阅读说明：本技术 一种n-甲基异丙胺的合成方法 (Synthesis method of N-methylisopropylamine ) 是由 王豪 张璞 吴耀军 葛永辉 侯远昌 于 2019-11-28 设计创作，主要内容包括：本发明涉及属于农药、医药中间体制备领域,尤其涉及一种N-甲基异丙胺制备方法,包括如下步骤：以异丙胺为原料,以碳酸二甲酯为反应溶剂,在碱性催化剂的催化下保温反应；反应结束后过滤除去催化剂,滤液经精馏分离,将溶剂碳酸二甲酯、与产物分离。本发明有效控制副产二取代的N,N-二甲基异丙胺的产生,有效控制原料的转换率与选择性,与现有技术相比,本发明具有以下有效效果：本发明提供的N-甲基异丙胺新的合成方法,原料易得,反应温和,反应步骤简易,原料成本较低,选用的溶剂碳酸二甲酯毒性较小,且能够循环使用,是一种具有发展前景的“绿色”化工产品,本发明三废量极少、具有较大的工业化应用前景。(The invention belongs to the field of preparation of pesticides and medical intermediates, and particularly relates to a preparation method of N-methylisopropylamine, which comprises the following steps: using isopropylamine as a raw material, using dimethyl carbonate as a reaction solvent, and carrying out heat preservation reaction under the catalysis of an alkaline catalyst; after the reaction is finished, the catalyst is removed by filtration, and the filtrate is separated by rectification to separate the solvent dimethyl carbonate from the product. The invention effectively controls the generation of the byproduct disubstituted N, N-dimethyl isopropylamine and effectively controls the conversion rate and the selectivity of the raw materials, and compared with the prior art, the invention has the following effective effects: the new synthesis method of N-methyl isopropylamine provided by the invention has the advantages of easily available raw materials, mild reaction, simple reaction steps, lower raw material cost, less toxicity of the selected solvent dimethyl carbonate, cyclic use, and great industrial application prospect, and the method is a green chemical product with development prospect, and has extremely little three wastes.)

1. A method for synthesizing N-methylisopropylamine is characterized by comprising the following steps:

using isopropylamine as a raw material, using dimethyl carbonate as a reaction raw material and a reaction solvent, adding an alkaline catalyst, carrying out heat preservation reaction, filtering to remove the catalyst after the reaction is finished, and rectifying and purifying the filtrate to obtain N-methylisopropylamine;

the reaction formula of the above reaction is as follows:

2. the method for synthesizing N-methylisopropylamine according to claim 1, wherein in the step (1), the basic catalyst comprises basic montmorillonite, basic kaolin, basic zeolite, basic molecular sieve, or the like.

3. The method for synthesizing N-methylisopropylamine according to claim 1, wherein in the step (1), the added mass of the basic catalyst is 1 to 30% of the mass of isopropylamine.

4. The method for synthesizing N-methylisopropylamine according to claim 3, wherein the amount of the basic catalyst added is 1 to 20% by mass of isopropylamine.

5. The method for synthesizing N-methylisopropylamine according to claim 4, wherein the mass of the basic catalyst added is 2 to 15% of the mass of isopropylamine.

6. The method for synthesizing N-methylisopropylamine according to claim 1, wherein the mass ratio of isopropylamine to dimethyl carbonate in the step (1) is 1:1 to 20.

7. The method for synthesizing N-methylisopropylamine according to claim 6, wherein the mass ratio of isopropylamine to dimethyl carbonate in the step (1) is 1:5 to 20.

8. The method for synthesizing N-methylisopropylamine according to claim 1, wherein the temperature for the heat preservation reaction in the step (1) is 80 to 120 ℃ and the reaction time is 5 to 20 hours.

9. The method for synthesizing N-methylisopropylamine according to claim 1, wherein the catalyst filtered in the step (2) is treated with an inorganic base, washed with water, dried and recycled.

10. The method for synthesizing N-methylisopropylamine according to claim 9, wherein the catalyst filtered in the step (2) is reacted in a 5-40% by mass aqueous solution of sodium hydroxide for 1-24 hours under stirring, washed with water, dried at 80-120 ℃ for 2-10 hours, and then recycled.

Technical Field

The invention belongs to the field of preparation of pesticides and medical intermediates, and particularly relates to a synthesis method of N-methylisopropylamine.

