A process for the production of isosorbide dimethyl ether

Abstract

The application belongs to the field of synthesis of heterocyclic compounds and provides a production method of isosorbide dimethyl ether, which comprises the following steps: dissolving isosorbide in dimethyltetrahydrofuran, adding alkali and a stabilizer, mixing uniformly under a preset temperature in a vacuum condition, introducing chloromethane for reaction, collecting a reaction liquid, distilling, and collecting a fraction, and thus obtaining the product. Through the above process operation, the product with a purity greater than 96% and a yield greater than 90% can be obtained, and the recovery rate of the solvent reaches more than 92%. The production method is green and environmentally friendly, has small investment, mild process conditions, good economic feasibility, and solves the problem of low purity (about 70%) of the phase transfer catalysis method.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of synthesis of heterocyclic compounds, and relates to a production method of dimethyl isosorbide. BACKGROUND

[0002] The information disclosed in this BACKGROUND section is only for the purpose of increasing the understanding of the general background of the application and does not necessarily constitute an admission by the patent applicant(s) that this information constitutes prior art.

[0003] Dimethyl isosorbide (DMI, CAS No. 5306-85-4) is an important high-boiling green solvent, which is widely used in the fields of cosmetics, medicine, pesticides and industry. At present, its production technologies mainly include phase transfer catalysis method, direct etherification method, dimethyl carbonate method and dimethyl sulfate method.

[0004] Among them, the phase transfer catalysis method has replaced the traditional dimethyl carbonate method and dimethyl sulfate method to become the mainstream production method. The direct etherification method has not been widely used due to the high equipment investment, high reaction temperature and high energy consumption.

[0005] At present, the phase transfer catalysis method uses isosorbide, chloromethane (methylating agent), sodium hydroxide (alkali), alkyl-terminated low molecular weight polyether (solvent) and phase transfer catalyst (such as tetrabutylammonium bromide) to prepare dimethyl isosorbide, but there are problems of difficult control of reaction and low purity (about 70%). SUMMARY

[0006] In order to solve the above problems, the present application provides a production method of dimethyl isosorbide, which realizes the mild preparation of dimethyl isosorbide by using vacuum and solvent in cooperation under the condition of omitting phase transfer catalyst, significantly improves the purity and yield of the product, and the method of the present application also has the advantages of high solvent recovery rate, low cost and green and environmentally friendly raw materials.

[0007] In order to achieve the above purpose, the present application adopts the following technical solutions:

[0008] In a first aspect, the present application provides a production method of dimethyl isosorbide, comprising:

[0009] The isosorbide is dissolved in dimethyltetrahydrofuran, then the alkali and the stabilizer are added, and the mixture is uniformly mixed under vacuum at a preset temperature, and then chloromethane is introduced for reaction, the reaction liquid is collected, distilled, and the fraction is collected to obtain the product.

[0010] The stabilizer is dibutylhydroxytoluene;

[0011] The mass ratio of the stabilizer to isosorbide is (0.5-4):(100-300).

[0012] The preset temperature is 50-80℃.

[0013] The reaction route of the present application is as follows:

[0014]

[0015] The beneficial effects of the present application

[0016] (1) Compared with the traditional phase transfer catalysis method, the present application realizes the mild preparation of isosorbide dimethyl ether by combining vacuum and solvent under the condition of omitting the phase transfer catalyst, and significantly improves the purity and yield.

[0017] (2) The purity of isosorbide dimethyl ether prepared by the method of the present application is >96%, the yield is >90%, and the recovery rate of the solvent is >92%.

[0018] (3) The method of the present application is green and environmentally friendly, has small investment, mild process conditions, and good economic feasibility. BRIEF DESCRIPTION OF DRAWINGS

[0019] The drawings constituting a part of the specification of the present application are used to provide further understanding of the present application, and the exemplary embodiments of the present application and the description thereof are used to explain the present application, and do not constitute improper limitation on the present application.

