A method for synthesizing 3-methoxy-n,n-dimethylpropanamide

Abstract

This application relates to a method for synthesizing 3-methoxy-N,N-dimethylpropionamide, belonging to the field of organic synthesis technology. It includes the following steps: S1, catalytic reaction: methyl 3-methoxypropionate, dimethylamine, and catalyst are added to a sealed container in a specific ratio, and the temperature is raised to 60-180℃ to carry out a condensation reaction; S2, distillation: after the reaction is complete, the reaction solution is cooled and the catalyst is separated. The filtrate is distilled to remove dimethylamine and the byproduct methanol, and then the unreacted methyl 3-methoxypropionate is separated by vacuum distillation. The product is obtained by further heating and vacuum distillation. This invention uses methyl 3-methoxypropionate and dimethylamine as raw materials, and neutral silicate natural minerals as catalysts. The catalyst is inexpensive, readily available, and can be reused multiple times. The recovered methyl 3-methoxypropionate pre-fraction can be continuously reused. The overall yield is high, the product quality is good, the process is simple and easy to implement, environmentally friendly, and has low production costs, making it highly valuable for industrial applications.

Description

Technical Field

[0001] This invention relates to the field of organic chemical synthesis technology, specifically to a method for synthesizing 3-methoxy-N,N-dimethylpropionamide. Background Technology

[0002] 3-Methoxy-N,N-dimethylpropionamide (MMPA), CAS No. 53185-52-7, is a high-boiling-point, highly polar, aprotic, colorless, and transparent solvent containing amide and alkyl groups. As an amide solvent, MMPA exhibits extremely strong solubility, high permeability, low viscosity, low volatility, and non-corrosiveness. It can effectively replace the traditional solvent N-methylpyrrolidone (NMP) and is widely used in the chemical, resin plastics, coating, pesticide, pharmaceutical, and electronics industries.

[0003] Patents WO 2008 / 102615 and WO 2013 / 153754 describe the synthesis of 3-methoxy-N,N-dimethylpropionamide using methyl 3-methoxypropionate and dimethylamine as raw materials and polyols (such as glycerol and ethylene glycol) as solvents, catalyzed by strong bases (such as sodium methoxide and potassium tert-butoxide). In this method, polyols are essential as solvents, significantly improving reaction selectivity. However, polyols have high boiling points, leading to high recovery costs. Even when reused as residues after product distillation, their high viscosity makes the process cumbersome. Furthermore, in the presence of strong bases, MMPA readily undergoes a reverse Michael addition reaction to generate N,N-dimethylacrylamide (DMAA). DMAA readily reacts with dimethylamine to form the impurity 3-dimethylamino-N,N-dimethylpropionamide, resulting in reduced selectivity. Post-reaction processing also requires acid neutralization of the strong base catalyst followed by filtration, making the process cumbersome and generating substantial solid waste.

[0004] The reaction equation is as follows:

[0005]

[0006] Chinese patent CN106883136A discloses a method for the preparation of 3-methoxy-N,N-dimethylpropionamide. This patent uses 3-methoxypropionic acid and dimethylamine as raw materials, and obtains MMPA through high-temperature dehydration in a closed reactor. However, this method suffers from several drawbacks. 3-methoxypropionic acid has limited applications and is difficult to purchase in large quantities from the market. It requires the use of acrylonitrile as a raw material, reacting it with methanol under strong alkaline catalysis to synthesize 3-methoxypropionitrile, followed by hydrolysis under acidic conditions. This process is lengthy. Furthermore, the raw material 3-methoxypropionic acid is highly acidic and easily corrodes equipment, resulting in high costs. The reaction also produces a water molecule as a byproduct, which can easily lead to acidic or alkaline wastewater in actual production.

[0007] Besides the two condensation strategies mentioned above, other methods for preparing 3-methoxy-N,N-dimethylpropionamide mainly include: 1) N,N-dimethylacrylamide undergoes a Michael addition reaction with methanol under the action of a catalyst, but the former is too expensive and not conducive to the industrial application of the product MMPA; 2) 3-methoxypropionamide is prepared by N-methylation, but it usually requires unstable, volatile or toxic methylating agents such as iodomethane, dimethyl sulfate, etc., and also requires an excess of strong base.

[0008] Therefore, there is an urgent need to develop a low-cost, green method for synthesizing 3-methoxy-N,N-dimethylpropionamide. Summary of the Invention

[0009] To overcome the shortcomings of existing technologies, this invention provides a method for synthesizing 3-methoxy-N,N-dimethylpropionamide. This method is relatively simple to operate, avoids the use of high-boiling-point polyols and strong base catalysts, has low cost, good catalyst stability and can be recycled, has high reaction selectivity, and produces high-quality products with a purity of over 99.9%.

[0010] A method for synthesizing 3-methoxy-N,N-dimethylpropionamide, comprising the following steps:

[0011] S1. Catalytic reaction: Methyl 3-methoxypropionate, dimethylamine, and catalyst are added to a sealed container in proportion, and the temperature is raised to carry out a condensation reaction.

[0012] S2. Distillation: After the reaction is complete, the reaction solution is cooled and the catalyst is separated. The filtrate is distilled to remove dimethylamine and the byproduct methanol. Then, the unreacted methyl 3-methoxypropionate is separated by vacuum distillation. The product 3-methoxy-N,N-dimethylpropionamide is obtained by further heating and vacuum distillation.

[0013] The specific reaction equation is as follows:

[0014]

[0015] Preferably, in step S2, the separated catalyst, dimethylamine, and methyl 3-methoxypropionate are recycled in step S1 for the next reaction.

[0016] Preferably, the catalyst is at least one of porous natural minerals containing SiO2 or silicates, such as diatomaceous earth, kaolin, montmorillonite, bentonite, and zeolite molecular sieve, or at least one of the above substances that has been modified, and the catalyst is in powder form.

[0017] By adopting the above technical solutions, the alkaline components in natural mineral catalysts, such as alumina, magnesium oxide, and calcium oxide, can serve as active centers for the catalyst. The acidic sites of SiO2 in the crystals facilitate the adsorption of alkaline dimethylamine, promoting the condensation reaction on the catalyst surface. The mineral catalyst is generally neutral, avoiding the reverse Michael addition side reaction of MMPA in the product, improving the selectivity of the reaction, and contributing to obtaining high-purity, high-quality products. Using the above-mentioned neutral mineral catalyst eliminates the need for large-scale acid neutralization after the reaction, and the separated catalyst can be directly recycled multiple times. The operation is convenient, and the catalyst is inexpensive and readily available, resulting in low costs and facilitating large-scale industrial production.

[0018] Preferably, the molar ratio of methyl 3-methoxypropionate to dimethylamine is 1:0.5-2, more preferably 1:0.8-1. Methyl 3-methoxypropionate is widely used in industries such as coatings and is readily available; alternatively, it can be prepared from inexpensive methyl acrylate and methanol under strong alkaline catalysis. The reaction is preferably carried out in a slight excess of methyl 3-methoxypropionate to ensure complete reaction of the dimethylamine, reduce investment in dimethylamine recovery equipment for large-scale industrial production, and facilitate the obtaining of pure methanol as a byproduct during distillation.

[0019] Preferably, the catalyst is 0.5%-15% of the mass of methyl 3-methoxypropionate, more preferably 5%-10%.

[0020] Preferably, the condensation reaction temperature is 60-180°C, more preferably 80-120°C. When the reaction temperature is below 60°C, the reaction rate is too slow; when the reaction temperature is above 180°C, the MMPA product is prone to cracking, resulting in decreased selectivity.

[0021] Preferably, the pressure of the condensation reaction is 0.1-10 MPa, more preferably 0.5-2 MPa. If the pressure is too low, dimethylamine gas needs to be introduced multiple times; if the pressure is too high, the equipment requirements are higher, leading to increased costs. Preferably, the system is pressurized automatically by introducing dimethylamine or by using inert nitrogen gas to reach the required pressure.

[0022] Preferably, the sealed container is one or more of a high-pressure autoclave reactor, a pressurized tower reactor, and a pressurized tubular reactor, with a high-pressure autoclave reactor being the most preferred.

[0023] Preferably, the catalyst is separated by filtration after the reaction using one or more of sedimentation, plate and frame filtration, and centrifugal filtration, with plate and frame filtration being the preferred method.

[0024] Preferably, the equipment for atmospheric distillation of the filtrate can be one or more of a conventional reaction vessel, an atmospheric distillation column, and a vacuum distillation column, with a vacuum distillation column being the preferred option. Atmospheric distillation removes dimethylamine and the byproduct methanol, and the residue is transferred to a vacuum distillation column; more preferably, dimethylamine and the byproduct methanol are removed in a vacuum distillation column, and the remaining residue is directly distilled under vacuum.