Background

N-methyl isopropylamine, also called N-methyl isopropylamine or N-isopropylmethylamine, is a colorless liquid, an important medical intermediate, and is a main raw material for synthesizing Piramide (which can be used as an antipyretic and pain-relieving agent).

Specifically, the synthesis method of N-methylisopropylamine is very diverse, and can be divided into the following methods according to different reaction routes:

the invention discloses a preparation method for synthesizing N-methyl isopropylamine from isopropylamine, which comprises the following steps of Mannich reaction and decomposition reaction, wherein the yield of the first step of Mannich reaction is 85.9%, and the yield of the second step of decomposition reaction and subsequent rectification is only 50-60%. The reaction formula is as follows:

② patent No. CN106866424A A batch preparation method of N-methyl isopropylamine, which comprises putting acetone and Raney nickel into a stainless steel hydrogenation kettle, introducing monomethylamine gas for pressurized reaction, then introducing hydrogen for pressurized reaction, filtering after the reaction is finished, and rectifying the filtrate under normal pressure to obtain N-methyl isopropylamine. The synthesis process adopts 5-20% of Raney nickel as a catalyst, the usage amount is too large, high-temperature and high-pressure reaction kettles are adopted for two times of aeration, the process has relative risks, a large amount of methylamine gas residues are difficult to remove after the methylamine gas is aerated for reaction, and the difficulty is brought to the post-separation and purification because the boiling points of acetone and N-methylisopropylamine which are raw materials are very close. The reaction formula is as follows:

③ German Passion patent technology, zirconium dioxide, 0.1-5% palladium and 0.1-5% platinum are used as catalysts, acetone, monomethylamine and hydrogen are preheated to pass through a tubular reactor filled with Sichuan catalyst, and the product is obtained by high-temperature high-pressure reaction and rectification. The method has large equipment investment, the process adopts high-temperature and high-pressure reaction, the process is relatively dangerous, and the total material yield is 87%. The reaction formula is as follows:

fourthly, a third method: the method adopts water as a solvent, monomethylamine and acetone react under hydrogen conditions in the presence of catalysts of copper chromite or potassium dihydrogen phosphate and potassium hydroxide, although the reaction conditions of materials become mild, the total yield of the materials is only 60%, and a large amount of high-salt wastewater is produced and generated, and the reaction formula is as follows:

the four routes all belong to methylation reaction and have respective disadvantages, but a common disadvantage is that disubstituted N, N-dimethyl isopropylamine and a small amount of polymer are generated, the conversion rate and the selectivity of raw materials cannot be simultaneously met, and the generated byproduct N, N-dimethyl isopropylamine is very difficult to separate due to the fact that the property of the generated byproduct N, N-dimethyl isopropylamine is very similar to that of a product, so that a synthetic method capable of selectively synthesizing N-methyl isopropylamine and avoiding dimethyl substituted N-methyl isopropylamine is needed at present.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: provides a high-selectivity, efficient, green and environment-friendly N-methylisopropylamine synthesis process.

In a first aspect of the invention, a method for synthesizing N-methylisopropylamine is provided, which comprises the following steps:

using isopropylamine as a raw material, using dimethyl carbonate as a reaction raw material and a reaction solvent, adding an alkaline catalyst, carrying out heat preservation reaction, filtering to remove the catalyst after the reaction is finished, and rectifying and purifying the filtrate to obtain N-methylisopropylamine;

the reaction formula of the above reaction is as follows:

preferably, in the step (1), the basic catalyst comprises basic montmorillonite, basic kaolin, basic zeolite, basic molecular sieve and the like. Further, the molecular sieve is selected from the group consisting of alkali montmorillonite, alkali kaolin, and alkali molecular sieves.

Preferably, in the step (1), the addition mass of the basic catalyst is 1-30% of the mass of isopropylamine; further, the adding mass of the basic catalyst is 1-20% of the mass of isopropylamine; furthermore, the adding mass of the basic catalyst is 2-15% of the mass of the isopropylamine.

Preferably, the mass ratio of the isopropylamine to the dimethyl carbonate in the step (1) is 1: 1-20; further, the mass ratio of the isopropylamine to the dimethyl carbonate in the step (1) is 1: 5-20; furthermore, the mass ratio of the isopropylamine to the dimethyl carbonate in the step (1) is 1: 6-15.

Preferably, the temperature of the heat preservation reaction in the step (1) is 80-120 ℃, and the heat preservation reaction time is 5-20 hours; the reaction can be carried out under normal pressure or in a pressurized reaction kettle.

