CN115504899A

CN115504899A - Synthesis process of N, N-dialkyl-3-methoxypropionamide

Info

Publication number: CN115504899A
Application number: CN202211255571.0A
Authority: CN
Inventors: 傅人俊
Original assignee: Suzhou Qitian New Material Co ltd
Current assignee: Suzhou Qitian New Material Co ltd
Priority date: 2022-10-13
Filing date: 2022-10-13
Publication date: 2022-12-23

Abstract

The application relates to the field of material preparation, and particularly discloses a synthesis process of N, N-dialkyl-3-methoxypropionamide, which comprises the following steps:

Description

Synthesis process of N, N-dialkyl-3-methoxypropionamide

Technical Field

The application relates to the field of material preparation, in particular to a synthesis process of N, N-dialkyl-3-methoxypropionamide.

Background

The structural general formula of the N, N-dialkyl-3-alkoxy propionamide is as follows:

the N, N-dialkyl-3-alkoxy propionamide is a colorless transparent solvent, has an amide group and an alkyl group, can be mixed with various solvents, and can dissolve polymer polyamide to a high degree; has the characteristics of high solubility, high permeability, high fluidity, low viscosity, low surface tension and the like. And the N, N-dialkyl-3-alkoxy propionamide has no irritation to the skin, has low toxicity, is safe and environment-friendly, can well replace the traditional solvent N-methyl pyrrolidone, and is widely applied to the industries of electronics, medicines, pesticides, pigments, cleaning agents, insulating materials and the like.

However, the related art for synthesizing N, N-dialkyl-3-alkoxypropionamide is not mature enough and there are few reports on the synthesis, so it is a necessary research subject to design a synthetic route for N, N-dialkyl-3-alkoxypropionamide and to prepare N, N-dialkyl-3-alkoxypropionamide with excellent performance.

Disclosure of Invention

The application provides a synthesis process of N, N-dialkyl-3-methoxypropionamide, which has the advantages of relatively simple operation, easily obtained raw materials, short reaction production period, high yield and contribution to reducing the product cost; and the product has high purity and low impurity content, and can realize large-scale production and application.

The synthesis process of the N, N-dialkyl-3-methoxypropionamide provided by the application adopts the following technical scheme: a synthesis process of N, N-dialkyl-3-methoxypropionamide is characterized in that: the synthetic process has the following route:

the reaction steps of the synthesis process are as follows:

step S1: performing alkylation reaction on the amino group of the compound III to obtain a compound II;

step S2: and reacting the compound II with an alcohol compound to obtain a compound I.

By adopting the technical scheme, the compound III, namely acrylamide is adopted as a raw material, and the acrylamide is a white crystal chemical substance, is odorless and has small use limitation. And the amino of the compound III can be added with alcohol compounds after alkylation to obtain a compound I; the whole process route is very simple, the reaction period is short, and the industrial scale production is facilitated; meanwhile, the compound I obtained by the process route has excellent yield and higher purity, and is beneficial to reducing the production cost. Therefore, the compound I prepared by the synthesis process has high product purity and low impurity content, and can realize large-scale production and application.

In a specific embodiment, the prepared compound I is subjected to at least one of rectification and distillation under reduced pressure to obtain a refined compound I.

By adopting the technical scheme, the compound I prepared by the synthesis process has high yield and high purity, and byproducts and impurities generated in the process reaction are very easy to purify and separate; further reducing the production cost and meeting the requirement of large-scale production. Therefore, the compound I prepared by the synthesis process can remove by-products and impurities by simple operations such as rectification, distillation and the like.

In a specific embodiment, compound II is prepared by reacting compound III with a dialkyl carbonate in step S1.

By adopting the technical scheme, dialkyl carbonate reacts with the compound III to alkylate the amino group of the compound III, so that the reaction process is more stable, and the compound I with high purity and high yield can be obtained.

In a specific embodiment, compound III and dialkyl carbonate are reacted in a reaction solvent, which is at least one of alcohols, tetrahydrofuran, ethyl acetate, isopropyl ether, acetonitrile, petroleum ether.

By adopting the technical scheme, the use of the reaction solvent is beneficial to promoting the reaction of the compound III and the dialkyl carbonate, so that the reaction is carried out more stably, the yield and the purity of the final product compound I are improved, the production cost is reduced, and the industrial scale production is matched.

In a particular possible embodiment, the molar ratio of compound III to dialkyl carbonate is 1: (0.1-100). Further, the molar ratio of compound III to dialkyl carbonate is 1: (40-60).

