阅读说明：本技术 一种对甲氧基苯乙胺的制备方法 (Preparation method of p-methoxyphenethylamine ) 是由 郭建国 秦建国 吴孝兰 夏晓晗 于 2020-05-07 设计创作，主要内容包括：本发明属于化学合成领域,具体涉及一种对甲氧基苯乙胺的制备方法,包括如下步骤：(1)向碱溶液中加入溴化钠,搅拌均匀后,加入对甲氧基苯丙酰胺,混合均匀,得到第一溶液；(2)加热所述第一溶液,搅拌条件下滴加浓度为28wt％双氧水,升温,双氧水和溴化钠反应生成次溴酸钠,进而和酰胺发生霍夫曼反应；(3)将步骤(2)反应后的反应液冷却、萃取、脱溶,得淡黄色油状的对甲氧基苯乙胺。有益效果：本发明的制备方法用绿色试剂双氧水替代次氯酸钠(或次溴酸钠),可以减少用碱量,大大降低反应体系盐含量,反应条件温和可控、收率高、成本低等优点,适合工业化生产使用。(The invention belongs to the field of chemical synthesis, and particularly relates to a preparation method of p-methoxyphenethylamine, which comprises the following steps: (1) adding sodium bromide into an alkali solution, stirring uniformly, adding p-methoxy hydrocinnamamide, and mixing uniformly to obtain a first solution; (2) heating the first solution, dropwise adding 28 wt% hydrogen peroxide under stirring, heating, reacting the hydrogen peroxide with sodium bromide to generate sodium hypobromite, and further carrying out Hofmann reaction with amide; (3) and (3) cooling, extracting and desolventizing the reaction liquid obtained after the reaction in the step (2) to obtain the yellowish oily p-methoxyphenethylamine. Has the advantages that: the preparation method of the invention uses the green reagent hydrogen peroxide to replace sodium hypochlorite (or sodium hypobromite), can reduce the alkali consumption, greatly reduce the salt content of the reaction system, has the advantages of mild and controllable reaction conditions, high yield, low cost and the like, and is suitable for industrial production.)

1. The preparation method of the p-methoxyphenethylamine is characterized by comprising the following steps:

(1) adding sodium bromide into an alkali solution, stirring uniformly, adding p-methoxy hydrocinnamamide, and mixing uniformly to obtain a first solution;

(2) heating the first solution, dropwise adding 28 wt% hydrogen peroxide under stirring, heating, and carrying out Hoffman reaction;

(3) and (3) cooling, extracting and desolventizing the reaction liquid obtained after the reaction in the step (2) to obtain the yellowish oily p-methoxyphenethylamine.

2. The method for preparing p-methoxyphenethylamine according to claim 1, wherein the alkali solution in step (1) is sodium hydroxide solution, and the molar concentration of sodium hydroxide is 3.5 to 5 mol/L.

3. The method for preparing p-methoxyphenylethylamine of claim 1 wherein the molar ratio of sodium hydroxide, sodium bromide and p-methoxyphenylalanyl amide in the first solution in step (1) is: (0.55-0.6):(0.014-0.016):0.28.

4. The method for preparing p-methoxyphenethylamine according to claim 1, wherein the hydrogen peroxide solution is added in the step (2) in an amount of H₂O₂The molar ratio of the molar weight of the p-methoxy hydrocinnamamide to the molar weight of the p-methoxy hydrocinnamamide is 1-1.01: 1.

5. The preparation method of p-methoxyphenethylamine according to claim 1, wherein the heating temperature in step (2) is 50 to 56 ℃, the temperature after temperature rise is 60 to 64 ℃, and the Hofmann reaction time is 30 to 45 min.

6. The method for preparing p-methoxyphenethylamine according to claim 1, wherein the cooling temperature in step (3) is 15-20 ℃; the extraction is carried out with dichloromethane.

Technical Field

The invention belongs to the field of chemical synthesis, and particularly relates to a preparation method of p-methoxyphenethylamine.

Background

The p-methoxyphenethylamine is an important intermediate in organic synthesis and pharmaceutical industry, and the development and research of the p-methoxyphenethylamine are concerned by the majority of chemical researchers. In the prior art, most of p-methoxyphenylethylamine adopts chlorine or sodium hypochlorite as an oxidant, and p-methoxyphenylethylamine is prepared by oxidizing p-methoxyphenylalanide through Hofmann reaction, but the process of using chlorine (highly toxic) or sodium hypobromoate (high salt content) as the oxidant is complex, has a high risk coefficient, and is not environment-friendly.

Therefore, it is important to provide a method for preparing p-methoxyphenethylamine with no pollution and high yield.

Disclosure of Invention

In order to overcome the defects of environmental pollution and low yield in the preparation of p-methoxyphenethylamine in the prior art, the invention provides a green, environment-friendly and efficient preparation method of p-methoxyphenethylamine. The invention utilizes modified Hoffmann (Hoffmann) degradation reaction, and uses a green oxidant hydrogen peroxide to replace sodium hypobromous (chlor) oxide or chlorine gas, and has the advantages of simple process, environmental protection and high yield.

The invention is realized by the following technical scheme:

a preparation method of p-methoxyphenethylamine comprises the following steps:

(1) adding sodium bromide into an alkali solution, stirring uniformly, adding p-methoxy hydrocinnamamide, and mixing uniformly to obtain a first solution;

(2) heating the first solution, dropwise adding 28 wt% hydrogen peroxide under stirring, heating, and carrying out Hoffman reaction;

(3) and (3) cooling, extracting and desolventizing the reaction liquid obtained after the reaction in the step (2) to obtain the yellowish oily p-methoxyphenethylamine.

Preferably, the alkali solution in the step (1) is sodium hydroxide solution, and the molar concentration of the sodium hydroxide is 3.5-5 mol/L.

Preferably, the molar ratio of the sodium hydroxide, the sodium bromide and the p-methoxy hydrocinnamamide in the first solution in the step (1) is: (0.55-0.6):(0.014-0.016):0.28.

Preferably, the hydrogen peroxide is added in the step (2) in an amount of H₂O₂The molar ratio of the p-methoxy hydrocinnamamide to the p-methoxy hydrocinnamamide is 1: 1. The invention uses green hydrogen peroxide as oxidant and uses bromide ion as oxidantIs a catalyst) is oxidized into active bromine positive ions (sodium hypobromite), then the p-methoxy phenethylamine is further prepared by carrying out Hofmann reaction with p-methoxy hydrocinnamamide, and the bromine positive ions are changed back to the bromine ions (sodium bromide) after the reaction, thereby having the advantages of green and no pollution, reducing the alkali consumption of the process, improving the yield and reducing the cost.

Preferably, the heating temperature in the step (2) is 50-56 ℃, the temperature after temperature rise is 60-64 ℃, and the Hofmann reaction time is 30-45 min.

Preferably, the temperature of the cooling in the step (3) is 15-20 ℃; the extraction is carried out with dichloromethane.

Compared with the prior art, the invention has the following beneficial effects:

(1) the method utilizes the modified Hoffmann degradation reaction, takes sodium bromide as a catalyst, adopts green hydrogen peroxide to oxidize bromide ions into active bromide positive ions, and then further reacts with p-methoxy hydrocinnamide to prepare the p-methoxy phenethylamine.

(2) The preparation method of the invention has the advantages of reduced alkali consumption, mild reaction conditions, high yield and the like, and is suitable for industrial production.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to specific embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. The following description of at least one exemplary embodiment is merely illustrative in nature and is in no way intended to limit the invention, its application, or uses. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Unless specifically stated otherwise, the numerical values set forth in these examples do not limit the scope of the invention. Techniques, methods known to those of ordinary skill in the relevant art may not be discussed in detail, but are intended to be part of the specification where appropriate. In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values.