阅读说明：本技术 一种微反应器制备对羟基苯乙酸的方法 (Method for preparing p-hydroxyphenylacetic acid by using microreactor ) 是由 何强 周坤 赵建坤 谢学友 胡才勇 王康杨 于 2020-06-15 设计创作，主要内容包括：本发明涉及对羟基苯乙酸制备技术领域,尤其是一种微反应器制备对羟基苯乙酸的方法,其对羟基苯乙酸的制备步骤为：(1)通过恒流泵一和恒流泵二分别将对应的原料罐一和原料罐二内的物料泵入相应的的预热区一和二内；(2)预热完成后的物料置入反应区内进行反应；(3)再将氢氧化钠溶液和步骤(2)中产出的反应液输入微反应器内进行二次反应；(4)向流出的反应液中加入浓盐酸；(5)向酸化后的溶液中加入蒸馏水,然后将溶液加热,再在透明状溶液中加入活性炭；(6)在溶液加热10min后进行溶液过滤,再向滤液中加入晶种,冷却得到白色针状结晶,过滤烘干得到对羟基苯乙酸产品,本发明连续反应,减少人工操作,节省人力减轻成本,提高了安全性。(The invention relates to the technical field of preparation of p-hydroxyphenylacetic acid, in particular to a method for preparing p-hydroxyphenylacetic acid by a microreactor, which comprises the following steps: (1) respectively pumping the materials in the corresponding first raw material tank and the corresponding second raw material tank into the corresponding first preheating zone and the corresponding second preheating zone through the first constant flow pump and the second constant flow pump; (2) placing the preheated material into a reaction zone for reaction; (3) inputting the sodium hydroxide solution and the reaction liquid produced in the step (2) into a microreactor for secondary reaction; (4) adding concentrated hydrochloric acid into the effluent reaction solution; (5) adding distilled water into the acidified solution, heating the solution, and adding active carbon into the transparent solution; (6) and heating the solution for 10min, filtering the solution, adding seed crystals into the filtrate, cooling to obtain white needle crystals, filtering and drying to obtain the p-hydroxyphenylacetic acid product.)

1. A method for preparing p-hydroxyphenylacetic acid by a microreactor is characterized by comprising the following steps: the microreactor reaction equipment comprises a first raw material tank, a second raw material tank, a first constant flow pump, a second constant flow pump, a first preheating region, a second preheating region, a reaction region, a product quenching collecting region and a product collecting region, wherein the first raw material tank, the first constant flow pump and the first preheating region are sequentially communicated, the second raw material tank, the second constant flow pump and the second preheating region are sequentially communicated, the first preheating region and the second preheating region are combined and communicated with the reaction region, and the reaction region, the product quenching collecting region and the product collecting region are sequentially communicated;

the preparation method of the p-hydroxyphenylacetic acid comprises the following steps:

(1) dissolving chloroacetonitrile in water, adding chlorophenylacetic acid, mixing and stirring, putting into a first raw material tank,

dissolving sodium hydroxide in water, and placing the solution into a second raw material tank;

(2) respectively pumping the materials in the corresponding first raw material tank and the corresponding second raw material tank into the corresponding first preheating zone and the corresponding second preheating zone through the first constant flow pump and the second constant flow pump to preheat the materials;

(3) putting the preheated material into a reaction zone for reaction, and outputting a first reaction liquid after cooling;

(4) inputting the sodium hydroxide solution and the reaction liquid produced in the step (3) into a microreactor for secondary reaction, and outputting a second reaction liquid;

(5) adding concentrated hydrochloric acid into the effluent reaction liquid II, and adjusting the pH value of the reaction liquid II to be acidic;

(6) adding distilled water into the acidified solution to improve the solubility of substances in the solution, heating the solution to make the solution transparent, and adding activated carbon into the transparent solution to perform decolorization treatment;

(7) heating the solution for 10min, filtering the solution, adding seed crystal into the filtrate, cooling to obtain white needle crystal, filtering and drying to obtain p-hydroxyphenylacetic acid product.

2. The method for preparing p-hydroxyphenylacetic acid by using the microreactor as claimed in claim 1, wherein: the reaction temperature of the reaction zone in the step (3) is 110-.

3. The method for preparing p-hydroxyphenylacetic acid by using the microreactor as claimed in claim 1, wherein: the microreactor in the step (4) is an inner cavity microreactor with the inner diameter of 2 mm.

4. The method for preparing p-hydroxyphenylacetic acid by using the microreactor as claimed in claim 3, wherein: the reaction temperature in the micro-reactor is 240 ℃ and 280 ℃, the reaction pressure is 4-7 MPa, and the residence time is 2-4 min.

5. The method for preparing p-hydroxyphenylacetic acid by using the microreactor as claimed in claim 1, wherein: the pH value adjusted in the step (5) is between 1 and 2.

6. The method for preparing p-hydroxyphenylacetic acid by using the microreactor as claimed in claim 1, wherein: in step (6), the solution was heated to 65 ℃.

7. The method for preparing p-hydroxyphenylacetic acid by using the microreactor as claimed in claim 1, wherein: the micro-reactor is a copper micro-channel reactor.

Technical Field

The invention relates to the technical field of preparation of p-hydroxyphenylacetic acid, in particular to a method for preparing p-hydroxyphenylacetic acid by using a microreactor.

Background

The p-hydroxyphenylacetic acid is generally white or light yellow crystal, has a melting point of 151-153 ℃, can be sublimated, and is easily dissolved in solvents such as hot water, acetic acid, diethyl ether, ethyl acetate and the like. It has received much attention in recent years as an important pharmaceutical intermediate. The compound can be subjected to various chemical unit reactions such as amination, etherification, esterification, amidation and the like, so that the compound has wide application. The method can be used for synthesizing various medical products in the medical field, and the products can also be used in the fields of pesticides, photoelectronics, biochemistry and the like. The prior mature processes include the phenylacetonitrile process, the p-aminophenylacetic acid process, the chloral process, the glyoxylic acid process and the p-chlorobenzeneethylcyanide process.

The synthetic route of the phenethyl cyanide method has more reaction steps, more byproducts and lower yield. The synthesis line of the p-aminoacetic acid method has serious corrosion to the environmental pollution equipment. The three-filtration acetaldehyde method has less raw material of chloral. The glyoxylic acid method has expensive raw materials and high cost. The raw material p-chlorobenzeneacetonitrile is a common pesticide intermediate, is easy to obtain and has low price and the lowest cost.

The parachlorobenzene acetonitrile method has the advantages that the dropping speed of alkali is strictly controlled when the sodium parachlorobenzene acetate is prepared in the first step, a large amount of ammonia gas overflows to trigger material flushing due to the too fast process, and the reaction speed is reduced due to the too slow process. The reaction temperature is strictly controlled, the materials are pasty due to too low temperature, and the generated ammonia cannot overflow to cause the phenomenon of material flushing. The reaction time is longer. In the second step of preparation of p-hydroxyphenylacetic acid, the p-chlorophenylacetic acid sodium salt and the mixture are mixed to form paste, which is not beneficial to mixing the catalyst and the raw materials and mass and heat transfer, so that the reaction is not uniform and the byproducts are increased. The reaction pressure is 4-5 MPa, and the high-pressure reaction has potential safety hazard. The reaction time is longer.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a method for preparing p-hydroxyphenylacetic acid by using a microreactor.

In order to achieve the purpose, the invention provides the following technical scheme: a method for preparing p-hydroxyphenylacetic acid by a microreactor is disclosed, wherein microreactor reaction equipment comprises a raw material tank I, a raw material tank II, a constant flow pump I, a constant flow pump II, a preheating zone I, a preheating zone II, a reaction zone, a product quenching collecting zone and a product collecting zone, wherein the raw material tank I, the constant flow pump I and the preheating zone I are sequentially communicated, the raw material tank II, the constant flow pump II and the preheating zone II are sequentially communicated, the preheating zone I and the preheating zone II are combined and communicated with the reaction zone, and the reaction zone, the product quenching collecting zone and the product collecting zone are sequentially communicated;

the preparation method of the p-hydroxyphenylacetic acid comprises the following steps:

(1) dissolving chloroacetonitrile in water, adding chlorophenylacetic acid, mixing and stirring, putting into a first raw material tank,

dissolving sodium hydroxide in water, and placing the solution into a second raw material tank;

(2) respectively pumping the materials in the corresponding first raw material tank and the corresponding second raw material tank into the corresponding first preheating zone and the corresponding second preheating zone through the first constant flow pump and the second constant flow pump to preheat the materials;

(3) putting the preheated material into a reaction zone for reaction, and outputting a first reaction liquid after cooling;

(4) inputting the sodium hydroxide solution and the reaction liquid produced in the step (3) into a microreactor for secondary reaction, and outputting a second reaction liquid;

(5) adding concentrated hydrochloric acid into the effluent reaction liquid II, and adjusting the pH value of the reaction liquid II to be acidic;

(6) adding distilled water into the acidified solution to improve the solubility of substances in the solution, heating the solution to make the solution transparent, and adding activated carbon into the transparent solution to perform decolorization treatment;

(7) heating the solution for 10min, filtering the solution, adding seed crystal into the filtrate, cooling to obtain white needle crystal, filtering and drying to obtain p-hydroxyphenylacetic acid product.

Preferably, the reaction temperature of the reaction zone in the step (3) is 110-.

Preferably, the microreactor in the step (4) is a cavity microreactor with the inner diameter of 2 mm.

Preferably, the reaction temperature in the microreactor is 240-280 ℃, the reaction pressure is 4-7 MPa, and the residence time is 2-4 min.

Preferably, the pH adjusted in step (5) is between 1 and 2.

Preferably, in step (6), the solution is heated to a temperature of 65 ℃.

Preferably, the microreactor is a copper microchannel reactor. .

Compared with the prior art, the invention has the beneficial effects that: the invention uses the microchannel reactor to replace the traditional high-pressure reaction kettle, and hydrolyzes and replaces in the reaction kettle. P-chlorobenzeneacetonitrile and sodium hydroxide are used as raw materials, and p-chlorobenzenesodium acetate is used as a phase transfer catalyst. The two raw materials are accurately pumped into the microchannel reactor in a certain proportion by using a high-pressure pump, and the reaction temperature and the residence time can be accurately controlled by using the excellent heat and mass transfer efficiency and mixing capacity of the microchannel, so that the reaction time is shortened. The p-chlorobenzene sodium acetate generated by the reaction directly enters the next reaction, so that the acid and alkali dosage is reduced, and the discharge of three wastes is reduced. The product of the first step and the alkali liquor are pumped into the next group of microreactors, and by the method, the reaction materials can not become pasty, so that the material mixing effect can be improved, and meanwhile, the safety of the reaction is greatly improved due to the small liquid storage amount and the good pressure resistance of the microchannel reactor. Meanwhile, the reaction temperature and the reaction retention time can be accurately controlled, the generation of byproducts is reduced, the product purity is improved, and the discharge of three wastes is reduced. The reaction time is shortened, and the production efficiency is greatly improved. The reaction is continuous reaction, intelligent remote control is realized, manual operation is reduced, labor is saved, cost is reduced, and safety is improved. Meanwhile, errors possibly caused by manual operation are reduced, and the stability of the product is better.

Drawings

FIG. 1 is a schematic structural view of a microreactor reaction apparatus of the present invention.

In the figure: 1. a first raw material tank; 2. a second raw material tank; 3. a first constant flow pump; 4. a second constant flow pump; 5. a first preheating zone; 6. a second preheating zone; 7. a reaction zone; 8. a product quench collection zone; 9. a product collection region.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the 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. 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.