In a particular embodiment, the reaction temperature of compound III with dialkyl carbonate is 20 to 200 ℃ and the reaction time is 0.1 to 72 hours. Further, the reaction temperature of the compound III and the dialkyl carbonate is 130-140 ℃, and the reaction time is 5-9 hours.

By adopting the technical scheme, the dosage and the reaction conditions of the compound III and the dialkyl carbonate are optimized, so that the stability of the reaction can be improved, the occurrence of side reactions is reduced, and the yield and the purity of the product are improved.

In a specific embodiment, in step S2, compound II and the alcohol are reacted under catalysis of a solid base catalyst, which is a catalyst having a basic component supported on a carrier.

In a specific possible embodiment, in the solid base catalyst, the load carrier may be at least one of molecular sieve, alumina, zirconia, activated carbon, porous silica, hydrotalcite, montmorillonite, ion exchange resin, polymer carrier;

the alkaline component is at least one of alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal oxide, alkaline earth metal oxide, alkali metal carbonate, alkaline earth metal carbonate and tetraalkylammonium hydroxide.

By adopting the technical scheme, the alkaline component is used as an active center of the catalyst and has extremely strong electron donating or electron accepting capability. Compared with other catalysts, the solid base catalyst has the advantages of high activity, high selectivity, mild reaction conditions, easy product separation and recyclability; the solid base catalyst is adopted, so that not only is the reaction efficiency improved, but also the occurrence of side reactions can be reduced, the product yield and purity are improved, the production cost is reduced, and the industrial scale production is facilitated.

In a specific embodiment, the molar ratio of compound II to alcohol compound is 1: (0.1-100); the weight ratio of the solid base catalyst to the compound II is (0.001-0.10): 1. further, the molar ratio of the compound II to the alcohol compound is 1: (1.2-1.55); the weight ratio of the solid base catalyst to the compound II is (0.01-0.06): 1.

in a specific embodiment, the reaction temperature of the compound II and the alcohol compound is 20-200 ℃ and the reaction time is 0.1-72 hours. Further, the reaction temperature of the compound II and the alcohol compound is 40-60 ℃, and the reaction time is 6-9 hours.

By adopting the technical scheme, the dosage and the reaction conditions of the compound II and the alcohol compound are optimized, so that the reaction stability can be improved, the occurrence of side reactions is reduced, and the yield and the purity of the product are improved.

In a specific embodiment, the structural formula of compound I is as follows:

wherein R1 is a C1-C6 hydrocarbon group or a fluorinated hydrocarbon group; r2 is C1-C6 alkyl or fluorinated alkyl.

In conclusion, the application has the following beneficial effects:

1. according to the method, a compound III, namely acrylamide is selected as a raw material, a reaction route is reasonably designed, and the obtained N, N-dialkyl-3-alkoxy propionamide meets the requirements of the market on the purity, the impurity content, the cost and the like of the N, N-dialkyl-3-alkoxy propionamide; and the preparation process has the advantages of relatively simple operation, easily obtained raw materials, short reaction production period and high yield, is favorable for reducing the production cost and is favorable for large-scale production and application.

2. The by-products and impurities of the synthesis process are easy to purify and separate, and the prepared product can achieve higher purity through simple operations such as rectification, distillation and the like. Not only further simplifies the preparation process of the product, but also has excellent yield and purity of the product and can meet the requirements of large-scale application on yield and quality.

3. The method adopts the solid base catalyst, has the advantages of simple operation, difficult loss of the alkaline active center, large specific surface area, long service life, high mechanical strength, small equipment corrosivity, reusability, easy separation and recovery of the product after reaction, environmental friendliness and the like, reduces the production cost, and is favorable for industrial production.

Detailed Description

The present application will be described in further detail with reference to examples.

Since there are few data on the synthesis method of N, N-dialkyl-3-alkoxypropionamide, the present inventors have studied the synthesis method of N, N-dialkyl-3-alkoxypropionamide and have turned to the synthesis route of alkoxypropionamide compounds. The preparation method of the alkoxy propionamide compound mainly comprises the following steps: a beta-alkoxypropionamide compound represented by the formula (3) is produced by reacting a beta-alkoxypropionate compound represented by the formula (1) with an amine represented by the formula (2) in the presence of a polyol and a basic catalyst.