[0020] Figure 1 The gas chromatogram of isosorbide dimethyl ether prepared for Example 1 of the present application. DETAILED DESCRIPTION

[0021] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used in the present application have the same meaning as understood by those skilled in the art to which the present application belongs.

[0022] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as understood by those skilled in the art. The reagents or raw materials used in the present application can be purchased through conventional routes, and unless otherwise specified, the reagents or raw materials used in the present application are used according to the conventional manner in the art or according to the product instructions. Similarly, unless otherwise specified, the test methods of the present application are also tested according to the conventional manner in the art or the general method or standard in the industry. In addition, any method and material similar or equivalent to the described content can be applied in the method of the present application. The preferred implementation methods and materials described herein are only for demonstration.

[0023] The application provides a production method of isosorbide dimethyl ether, comprising the following steps:

[0024] Isosorbide is dissolved in dimethyltetrahydrofuran, and then a base and a stabilizer are added; the mixture is uniformly mixed under a preset temperature in a vacuum condition, and then chloromethane is introduced to perform a reaction; a reaction liquid is collected, and then distillation is performed to collect a fraction, so that isosorbide dimethyl ether is obtained.

[0025] The amount of the solvent affects the reaction rate, yield and purity, therefore, the mass ratio of isosorbide to dimethyltetrahydrofuran is researched in the application, and in some embodiments, the mass ratio of isosorbide to dimethyltetrahydrofuran is (1-3):(1.2-2.5), so as to improve the reaction rate, yield and purity.

[0026] The type of the base is not specially limited in the application, as long as the base can provide an alkaline environment required by the reaction, and in some embodiments, the base is sodium hydroxide, so as to facilitate subsequent recovery and utilization.

[0027] The amount of the base affects the yield and purity of isosorbide dimethyl ether, therefore, the amount of the base is researched in the application, and in some embodiments, the mass ratio of the base to isosorbide is (1-2.5):(1-3), so as to provide an alkaline environment and facilitate the generation of isosorbide dimethyl ether.

[0028] In view of the problem that the reaction is difficult to control in the traditional phase transfer catalyst method, an antioxidant is added as a stabilizer in the reaction, so as to reduce the occurrence of oxidation side reactions and improve the yield and purity of isosorbide dimethyl ether, therefore, in some embodiments, the mass ratio of the stabilizer to isosorbide is (0.5-4):(100-300), so as to obtain higher yield and purity.

[0029] The type of the stabilizer affects the antioxidant effect, therefore, the type of the stabilizer is researched in the application, and in some embodiments, the stabilizer is dibutylhydroxytoluene (BHT), so as to more efficiently inhibit the occurrence of oxidation side reactions.

[0030] Chloromethane and isosorbide perform etherification reaction to obtain isosorbide dimethyl ether, therefore, the amount of chloromethane and isosorbide is researched in the application, and in some embodiments, the mass ratio of chloromethane to isosorbide is (1-2.5):(1-3), so as to improve the yield and purity of isosorbide dimethyl ether.

[0031] The etherification reaction of chloromethane and isosorbide needs to be performed at a certain temperature, therefore, the temperature of the reaction is researched in the application, and in some embodiments, the preset temperature is 50-80 DEG C, so as to ensure that the reaction is performed smoothly.

[0032] The partial pressure of chloromethane affects the mixing effect with isosorbide, therefore, the partial pressure of chloromethane is studied in the present application, and in some embodiments, the partial pressure of chloromethane is 0.4-0.5 MPa, so as to obtain a more optimal reaction effect.

[0033] The reaction time affects the yield and purity of isosorbide dimethyl ether, therefore, the reaction time of isosorbide dimethyl ether is studied in the present application, and in some embodiments, the reaction time is 1-5 hours, so as to improve the yield and purity of isosorbide dimethyl ether.

[0034] The present application is further described in detail below in conjunction with specific examples, it should be pointed out that the specific examples are an explanation of the present application rather than a limitation.

