WO2019237327A1

WO2019237327A1 - Method for producing phloroglucinol

Info

Publication number: WO2019237327A1
Application number: PCT/CN2018/091473
Authority: WO
Inventors: 戴长喜; 周永广
Original assignee: 江苏鼎烨药业有限公司
Priority date: 2018-06-15
Filing date: 2018-06-15
Publication date: 2019-12-19
Also published as: ZA202005179B

Abstract

A method for producing phloroglucinol, comprising: using 2,6-dichlorophenol as a reaction raw material; carrying out reaction in the presence of a copper salt catalyst and 1,2,4-trimethylbenzene solvent; performing three-gradient cooling on a reaction liquid, and adding hot water at first and second stages to perform layering separation; and decoloring by using an activated carbon adsorption column and removing a copper ion and a potassium ion by using a metal ion adsorbent. The method has advantages such as a high yield, high purity, and low concentration of a metal ion.

Description

Method for producing resorcinol

A technical field

The invention relates to a method for producing resorcinol, and belongs to the technical field of organic chemical product preparation. This method is suitable for the production of resorcinol using dichlorophenol as a raw material.

Background technology

Resorcinol (1,3,5-trihydroxybenzene) is an important fine chemical product, mainly used in the synthesis of flavonoid isoflavone antitumor drugs. It can also be used as a dye coupling agent, tire tackifier and Azo composite inks and other raw materials; used in textile and leather dyeing processes, the production of plastic capsules, instead of silver iodide for artificial rainfall and preservatives for some synthetic materials. Resorcinol injection can be used for acute spastic pain caused by dysfunction of digestive system and biliary tract, acute spastic urethra, bladder, renal colic, and gynecological spastic pain.

Currently, there are two types of methods for the preparation of resorcinol: chemical synthesis and biosynthesis. Chemical synthesis includes: (1) 1,3,5-triaminobenzene hydrolysis method. Generally, it is prepared by using a halogenated compound of TNT or benzene through amination and hydrolysis, such as the halogenated aniline method CN1312128C reported by French PHV company. Using halogenated benzene or aminobenzene as raw materials, the price is expensive, the source of raw materials is difficult, and it is not suitable for industrial production; (2) 1,3,5-trialkoxybenzene hydrolysis method. CN1205158C of Zhejiang New Synthesis Company, CN1513821A of Zhejiang University, and CN102452902A of Tianjin Sannong Gold Company use 1,3,5-tribromobenzene or hexachlorobenzene as raw materials to prepare resorcinol through alkoxylation, complexation and hydrolysis. The main problems are acid decomposition, low yield and difficulty in treating waste acid; (3) Tricumene (TIP) oxidation method. The main process can be divided into 3 steps. The first step is the alkylation of benzene with propylene to generate TIP. The second step is the oxidation of TIP to 1,3,5-tris (2-hydroxyperoxy-2-methyl). Methyl ethyl) benzene (THPO), the third step is the decomposition of THPO into 1 in the presence of an acid, and by-product acetone. However, the yield of the reaction is relatively low, because the air oxidation reaction of TIP is more complicated and more by-products are generated (Ge Zhongxue, Ye Shaoning, Liu Hong. Preparation of Resorcinol by Tricumene Oxidation. Synthetic Chemistry. 2007, 15 ( 6): 735-739); (4) Dihydroxychlorobenzene method. Dihydroxychlorobenzene is hydrolyzed and acidified. Although this route has a simple reaction process, there is currently no good synthesis method for 2,4- or 2,6-dihydroxychlorobenzene, so the cost of raw materials is high and the source is difficult. At the same time, the problem of waste acid treatment also exists in the reaction process, and the process of separation and purification of the final product is complicated, the amount of solvent consumed is large, and the cost of the product is high; (5) Triglyceride derivative method. The reaction using a triglyceride derivative as a raw material is complicated, and the source of the raw material is difficult. It is only suitable for small-scale preparation in the laboratory, and currently cannot achieve industrial production. At the same time, a large amount of by-products are generated during the reaction, which seriously pollutes the environment, the yield of the product is relatively low, and separation and purification are difficult; (6) the dichlorophenol method. Nanjing Rein Pharmaceutical Technology Co., Ltd. CN1785948A prepared 2,4-dichlorophenol and 2,6-dichlorophenol by elimination, addition, and acidification to obtain the target compound. During the reaction, the reactor needs to be filled with nitrogen for protection. And the work-up requires a large amount of ethyl acetate. The main biosynthetic methods are: (1) CN101084311A, Michigan State University, USA, biosynthesis of resorcinol from malonyl-CoA, enzymes are obtained from simple starting materials such as glucose; (2) Qingdao Bioenergy and Process Research CN101724662B relates to a catalytic synthesis of resorcinol using engineering E. coli cells.