[0025] Preferably, the vacuum distillation process involves heating the column to 50-150°C and refluxing, adjusting the reflux ratio to 0.5-20, first collecting the unreacted methyl 3-methoxypropionate, and then continuing to raise the temperature or increase the vacuum to collect the product 3-methoxy-N,N-dimethylpropionamide until the distillation is complete. More preferably, the vacuum is increased to collect the product MMPA.

[0026] Preferably, the vacuum degree of the reduced-pressure distillation is 2-20 mmHg, more preferably 2-5 mmHg. Increasing the vacuum degree can prevent the thermal decomposition of the product 3-methoxy-N,N-dimethylpropionamide and improve the purity of the product.

[0027] In summary, the beneficial effects achieved by this invention are:

[0028] This invention provides a method for synthesizing 3-methoxy-N,N-dimethylpropionamide. Compared with the condensation method of 3-methoxypropionic acid, this method has a shorter process route, uses inexpensive and readily available raw materials, reduces the corrosion of reaction equipment by organic acids, and avoids the generation of acidic or alkaline wastewater. The neutral silicate-based porous natural mineral catalyst used in this method is inexpensive and readily available, avoiding the use of high-viscosity, high-boiling-point polyols and strong base catalysts. It exhibits good stability, can be directly recycled multiple times, and has high selectivity, contributing to the acquisition of high-quality products. The methyl 3-methoxypropionate fore-fraction obtained by vacuum distillation can participate in the next reaction, achieving material recycling, saving costs, and further improving the yield. The obtained methanol byproduct can be used to produce the raw material methyl 3-methoxypropionate or sold as a byproduct. This method has high raw material utilization, low production cost, reasonable process, and high industrial application value. Detailed Implementation

[0029] The present invention will now be described in detail with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] Example 1:

[0031] 500 g (4.23 mol) of methyl 3-methoxypropionate and 25 g of diatomaceous earth catalyst were added to a 1000 mL autoclave equipped with a heater and a stirrer. The autoclave was closed, and then dimethylamine (210 g (4.66 mol) was introduced through the gas feed pipe. The autoclave was then sealed. The temperature was raised to 120 °C; the pressure was naturally increased to 2.0 MPa, and the reaction was stirred for 24 hours. After cooling to room temperature, excess dimethylamine was recovered, and the catalyst was separated by centrifugation of the reaction mixture. The reaction mixture was distilled at atmospheric pressure to separate methanol as a byproduct; then, vacuum distillation was carried out at 10 mmHg, and the temperature was raised to reflux. The reflux ratio was adjusted to obtain the fore-fraction methyl 3-methoxypropionate, which can participate in the next reaction; the vacuum was increased to 5 mmHg and vacuum distillation was continued, and the product 3-methoxy-N,N-dimethylpropionamide was collected until the distillation was completed. The single-pass molar conversion of methyl 3-methoxypropionate was 83.4%, the purity of the product MMPA was 98.2%, the selectivity was 94.1%, and the single-pass molar yield was 78.4% (based on the feedstock methyl 3-methoxypropionate).

[0032] Examples 2-5 follow the same reaction process as Example 1, except that the type of catalyst is changed, as detailed in Table 1.

[0033] Table 1

[0034]

[0035] Note: Conversion rate and yield are calculated based on the raw material methyl 3-methoxypropionate.

[0036] Example 6:

[0037] 500 g (4.23 mol) of methyl 3-methoxypropionate and 25 g of diatomaceous earth catalyst were added to a 1000 mL autoclave equipped with a heater and a stirrer. The autoclave was closed, and then dimethylamine (191 g (4.23 mol) was introduced through the gas feed pipe. The autoclave was then sealed. The temperature was raised to 120 °C, and the pressure was naturally increased to approximately 2.0 MPa. The reaction was stirred for 24 hours. After cooling to room temperature, the catalyst was separated by centrifugation. The reaction mixture was distilled at atmospheric pressure to separate the byproduct methanol; then, vacuum distillation was carried out at 10 mmHg, and the temperature was raised to reflux. The reflux ratio was adjusted to obtain the fore-fraction methyl 3-methoxypropionate, which can participate in the next reaction; the vacuum was increased to 5 mmHg and vacuum distillation was continued, and the product 3-methoxy-N,N-dimethylpropionamide was collected until the distillation was completed. The single-pass molar conversion of methyl 3-methoxypropionate was 79.4%, the purity of the product MMPA was 98.5%, the selectivity was 94.7%, and the single-pass molar yield was 75.2% (based on the feedstock methyl 3-methoxypropionate).