[0035] Example 1

[0036] In this embodiment, the amount of each raw material is as follows: isosorbide: 100 g, dimethyl tetrahydrofuran: 120 g, NaOH: 100 g, stabilizer (BHT): 0.5 g, chloromethane: 100 g.

[0037] 1. In a pressure-resistant reaction kettle, first add isosorbide, then add dimethyl tetrahydrofuran, stir at 200 rpm until completely dissolved, then add NaOH and BHT.

[0038] 2. Vacuum to 0.05 MPa.

[0039] 3. Close the vacuum valve, heat the system to 80°C, and adjust the stirring speed to 300 rpm.

[0040] 4. Introduce chloromethane to a pressure of 0.5 MPa.

[0041] 5. React at 80°C until the chloromethane consumption is 100 g.

[0042] 6. Close the chloromethane inlet valve. Continue to heat for 5 hours.

[0043] 7. Discharge, filter, and obtain the crude product.

[0044] 8. The filtered gas enters the condenser to obtain "recovered solvent";

[0045] 9. Distill the crude product under vacuum (-0.098 MPa), and collect the liquid at 0-135°C, mix with "recovered solvent", and reuse as dimethyl tetrahydrofuran make-up liquid, the recovery rate of the solvent is 95.2%.

[0046] 10. Distill the crude product under vacuum (-0.098 MPa) to collect a fraction of 135-165 °C to obtain the refined product. Test the refined product for isosorbide dimethyl ether content using a gas chromatograph, as shown in Figure 1, which shows a retention time of 11.024 min for the isosorbide dimethyl ether chromatographic peak. Calculate the yield and purity, which are 93.4% and 96.3%, respectively. Figure 1

[0047] Example 2

[0048] In this example, the amounts of the raw materials are as follows: isosorbide, 200 g; dimethyltetrahydrofuran, 185 g; NaOH, 175 g; stabilizer (BHT), 2.25 g; and chloromethane, 175 g.

[0049] 1. In a pressure-resistant reaction kettle, first add isosorbide, then add dimethyltetrahydrofuran, and stir at 120 rpm until completely dissolved, then add NaOH and BHT.

[0050] 2. Vacuumize to 0.045 MPa.

[0051] 3. Close the vacuum valve, and raise the system temperature to 65 °C, and increase the stirring speed to 600 rpm.

[0052] 4. Introduce chloromethane to a pressure of 0.45 MPa.

[0053] 5. Perform the reaction at 60 °C until the chloromethane consumption is 175 g.

[0054] 6. Close the chloromethane inlet valve. Continue to maintain the temperature for 3 hours.

[0055] 7. Discharge the contents, and filter to obtain the crude product.

[0056] 8. Introduce the filter gas into a condenser to obtain "recovered solvent";

[0057] 9. Distill the crude product under vacuum (-0.098 MPa) to condense and collect a liquid at 0-135 °C, and mix it with the "recovered solvent" to be reused as a make-up liquid for dimethyltetrahydrofuran. The recovery rate of the solvent is 94.1%.

[0058] 10. Distill the crude product under vacuum (-0.098 MPa) to collect a fraction of 135-165 °C to obtain the refined product. Test the refined product for isosorbide dimethyl ether content using a gas chromatograph, as shown in Figure 1, which shows a retention time of 11.024 min for the isosorbide dimethyl ether chromatographic peak. Calculate the yield and purity, which are 93.4% and 96.3%, respectively.

[0059] Example 3

[0060] ​The amounts of each raw material used in this example are as follows: isosorbide: 300 g, dimethyltetrahydrofuran: 250 g, NaOH: 250 g, stabilizer (BHT): 4 g, chloromethane: 250 g.

[0061] 1. In a pressure-resistant reaction kettle, isosorbide was first added, followed by dimethyltetrahydrofuran, and stirring was performed at 40 rpm until complete dissolution, then NaOH and BHT were added.

[0062] 2. Vacuum was drawn to 0.04 MPa.