The applicant's earlier application patent CN103086847 A discloses a method in which 2,6-dichlorophenol and potassium hydroxide are used as raw materials, and 1,2,4-trimethylbenzene is used as a solvent. Heated to give resorcinol. The reaction after-treatment of this process is convenient, and the yield can reach 71%. The yield still needs to be further improved. At the same time, because a large amount of potassium hydroxide and copper salt catalysts are used in the reaction, the metal ion content in the product is relatively high, about 200-500 ppm, which restricts the direct use of the product.

The current method still has the defects of low product yield, low product purity, and high metal ion content. Therefore, it is necessary to develop a high-yield, high-purity, and easy-to-operate production room using 2,6-dichlorophenol as a raw material. Process of pyrogallol.

Three invention content

An object of the present invention is to provide a method for producing resorcinol using 2,6-dichlorophenol as a starting material. The invention overcomes the shortcomings of low yield, low purity and high metal ion content in the methods in the prior art, and has the advantages of simple operation and high efficiency.

The technical solution to achieve the purpose of the present invention is: a method for producing resorcinol, including the following steps:

1) Mix the raw material 2,6-dichlorophenol and the solvent 1,2,4-trimethylbenzene first;

2) Add 1,2,4-trimethylbenzene and potassium hydroxide to the reactor, heat and stir at normal pressure, and raise the temperature to 100-140 ° C;

3) On the basis of step 2), a copper salt catalyst is added at a time, and then the mixed liquid in step 1) is added dropwise to the reactor, and the temperature is raised to 160-180 ° C, and the reaction liquid is obtained for 12-15 hours;

4) The reaction solution in step 3) is cooled and left to stand. The cooling operation is performed in three stages. The first stage is reduced from 160 to 180 ° C to 100-120 ° C, and the second stage is reduced from 120-100 ° C to 60. -70 ℃, the third stage is reduced from 60-70 ℃ to 25-30 ℃; hot water of 60-80 ℃ is added in the first stage and the second stage respectively;

5) In step 4), the organic solvent phase in the upper layer is separated from the lower aqueous phase, the upper organic solvent phase is recycled, and the lower aqueous phase enters the neutralization kettle;

6) The neutralization kettle is neutralized with 31% to 37% hydrochloric acid and adjusted to a pH of 0.5 to 3.0, and the acid water is centrifuged to obtain a crude resorcinol;

7) Dissolve the crude resorcinol in step 6) with hot water at 60-80 ° C, and then decolorize it through an activated carbon adsorption column to obtain a resorcinol decolorization solution;

8) The resorcinol decolorizing solution in step 7) is passed through a column filled with a metal ion adsorbent to remove copper ions and potassium ions, the metal ion adsorbent containing 10-80 parts of alumina and 20- 90 parts of silica, metal ion adsorbent is honeycomb;

9) The resorcinol solution obtained in step 8) is recrystallized, centrifuged, dried and pulverized to obtain a finished resorcinol product with a purity of more than 99.6% and a total content of copper ions and potassium ions of 10-30 ppm.

Further, the molar ratio of 2,6-dichlorophenol to potassium hydroxide is 1: 8 to 10; the mass ratio of 1,2,4-trimethylbenzene to 2,6-dichlorophenol is 5 to 6: 1.

Further, the mass usage of 1,2,4-trimethylbenzene in step 1) is 60-75% of the total usage of 1,2,4-trimethylbenzene.

Further, the copper salt catalyst is selected from at least one of cuprous chloride and copper sulfate, and the amount of the copper salt catalyst is 0.1 to 1.0% of the mass of 2,6-dichlorophenol.

Further, the mass ratio of hot water to 2,6-dichlorophenol in step 4) is 4 to 5: 1, and the mass ratio of the amount of hot water in the first stage and the second stage is 1: 3-4.

Further, in step 7), the crude hot aqueous solution of pyrogallol is 0.1-0.3 times the volume of the activated carbon adsorption column per minute, and the maintenance time is 30-60 minutes.

Further, the amount of the metal ion adsorbent in step 8) is 5-10% of the mass of 2,6-dichlorophenol.

The beneficial effects of the present invention:

The inventors of the present invention have unexpectedly discovered that gradient cooling during the cooling process and the addition of hot water in the first and second stages can make the materials delaminate more quickly, and the resorcinol in the reaction solution is fully dissolved in the water layer. The product yield has been improved, and the yield can reach 79.5%. At the same time, the activated carbon adsorption column is used instead of activated carbon powder or particles to decolorize the product, which further improves the purity and color of the product, and the product purity can reach more than 96%. The honeycomb metal ion adsorbent treatment composed of alumina and silicon oxide can conveniently and effectively remove potassium and copper ions, especially potassium ions, which improves the quality of the product and can be directly used for resorcinol Injection.

Four specific implementations

The following describes the present invention in detail through examples. These examples are for the purpose of clearly disclosing the present invention and are not intended to limit the present invention.

Example 1

Mix 1.0 mol (163.0 g) of 2,6-dichlorophenol and 500 g of 1,2,4-trimethylbenzene to obtain mixed solution 1 for future use. In a 2000 mL four-necked flask, add 315 g of 1,2,4-triene in sequence. Methylbenzene, 8.0mol (448.8g) potassium hydroxide, heated and stirred at normal pressure, heated to 120 ° C, 0.163g of cuprous chloride catalyst was added at a time, and the mixture was added dropwise (dropping time is 2 hours) The reaction solution was heated to 170 ° C. and reacted for 14 hours to obtain a reaction solution. The reaction solution was first cooled to 120 ° C, and 150 g of 80 ° C hot water was added, and then cooled to 70 ° C, and 502 g of 80 ° C hot water was added, and then cooled to room temperature, transferred to a separation funnel, and left to stand. The upper layer of the solvent was separated. The lower layer was adjusted to pH 0.5 with 37% hydrochloric acid. The acid water was separated by centrifugation. The crude resorcinol was dissolved in hot water at 80 ° C, and the volume was 0.1 times per minute. The volume velocity of the activated carbon adsorption column was decolorized by the activated carbon adsorption column, and the treatment time was 40 minutes to obtain a decolorizing solution of resorcinol. The resorcinol decolorizing solution was passed through a column containing 10 g of a honeycomb metal ion adsorbent. The metal ion adsorbent contained 80 parts of alumina and 20 parts of silica, and the treatment time was 45 minutes. The resorcinol after the treatment was recrystallized, centrifuged, dried and pulverized to obtain a finished resorcinol product with a yield of 75.6%, a purity of 99.6%, and a total content of copper ion and potassium ion of 30 ppm.

Example 2

Mix 1.0 mol (163.0 g) of 2,6-dichlorophenol and 600 g of 1,2,4-trimethylbenzene to obtain mixed solution 1 for future use. In a 2000 mL four-necked flask, add 378 g of 1,2,4-triene in order. Methylbenzene, 9.0 mol (504.9 g) of potassium hydroxide, heated and stirred under normal pressure, heated up to 120 ° C, added 1.63 g of cuprous chloride catalyst at a time, and added 1 dropwise of the mixture (the drop time was 2 hours) The reaction solution was heated to 170 ° C. and reacted for 14 hours to obtain a reaction solution. The reaction solution was first cooled to 100 ° C, and 200 g of 80 ° C hot water was added, followed by cooling to 70 ° C, and 615g of 80 ° C hot water was added, and then cooled to room temperature, transferred to a separatory funnel, and left to stand. Layer, the upper solvent was separated, and the lower aqueous phase was adjusted to pH 3.0 with 37% by weight hydrochloric acid. The remaining steps were the same as in Example 1. The yield was 78.2%, the purity was 99.7%, and the total copper ion and potassium ion content was 25ppm. .

Example 3

Except in step 4), the reaction solution is first cooled to 100 ° C, and 165 g of 80 ° C hot water is added, and then cooled to 70 ° C, and 650 g of 80 ° C hot water is added, and then cooled to room temperature. In Example 2, the yield was 79.4%, the purity was 99.7%, and the total content of copper ions and potassium ions was 28 ppm.

Example 4

Except in step 8), the decolorizing solution of resorcinol is passed through a column containing 15 g of a honeycomb metal ion adsorbent. The metal ion adsorbent contains 90 parts of alumina and 10 parts of silica. The treatment time is 45 minutes. The remaining steps were the same as those in Example 3. The yield was 79.5%, the purity was 99.7%, and the total content of copper and potassium ions was 15 ppm.

