阅读说明：本技术 3-氨基丙醇的制备方法 (Preparation method of 3-aminopropanol ) 是由 李有桂 陈建飞 张昕 吴祥 朱成峰 付延明 于 2021-10-26 设计创作，主要内容包括：本发明公开3-氨基丙醇的制备方法,涉及有机合成技术领域,本发明包括以下步骤：(1)将1,3-丙二醇和35％的盐酸在N,N-二甲基甲酰胺催化下进行取代反应,从所得反应液中萃取、精馏分离得到3-氯丙醇；(2)在密闭体系中,将所述3-氯丙醇与氨水进行反应,从所得反应液中萃取、精馏分离得到3-氨基丙醇。本发明的有益效果在于：本发明提供的一种3-氨基丙醇的简便合成方法,仅有两步反应,反应流程简单,且具有较高收率。(The invention discloses a preparation method of 3-aminopropanol, relating to the technical field of organic synthesis and comprising the following steps: (1) carrying out substitution reaction on 1, 3-propylene glycol and 35% hydrochloric acid under the catalysis of N, N-dimethylformamide, and extracting, rectifying and separating the obtained reaction liquid to obtain 3-chloropropanol; (2) and (2) reacting the 3-chloropropanol with ammonia water in a closed system, and extracting, rectifying and separating the obtained reaction liquid to obtain the 3-aminopropanol. The invention has the beneficial effects that: the simple synthesis method of 3-aminopropanol provided by the invention has the advantages of only two-step reaction, simple reaction flow and higher yield.)

A method for preparing 3-aminopropanol, which is characterized in that: the method comprises the following steps:

(1) carrying out substitution reaction on 1, 3-propylene glycol and 30-36% hydrochloric acid under the catalysis of N, N-dimethylformamide, and extracting, rectifying and separating the obtained reaction liquid to obtain 3-chloropropanol;

(2) in a closed system, reacting the 3-chloropropanol with ammonia water, extracting, rectifying and separating the obtained reaction liquid to obtain the 3-aminopropanol, wherein the molar ratio of the 3-chloropropanol to the ammonia water is 1: (2-5).

2. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the reaction temperature in the step (1) is 60-100 ℃.

3. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the reaction time in the step (1) is 8-10 h.

4. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the step of separating and obtaining 3-chloropropanol from the reaction liquid in the step (1) comprises the following steps: adding an extracting agent for extraction, and then rectifying to obtain the 3-chloropropanol.

5. The process for the preparation of 3-aminopropanol according to claim 4, characterized in that: the extracting agent is dichloromethane, ethyl acetate and trichloromethane.

6. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the reaction temperature in the step (2) is 80-130 ℃.

7. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the step of separating the aminopropanol from the reaction solution in the step (2) comprises the following steps: adding an extracting agent for extraction, and then rectifying to obtain the 3-aminopropanol.

8. The process for the preparation of 3-aminopropanol according to claim 7, characterized in that: the extracting agent is dichloromethane or trichloromethane.

9. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the molar ratio of the 1, 3-propanediol to the hydrochloric acid is 1: (0.5 to 1.5).

10. The process for the preparation of 3-aminopropanol according to claim 1, characterized in that: the dosage of the N, N-dimethylformamide is calculated by the weight of 1, 3-propylene glycol, and the dosage of the N, N-dimethylformamide is 5 to 30 weight percent.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of 3-aminopropanol.

Background

The 3-aminopropanol is a relatively representative substance in amino alcohol compounds, is mainly used for producing medicines, pesticides and surfactants, and can be used for synthesizing anticancer drugs such as cyclophosphamide, cardioclonidine, pantothenic acid and the like in the aspect of medicines. In particular, cyclophosphamide is an alkylating agent, is mainly used for tumor immunity, has obvious inhibiting effect on various tumors, and has strong indications on different systemic necrotizing vasculitis, dermatomyositis, multiple myositis, scleroderma and the like. In addition, it is a raw material for synthesizing provitamin B5 (panthenol). In recent years, due to the improvement of living standard of people, the application of panthenol in daily chemical products is continuously improved, and particularly, the application of panthenol in hair care products and other cosmetics used locally is more and more extensive, so that the market demand of 3-aminopropanol is greatly driven.

In the prior art, various methods exist for synthesizing 3-aminopropanol, mainly an acrylonitrile method, a 1, 4-butyrolactone method, a hydroxypropionitrile method and the like. Patent application publication No. CN111056963A describes that acrylonitrile is used as a raw material, and phenethyl alcohol is reacted in the presence of an alkali catalyst, 3-benzyloxypropionitrile is separated from the obtained reaction solution, the 3-benzyloxypropionitrile is subjected to a hydrogenation reaction in a liquid-phase reaction system in the presence of a hydrogenation catalyst, and 3-aminopropanol is separated from the obtained reaction solution. However, the alkali catalyst is sodium hydroxide, potassium hydroxide, etc., and the subsequent treatment increases the cost.

Patent application publication No. CN103012165A describes the ring opening of 1, 4-butyrolactone as raw material under the action of hydrazine hydrate, addition of aqueous sodium nitrite solution to produce acyl azide, and finally rearrangement to produce 3-aminopropanol. The method has the obvious defects that the raw material price is high, hydrazine hydrate with high toxicity and nitrite with carcinogenic effect are used as substrates, and the problem that the generated intermediate acyl azide is easy to explode and the like exists.

Patent application with publication number CN109456207A describes that hydroxypropionitrile is used as a raw material, and is added into a reactor with a nickel catalyst and a silver nitrate solution, and then an amine reagent is added into nitrogen; then adding hydrogen into the reactor, stirring for reduction reaction, and then carrying out precipitation and distillation to prepare the 3-aminopropanol. However, the catalyst used in the method is Raney nickel, so that the price is high, more gas is used, and the economic value is not high.

The patent application with the publication number of CN109806883A describes a supported heterogeneous catalyst, the main active component is Ni and/or Co, the auxiliary agent is one or two of Fe, Cu, Ru, Re, K and Zn, the carrier is one or more of insoluble solid material graphite, active carbon, carbon nano tube, graphene, silicon dioxide, aluminum oxide and titanium dioxide, and the catalyst is prepared by multi-step steps; mixing 3-hydroxypropionitrile and liquid ammonia in proportion, mixing with hydrogen, and reacting at 60-230 ℃ and 1.0-30.0 MPa; the product is obtained by reaction in a reactor in the presence of a supported heterogeneous catalyst prepared by an ultrasonic supported method. The method has complicated catalyst preparation process, expensive carriers such as noble metal Ru, carbon nano tubes and the like are used, equipment and flow required by a reaction system are complex, and the method has no practical application value.

Patent application publication No. CN111196761A describes a reaction apparatus for catalytically hydrogenating a feed containing 3-hydroxypropionitrile in the presence of ammonia, separating and purifying the product obtained to obtain 3-aminopropanol and recycling liquid ammonia and/or 3-hydroxypropionitrile. The method has the problems that more byproducts such as water, n-propylamine, propylene diamine, dipropylene triamine and the like are obtained, and the subsequent treatment is time-consuming and labor-consuming.

Disclosure of Invention

The technical problem to be solved by the invention is that the preparation method of 3-aminopropanol in the prior art has high cost, high toxicity, great harm to the environment, expensive catalyst and complex flow, and provides a new preparation method of 3-aminopropanol.

The invention solves the technical problems through the following technical means:

the preparation method of the 3-aminopropanol comprises the following steps:

(1) carrying out substitution reaction on 1, 3-propylene glycol and 30-36% hydrochloric acid under the catalysis of N, N-dimethylformamide, and extracting, rectifying and separating the obtained reaction liquid to obtain 3-chloropropanol;

(2) in a closed system, reacting the 3-chloropropanol with ammonia water, extracting, rectifying and separating the obtained reaction liquid to obtain the 3-aminopropanol, wherein the molar ratio of the 3-chloropropanol to the ammonia water is 1: (2-5).

Has the advantages that: the simple synthesis method of 3-aminopropanol provided by the invention has the advantages of only two-step reaction, simple reaction flow and higher yield.

In the steps (1) and (2), the starting raw materials of 1, 3-propylene glycol, hydrochloric acid, N-dimethylformamide and ammonia water are cheap and easily available, expensive raw materials such as noble metals and noble carriers are not needed, and toxic materials such as nitrite are not needed.

The boiling point difference of main and side products in the steps (1) and (2) is large, the products can be simply separated by using a rectification method, the by-products dichloropropane and propane diamine also have economic value, and escaping gas can be absorbed and then recycled, so that the method is environment-friendly.

The method has the advantages of simple operation process, mild condition, low requirement on instruments and equipment and lower production cost.

The equivalent of the ammonia water is only 3-6, the using amount of the ammonia water is small, the ammonia gas is only required to be evaporated and recovered subsequently, extra carbon dioxide is not required to participate in the reaction, and the 3-aminopropanol can be roughly prepared by extraction.

The concentration of the hydrochloric acid in the invention is the concentration of industrial hydrochloric acid, so that the invention has wider application prospect.

Preferably, the reaction temperature in the step (1) is 60 ℃ to 100 ℃.

Preferably, the reaction temperature in the step (1) is 80 to 90 ℃.

Preferably, the reaction time in the step (1) is 8 to 10 hours.

Preferably, the step of separating 3-chloropropanol from the reaction liquid in the step (1) comprises the following steps: adding an extracting agent for extraction, and then rectifying to obtain the 3-chloropropanol.

Preferably, the extractant is dichloromethane, ethyl acetate, chloroform, etc.

Preferably, the extractant is ethyl acetate, and the rectification temperature is 150-165 ℃.

Preferably, the hydrochloric acid component is rectified in the step (1) for the next reaction.

Preferably, the reaction temperature in the step (2) is 80-130 ℃.

Preferably, the reaction temperature in the step (2) is 100-120 ℃.

Preferably, the step of separating the aminopropanol from the reaction solution in the step (2) comprises: adding an extracting agent for extraction, and then rectifying to obtain the 3-aminopropanol.

Preferably, the extractant is dichloromethane, trichloromethane, and the like.

Preferably, the extractant is dichloromethane, and the rectification temperature is 160-185 ℃. Wherein the ammonia water can be reused after being evaporated and absorbed by water.

Preferably, the molar ratio of the 1, 3-propanediol to the hydrochloric acid is 1: (0.5 to 1.5).

Preferably, the N, N-dimethylformamide is used in an amount of 5 to 30 wt% based on the weight of the 1, 3-propanediol.

Preferably, the molar ratio of the 3-chloropropanol to the ammonia water is 1: (3-4).

The invention has the advantages that: the simple synthesis method of 3-aminopropanol provided by the invention has the advantages of only two-step reaction, simple reaction flow and higher yield.

In the steps (1) and (2), the starting raw materials of 1, 3-propylene glycol, hydrochloric acid, N-dimethylformamide and ammonia water are cheap and easily available, expensive raw materials such as noble metals and noble carriers are not needed, and toxic materials such as nitrite are not needed.

The boiling point difference of main and side products in the steps (1) and (2) is large, the products can be simply separated by using a rectification method, the by-products dichloropropane and propane diamine also have economic value, and escaping gas can be absorbed and then recycled, so that the method is environment-friendly.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some embodiments of the present invention, but not all embodiments. 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.

Test materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

The specific techniques or conditions not specified in the examples can be performed according to the techniques or conditions described in the literature in the field or according to the product specification.

Example 1

The preparation method of the 3-aminopropanol specifically comprises the following steps:

(1) adding 7.6g of 1, 3-propylene glycol and 0.38g N N-dimethylformamide (5 wt%) into a reaction kettle, slowly stirring and heating to 80 ℃, keeping the temperature for 0.5h, then slowly adding 5g of hydrochloric acid (the feeding molar ratio is 1: 0.5) with the mass concentration of 35% by using a dropping funnel, carrying out condensation reflux reaction at 80 ℃ for 8h, extracting the reaction liquid for three times by using ethyl acetate, collecting an organic phase, and rectifying to obtain a crude product of 3-chloropropanol, wherein the product yield is 63.3%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 3 equivalents of ammonia water, carrying out closed reaction for 4 hours at 80 ℃, evaporating reaction liquid, recovering ammonia gas by using water, then extracting with dichloromethane for three times, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 85.3%.

Example 2

The preparation method of the 3-aminopropanol specifically comprises the following steps:

(1) adding 7.6g of 1, 3-propylene glycol and 0.76g N N-dimethylformamide (10 wt%) into a reaction kettle, slowly stirring and heating to 80 ℃, keeping the temperature for 0.5h, then slowly adding 10g of hydrochloric acid (the feeding molar ratio is 1: 1) with the mass concentration of 35% by using a dropping funnel, heating to 80 ℃, after condensation reflux reaction for 8h, extracting the reaction liquid for three times by using ethyl acetate, collecting an organic phase, and rectifying to obtain a crude product of 3-chloropropanol, wherein the product yield is 69.7%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 3 equivalents of ammonia water, reacting for 4 hours at 90 ℃ in a closed manner, evaporating reaction liquid, recovering ammonia gas by using water, extracting for three times by using dichloromethane, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 86.4%.

Example 3

The preparation method of the 3-aminopropanol specifically comprises the following steps:

(1) adding 7.6g of 1, 3-propylene glycol and 1.14g of 1.14g N N-dimethylformamide (15 wt%) into a reaction kettle, slowly stirring and heating to 60 ℃, keeping the temperature for 0.5h, then slowly adding 10g of 35% hydrochloric acid (the feeding molar ratio is 1: 1) by using a dropping funnel, heating to 90 ℃, after condensation reflux reaction for 9h, extracting the reaction liquid for three times by using ethyl acetate, collecting an organic phase, and rectifying to obtain a crude product of 3-chloropropanol, wherein the product yield is 71.2%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 4 equivalents of ammonia water, carrying out closed reaction for 5 hours at 100 ℃, evaporating reaction liquid, recovering ammonia gas by using water, then extracting with dichloromethane for three times, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 88.3%.

Example 4

The preparation method of the 3-aminopropanol specifically comprises the following steps:

(1) adding 7.6g of 1, 3-propylene glycol and 1.56g N N-dimethylformamide (20 wt%) into a reaction kettle, slowly stirring and heating to 60 ℃, keeping the temperature for 0.5h, then slowly adding 15g of hydrochloric acid with the mass concentration of 35% (the feeding molar ratio is 1:1.5) by using a dropping funnel, heating to 90 ℃, carrying out condensation reflux reaction for 9h, extracting the reaction liquid for three times by using ethyl acetate, collecting an organic phase, and rectifying to obtain a crude product of 3-chloropropanol, wherein the product yield is 73.6%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 4 equivalents of ammonia water, carrying out closed reaction for 5 hours at 110 ℃, evaporating reaction liquid, recovering ammonia gas by using water, then extracting with dichloromethane for three times, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 89.7%.

Example 5

The preparation method of the 3-aminopropanol specifically comprises the following steps:

(1) adding 7.6g of 1, 3-propylene glycol and 1.56g of N, N-dimethylformamide (20 wt%) into a reaction kettle, slowly stirring and heating to 60 ℃, keeping the temperature for 0.5h, then slowly adding 15g of hydrochloric acid with the mass concentration of 35% (the feeding molar ratio is 1:1.5) by using a dropping funnel, heating to 100 ℃, carrying out condensation reflux reaction for 10h, extracting the reaction liquid for three times by using ethyl acetate, collecting an organic phase, and rectifying to obtain a crude product of 3-chloropropanol, wherein the product yield is 70.5%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 5 equivalents of ammonia water, carrying out closed reaction at 120 ℃ for 6 hours, evaporating reaction liquid, recovering ammonia gas by using water, then extracting with dichloromethane for three times, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 84.3%.

Comparative example 1

(1) 7.6g of 1, 3-propylene glycol and 5g of hydrochloric acid with the mass concentration of 35% (the feeding molar ratio is 1: 0.5) are condensed and refluxed at the temperature of 80 ℃ for 8 hours, then the reaction liquid is extracted three times by ethyl acetate, an organic phase is collected and rectified to obtain a crude product of 3-chloropropanol, and the product yield is 20.2%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 5 equivalents of ammonia water, carrying out closed reaction at 130 ℃ for 6 hours, evaporating reaction liquid, recovering ammonia gas by using water, then extracting with dichloromethane for three times, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 83.7%.

Table 1 is a table showing the analysis of the composition of the product of step (1) in each of examples and comparative examples

As can be seen from Table 1, the yield of 3-chloropropanol can be greatly increased by using N, N-dimethylformamide as a reaction catalyst in the present invention.

Comparative example 2

(1) Adding 7.6g of 1, 3-propylene glycol and 1.94 of 1.94g N N-dimethylformamide (20 wt%) into a reaction kettle, slowly stirring and heating to 60 ℃, keeping the temperature for 0.5h, then slowly adding 15g of hydrochloric acid with the mass concentration of 35% (the feeding molar ratio is 1:1.5) by using a dropping funnel, heating to 100 ℃, carrying out condensation reflux reaction for 10h, extracting the reaction liquid for three times by using ethyl acetate, collecting an organic phase, and rectifying to obtain a crude product of 3-chloropropanol, wherein the product yield is 74.4%.

(2) Adding the crude product of 3-chloropropanol into a high-temperature high-pressure reaction kettle, adding 5 equivalents of ammonia gas, carrying out closed reaction at 130 ℃ for 6 hours, evaporating reaction liquid, recovering ammonia gas by using water, then extracting with dichloromethane for three times, collecting an organic phase, and rectifying to obtain the crude product of aminopropanol, wherein the product yield is 50.2%.

Table 2 is a table showing the analysis of the composition of the product of step (2) in each of examples and comparative examples

As can be seen from Table 2, by using the ammonia water of the present invention as an ammonia providing agent, the yield of the aminopropanol can be greatly increased compared with the case of using ammonia gas, and the ammonia water is safer than ammonia gas in use conditions and has lower equipment requirements.

The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.