[0038] Examples 7 and 8 follow the same reaction process as Example 6, except that the molar ratio of dimethylamine to methyl 3-methoxypropionate is changed, as detailed in Table 2.

[0039] Table 2

[0040]

[0041]

[0042] Note: Conversion rate and yield are based on the raw material methyl 3-methoxypropionate.

[0043] Examples 9-13 follow the same reaction process as Example 7, except that the reaction temperature is changed, as detailed in Table 3.

[0044] Table 3

[0045]

[0046] Note: Conversion rate and yield are based on the raw material methyl 3-methoxypropionate.

[0047] Example 14: Based on Example 11, the vacuum level of vacuum distillation was changed.

[0048] Methyl 3-methoxypropionate (500 g, 4.23 mol) and diatomaceous earth catalyst (25 g) were added to a 1000 mL autoclave equipped with a heater and a stirrer. The autoclave was closed, and dimethylamine (171.3 g, 3.8 mol) was introduced through the gas feed pipe. The autoclave was then sealed. The temperature was raised to 100 °C, and the pressure was naturally increased to approximately 2.0 MPa. The reaction was stirred for 24 hours. After cooling to room temperature, the catalyst was separated by centrifugation. The reaction mixture was distilled at atmospheric pressure to separate methanol as a byproduct. Then, vacuum distillation was carried out at 10 mmHg, and the temperature was raised to reflux. The reflux ratio was adjusted to obtain the fore-fraction methyl 3-methoxypropionate, which can participate in the next reaction. The vacuum was increased to 2 mmHg and vacuum distillation was continued. The product 3-methoxy-N,N-dimethylpropionamide was collected until the distillation was completed. The single-pass molar conversion of methyl 3-methoxypropionate was 81.2%, the purity of the product MMPA was 99.9%, the selectivity was 99.0%, and the single-pass molar yield was 80.4% (based on the feedstock methyl 3-methoxypropionate).

[0049] Examples 15-18 follow the same reaction process as Example 14, except that the amount of catalyst is changed, as detailed in Table 4.

[0050] Table 4

[0051]

[0052] Note: 1) Catalyst weight content refers to the percentage of catalyst content relative to the weight of methyl 3-methoxypropionate in the raw material; 2) Conversion rate and yield are based on methyl 3-methoxypropionate in the raw material.

[0053] Example 19: Methyl 3-methoxypropionate (500 g, 4.23 mol) and diatomaceous earth catalyst (25 g) were added to a 1000 mL autoclave equipped with a heater and a stirrer. The autoclave was closed, and dimethylamine (171.3 g, 3.8 mol) was introduced through the gas feed pipe. The autoclave was then sealed. The temperature was raised to 100 °C, and the pressure was naturally increased to approximately 2.0 MPa. The reaction was stirred for 24 hours. After cooling to room temperature, the reaction solution was centrifuged to separate the catalyst. The reaction mixture was distilled at atmospheric pressure to separate the byproduct methanol; then vacuum distillation was carried out at 10 mmHg, and the temperature was raised to reflux. The reflux ratio was adjusted to obtain the fore-fraction methyl 3-methoxypropionate, which could participate in the next reaction; the vacuum was increased to 2 mmHg and vacuum distillation was continued, and the product 3-methoxy-N,N-dimethylpropionamide was collected until the distillation was completed. The recovered catalyst was reused 5 times, and the recovered fore-fraction methyl 3-methoxypropionate was also continuously reused in the next reaction. The overall molar conversion of methyl 3-methoxypropionate was 94.3%, the purity of the product MMPA was 99.9%, the selectivity was 97.3%, and the overall molar yield was 91.8% (based on the raw material methyl 3-methoxypropionate).

