阅读说明：本技术 一种邻苯二甲醚的制备方法 (Preparation method of o-dimethyl ether ) 是由 王栋伟 赵宏洋 王诚 刘涛 于 2020-12-30 设计创作，主要内容包括：本发明提供了一种邻苯二甲醚的制备方法,属于有机合成技术领域。本发明提供了一种邻苯二甲醚的制备方法,包括以下步骤：将邻苯二酚与甲基化试剂在负载型磷钨钼杂多酸催化剂存在的条件下,进行取代反应,得到所述邻苯二甲醚。本发明所用原料安全环保,反应条件温和,原料利用率高,解决了传统邻苯二甲醚合成方法原料毒性大,反应条件苛刻,催化剂昂贵难制备,生成成本高的问题,是一种适合工业生产的新方法。(The invention provides a preparation method of o-dimethyl ether, belonging to the technical field of organic synthesis. The invention provides a preparation method of o-dimethyl ether, which comprises the following steps: performing substitution reaction on catechol and a methylating agent in the presence of a supported phosphotungstic molybdenum heteropoly acid catalyst to obtain the catechol ether. The method has the advantages of safe and environment-friendly raw materials, mild reaction conditions and high utilization rate of the raw materials, solves the problems of high toxicity of the raw materials, harsh reaction conditions, expensive and difficult preparation of the catalyst and high generation cost of the traditional o-dimethyl ether synthesis method, and is a novel method suitable for industrial production.)

1. The preparation method of the o-dimethyl ether is characterized by comprising the following steps:

performing substitution reaction on catechol and a methylating agent in the presence of a supported phosphotungstic molybdenum heteropoly acid catalyst to obtain the catechol ether.

2. The method of claim 1, wherein the methylating agent is methyl chloride, methyl iodide or methyl bromide.

3. The preparation method according to claim 1 or 2, wherein the molar ratio of the catechol to the methylating agent is 1 (2-2.2).

4. The preparation method according to claim 1, wherein the temperature of the substitution reaction is 25-40 ℃ and the time is 4-6 h.

5. The preparation method of claim 1, wherein the amount of the supported phosphotungstic molybdenum heteropoly acid catalyst is 1-1.5% of the mass of catechol.

6. The method according to claim 1 or 4, wherein the substitution reaction is carried out under basic conditions.

7. The method of claim 6, wherein the basic condition is provided by an aqueous solution of sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate.

8. The method according to claim 7, wherein the aqueous sodium hydroxide solution, the aqueous potassium hydroxide solution, the aqueous sodium carbonate solution and the aqueous potassium carbonate solution have a mass concentration of 30 to 35% independently.

9. The preparation method according to claim 1, further comprising, after the substitution reaction, sequentially filtering the obtained substitution reaction product, allowing the mother liquor to stand for separation, and distilling the obtained upper oily substance under reduced pressure.

10. The method according to claim 9, wherein the temperature of the reduced pressure distillation is 100 to 120 ℃.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of o-dimethyl ether.

Background

O-dimethyl ether is also called veratrole (CAS number 91-16-7, molecular formula C)₈H₁₀O₂Colorless liquid or crystal with melting point of 15 ℃ and boiling point of 206-207 ℃), is dissolved in ethanol, ether, fatty oil and the like, is an important fine chemical product, and is widely applied to the fields of medicines and pesticides. In the chemical industry, the method is mainly used for synthesizing veratraldehyde, tetrahydropalmatine and verapamil, can also be used for detecting lactic acid in blood and glycerol and has good market prospectTherefore, the research and development of the product have important significance.

The currently reported methods for synthesizing the o-dimethyl ether include the following methods:

(1) for example, the method for synthesizing the dimethyl phthalate by using catechol as a raw material and dimethyl sulfate as a methylating agent, which is disclosed in Chinese patent with publication No. CN102863320A, wherein the toxicity of the dimethyl sulfate is high.

(2) For example, chinese patent publication No. CN103183588A discloses that catechol is used as a raw material, dimethyl carbonate is used as a methylating agent to synthesize dimethyl phthalate, which has lower toxicity than dimethyl sulfate, but has low reaction activity, so that there is a mono-substituted impurity of catechol, and the product quality is low.