Although the structure of the beta-alkoxy propionamide shown in the formula (3) is similar to that of the N, N-dialkyl-3-alkoxy propionamide, on one hand, for organic matters, small differences in structure can cause changes in material properties and change in reaction mechanism of materials in the synthesis process; on the other hand, the inventor aims to obtain a synthetic route which has the advantages of relatively simple operation, easily obtained raw materials, short reaction production period, high yield and contribution to reducing the product cost, thereby being capable of producing the N, N-dialkyl-3-alkoxy propionamide in large batch.

However, one of the raw materials of the β -alkoxypropionamide compounds represented by the formula (3) is an amine, and the amine, particularly dimethylamine, is a gas at room temperature, has a strong unpleasant atmospheric temperature, and has a large limitation in use. Therefore, the synthesis route of the beta-alkoxy propionamide compound shown in the formula (3) has little reference to the application.

The inventor has made a lot of research, and the inventor focuses on acrylamide, and firstly, the acrylamide is not only easily obtained, but also belongs to a solid, and the limitation on the use is less; however, how to successfully prepare the N, N-dialkyl-3-alkoxy propionamide with high yield and high purity by utilizing the acrylamide becomes a new problem.

In view of the large object of the present application to achieve industrial scale production of N, N-dialkyl-3-alkoxypropionamides, the inventors have come to mind whether it is possible to alkylate the amino group of acrylamide directly to give the final desired product. In subsequent studies, the inventors focused on dimethyl carbonate, which is an environmentally friendly reagent on the one hand and meets the structural requirements of the target product on the other hand. However, how to make acrylamide and dimethyl carbonate smoothly react to obtain the target product and also can fit industrial scale production becomes a big problem which troubles the inventor.

The inventors finally made extensive efforts to finally determine the reaction conditions and the operation steps of the whole synthetic route, and obtained N, N-dialkyl-3-alkoxypropionamide with excellent yield and purity. The specific synthetic route is as follows:

the synthetic route is also suitable for the reaction of acrylamide and other types of dialkyl carbonates, and has positive significance for the industrial scale of N, N-dialkyl-3-alkoxy propionamide.

The pressure values mentioned in the present embodiment refer to gauge pressure if not otherwise specified, and gauge pressure refers to the number of total absolute pressures exceeding the ambient atmospheric pressure or the pressure at a point in the liquid above atmospheric pressure.

The reaction temperature is generally referred to as the oil bath temperature of the reaction unless otherwise specified.

The product purity was checked by gas chromatography.

The yield is the percentage ratio of the actual product mass to the theoretical product mass, calculated as the raw material not in excess in the reaction equation.

The present application will be described in further detail with reference to the following preparation examples and examples, and all of the starting materials referred to in the present application are commercially available.

Preparation example of solid base catalyst

Preparation example 1

Preparation of sodium hydroxide-loaded molecular sieve solid base catalyst: the method comprises the following steps:

(a) Adding a carrier into the round-bottom flask, wherein the carrier is a 13X type molecular sieve.

(b) Adding an alkaline component and a solvent into a round-bottom flask, dipping while stirring, and treating at normal temperature for 12 hours to obtain a crude solid base catalyst. Wherein the alkaline component is sodium hydroxide, the solvent is methanol, and the mass ratio of the carrier to the alkaline component is 4.

(c) And filtering, drying and drying the crude product of the solid base catalyst to obtain the sodium hydroxide-loaded molecular sieve solid base catalyst.

Preparation example 2

Preparation of alumina solid base catalyst loaded with potassium carbonate: the method comprises the following steps:

(a) Adding a carrier into the round-bottom flask, wherein the carrier is alumina.

(b) Adding an alkaline component and a solvent into a round-bottom flask, soaking under stirring, and treating at the temperature of 30 ℃ for 12 hours under the protection of inert gas to obtain a crude solid base catalyst. Wherein the alkaline component is potassium carbonate, the solvent is ethanol, and the mass ratio of the carrier to the alkaline component is 4.

(c) And cooling, filtering, drying and drying the crude product of the solid base catalyst to obtain the potassium carbonate-loaded alumina solid base catalyst.

Preparation example 3

Preparation of montmorillonite solid base catalyst loaded with calcium hydroxide: the method comprises the following steps:

(a) Adding a carrier into the round-bottom flask, wherein the carrier is montmorillonite.

(b) Adding an alkaline component and a solvent into a round-bottom flask, dipping under stirring, and treating at 40 ℃ for 12 hours under the protection of inert gas to obtain a crude solid catalyst. Wherein the alkaline component is calcium hydroxide, the solvent is ethanol, and the mass ratio of the carrier to the alkaline component is 4.