[0054] As shown in Examples 1-5, porous natural minerals containing SiO2 or silicates can serve as catalysts in the synthesis method of 3-methoxy-NN-dimethylpropionamide of the present invention. Component analysis reveals that diatomaceous earth, montmorillonite, and zeolite molecular sieves containing more alkaline components such as alumina, magnesium oxide, and calcium oxide exhibit better catalytic effects. As shown in Examples 1 and 6-8, the dimethylamine content has a relatively small impact on reaction selectivity in the synthesis method of 3-methoxy-NN-dimethylpropionamide of the present invention. Considering the large investment required for dimethylamine recovery equipment in large-scale industrial production, a slight excess of methyl 3-methoxypropionate is preferred to facilitate complete dimethylamine reaction. As shown in Examples 7 and 9-13, the condensation reaction temperature significantly affects the conversion rate and selectivity in the synthesis method of MMPA of the present invention. High temperatures greatly affect reaction selectivity, and reactions below 60°C proceed too slowly; the preferred reaction temperature is 80-120°C. A comparison of Examples 11 and 14 shows that in the synthesis method of 3-methoxy-N,N-dimethylpropionamide of the present invention, increasing the vacuum degree of vacuum distillation can avoid the thermal decomposition of the product 3-methoxy-N,N-dimethylpropionamide and improve the purity of the product. Examples 14-18 show that in the synthesis method of 3-methoxy-N,N-dimethylpropionamide of the present invention, a lower catalyst content leads to a slower reaction rate, and the reduction in acidic sites may lead to a decrease in reaction selectivity; the preferred catalyst mass percentage is 5%-10%. Example 19 shows that in the synthesis method of 3-methoxy-N,N-dimethylpropionamide of the present invention, in simulated actual industrial production, the catalyst can be reused more than 5 times, and the recovered foremilk fraction methyl 3-methoxypropionate is continuously reused in the next reaction. The overall molar conversion rate of methyl 3-methoxypropionate and the overall molar yield of the product MMPA both exceed 90%, and the purity of the product MMPA reaches 99.9%, indicating that this method has high industrial application value.

[0055] In summary, this invention uses methyl 3-methoxypropionate and dimethylamine as raw materials and neutral silicate porous natural minerals as catalysts for condensation reactions. This avoids the use of corrosive acidic raw materials, high-viscosity, high-boiling-point polyols, and strong base catalysts. The catalyst is inexpensive, readily available, and can be reused multiple times. The recovered methyl 3-methoxypropionate pre-fraction can be continuously reused. The overall yield is high, the product quality is good, the process is simple and easy to implement, generates little waste, and has low production costs, making it highly valuable for industrial applications.

[0056] It should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for the synthesis of 3-methoxy-N,N-dimethylpropanamide, characterized by, The synthesis method includes: S1. Catalytic reaction: Methyl 3-methoxypropionate, dimethylamine, and catalyst are added to a sealed container in proportion, and the temperature is raised to 60-180℃ to carry out a condensation reaction. The molar ratio of methyl 3-methoxypropionate to dimethylamine is 1:0.5-2; the mass of the catalyst is 0.5%-15% of the mass of methyl 3-methoxypropionate. S2. Distillation: After the reaction is complete, the reaction solution is cooled and the catalyst is separated. The filtrate is distilled to remove dimethylamine and the byproduct methanol. Then, the unreacted methyl 3-methoxypropionate is separated by vacuum distillation. The product 3-methoxy-N,N-dimethylpropionamide is obtained by further heating and vacuum distillation. The reaction equation is: ； The catalyst includes at least one of diatomaceous earth, kaolin, montmorillonite, and bentonite.

2. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The molar ratio of methyl 3-methoxypropionate to dimethylamine is 1:0.8-1; the mass of the catalyst is 5%-10% of the mass of methyl 3-methoxypropionate.

3. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The condensation reaction is carried out at a temperature of 80-120℃.

4. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The pressure of the condensation reaction is 0.1-10 MPa.

5. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The sealed container is one or more of the following: a high-pressure autoclave reactor, a pressurized tower reactor, and a pressurized tubular reactor.

6. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, In step S2, the catalyst is separated by filtration after the reaction using one or more of the following methods: sedimentation, plate and frame filtration, and centrifugal filtration.

7. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The equipment used for distilling the filtrate is one or more of the following: a conventional reaction vessel, an atmospheric distillation column, and a vacuum distillation column.

8. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The vacuum distillation process is specifically as follows: Heat to reflux, adjust the reflux ratio, first collect the unreacted methyl 3-methoxypropionate, continue heating or increase the vacuum to collect the product 3-methoxy-N,N-dimethylpropionamide until the distillation is complete; the vacuum degree of the vacuum distillation is 2-20 mmHg.

9. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide as described in claim 1, characterized in that, The vacuum distillation process is specifically as follows: Heat to reflux, adjust the reflux ratio, first collect the unreacted methyl 3-methoxypropionate, continue heating or increase the vacuum to collect the product 3-methoxy-N,N-dimethylpropionamide until the distillation is complete; the vacuum degree of the vacuum distillation is 2-5 mmHg.

10. The method for synthesizing 3-methoxy-N,N-dimethylpropionamide according to any one of claims 1-9, characterized in that, In step S2, the separated catalyst, dimethylamine, and methyl 3-methoxypropionate are recycled in the next reaction in step S1.

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