Referring to fig. 1, the present invention provides a technical solution: a method for preparing p-hydroxyphenylacetic acid by a microreactor is disclosed, wherein microreactor reaction equipment comprises a raw material tank I, a raw material tank II, a constant flow pump I, a constant flow pump II, a preheating zone I, a preheating zone II, a reaction zone, a product quenching collecting zone and a product collecting zone, wherein the raw material tank I, the constant flow pump I and the preheating zone I are sequentially communicated, the raw material tank II, the constant flow pump II and the preheating zone II are sequentially communicated, the preheating zone I and the preheating zone II are combined and communicated with the reaction zone, and the reaction zone, the product quenching collecting zone and the product collecting zone are sequentially communicated;

the preparation method of the p-hydroxyphenylacetic acid comprises the following steps:

(1) dissolving chlorophenylacetonitrile in water, adding chlorophenylacetic acid, fully mixing and stirring, and then placing into a raw material tank I, (p-chlorophenylacetic acid is used as a phase transfer catalyst to fully mix two phases without introducing new impurities, the p-chlorophenylacetonitrile is insoluble in water, and can be fully mixed with water by adding the phase transfer catalyst, meanwhile, the product is the p-chlorophenylacetic acid, no new impurities are introduced, and separation is not needed);

dissolving sodium hydroxide in water, and placing the solution into a second raw material tank;

(2) respectively pumping the materials in the corresponding first raw material tank and the corresponding second raw material tank into the corresponding first preheating zone and the corresponding second preheating zone through the first constant flow pump and the second constant flow pump to preheat the materials;

(3) putting the preheated material into a reaction zone for reaction, and outputting a first reaction liquid after cooling;

(4) inputting the sodium hydroxide solution and the reaction liquid produced in the step (3) into a microreactor for secondary reaction, and outputting a second reaction liquid;

(5) adding concentrated hydrochloric acid into the effluent reaction liquid II, and adjusting the pH value of the reaction liquid II to be acidic;

(6) adding distilled water into the acidified solution to improve the solubility of substances in the solution, heating the solution to make the solution transparent, and adding activated carbon into the transparent solution to perform decolorization treatment;

(7) heating the solution for 10min, filtering the solution, adding seed crystal into the filtrate, cooling to obtain white needle crystal, filtering and drying to obtain p-hydroxyphenylacetic acid product.

The reaction temperature of the reaction zone in the step (3) is 110-.

The microreactor in the step (4) is an inner cavity microreactor with the inner diameter of 2 mm.

The reaction temperature in the micro-reactor is 240 ℃ and 280 ℃, the reaction pressure is 4-7 MPa, and the residence time is 2-4 min.

The pH value adjusted in the step (5) is between 1 and 2.

In step (6), the solution was heated to 65 ℃.

The micro-reactor is a copper micro-channel reactor, the copper micro-reactor improves the reaction yield and reduces the reaction time, the micro-channel reactor has high mass transfer and heat transfer efficiency, the reaction temperature, the raw material proportion and the reaction time are accurately controlled, the reaction operation is safe and reliable, the side reaction is greatly reduced or even completely eliminated, and the reaction temperature and the reaction pressure can be accurately controlled by utilizing the high heat transfer and mass transfer effect of the micro-channel. Meanwhile, the continuous flow can accurately control the reaction residence time, greatly improve the product conversion rate and reduce the generation of three wastes. Meanwhile, the micro-reactor has small liquid storage amount and high pressure resistance, and can greatly improve the safety of the production process of products. The microreactor is made of copper, no catalyst is required to be added in the reaction, the catalytic reaction effect is better, and no copper is contained in the wastewater.

Through the technical scheme, the reaction principle is as follows:

hydrolysis of p-chlorobenzene acetonitrile under alkaline condition

C₈H₆ClN+NaOH+H₂O→C₈H₆O₂ClNa+NH₃

The p-chlorophenylacetic acid sodium salt takes copper as a catalyst to perform substitution reaction under the alkaline condition

C₈H₆O₂ClNa+2NaOH→C₈H₆O₃Na₂+NaCl

Finally, the paracritical hydroxyphenylacetic acid is generated by acidification;