[0063] 3. The vacuum valve was closed, the system was warmed to 50°C, and the stirring speed was increased to 900 rpm.

[0064] 4. Chloromethane was introduced until the pressure reached 0.4 MPa.

[0065] 5. The reaction was performed at 50°C until the chloromethane consumption reached 250 g.

[0066] 6. The chloromethane inlet valve was closed. The reaction was continued for 1 hour while maintaining the temperature.

[0067] 7. The contents were discharged and filtered to obtain the crude product.

[0068] 8. The filtered gas was introduced into a condenser to obtain "recovered solvent";

[0069] 9. The crude product was distilled under vacuum (-0.098 MPa), and the liquid collected at 0°C-135°C was mixed with the "recovered solvent" and reused as the make-up liquid for dimethyltetrahydrofuran. The recovery rate of the solvent was 92.3%.

[0070] 10. The crude product was distilled under vacuum (-0.098 MPa) to collect the fraction at 135°C-165°C, which was the refined product. The content of isosorbide dimethyl ether in the refined product was tested using a gas chromatograph to calculate the yield and purity. The results showed that the yield was 90.0% and the purity was 96.3%.

[0071] Comparative Example 1

[0072] The difference from Example 1 is that no stabilizer (BHT) was added.

[0073] The test results showed that the yield was 89.3%, the purity was 93.5%, and the recovery rate of the solvent was 89.6%.

[0074] The recovery rate of the solvent was 95.2%.

[0075] Comparative Example 2

[0076] The difference from Example 1 is that methyl-terminated polyethylene glycol was used instead of dimethyltetrahydrofuran.

[0077] The test results show that the yield is 88.7%, the purity is 94.3%, and the solvent recovery rate is 94.3%.

[0078] Comparative Example 3

[0079] The difference from Example 1 is that tetrahydrofuran is used instead of dimethyl tetrahydrofuran.

[0080] The test results show that the yield is 89.4%, the purity is 95.8%, and the solvent recovery rate is 87.6%.

[0081] From the comparison of Example 1 and Comparative Example 1, it can be seen that the addition of the stabilizer (BHT) effectively improves the purity and yield of isosorbide dimethyl ether, and the solvent recovery rate is also improved.

[0082] From the comparison of Example 1 and Comparative Examples 2 and 3, it can be seen that compared with methyl-terminated polyethylene glycol / tetrahydrofuran, the use of dimethyl tetrahydrofuran can better improve the purity and yield of isosorbide dimethyl ether and the solvent recovery rate.

[0083] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A method for producing isosorbide dimethyl ether, characterized in that, include: Isosorbide is dissolved in dimethyltetrahydrofuran, then alkali and stabilizer are added, the vacuum is drawn to 0.04-0.05 MPa, and the mixture is stirred evenly at a preset temperature. Chloromethane is then introduced to carry out the reaction. The reaction solution is collected, distilled, and the fraction is collected to obtain the product. The stabilizer is butylated hydroxytoluene; the mass ratio of the stabilizer to isosorbide is (0.5-4):(100-300). The preset temperature is 50℃-80℃.

2. The method for producing isosorbide dimethyl ether as described in claim 1, characterized in that, The mass ratio of isosorbide to dimethyltetrahydrofuran is (1-3):(1.2-2.5).

3. The method for producing isosorbide dimethyl ether as described in claim 1, characterized in that, The alkali is sodium hydroxide.

4. The method for producing isosorbide dimethyl ether as described in claim 1, characterized in that, The mass ratio of the alkali to isosorbide is (1-2.5):(1-3).

5. The method for producing isosorbide dimethyl ether as described in claim 1, characterized in that, The mass ratio of chloromethane to isosorbide is (1-2.5):(1-3).

6. The method for producing isosorbide dimethyl ether as described in claim 1, characterized in that, The partial pressure of the chloromethane is 0.4 MPa-0.5 MPa.

7. The method for producing isosorbide dimethyl ether as described in claim 1, characterized in that, The reaction time is 1-5 hours.

Images