(c) And cooling, filtering, drying and drying the crude product of the solid catalyst to obtain the calcium hydroxide-loaded montmorillonite solid base catalyst.

Preparation example 4

Preparation of zirconium oxide catalyst loaded with tetraalkylammonium hydroxide: the method comprises the following steps:

(a) Adding a carrier into the round-bottom flask, wherein the carrier is zirconium oxide.

(b) Adding an alkaline component and a solvent into a round-bottom flask, dipping under stirring, and treating at normal temperature for 12 hours to obtain a crude solid catalyst. Wherein the alkaline component is tetraalkylammonium hydroxide, the solvent is water, and the mass ratio of the carrier to the alkaline component is 4.

(c) And filtering, drying and drying the crude solid base catalyst to obtain the zirconium oxide catalyst loaded with the tetraalkylammonium hydroxide.

Examples

Example 1

Embodiment 1 provides a process for the synthesis of N, N-dialkyl-3-alkoxypropionamide, comprising the steps of:

(1) Step S1: adding a compound III and dimethyl carbonate into an autoclave provided with a stirrer; the mass ratio of the compound III to the dimethyl carbonate is 1. Wherein the reaction route of step S1 is as follows:

(2) Step S2: in a reactor equipped with a stirrer, methanol and a catalyst were first added, the catalyst in this example being the sodium hydroxide-loaded molecular sieve solid base catalyst of preparation example 1; the molar ratio of compound II to methanol was 1.35, and the weight ratio of catalyst to compound II was 0.03:1.

slowly adding a methanol solution of a compound II under stirring to react, wherein in the methanol solution of the compound II, the molar ratio of the compound II to the methanol is 1; the reaction temperature is 55 ℃, the reaction pressure is normal pressure, the reaction time is 8 hours, after the reaction is finished, the temperature is reduced to room temperature, hydrochloric acid is used for neutralizing to be neutral, the precipitate is filtered, the filtrate is subjected to reduced pressure distillation to remove the solvent, and then the crude compound II is obtained, wherein the yield of the crude compound is 72%. The reaction route of step S2 is as follows:

(3) And step S3: in a reactor, the crude product of the compound I is purified and rectified, main fraction is collected, the temperature of the fraction is 100 ℃/2mmHg, a fine product is obtained, the purification yield is 78%, and the purity of the product is 99.5%.

Example 2

Embodiment 2 provides a process for synthesizing N, N-dialkyl-3-alkoxypropionamide, comprising the steps of:

(1) Step S1: adding the compound III and diethyl carbonate into an autoclave provided with a stirrer; the mass ratio of the compound II to diethyl carbonate is 1. Wherein the reaction route of step S1 is as follows:

(2) Step S2: the reaction scheme of step S2 is as follows: in a reactor equipped with a stirrer, ethanol and a catalyst were first added, the catalyst in this example being the solid base catalyst of alumina supported potassium carbonate of preparation example 2, the molar ratio of compound II to ethanol being 1.55, the weight ratio of catalyst to compound II being 0.05:1.

slowly adding an ethanol solution of a compound II under stirring to react, wherein the molar ratio of the compound II to ethanol in the ethanol solution of the compound II is 1; the reaction temperature is 60 ℃, the reaction pressure is normal pressure, the reaction time is 9 hours, after the reaction is finished, the temperature is reduced to room temperature, hydrochloric acid is used for neutralizing to be neutral, the precipitate is filtered, the filtrate is subjected to reduced pressure distillation to remove the solvent, and then the crude compound II is obtained, wherein the yield of the crude compound is 65%. The reaction route of step S is as follows:

(3) And step S3: and (3) purifying the crude product of the compound I in a reactor, distilling under reduced pressure, and collecting a main fraction at the temperature of 100 ℃/2mmHg to obtain a refined product, wherein the purification yield is 62 percent, and the product purity is 99.1 percent.