Preferably, the catalyst filtered in the step (2) is treated by inorganic base, washed by water, dried and recycled; further, the catalyst filtered in the step (2) is stirred and reacts in a sodium hydroxide water solution with the mass concentration of 5-40% for 1-24 hours, and the catalyst is washed by water, dried at 80-120 ℃ for 2-10 hours and recycled.

Compared with the prior art, the invention has the following beneficial effects: the novel synthesis method of N-methylisopropylamine provided by the invention has the advantages of easily available raw materials, mild reaction, simple reaction steps, effective control of the generation of the byproduct disubstituted N, N-dimethylisopropylamine, effective control of the conversion rate and selectivity of the raw materials, lower raw material cost, higher yield after purification, low toxicity of the selected solvent dimethyl carbonate, environmental protection, safety and low three-waste output, and is a very competitive green chemical process.

Drawings

FIG. 1 is a hydrogen spectrum of N-methylisopropylamine synthesized in an embodiment of the present invention.

Detailed Description

The invention is illustrated but not limited by the following examples. The technical solutions protected by the present invention are all the simple replacements or modifications made by the skilled person in the art.

Example 1:

100g of dimethyl carbonate, 15g (0.254mol) of isopropylamine and 0.3g of catalyst basic kaolin are added into a 250ml reaction bottle, and the mixture is stirred and heated to reflux under normal pressure for 16 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the material to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure through a 20-30 cm rectifying column, and collecting main fraction at 42-45 ℃ to obtain 17.95g of N-methylisopropylamine, wherein the appearance of the material is colorless and transparent, the GC purity is 99.21%, the yield after rectification is 96.69%, and the byproduct N, N-dimethyl isopropylamine is 0.43%.

Example 2:

100g of dimethyl carbonate, 15g (0.254mol) of isopropylamine and 0.75g of catalyst basic montmorillonite are added into a 250ml reaction bottle, stirred and heated to reflux under normal pressure, and the reflux time is 16 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the material to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure through a 20-30 cm rectifying column, and collecting main fraction at 42-45 ℃ to obtain 18.10g of N-methylisopropylamine, wherein the appearance of the material is colorless and transparent, the GC purity is 99.10%, the yield after rectification is 97.51%, and the byproduct N, N-dimethyl isopropylamine is 0.56%.

Example 3:

100g of dimethyl carbonate, 15g (0.254mol) of isopropylamine and 0.75g of basic kaolin are added into a 250ml reaction bottle, and the mixture is stirred and heated to reflux under normal pressure for 18 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the material to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure through a 20-30 cm rectifying column, and collecting main fraction at 42-45 ℃ to obtain 18.27g of N-methylisopropylamine, wherein the appearance of the material is colorless and transparent, the GC purity is 98.63%, the yield after rectification is 98.43%, and the byproduct N, N-dimethyl isopropylamine is 1.04%.

Example 4:

150g of dimethyl carbonate, 15g (0.254mol) of isopropylamine and 2.25g of catalyst basic montmorillonite are added into a 250ml reaction bottle, stirred and heated to reflux under normal pressure, and the reflux time is 10 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the material to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure by using a 20-30 cm rectifying column, and collecting a main fraction at 42-45 ℃ to obtain 18.30g of N-methylisopropylamine, wherein the appearance of the material is colorless and transparent, the GC purity is 98.63%, the molar yield after rectification is 96.6%, and the byproduct N, N-dimethyl isopropylamine is 1.05%.

Example 5:

220g of dimethyl carbonate, 15g (0.254mol) of isopropylamine and 1.5g of catalyst basic molecular sieve NaY are added into a 250ml reaction bottle, stirred and heated until reflux is carried out for 15 hours. The reaction was deemed complete by following the GC to the point where the starting material disappeared. And then cooling the material to room temperature, filtering to remove the catalyst, rectifying the filtrate at normal pressure by using a 20-30 cm rectifying column, and collecting a main fraction at 42-45 ℃ to obtain 18.32g of N-methylisopropylamine, wherein the appearance of the material is colorless and transparent, the GC purity is 99.12%, the molar yield after rectification is 97.9%, and the byproduct N, N-dimethyl isopropylamine is 0.27%.

The products of the examples of the invention were confirmed by hydrogen and mass spectrometry.

While only the preferred embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims.