpholine according to any one of claims 1 to 8 or the use of 4-acryloylmorpholine according to claim 9.

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