WO2011113228A1

WO2011113228A1 - A process for preparing guaiacol glycidyl

Info

Publication number: WO2011113228A1
Application number: PCT/CN2010/073337
Authority: WO
Inventors: 王磊; 王鹏; 甘立新
Original assignee: 浙江华海药业股份有限公司
Priority date: 2010-03-19
Filing date: 2010-05-28
Publication date: 2011-09-22
Also published as: CN101838249B; CN101838249A

Abstract

Disclosed is a process for preparing guaiacol glycidyl ether, which comprising the following steps: guaiacol and epichlorohydrin are reacted in the presence of an inorganic alkali aqueous solution and a phase transfer catalyst; thereafter, the crude guaiacol glycidyl ether is obtained by distilling under reduced pressure; the crude guaiacol glycidyl ether is recrystallizated by lower alcohol to obtain guaiacol glycidyl ether with a purity over 99.5%. According to the present process, the yield is high, the operation is easy and the demand to the equipment is low. Therefore, the process is suitable for industrial process.

Description

Method for preparing guaiacol phenol glycidyl ether

This application claims priority to Chinese Patent Application No. 201010144102.2, entitled "A Method for Preparing High Purity Guaiacol Glycidyl Ether", filed on March 19, 2010, the entire contents of which is incorporated herein by reference. This is incorporated herein by reference. Technical field

The present invention relates to a process for the preparation of a compound, and in particular to a process for the preparation of guaiacol condensed glycerol ether. Background technique

Guaiacol glycidyl ether is widely used as an intermediate of ranolazine and motoprol, and its structural formula is as shown in formula (I):

This product is mainly formed by the condensation of guaiacol and epichlorohydrin in the presence of a base. The reaction formula is as follows:

In the actual reaction, a two-step reaction is carried out; epichlorohydrin is first opened and guaiacol is condensed, and then a hydrogen chloride is removed by the action of a base to form an epoxy ring.

Patent GB2216520 discloses a preparation method for preparing epichlorohydrin, in which, after the reaction of epichlorohydrin and guaiacol is completed, it is diluted with dichlorosilane, and then extracted and distilled to obtain a crude product, which is then high. The crude product was fractionated under vacuum to obtain a finished product. In the above method, a large amount of dichloromethane is consumed, which has a great influence on the environment, and it is necessary to decompose at a high temperature in the purification process. Distillation, so the equipment is demanding.

Patent WO2008047388 describes that in the reaction process, terpene is used as a solvent, and epichlorohydrin and guaiacol are reacted. After the reaction is completed, it is extracted with terpene and then washed with water, and then distilled at 130 to 150 ° C and 3 bar. product. This method also involves a large amount of solvent, and since the product density is larger than water, it is easy to emulsify in the extraction process using benzene as a solvent. The purification method is also not mentioned in the patent, and the purity of the obtained product is only about 96%.

Other refining methods have not been mentioned in other documents currently disclosed except for vacuum distillation under high temperature. Moreover, the product tends to be polymerized at a high temperature. With this method, the purity of the product is difficult to increase, and the yield is relatively low. Summary of the invention

The object of the present invention is to provide a preparation method of a product having high purity, which is advantageous for industrialization and low cost guaiacol glycidyl ether.

In order to solve the above technical problems, the present invention provides a method for preparing guaiacol glycidyl ether, which comprises:

The guaiacol and epichlorohydrin are subjected to a condensation reaction under the action of an aqueous solution of an inorganic base and a phase transfer catalyst;

The crude guaiacol glycidic acid obtained by the condensation reaction was recrystallized from a lower alcohol to obtain a guaiacol glycidyl ether.

The method has the advantages of high yield, good quality, convenient operation and low requirement on equipment, and is a method for preparing high-purity guaiacol glycidyl ether which is very suitable for industrial production. detailed description

The following embodiments may be helpful in understanding the present invention, but the scope of protection of the present invention is not limited thereto.

An embodiment of a method for preparing a guaiacol glycidyl ether provided by the present invention comprises:

The guaiacol and epichlorohydrin are subjected to a condensation reaction under the action of an aqueous solution of an inorganic base and a phase transfer catalyst; The crude guaiacol glycidic acid obtained by the condensation reaction is recrystallized from a lower alcohol to obtain guaiacol glycidyl ether.

According to the present invention, in order to obtain a high-purity product, there are several key points in the synthesis process of the product: (1) The raw material needs to be added with a base during the reaction, and in order to control the residue of the alkali in the product, the selected base should be The product is well separated. (2) After the reaction is completed, the unreacted raw materials and the impurities formed during the reaction should be well separated from the product. (3) In order to control the cost of the product, the first choice should be to select cheap materials. Secondly, the input on the production equipment should be well controlled. The process should be easy to operate. The unreacted raw materials should be recycled. The solvent should not be used as much as possible. .

Based on the above three key points, the use of the alkali used in the reaction of the present invention has obvious advantages in the above three aspects: First, the use of inorganic bases in the reaction, the use of two-phase reaction, can effectively control the alkali substances Residue in the product; Secondly, since the two raw materials and the main impurities formed during the reaction are liquid at room temperature, and the product is solid at room temperature, the use of crystallization is advantageous for the separation of the product and the inorganic base. It has a very good effect on improving the purity of the product. Further, one of the raw materials used in the reaction of the present invention is epichlorohydrin, and after the excess epoxy is added to the solvent after the reaction, the solvent can be directly recovered and applied, which has little environmental pollution and is costly.

According to the present invention, the preparation method of guaiacol glycidyl ether according to the present invention is preferably carried out as follows:

(1) Dissolving guaiacol in an excess amount of epichlorohydrin, and then performing a condensation reaction under the action of an aqueous solution of an inorganic base and a phase transfer catalyst. After the reaction is completed, the aqueous layer is separated, and excess is recovered by distillation under reduced pressure. The epichlorohydrin was continuously concentrated and collected into a fraction of 148-153 ° C / 1.33 KPa to obtain a crude guaiacol glycidyl ether.

(2) The crude product obtained in the step (1) is recrystallized from an organic solvent to obtain a high-purity guaiacol glycidyl ether.

In the step (1), the amount of epichlorohydrin may be selected from 1 to 8 equivalents, preferably from 2 to 5 equivalents, to guaiacol. As the inorganic base, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or the like can be selected, and sodium hydroxide and potassium hydroxide are preferred. The aqueous solution concentration of the base may be selected from 10% by weight to 50% by weight. The phase transfer catalyst can be selected from tetrabutylammonium bromide, benzyltriethylammonium chloride, tetrabutyl One or more of ammonium hydrogen sulfate and tetrabutylammonium chloride. The reaction temperature is preferably from 20 ° C to 80 ° C, more preferably from 30 to 60 ° C. The reaction time is preferably from 1 to 10 hours, more preferably from 2 to 5 hours.

In the step (2), the organic solvent may be selected from the group consisting of alcohols, esters and ethers, of which lower alcohols are preferred. More preferred are C1 to C4 lower alcohol solvents such as decyl alcohol, ethanol, n-propanol, isopropanol and butanol. The amount of the solvent to be crystallized is 1 to 10 ml/g (crude xylanol glycidic acid crude), and preferably 2 to 5 ml/g (crude xylanol glycidic acid crude). The crystallization can be naturally stirred and crystallized or crystallized to induce crystallization. In order to control the crystallization rate to ensure the purity of the product, it is preferred to add seed crystals to induce crystallization.

The technical solutions of the present invention will be described below with reference to specific embodiments, but the scope of protection of the present invention is not limited to the following embodiments.

Example 1: Preparation of crude guaiacol glycidyl ether

44.4 g of guaiacol was placed in a 250 ml reaction flask, and then 99.8 g of epichlorohydrin and 1.16 g of tetrabutylammonium bromide were added and stirred. 64 g of a 25% sodium hydroxide solution was added dropwise, and the reaction was carried out at a temperature of 50 to 55 ° C for 2 hours. After completion of the reaction, it was washed once with water, then layered, and the organic phase was used to recover excess epichlorohydrin under reduced pressure. After the recovery was completed, the temperature was further distilled, and a fraction of 148 to 153 ° C / 1.33 KPa was collected to obtain a colorless transparent liquid of 45.1 g, yield 70%, purity: 98% (GC measurement) Example 2: Preparation of high purity guaiac wood Phenol glycidyl ether

The crude product of 30 g of guaiacol glycidol obtained in Example 1 was added to 90 ml of ethanol, heated to 40 ° C, and stirred until the solution was dissolved. Filtration, the filtrate was slowly cooled to 20 ° C, seed crystals were added, and the temperature was maintained at 18 to 20 ° C for 2 hours with stirring, and then the temperature was slowly lowered to 0 to 5 ° C and stirred for 1 hour, and filtered. The filter cake was dried under vacuum at 25 ° C for 12 hours to give a white solid (25.5 g, yield: 85%, purity: 99.8% (GC). Example 3: Preparation of high purity guaiacol glycidyl ether

The crude product of 30 g of guaiacol glycidol obtained in Example 1 was added to 90 ml of decyl alcohol, heated to 40 ° C, and stirred until the solution was dissolved. Filtration, the filtrate was slowly cooled to 14 ° C, seeded After stirring at 14 to 16 ° C for 2 hours, the temperature was slowly reduced to 0 to 5 ° C and stirred for 1 hour, filtered, and the filter cake was vacuum dried at 25 ° C for 12 hours to obtain 24 g of a white solid, yield 80%. Purity: 99.6% (determined by GC). Example 4: Preparation of high purity guaiacol glycidyl ether

The crude product of 30 g of guaiacol glycidol obtained in Example 1 was added to 120 ml of isopropyl alcohol, heated to 50 ° C, and stirred until the solution was dissolved. Filtration, the filtrate was slowly cooled to 20 ° C, seeded and stirred at 15 ~ 20 ° C for 2 hours, then slowly reduced to 0 ~ 5 ° C for 1 hour, filtered, filter cake 25 ° C vacuum Drying for 12 hours gave a white solid 26.4 g, yield 88%, purity: 99.5% (GC). Example 5: Preparation of high purity guaiacol glycidyl ether

The crude product of 30 g of guaiacol glycidol obtained in Example 1 was added to 120 ml of n-propanol, heated to 50 ° C, and stirred until the solution was dissolved. Filtration, the filtrate was slowly cooled to 20 ° C, seeded and stirred at 15 ~ 20 ° C for 2 hours, then slowly reduced to 0 ~ 5 ° C for 1 hour, filtered, filter cake 25 ° C vacuum After drying for 12 hours, 26.1 g of a white solid was obtained, yield 87%, purity: 99.7% (GC).

It can be seen from the above examples that the method of the guaiacol prepared by the invention has high yield and good quality.

Claims

Rights request

A method for preparing guaiacol glycidyl ether, comprising:

The guaiacol and epichlorohydrin are subjected to a condensation reaction under the conditions of an aqueous solution of an inorganic base and a phase transfer catalyst.

The crude guaiacol glycidyl ether obtained by the condensation reaction was recrystallized from a lower alcohol to obtain guaiacol glycidyl ether.

The method according to claim 1, wherein the aqueous solution of the inorganic base is an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution or an aqueous sodium carbonate solution.

The method according to claim 2, wherein the aqueous solution of the inorganic base is an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution.

4. The method as claimed in claim 2, wherein the concentration of the inorganic alkali aqueous solution is 10wt% ~ 50wt% _o

5. The method according to claim 1, wherein the phase transfer catalyst is tetrabutylammonium bromide, benzyltriethylammonium chloride, tetrabutylammonium hydrogen sulfate, tetrabutylammonium chloride. One or more of them.

6. The method according to claim 1, wherein the lower alcohol is one or more of decyl alcohol, ethanol, n-propanol, isopropanol or butanol.

7. The method according to claim 6, wherein the crude guaiacol glycidol is recrystallized from a lower alcohol, and the lower alcohol is used in an amount of 1 ml per gram of guaiacol glycidyl ether. ~ 10ml.

8. The method according to claim 7, wherein the amount of the lower alcohol in the crude guaiacol glycidol is recrystallized from the lower alcohol is in accordance with the crude product of guaiacol glycidyl ether per gram. Calculated as 2ml ~ 5ml.