(3) For example, chinese patent publication No. CN101811942A discloses synthesis of dimethyl phthalate using catechol as raw material and methyl chloride as methylation reagent, and the method has no effective catalyst in the reaction and uses a large amount of methyl chloride.

(4) For example, Chinese patent publication No. CN106914270A discloses that catechol is used as raw material, methanol is used as methylating agent, KNO is used₃/γ-Al₂O₃-SiO₂The catalyst is difficult to prepare and recover and harsh in reaction conditions for synthesizing the o-dimethyl ether by using the catalyst, and the o-dimethyl ether product is partially dissolved in methanol and exists in a water layer when the methanol is a methylating agent, so that the product yield is influenced.

Disclosure of Invention

In view of the above, the present invention aims to provide a method for preparing o-dimethyl ether. The method has the advantages of safe and environment-friendly raw materials, mild reaction conditions and high utilization rate of the raw materials, solves the problems of high toxicity of the raw materials, harsh reaction conditions, expensive catalyst and high generation cost of the traditional method for synthesizing the o-dimethyl ether, and is a novel method suitable for industrial production.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a preparation method of o-dimethyl ether, which comprises the following steps:

performing substitution reaction on catechol and a methylating agent in the presence of a supported phosphotungstic molybdenum heteropoly acid catalyst to obtain the catechol ether.

Preferably, the methylating agent is methyl chloride, methyl iodide or methyl bromide.

Preferably, the molar ratio of the catechol to the methylating agent is 1 (2-2.2).

Preferably, the temperature of the substitution reaction is 25-40 ℃ and the time is 4-6 h.

Preferably, the dosage of the supported phosphotungstic molybdenum heteropolyacid catalyst is 1-1.5% of the mass of the catechol.

Preferably, the substitution reaction is carried out under basic conditions.

Preferably, the basic conditions are provided by aqueous sodium hydroxide, aqueous potassium hydroxide, aqueous sodium carbonate or aqueous potassium carbonate.

Preferably, the mass concentration of the sodium hydroxide aqueous solution, the potassium hydroxide aqueous solution, the sodium carbonate aqueous solution and the potassium carbonate aqueous solution is 30-35% independently.

Preferably, the method further comprises the steps of sequentially filtering the obtained substitution reaction product, standing and layering mother liquor, and distilling the obtained upper oily substance under reduced pressure.

Preferably, the temperature of the reduced pressure distillation is 100-120 ℃.

The invention provides a preparation method of o-dimethyl ether, which comprises the following steps: performing substitution reaction on catechol and a methylating agent in the presence of a supported phosphotungstic molybdenum heteropoly acid catalyst to obtain the catechol ether.

Compared with the prior art, the invention has the following beneficial technical effects:

the method has the advantages of safe and environment-friendly raw materials, mild reaction conditions and high utilization rate of the raw materials, solves the problems of high toxicity of the raw materials, harsh reaction conditions, expensive and difficult preparation of the catalyst and high production cost of the traditional o-dimethyl ether synthesis method, and is a novel method suitable for industrial production.

Detailed Description

The invention provides a preparation method of o-dimethyl ether, which comprises the following steps:

performing substitution reaction on catechol and a methylating agent in the presence of a supported phosphotungstic molybdenum heteropoly acid catalyst to obtain the catechol ether.

In the present invention, the starting materials used are all commercial products in the art unless otherwise specified.

In the present invention, the methylating agent is preferably methyl chloride, methyl iodide or methyl bromide.

In the invention, the molar ratio of the catechol to the methylating agent is preferably 1 (2-2.2).

In the invention, the temperature of the substitution reaction is preferably 25-40 ℃, more preferably 30-35 ℃, and the time is preferably 4-6 h, more preferably 5 h. In the embodiment of the invention, the time of the substitution reaction is preferably the end of the reaction when the hydroquinone raw material is less than 0.2% (HPLC area normalized content) in liquid phase detection.

In the invention, the dosage of the supported phosphotungstic molybdenum heteropolyacid catalyst is preferably 1-1.5% of the mass of catechol.

In the present invention, the substitution reaction is preferably carried out under basic conditions.

In the present invention, the basic condition is preferably provided by an aqueous sodium hydroxide solution, an aqueous potassium hydroxide solution, an aqueous sodium carbonate solution or an aqueous potassium carbonate solution.

In the present invention, the mass concentration of the sodium hydroxide aqueous solution, the potassium hydroxide aqueous solution, the sodium carbonate aqueous solution and the potassium carbonate aqueous solution is preferably 30 to 35% independently.

In the present invention, taking an aqueous solution of sodium hydroxide and methyl chloride as an example, the substitution reaction equation is as follows:

in the present invention, the substitution reaction preferably further comprises sequentially filtering the obtained substitution reaction product, standing and layering the mother liquor, and distilling the obtained upper oily substance under reduced pressure.

In the present invention, the filtration enables recovery of the supported phosphotungstomolybdenum heteropolyacid catalyst.

In the invention, the temperature of the reduced pressure distillation is preferably 100-120 ℃, and the pressure is preferably less than 500 Pa.

The filtration and mother liquor standing layering of the invention have no special mode, and the mode known by persons skilled in the art can be adopted.

In order to further illustrate the present invention, the method for preparing the o-dimethylether provided by the present invention will be described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.

Example 1

Adding 110.1g of catechol and 220mL of sodium hydroxide aqueous solution with the mass concentration of 30 percent into a 1L four-mouth bottle, stirring at 25 ℃ to completely dissolve the catechol, adding 1.1g of supported phosphotungstic molybdenum polyacid catalyst, keeping the temperature at 25 ℃, continuously introducing 101g of chloromethane gas, detecting the raw material hydroquinone at a liquid phase, filtering the system to recover the catalyst after the reaction is finished and filtering the mother solution to be kept stand and layered, wherein the oily matter at the upper layer is the crude product of the phthalic ether, the content of the liquid chromatogram is more than 98.0 percent (the content of the HPLC area is normalized), distilling the crude product under reduced pressure to collect 100-120 ℃ fraction to obtain 129.9g of colorless clear liquid, namely the phthalic ether, the yield is 94 percent, detecting by a Fuli 9790 gas chromatograph and a FID detector, wherein a chromatographic column is SE-543m x 0.32mm x 0.4 m, hydrogen is 0.06MPa, nitrogen is 0.10MPa, and air is 0.1MPa, a sample inlet: 200 ℃, detector: 250 ℃, column temperature: 150 ℃ C.) has a GC content of 99.5%.

The o-dimethyl ether prepared in example 1 was characterized by the following nuclear magnetic mass spectrometry data:

¹H NMR(400MHz，CDCl₃)，δ＝3.73(6H，CH₃、CH₃)，6.66(2H，ArH)，6.73(2H，ArH)；

MS(ESI)，m/z:139.3[M+H]⁺。

example 2

Adding 110.1g of catechol and 220mL of sodium hydroxide aqueous solution with the mass concentration of 32 percent into a 1L four-mouth bottle, stirring at 35 ℃ to completely dissolve the catechol, adding 1.1g of supported phosphotungstic molybdenum polyacid catalyst, keeping the temperature at 35 ℃, continuously introducing 102g of chloromethane gas, detecting the raw material hydroquinone in a liquid phase to be less than 0.2 percent (the area normalized content by HPLC) after the reaction is finished, filtering and recovering the catalyst by a system, filtering mother liquor, standing and layering, collecting the oily substance in the upper layer to be a crude product of the phthalic ether, the chromatographic content in the liquid phase to be more than 98.0 percent (the area normalized content by HPLC), distilling the crude product under reduced pressure to collect 100-120 ℃ fractions to obtain 132.7g of colorless clear liquid, namely the phthalic ether, the yield is 96 percent, detecting by a gas chromatography (detecting by using a Fuli 9790 gas chromatograph and a FID detector, chromatographic columns SE-543m x 0.32mm x 0.4 μm, hydrogen is 0.06MPa, nitrogen is 0.10, a sample inlet: 200 ℃, detector: 250 ℃, column temperature: 150 ℃ C.) has a GC content of 99.6%.