Example 3

Embodiment 3 provides a process for the synthesis of N, N-dialkyl-3-alkoxypropionamide, comprising the steps of:

(1) Step S1: the reaction scheme of step S1 is as follows: adding the compound III and dipropyl carbonate into an autoclave provided with a stirrer; and (3) the mass ratio of the compound II to dipropyl carbonate is 1. Wherein the reaction route of step S1 is as follows:

(2) Step S2: in a reactor equipped with a stirrer, propanol and a catalyst were first added, the catalyst in this example being the calcium hydroxide-supporting montmorillonite solid base catalyst in preparation example 3, the molar ratio of compound II to propanol was 1.4, and the weight ratio of catalyst to compound II was 0.045:1.

slowly adding a petroleum ether solution of a compound II under stirring for reaction, wherein the molar ratio of the compound II to petroleum ether in the petroleum ether solution of the compound II is 1. The reaction scheme of step S2 is as follows:

(3) And step S3: and (3) purifying the crude product of the compound I in a reactor, distilling under reduced pressure, and collecting a main fraction at the temperature of 100 ℃/2mmHg to obtain a refined product, wherein the purification yield is 78% and the product purity is 99.2%.

Example 4

Embodiment 4 provides a process for the synthesis of N, N-dialkyl-3-alkoxypropionamide, comprising the steps of:

(1) Step S1: adding the compound III and trifluoroethyl carbonate into an autoclave provided with a stirrer; the mass ratio of the compound II to the trifluoroethyl carbonate is 1. Wherein the reaction route of step S1 is as follows:

(2) Step S2: in a reactor equipped with a stirrer, trifluoroethanol, a catalyst, which was the zirconium oxide catalyst supporting tetraalkylammonium hydroxide of preparation example 4, was first added, the molar ratio of compound II to trifluoroethanol was 1.2, and the weight ratio of catalyst to compound II was 0.02:1.

slowly adding acetonitrile solution of a compound II under stirring for reaction; in the acetonitrile solution of the compound II, the molar ratio of the compound II to acetonitrile is 1; the reaction temperature is 40 ℃, the reaction pressure is normal pressure, the reaction time is 6 hours, after the reaction is finished, the temperature is reduced to room temperature, hydrochloric acid is used for neutralizing to be neutral, the precipitate is filtered, the filtrate is subjected to reduced pressure distillation to remove the solvent, and then the crude product of the compound I is obtained, wherein the yield of the crude product is 60%. The reaction route of step S2 is as follows:

(3) And step S3: and (3) purifying the crude product of the compound I in a reactor, distilling under reduced pressure, and collecting a main fraction at the temperature of 100 ℃/2mmHg to obtain a refined product, wherein the purification yield is 80 percent, and the product purity is 99.0 percent.

In conclusion, the synthesis process of the N, N-dialkyl-3-alkoxy propionamide provided by the application is relatively simple to operate, easily available in raw materials, short in reaction production period, high in yield and beneficial to reduction of product cost; and the product has high purity and low impurity content, the yield of the final refined product reaches up to 80 percent, the purity reaches up to 99.5 percent, and mass production and application can be realized.

The present embodiment is only for explaining the present application, and it is not limited to the present application, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present application.

Claims

1. A synthesis process of N, N-dialkyl-3-methoxypropionamide is characterized in that: the synthetic process has the following route:

the reaction steps of the synthesis process are as follows:

2. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 1, wherein: and (3) carrying out at least one of rectification and reduced pressure distillation on the prepared compound I to obtain a refined compound I.

3. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 1, wherein: in step S1, compound III is reacted with dialkyl carbonate to produce compound II.

4. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 3, wherein: and reacting the compound III with dialkyl carbonate in a reaction solvent, wherein the reaction solvent is at least one of alcohol, tetrahydrofuran, ethyl acetate, isopropyl ether, acetonitrile and petroleum ether.

5. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 3, wherein: the molar ratio of compound III to dialkyl carbonate is 1: (0.1-100).

6. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 3, wherein: the reaction temperature of the compound III and dialkyl carbonate is 20-200 ℃, and the reaction time is 0.1-72 hours.

7. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 1, wherein: in step S2, the compound II reacts with alcohols under the catalysis of a solid base catalyst, which is a catalyst having a carrier on which an alkaline component is supported.

8. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 7, wherein: in the solid base catalyst, the load carrier can be at least one of molecular sieve, alumina, zirconia, activated carbon, porous silica, hydrotalcite, montmorillonite, ion exchange resin and polymer carrier;

the alkaline component is at least one of alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal oxide, alkaline earth metal oxide, alkali metal carbonate, alkaline earth metal carbonate and tetraalkyl ammonium hydroxide.

9. The process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 1, wherein: the molar ratio of the compound II to the alcohol compound is 1: (0.1-100); the weight ratio of the solid base catalyst to the compound II is (0.001-0.10): 1.

10. the process for synthesizing N, N-dialkyl-3-methoxypropionamide according to claim 1, wherein: the structural formula of compound I is as follows: