阅读说明：本技术 一种3-苯氧基丙醇的制备方法 (Preparation method of 3-phenoxypropanol ) 是由 吴孝兰 郭建国 夏晓涵 孙蔚晨 于 2020-07-13 设计创作，主要内容包括：本发明属于有机合成技术领域,具体涉及一种3-苯氧基丙醇的制备方法。所述方法包括：(1)将氢氧化钠和氢氧化钾加入1,3-丙二醇中,通入氮气,搅拌、加热反应,然后蒸除水,得到含丙二醇单钠盐和丙二醇单钾盐的丙二醇溶液；(2)冷却步骤(1)得到的含丙二醇单钠盐和丙二醇单钾盐的丙二醇溶液,加入卤代苯和碘化钾,搅拌,加热进行反应；(3)反应毕,搅拌下降温,过滤,得到3-苯氧基丙醇的丙二醇溶液；(4)减压精馏,回收1,3-丙二醇,得到3-苯氧基丙醇。本发明采用卤代苯代替苯酚,采用无酚工艺,避免了含酚废水处理工程造成的人力物力消耗,绿色环保。(The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 3-phenoxypropanol. The method comprises the following steps: (1) adding sodium hydroxide and potassium hydroxide into 1, 3-propylene glycol, introducing nitrogen, stirring, heating for reaction, and then evaporating water to obtain a propylene glycol solution containing propylene glycol monosodium salt and propylene glycol monopotassium salt; (2) cooling the propylene glycol solution containing the propylene glycol monosodium salt and the propylene glycol monopotassium salt obtained in the step (1), adding halogenated benzene and potassium iodide, stirring, and heating for reaction; (3) after the reaction is finished, cooling and filtering under stirring to obtain a propylene glycol solution of 3-phenoxypropanol; (4) and (3) carrying out reduced pressure rectification, and recovering the 1, 3-propylene glycol to obtain the 3-phenoxypropanol. The method adopts the halogenated benzene to replace the phenol, adopts the phenol-free process, avoids the consumption of manpower and material resources caused by the phenol-containing wastewater treatment project, and is green and environment-friendly.)

1. The preparation method of the 3-phenoxypropanol is characterized by comprising the following steps:

(1) adding sodium hydroxide and potassium hydroxide into 1, 3-propylene glycol, introducing nitrogen, stirring, heating for reaction, and then evaporating water to obtain a propylene glycol solution containing propylene glycol monosodium salt and propylene glycol monopotassium salt;

(2) cooling the propylene glycol solution containing the propylene glycol monosodium salt and the propylene glycol monopotassium salt obtained in the step (1), adding halogenated benzene and potassium iodide, stirring, and heating for reaction;

(3) after the reaction is finished, cooling and filtering under stirring to obtain a propylene glycol solution of 3-phenoxypropanol;

(4) and (3) carrying out reduced pressure rectification, and recovering the 1, 3-propylene glycol to obtain the 3-phenoxypropanol.

2. The process for producing 3-phenoxypropanol as claimed in claim 1, wherein the molar ratio of sodium hydroxide to potassium hydroxide in step (1) is (1-1.05): (0.04-0.06).

3. The method for preparing 3-phenoxypropanol according to claim 1, wherein the heating reaction in step (1) is heating to 110 ℃ to 120 ℃; the heating in the step (2) is carried out for reaction, namely heating to 80-100 ℃, and the reaction time is 2 hours.

4. The method of claim 1, wherein the molar ratio of the halogenated benzene to the sodium hydroxide and the potassium hydroxide is 1 (1-1.05) to 0.04-0.06.

5. The process according to claim 1, wherein the molar ratio of halogenated benzene to potassium iodide is 1 (0.004-0.006).

6. A process for preparing 3-phenoxypropanol according to claim 1, 4 or 5, wherein the halogenated benzene is one of chlorobenzene and bromobenzene.

7. The process for producing 3-phenoxypropanol as claimed in claim 1, wherein the cooling in step (2) is carried out by cooling the propylene glycol solution containing the propylene glycol monosodium salt and the propylene glycol monopotassium salt to 60 ℃.

8. The method for preparing 3-phenoxypropanol according to claim 1, wherein the temperature reduction in step (3) is to reduce the temperature of the reacted solution to 25 ℃.

9. The method of claim 1, wherein the 1, 3-propanediol is replaced with any of ethylene glycol, butanediol, or an alkyl diol.

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 3-phenoxypropanol.

Background

3-phenoxypropanol is often used as a commonly used pharmaceutical intermediate, especially as a key intermediate of aclidinium bromide (a long-acting M3 cholinergic receptor antagonist). Therefore, the development of a production process of 3-phenoxypropanol is of great significance.

The common synthesis process of the 3-phenoxypropanol is prepared by condensation reaction of phenol and 3-bromopropanol, but phenol in the raw material can generate phenol-containing wastewater, so that the environment is easily polluted, and particularly the industrial production of the phenol-containing process can also aggravate the difficulty of wastewater treatment.

In view of this, the invention is particularly proposed.

Disclosure of Invention

In order to solve the defect that phenol is adopted to prepare 3-phenoxypropanol in the prior art and easily causes environmental pollution, the invention aims to provide the preparation method of the 3-phenoxypropanol, halogenated benzene is used for replacing phenol, a phenol-free process is adopted, the consumption of manpower and material resources caused by a phenol-containing wastewater treatment project is avoided, and the preparation method is green and environment-friendly.

The reaction equation of the invention is as follows:

the invention is realized by the following technical scheme:

a preparation method of 3-phenoxypropanol comprises the following steps:

(1) adding sodium hydroxide and potassium hydroxide into 1, 3-propylene glycol, introducing nitrogen, stirring, heating for reaction, and then evaporating water to obtain a propylene glycol solution containing propylene glycol monosodium salt and propylene glycol monopotassium salt;

(2) cooling the propylene glycol solution containing the propylene glycol monosodium salt and the propylene glycol monopotassium salt obtained in the step (1), adding halogenated benzene and potassium iodide, stirring, and heating for reaction;

(3) after the reaction is finished, cooling and filtering under stirring to obtain a propylene glycol solution of 3-phenoxypropanol;

(4) and (3) carrying out reduced pressure rectification, and recovering the 1, 3-propylene glycol to obtain the 3-phenoxypropanol.

Preferably, the molar ratio of the sodium hydroxide to the potassium hydroxide in the step (1) is (1-1.05): 0.04-0.06.

Preferably, the heating reaction in step (1) is heating to 110-120 ℃; the heating in the step (2) is carried out for reaction, namely heating to 80-100 ℃, and the reaction time is 2 hours.

Preferably, the molar ratio of the halogenated benzene to the sodium hydroxide and the potassium hydroxide is 1 (1-1.05) to 0.04-0.06.

Preferably, the molar ratio of the halogenated benzene to the potassium iodide is 1 (0.004-0.006).

Preferably, the halogenated benzene is one of chlorobenzene and bromobenzene.

Preferably, the cooling in step (2) is to cool the propylene glycol solution containing the propylene glycol monosodium salt and the propylene glycol monopotassium salt to 60 ℃.

Preferably, the temperature reduction in the step (3) is to reduce the temperature of the solution after the reaction to 25 ℃.

Preferably, the propylene glycol is replaced by any one of ethylene glycol, butylene glycol or an alkyl diol.

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

(1) the method adopts halogenated benzene and 1, 3-propylene glycol to carry out one-step reaction under the alkaline condition to obtain the target product 3-phenoxypropanol, and because the activity of the C-X bond on the halogenated benzene is poor, the method utilizes the high reaction activity of the oxyanion in the generated propylene glycol monosodium salt or propylene glycol monopotassium salt to attack the C-X bond on the phenyl, and combines the action of a potassium iodide catalyst to finally react to generate the target product.

(2) The potassium iodide added in the preparation method is used as a catalyst, and because the reaction activity of iodide ions is strong, chloride ions or bromide ions in halogenated benzene are easily replaced, then are replaced by anions in sodium alkoxide or potassium alkoxide, and simultaneously the replaced chloride ions or bromide ions and the sodium alkoxide or potassium alkoxide generate sodium (potassium) chloride or sodium (potassium) bromide, and then the reaction balance is carried out towards the direction of a generated product through cooling and filtering, so that the yield of the 3-phenoxypropyl is improved.

(3) The raw materials used in the invention are cheap and easy to obtain, and do not contain phenol, the residual 1, 3-propylene glycol after the reaction can be recycled, and phenol-containing wastewater can not be generated, thus the invention is green and environment-friendly.

(4) The method has the advantages of simple and convenient process, easy control and easy process scale.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all 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.