Example 3

Adding 110.1g of catechol and 220mL of 35 mass percent sodium hydroxide aqueous solution into a 1L four-mouth bottle, stirring at 40 ℃ to completely dissolve the catechol, adding 1.1g of supported phosphotungstic molybdenum polyacid catalyst, keeping the temperature at 40 ℃, continuously introducing 102g of chloromethane gas, detecting the reaction of the raw material hydroquinone in a liquid phase of less than 0.2 percent (area normalized content by HPLC) to finish, filtering and recovering the catalyst, filtering mother liquor, standing and layering, collecting the oily matter in the upper layer which is a crude product of the o-dimethyl ether, the content of liquid chromatogram of more than 98.0 percent (area normalized content by HPLC), distilling the crude product under reduced pressure to collect 100-120 ℃ fractions to obtain 131.3g of colorless clear liquid which is the o-dimethyl ether, the yield is 95 percent, detecting by gas chromatography (detecting by using a Fuli 9790 gas chromatograph and a FID detector, a chromatographic column SE-543m x 0.32mm x 0.4 μm, hydrogen gas of 0.06MPa, 0.10MPa and air of 0.1MPa, a sample inlet: 200 ℃, detector: 250 ℃, column temperature: 150 ℃ C.) has a GC content of 99.6%.

Example 4

Adding 110.1g of catechol and 220mL of sodium hydroxide aqueous solution with the mass concentration of 32 percent into a 1L four-mouth bottle, stirring at 30 ℃ to completely dissolve the catechol, adding 1.1g of supported phosphotungstic molybdenum polyacid catalyst, keeping the temperature at 30 ℃, continuously introducing 283.9g of methyl iodide gas, detecting the reaction of the raw material hydroquinone in a liquid phase of less than 0.2 percent (the area normalized content by HPLC), filtering and recovering the catalyst, standing and layering the filtered mother solution, collecting the oily substance in the upper layer which is a crude product of the phthalic ether, the liquid chromatogram content of more than 98.0 percent (the area normalized content by HPLC), distilling the crude product under reduced pressure to collect 100-120 ℃ fractions to obtain 132.6g of colorless clear liquid which is the phthalic ether, the yield is 96 percent, detecting by gas chromatography (detecting by a Fuli 9790 gas chromatograph and a FID detector, a chromatographic column SE-543m x 0.32mm x 0.4 m, hydrogen gas of 0.06MPa, 0.10MPa and air of 0.1MPa, a sample inlet: 200 ℃, detector: 250 ℃, column temperature: 150 ℃ C.) has a GC content of 99.6%.

Example 5

Adding 110.1g of catechol and 220mL of sodium hydroxide aqueous solution with the mass concentration of 30 percent into a 1L four-mouth bottle, stirring at 25 ℃ to completely dissolve the catechol, adding 1.1g of supported phosphotungstic molybdenum polyacid catalyst, keeping the temperature at 25 ℃, continuously introducing 199.4g of methyl bromide gas, detecting the raw material hydroquinone in a liquid phase, filtering the system to recover the catalyst after the reaction is finished and filtering the mother solution to be layered, wherein the oily matter in the upper layer is the crude product of the dimethyl ether, the liquid chromatographic content is more than 98.0 percent (the normalized content in the HPLC area), and the crude product is subjected to reduced pressure distillation to collect 100-120 ℃ fractions to obtain 129.1g of colorless clear liquid, namely the dimethyl ether, the yield is 94 percent, detecting by using a Fuli 9790 gas chromatograph and a FID detector, wherein a chromatographic column is SE-543m x 0.32mm x 0.4 m, hydrogen is 0.06MPa, nitrogen is 0.10MPa, and air is 0.1MPa, a sample inlet: 200 ℃, detector: 250 ℃, column temperature: 150 ℃ C.) has a GC content of 99.5%.

Comparative example 1

1400mL of dimethyl carbonate, 1101g of catechol, 6g of tetrabutylammonium bromide catalyst and 2000mL of 40 mass percent sodium hydroxide aqueous solution are added into a 5L four-mouth bottle, after the addition is finished, the temperature is raised to 95 ℃ for reflux for 8 hours, after the reflux is finished, the mixture is kept stand for 1 hour, a lower water layer is separated, an upper oil layer is a crude product, reduced pressure distillation is carried out to obtain 1280g of a dimethyl ether product, the yield is 92.6%, and the gas phase content GC is 99.4%.

The foregoing is merely a preferred embodiment of the invention and is not intended to limit the invention in any manner. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be construed as the protection scope of the present invention.