A process for the synthesis of 2,5-dimethylphenol catalyzed by a Lewis acid-promoter system

Abstract

This invention discloses a method for the catalytic synthesis of 2,5-dimethylphenol using a Lewis acid-co-catalyst system, comprising the following steps: 1. Sequentially reacting a Lewis acid catalyst, a co-catalyst, and 2,6-dimethylphenol at a controlled temperature, followed by cooling to room temperature to obtain the reaction mixture; 2. Hydrolyzing the reaction mixture and finally filtering to obtain crude 2,5-dimethylphenol; 3. Recrystallizing and purifying the crude 2,5-dimethylphenol to obtain 2,5-dimethylphenol. This invention, by adding a small amount of co-catalyst, can suppress the excessively high catalytic activity of the Lewis acid. With a low addition amount, the raw material conversion rate is high, and the target product maintains high selectivity. The catalyst can be removed by hydrolysis and filtration, further simplifying the post-reaction processing procedure, reducing costs, and increasing yield. The catalyst system used in this invention has good safety, and the reaction process is mild.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of chemical synthesis, and particularly relates to a method for synthesizing 2,5-dimethylphenol by using a Lewis acid-assisted catalyst system. BACKGROUND

[0002] 2,5-dimethylphenol is an important medicine and dye intermediate, and is a main raw material for manufacturing the new blood lipid-lowering drug gemfibrozil. 2,5-dimethylphenol can be conveniently converted into 2,3,6-trimethylphenol by using a gas-phase methylation technology, and the latter is mainly used in the pharmaceutical industry to synthesize the main ring 2,3,5-trimethylhydroquinone of vitamin E. 2,5-dimethylphenol is also used as a monomer of heat-resistant polyphenyl ether engineering plastic and a raw material of plastic alloy, and is an indispensable intermediate in the production of some pesticides and disinfectants.

[0003] 2,5-dimethylphenol can be separated from coal tar, but its content is low, the operation is complicated, and the cost is high. At present, the synthesis methods of 2,5-dimethylphenol mainly include p-xylene sulfonation-alkali fusion method, direct catalytic hydroxylation of p-xylene, and 2,5-dimethylaniline diazotization-hydrolysis method. In the above three methods, the p-xylene sulfonation-alkali fusion method uses strong acid and strong base in the reaction process, which is seriously polluting and has many by-products; the direct catalytic hydroxylation of p-xylene has the advantage of good atom economy, but the product yield is extremely low. For example, in the patent with the publication number CN102199072A, Zhang Tianyong et al. use acetonitrile as a solvent, H2O2 as a hydroxylation reagent, and C.I. pigment green 8 as a catalyst to catalytically hydroxylate p-xylene into 2,5-dimethylphenol, and the highest yield is only 10.1%; the 2,5-dimethylaniline diazotization-hydrolysis method also has the characteristics of poor process safety, serious pollution, and poor atom economy, and 2,5-dimethylaniline is highly toxic and expensive. In addition, 2,5-dimethylphenol can also be synthesized by catalytic methylation of m-cresol, but this method has low selectivity and high production cost due to the high price of m-cresol. In the patent with the publication number WO2015110655A1 (the same family patents CN105939988A, EP3099657A1, US20170001935) of the Dutch company Evonik, a new synthesis route of 2,5-dimethylphenol is disclosed, which has a good development prospect. The specific method is to directly synthesize 2,5-dimethylphenol by reacting 2,5-dimethylfuran with acetylene or trimethylsilane acetylene under the action of a catalyst. This process has good atom economy, but the highest yield is only 20%, and like the direct catalytic hydroxylation of p-xylene, the improvement of the catalyst performance has not yet made a breakthrough. In the paper “Research on the isomerization reaction molecular sieve catalyst of dimethylphenol” by Ren Xiwie, the prepared multi-level hole ZSM-5 molecular sieve is used to catalyze the isomerization reaction of 2,6-dimethylphenol, and the optimal reaction temperature is 430℃ and the optimal mass space velocity is 2.1h-1. The highest yield of 2,5-dimethylphenol is only 20.6%, and the catalyst needs to be regenerated after 10h of reaction. -1The conversion rate of one-way is 85.91%, the selectivity of 2,5-dimethylphenol is 33.25%, and the conversion rate and the selectivity are low, and the yield of 2,5-dimethylphenol is 28.57%. Zhao Zhili et al. disclosed a method for synthesizing 2,5-dimethylphenol by isomerization of 2,6-dimethylphenol with an aluminum chloride catalyst in a patent with the publication number CN109078656A. The fixed bed process is still used, but the conversion rate of 2,6-dimethylphenol and the selectivity of 2,5-dimethylphenol are in a seesaw relationship, and the highest yield of 2,5-dimethylphenol is only 33.95%. In the patent with the publication number CN109251132A, aluminum chloride is directly used as a catalyst for the isomerization reaction of 2,6-dimethylphenol, which has the advantages of high conversion rate and short reaction time, but also has the disadvantages of violent reaction and many by-products.

[0004] In summary, in the process of preparing 2,5-dimethylphenol, there are various deficiencies in the prior art. Therefore, it is necessary to develop a method for synthesizing 2,5-dimethylphenol with high conversion rate of 2,6-dimethylphenol and high selectivity of 2,5-dimethylphenol, to solve the problems of many by-products, violent reaction and low yield of 2,5-dimethylphenol in the isomerization reaction of 2,6-dimethylphenol catalyzed by aluminum chloride. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a method for synthesizing 2,5-dimethylphenol using a Lewis acid-cocatalyst system, which solves the above-mentioned problems of the prior art. The method uses a Lewis acid as a main catalyst and adds a cocatalyst for catalytic isomerization reaction. In the case of low addition amount of the cocatalyst, high selectivity can be maintained under high conversion rate, the post-reaction processing procedure is further simplified, the cost is reduced, and the yield is improved. The catalyst system used in the present application is safe and the reaction process is mild.

[0006] To solve the above technical problems, the technical solution adopted by the present application is: a method for synthesizing 2,5-dimethylphenol using a Lewis acid-cocatalyst system, characterized in that the method comprises the following steps:

[0007] Step one, sequentially put the Lewis acid catalyst, the cocatalyst and 2,6-dimethylphenol into the reaction bottle, stir uniformly, then warm and react, cool to room temperature, and obtain the reaction material;

[0008] Step two, batch the reaction material obtained in step one into deionized water for hydrolysis reaction, then stir, and finally filter to obtain the water phase and 2,5-dimethylphenol crude product;

[0009] Step three, purify the 2,5-dimethylphenol crude product obtained in step two by recrystallization to obtain 2,5-dimethylphenol.

[0010] The present application converts 2,6-dimethylphenol into 2,5-dimethylphenol with wider application and higher added value through methyl rearrangement isomerization reaction under the action of catalyst-cocatalyst, and the reaction formula is Then, the catalyst is removed through hydrolysis and filtration, so as to convert low-value products into high-value products. Since the raw material of the isomerization reaction is easy to obtain, the process is simple, and the reaction condition is mild, the raw material and process cost are greatly reduced.

[0011] The present application inhibits the excessive catalytic activity of the main catalyst, i.e. Lewis acid catalyst, by adding a cocatalyst, so that more 2,6-dimethylphenol is isomerized to form 2,5-dimethylphenol, and the further migration of methyl on the benzene ring to form 3,5-dimethylphenol and other methyl phenol byproducts is inhibited. The addition of the cocatalyst also helps to stabilize the intermediate formed by the isomerization of 2,6-dimethylphenol catalyzed by the Lewis acid catalyst, and reduces the generation of byproducts. The hydrolysis reaction of the present application is an exothermic reaction. The reaction heat can be removed in time by adding the reaction material obtained in step one into deionized water in batches to improve the safety of the reaction. During the hydrolysis reaction, the main catalyst is hydrolyzed into hydrate and acid gas, which can be dissolved in the aqueous solution. The cocatalyst is also easily soluble in water, while the product 2,5-dimethylphenol is slightly soluble in water. Therefore, the Lewis acid catalyst and the cocatalyst can be removed by filtration.

[0012] The above-mentioned method for synthesizing 2,5-dimethylphenol using a Lewis acid-cocatalyst system, characterized in that the Lewis acid catalyst in step one is one or more of aluminum chloride, aluminum tribromide, aluminum triiodide, aluminum trifluoride, aluminum fluorosilicate, iron trichloride, and zirconium tetrachloride; and the cocatalyst is one or more of choline chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetramethylurea, 1,3-dimethylurea, tetraethylurea, N,N-dimethylacrylurea, 1,3-diethylurea, and tetrabutylurea. In the present application, the specific components of the Lewis acid catalyst and the cocatalyst are controlled to effectively convert 2,6-dimethylphenol into 2,5-dimethylphenol, and the catalyst has a wide range of applications.

[0013] It should be noted that the cocatalyst is preferably N,N-dimethylacrylurea (DMPU).

[0014] The above-mentioned method for synthesizing 2,5-dimethylphenol using a Lewis acid-cocatalyst system, characterized in that the molar ratio of 2,6-dimethylphenol to the Lewis acid catalyst in step one is 1.0:1.8. In the present application, the molar ratio of 2,6-dimethylphenol to the Lewis acid catalyst is controlled to make the conversion rate of 2,6-dimethylphenol reach more than 95%.

[0015] The method for synthesizing 2,5-dimethylphenol by using a Lewis acid-promoter catalyst system, characterized in that the molar ratio of 2,6-dimethylphenol to the promoter in step one is 1.0:0.01-0.05. The present application ensures a high conversion rate and high selectivity of the product by controlling the molar ratio of 2,6-dimethylphenol to the promoter.

[0016] The method for synthesizing 2,5-dimethylphenol by using a Lewis acid-promoter catalyst system, characterized in that the temperature of the holding reaction in step one is 90-130 DEG C and the time is 2-14 h. The present application ensures the catalytic performance of the catalyst, reduces the generation of side reactions, improves the conversion rate and the selectivity of the product, and ensures a conversion rate of the raw material of not less than 95% by controlling the temperature and time of the holding reaction.

[0017] The method for synthesizing 2,5-dimethylphenol by using a Lewis acid-promoter catalyst system, characterized in that the holding reaction in step one and the hydrolysis reaction in step two are carried out in the absence of solvent. The present application can reduce the cost and avoid the introduction of new impurities into the reaction system by carrying out the reaction in the absence of solvent.

[0018] The method for synthesizing 2,5-dimethylphenol by using a Lewis acid-promoter catalyst system, characterized in that the temperature of the hydrolysis reaction in step two is 20-50 DEG C, the stirring is carried out at 20-30 DEG C, and the time is more than 30 min. The present application reduces the generation of side reactions, the loss of phenolic compounds due to sublimation, and the escape of hydrogen chloride in the reaction system by controlling the temperature of the hydrolysis and the parameters of the stirring.

[0019] The method for synthesizing 2,5-dimethylphenol by using a Lewis acid-promoter catalyst system, characterized in that the solvent used in the recrystallization and purification in step three is one or more than two of methanol, ethanol, n-propanol, isopropanol, n-propanol, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, and a mixture of deionized water. The organic solvent used in the present application is easily soluble in water and has a strong ability to dissolve 2,5-dimethylphenol, which can effectively purify 2,5-dimethylphenol and remove the residual main catalyst hydrolysate and promoter in the 2,5-dimethylphenol crude product.

[0020] Compared with the prior art, the present application has the following advantages:

[0021] 1. The method for synthesizing 2,5-dimethylphenol by isomerization of 2,6-dimethylphenol using a Lewis acid-cocatalyst system in the application, which can produce 2,5-dimethylphenol with wider application and higher added value. The cost of raw materials and catalyst is low, and the process is simple, the reaction condition is mild, which greatly reduces the cost of raw materials and process, and has less environmental pollution. It provides a cost-effective synthetic route for the production of 2,5-dimethylphenol, and solves the problem of narrow market for 2,6-dimethylphenol.

[0022] 2. The conversion rate of the raw material 2,6-dimethylphenol in the synthesis method of the application can reach more than 95%, and the selectivity of the product 2,5-dimethylphenol can reach more than 90%.

[0023] 3. The application adopts a filtering method to separate 2,5-dimethylphenol from Lewis acid catalyst and cocatalyst, which is simple to operate and improves the separation efficiency of 2,5-dimethylphenol crude product.

[0024] 4. The crude 2,5-dimethylphenol is purified by recrystallization, which can reduce the equipment investment and energy consumption in the industrialization process.

[0025] 5. The Lewis acid catalyst hydrolysate is easily soluble in water, and the cocatalyst has very low toxicity and is easily soluble in water, so the catalyst can be easily removed.

[0026] The technical solutions of the application will be further described in detail below with the help of drawings and examples. DETAILED DESCRIPTION

[0027] Figure 1 The gas chromatogram of the product obtained by recrystallization purification in step three of Example 5 of the application.

[0028] Figure 2 The gas chromatogram of the product obtained by recrystallization purification in step three of Example 6 of the application.

[0029] Figure 3 The gas chromatogram of the product obtained by recrystallization purification in step three of Example 7 of the application. DETAILED DESCRIPTION

[0030] Example 1

[0031] This example includes the following steps:

[0032] Step one, 0.18 mol of anhydrous aluminum chloride, 0.005 mol of N, N-dimethylpropenyl urea (DMPU), and 0.10 mol of 2,6-dimethylphenol are sequentially put into a 500 mL four-necked flask, stirred uniformly, then heated to 130°C, and reacted after being kept warm. During the reaction, a gas chromatograph is used to monitor the reaction progress. After being kept warm for 4 h, the conversion rate of 2,6-dimethylphenol is not less than 95%, and the reaction material is cooled to room temperature;

[0033] Step two, the reaction material obtained in step one is added into deionized water at 20-50°C for hydrolysis reaction, then stirred at 20-30°C for more than 30 min, and finally filtered to obtain a water phase and a 2,5-dimethylphenol crude product.

[0034] Step three, the 2,5-dimethylphenol crude product obtained in step two is recrystallized and purified by using a methanol-deionized water mixture to obtain 2,5-dimethylphenol.

[0035] The product obtained in Example 1 is detected, and the obtained results are shown in Table 1.

[0036] Table 1

[0037]

[0038] In step one of the embodiment, the Lewis acid catalyst can also be one or more than two of aluminum tribromide, aluminum triiodide, aluminum trifluoride, aluminum fluorosilicate, ferric chloride, and zirconium tetrachloride.

[0039] In step one of the embodiment, the co-catalyst can also be one or more than two of choline chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetramethylurea, 1,3-dimethylurea, tetraethylurea, N, N-dimethylpropenyl urea, 1,3-diethylurea, and tetrabutylurea.

[0040] In step three of the embodiment, the recrystallization and purification solvent can also be a mixture of one or more than two of ethanol, n-propanol, isopropanol, n-propanol, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, and deionized water.

[0041] Example 2

[0042] The difference between the embodiment and Example 1 is that in step one, the temperature is raised to 105°C, and then kept warm for 10 h after the reaction.

[0043] Example 3

[0044] The difference between this embodiment and embodiment 1 is that 0.0025 mol of N,N-dimethylacrylurea is used in step one, and the reaction is carried out after being heated to 105°C, the reaction process is monitored by using a gas chromatograph in the heat preservation reaction, and the heat preservation reaction is carried out for 7 hours.

[0045] Embodiment 4

[0046] The difference between this embodiment and embodiment 1 is that 0.0001 mol of N,N-dimethylacrylurea is used in step one, and the reaction is carried out after being heated to 105°C, the reaction process is monitored by using a gas chromatograph in the heat preservation reaction, and the heat preservation reaction is carried out for 6 hours.

[0047] The products obtained in embodiments 2-4 are detected, and the results are shown in Table 2.

[0048] Table 2

[0049]

[0050] Embodiment 5

[0051] This embodiment includes the following steps:

[0052] Step one, 0.90 mol of anhydrous aluminum chloride, 0.0125 mol of N,N-dimethylacrylurea, and 0.50 mol of 2,6-dimethylphenol are sequentially added into a 500 mL four-necked flask, and then stirred uniformly, and then heated to 95°C to carry out a heat preservation reaction, the reaction process is monitored by using a gas chromatograph in the heat preservation reaction, and the heat preservation reaction is carried out for 7 hours, and then cooled to room temperature after the conversion rate of 2,6-dimethylphenol is not less than 95%, to obtain a reaction material;

[0053] Step two, the reaction material obtained in step one is added into deionized water at 20-50°C to carry out a hydrolysis reaction, and then stirred at 20-30°C for more than 30 minutes, and finally filtered to obtain an aqueous phase and a 2,5-dimethylphenol crude product;

[0054] Step three, the 2,5-dimethylphenol crude product obtained in step two is recrystallized and purified by using a methanol-deionized water mixture to obtain 2,5-dimethylphenol.

[0055] Figure 1 The gas chromatogram of the product obtained in step three of this embodiment is shown in FIG. 2, and it can be seen from FIG. 2 that the product obtained in this embodiment is mainly 2,5-dimethylphenol. Figure 1

[0056] Embodiment 6

[0057] The difference between this embodiment and embodiment 5 is that the heat preservation reaction is carried out for 9 hours in step one.

[0058] Figure 2 ​is the gas chromatogram of the product obtained by recrystallization purification in step three of this example, from which it can be seen that the product obtained in this example is mainly 2,5-dimethylphenol. Figure 2

[0059] Example 7

[0060] The difference between this example and Example 5 is that the temperature is kept at 80°C for 10h in step one.

[0061] Figure 3 is the gas chromatogram of the product obtained by recrystallization purification in step three of this example, from which it can be seen that the product obtained in this example is mainly 2,5-dimethylphenol. Figure 3

[0062] Example 8

[0063] The difference between this example and Example 5 is that the temperature is kept at 80°C for 11h in step one.

[0064] Example 9

[0065] The difference between this example and Example 5 is that the temperature is kept at 80°C for 11h in step one.

[0066] The products obtained in Examples 5-9 are detected, and the results are shown in Table 3.

[0067] Table 3

[0068]

[0069] Comparative Example 1

[0070] The difference between this comparative example and Example 7 is that N,N-dimethylpropenylurea is not used.

[0071] The product obtained in Comparative Example 1 is detected, and the results are shown in Table 4.

[0072] Table 4

[0073]

[0074] It can be seen from the comparison between Example 7 and Comparative Example 1 that no catalyst is added in Comparative Example 1, and the selectivity, yield, recovery and purity in Comparative Example 1 are lower than those in Example 7 when the conversion rates in Comparative Example 1 and Example 7 are similar.

[0075] The above is only the preferred embodiment of the present application, and does not limit the present application. Any simple modification, change and equivalent change made according to the technical essence of the present application to the above embodiment are still within the protection scope of the technical solution of the present application.​​

Claims

1. A process for the synthesis of 2,5-dimethylphenol catalyzed by a Lewis acid-co-catalyst system, characterized in that, The method comprises the following steps: Step one, sequentially put Lewis acid catalyst, cocatalyst and 2,6-dimethyl phenol into the reaction bottle, then stir uniformly, then warm up and carry out the holding reaction, then cool to room temperature to obtain the reaction material; the Lewis acid catalyst is one or more than two of aluminum chloride, aluminum bromide and ferric chloride; the cocatalyst is one or more than two of choline chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetramethylurea, 1,3-dimethylurea, tetraethylurea, N,N-dimethylacrylurea, 1,3-diethylurea and tetrabutylurea; the molar ratio of 2,6-dimethyl phenol to cocatalyst is 1.0:0.01-0.05; the temperature of the holding reaction is 90-130 DEG C, and the time is 2-14 h; the holding reaction is carried out in the absence of solvent; Step two, batch the reaction material obtained in step one into deionized water to carry out the hydrolysis reaction, then stir, and finally filter to obtain the water phase and 2,5-dimethyl phenol crude product; the temperature of the hydrolysis reaction is 20-50 DEG C, the stirring is carried out at 20-30 DEG C, and the time is more than 30 min; the hydrolysis reaction is carried out in the absence of solvent; Step three, carry out the recrystallization purification of the 2,5-dimethyl phenol crude product obtained in step two to obtain 2,5-dimethyl phenol.

2. A process for the synthesis of 2,5-dimethylphenol catalyzed by a Lewis acid-co-catalyst system according to claim 1, characterized in that, The molar ratio of 2,6-dimethyl phenol to Lewis acid catalyst in step one is 1.0:1.

8.

3. A process for the synthesis of 2,5-dimethylphenol catalyzed by a Lewis acid-co-catalyst system according to claim 1, characterized in that, The solvent used in the recrystallization purification in step three is a mixture of one or more than two of methanol, ethanol, n-propanol, isopropanol, n-propanol, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether and deionized water.

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