Comparative Example 1

Example 1 in document CN103086847 A was repeated with a yield of 68.4%, a purity of 95.5%, and a total copper ion and potassium ion content of 230 ppm.

Comparative Example 2

Except in step 4), the reaction solution was directly cooled to room temperature, and 815 g of water at room temperature was added. The rest of the steps were the same as in Example 3. The yield was 69.1%, the purity was 99.6%, and the total copper ion and potassium ion content was 30 ppm.

Comparative Example 3

Except that step 8) is omitted, the remaining steps are the same as those in Example 4, the yield is 79.2%, the purity is 99.7%, and the total copper ion and potassium ion content is 195 ppm.

The invention can be summarized in other specific forms without departing from the spirit or main characteristics of the invention. The above embodiments of the present invention can only be considered as an illustration rather than a limitation of the present invention. Any minor modifications, equivalent changes, and modifications made to the above embodiments in accordance with the essential technology of the present invention belong to the scope of the technical solution of the present invention. .

Claims

A method for producing resorcinol, which comprises the following steps:

1) Mix the raw material 2,6-dichlorophenol and the solvent 1,2,4-trimethylbenzene first;

2) Add 1,2,4-trimethylbenzene and potassium hydroxide to the reactor, heat and stir at normal pressure, and raise the temperature to 100-140 ° C;

3) On the basis of step 2), a copper salt catalyst is added at a time, and then the mixed liquid in step 1) is added dropwise to the reactor, and the temperature is raised to 160-180 ° C, and the reaction liquid is obtained for 12-15 hours;

4) The reaction solution in step 3) is cooled and left to stand. The cooling operation is performed in three stages. The first stage is reduced from 160 to 180 ° C to 100-120 ° C, and the second stage is reduced from 120-100 ° C to 60. -70 ℃, the third stage is reduced from 60-70 ℃ to 25-30 ℃; hot water of 60-80 ℃ is added in the first stage and the second stage respectively;

5) In step 4), the organic solvent phase in the upper layer is separated from the lower aqueous phase, the upper organic solvent phase is recycled, and the lower aqueous phase enters the neutralization kettle;

6) The neutralization kettle is neutralized with 31% to 37% hydrochloric acid and adjusted to a pH of 0.5 to 3.0, and the acid water is centrifuged to obtain a crude resorcinol;

7) Dissolve the crude resorcinol in step 6) with hot water at 60-80 ° C, and then decolorize it through an activated carbon adsorption column to obtain a resorcinol decolorization solution;

8) The resorcinol decolorizing solution in step 7) is passed through a column filled with a metal ion adsorbent to remove copper ions and potassium ions, the metal ion adsorbent containing 10-80 parts of alumina and 20- 90 parts of silica, metal ion adsorbent is honeycomb;

9) The resorcinol solution obtained in step 8) is recrystallized, centrifuged, dried and pulverized to obtain a finished resorcinol product with a purity of more than 99.6% and a total content of copper ions and potassium ions of 10-30 ppm.
The method according to claim 1, characterized in that the molar ratio of 2,6-dichlorophenol to potassium hydroxide is 1: 8-10; 1,2,4-trimethylbenzene and 2,6-dichlorophenol The mass ratio is 5 to 6: 1.
The method according to claim 2, characterized in that the mass amount of 1,2,4-trimethylbenzene in step 1) is 60-75% of the total amount of 1,2,4-trimethylbenzene.
The method according to claim 1, characterized in that in step 3) the copper salt catalyst is selected from at least one of cuprous chloride and copper sulfate, and the amount of the copper salt catalyst is 0.1 to the mass of 2,6-dichlorophenol. 1.0%.
The method according to claim 1, characterized in that the mass ratio of hot water to 2,6-dichlorophenol in step 4) is 4 to 5: 1, wherein the mass ratio of the amount of hot water in the first stage and the second stage is It is 1: 3-4.
The method according to claim 1, characterized in that step 7) the crude hot aqueous solution of pyrogallol is 0.1-0.3 times the volume of activated carbon adsorption column per minute, and the holding time is 30-60 minutes.
The method according to claim 1, characterized in that the amount of the metal ion adsorbent used in step 8) is 5-10% of the mass of 2,6-dichlorophenol.