Preparation method for synthesizing trimethyl sulfonium bromide by DMSO (dimethylsulfoxide)

Abstract

The invention relates to the technical field of trimethyl sulfonium bromide, in particular to a preparation method for synthesizing trimethyl sulfonium bromide from DMSO (dimethylsulfoxide), which comprises the following steps: stirring and mixing DMSO and a reducing solvent, heating to 30-80 DEG C, keeping the temperature, introducing bromomethane for reaction, cooling and filtering when the residual quantity of DMSO is less than or equal to 0.5%, and cleaning and drying to obtain trimethyl sulfonium bromide. The DMSO (dimethyl sulfoxide) and the reducing solvent are used for replacing dimethyl sulfide, so that the trimethyl sulfonium bromide meeting the requirements can be effectively prepared, the influence of the dimethyl sulfide on the environment can be avoided, and the production limitation of the trimethyl sulfonium bromide is further reduced.

Description

Technical Field

[0001] The present application relates to the technical field of trimethylsulfonium bromide, and more specifically, to a preparation method of trimethylsulfonium bromide synthesized from DMSO. Background Art

[0002] Trimethylsulfonium bromide is an organic compound, which is usually used as a brominating agent to introduce bromine atoms in organic synthesis reactions. It can be used as a brominating agent to synthesize brominated aromatics, and is also a precursor of sulfur ylide reagents. It can also be used as a catalyst in organic synthesis reactions. The current conventional method for producing trimethylsulfonium bromide is to react dimethyl sulfide with methyl bromide or bromonitromethane, and the reaction equation is as follows: In the above production of trimethylsulfonium bromide, dimethyl sulfide is used as the reaction raw material. However, dimethyl sulfide is an organic sulfur malodorous gas. When its content in the air reaches one part per billion, it can produce an odor, which has a great impact on the environment. In many cases, its use is prohibited or restricted. Summary of the invention

[0003] In order to solve the above problems, the present application provides a preparation method of trimethylsulfonium bromide synthesized from DMSO, which uses DMSO (dimethyl sulfoxide) and a reducing solvent to replace dimethyl sulfide, not only can trimethylsulfonium bromide that meets the requirements be effectively prepared, but also the use of dimethyl sulfide can be avoided and the impact on the environment is avoided, thereby reducing the production restrictions of trimethylsulfonium bromide.

[0004] The present application provides a preparation method of trimethylsulfonium bromide synthesized from DMSO, comprising the following steps: stirring and mixing DMSO and a reducing solvent, heating to 30-80°C, keeping the temperature and introducing methyl bromide to react, cooling and filtering until the residual DMSO content is ≤0.5%, and then washing and drying to obtain trimethylsulfonium bromide.

[0005] Preferably, the temperature is raised to 60-65° C. and then kept warm and methyl bromide is introduced for reaction.

[0006] Preferably, the reducing solvent is one or more of an alcohol solvent and an aldehyde ketone solvent with reducing properties; wherein the alcohol solvent with reducing properties includes ethanol, isopropanol, n-butanol, sec-butanol, etc., and the aldehyde ketone solvent with reducing properties includes formic acid (whose molecular structure contains -CHO), formaldehyde, acetaldehyde, acetone, etc.

[0007] Preferably, the reducing solvent is selected from one or more of isopropanol and acetone.

[0008] The present application uses DMSO (dimethyl sulfoxide) and a reducing solvent to replace dimethyl sulfide. Taking isopropanol and acetone as an example, the reaction equation is as follows: During the preparation, due to the low boiling point of methyl bromide, the present application first stirs DMSO and the reducing solvent to ensure that the two are fully mixed, and then adds methyl bromide. This can shorten the mixing time of the raw materials to a certain extent and ensure that the reaction proceeds in an orderly manner. In order to further improve the reaction efficiency, the present application can choose to be carried out in a pressure reactor.

[0009] On this basis, the reaction temperature of the system is one of the key factors that determine the direction of the reaction progress. The present application directly controls the system temperature at 30-80°C, and further preferably at 60-65°C, which is the temperature at which methyl bromide reacts more actively with DMSO and reducing solvents. If the reaction temperature is lower than 30°C, the reaction cannot proceed; if the reaction temperature exceeds 80°C, the system will tend to generate more by-products.

[0010] After the reaction is completed, due to the poor solubility of trimethylsulfonium bromide in organic solvents, the present application can obtain trimethylsulfonium bromide with a high yield after direct filtering, washing and drying. The operation is simple and can directly avoid the use of dimethyl sulfide, reduce the impact of the production of trimethylsulfonium bromide on the environment, and further help reduce the production restrictions of trimethylsulfonium bromide, facilitating the production approval of trimethylsulfonium bromide.

[0011] Preferably, the molar ratio of DMSO to the reducing solvent is 1:1-20.

[0012] Preferably, the molar ratio of DMSO to methyl bromide is 1:0.9-2.

[0013] In the present application, an excess reducing solvent is used as both a reaction solvent and a reaction raw material. If the amount added is too low, methyl bromide will directly react with DMSO to generate trimethylsulfoxide bromide; in addition, if the amount of methyl bromide is too much, the excess methyl bromide will react with the water produced in the main reaction to generate methanol and hydrogen bromide; and hydrogen bromide will further promote the hydrolysis of water molecules in the system of the present application, thereby causing the side reaction to intensify. Therefore, in the present application, the amount of DMSO, reducing solvent and methyl bromide is strictly controlled to ensure that trimethylsulfoxide bromide has a relatively high yield.

[0014] Preferably, in the cleaning step, a reducing solvent is used for elution 1-5 times.

[0015] The present application adopts a reducing solvent for elution, which can reduce the additional water or other washing reagents in the system, thereby helping to harvest a higher content of trimethylsulfonium bromide; the number of elutions can be adjusted according to the actual content changes, but the more elutions, the lower the yield will be, and 2-3 times is more preferred.

[0016] In summary, this application has the following beneficial effects: 1. The present application adopts DMSO, a reducing solvent and methyl bromide to prepare trimethylsulfonium bromide, which can not only effectively prepare trimethylsulfonium bromide that meets the requirements, but also avoid the use of dimethyl sulfide and the impact on the environment, thereby reducing the production restrictions of trimethylsulfonium bromide.

[0017] 2. This application helps to reduce side reactions and further improve the yield and content of trimethylsulfonium bromide by strictly controlling the dosage of DMSO, isopropanol and methyl bromide, the circulation rate of methyl bromide and other reaction parameters. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the H NMR spectrum of trimethylsulfonium bromide prepared in Example 1 of the present application.

[0019] Figure 2 This is the carbon NMR spectrum of trimethylsulfonium bromide prepared in Example 1 of the present application. DETAILED DESCRIPTION

[0020] In order to make the above-mentioned purpose, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below.

[0021] The detection of trimethylsulfonium bromide in this application includes component analysis, yield detection and content detection. The detection standards of the above detection items are as follows: 1. Composition analysis: Nuclear magnetic hydrogen spectrum and carbon spectrum analysis were adopted. The hydrogen spectrum parameter was 1H NMR (400 MHz, DMSO) δ2.98 (s, 1H), and the carbon spectrum parameter was 13C NMR (101 MHz, DMSO) δ26.53. The present application takes the trimethylsulfonium bromide obtained in Example 1 as an example for illustration.

[0022] 2. Yield calculation formula: Yield of trimethylsulfonium bromide = (product weight / 157.069) ÷ (DMSO added amount / 78.13).

[0023] 3. Content detection: Determine by titration method. The specific operation method is as follows: Prepare a 0.1 mol / L silver nitrate standard titration solution for later use; Weigh 0.2 g of sample accurately to 0.0001 g, place in a 250 ml beaker, add 100 ml of water to dissolve to obtain a sample solution; titrate the sample solution with a silver nitrate standard solution using a potentiometric titrator, and calculate the mass fraction W of trimethylsulfonium bromide according to the following formula: Where: V——The volume of the standard silver nitrate solution consumed in the titration, in milliliters (ml); c——The actual concentration of the silver nitrate standard titration solution, in moles per liter (mol / L); m——the value of the mass of the sample, in grams (g); M is the numerical value of the molar mass of trimethylsulfide bromide, in grams per mole (M = 157.07 g / mol).

[0024] DMSO (dimethyl sulfoxide), isopropanol and methyl bromide used in the present application are all purchased from commercial products. The present application is further described in detail below in conjunction with the accompanying drawings and examples. Example

[0025] Example 1 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed with 50g of isopropanol twice. The number of rinses can be adjusted according to the actual content change, preferably 1-5 times. The mixture was then dried under reduced pressure to obtain 182.00g of trimethylsulfonium bromide. The yield was about 92.70%. The chemical composition and content were determined. The nuclear magnetic hydrogen spectrum was shown in Figure 1 , see the NMR carbon spectrum Figure 2 , the content is about 99.5%.

[0026] Example 2 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 30°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 300h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 15°C and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 137.05g of trimethylsulfonium bromide. The yield was about 69.80% and the content was about 98.1%.

[0027] Example 3 In a 500mL four-necked reaction flask, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 80°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 30h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 20°C and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 139.32g of trimethylsulfonium bromide. The yield was about 70.96% and the content was about 97.4%.

[0028] Example 4 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 60°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 75h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 178.3g of trimethylsulfonium bromide. The yield was about 90.81% and the content was about 99.2%.

[0029] Example 5 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 65°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 68h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 172.25g of trimethylsulfonium bromide. The yield was about 87.73% and the content was about 98.7%.

[0030] Example 6 In a 500mL four-necked reaction flask, 97.66g (about 1.25mol) of DMSO and 189.92g (about 3.27mol) of acetone were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The temperature was lowered to 18°C ​​and filtered. The mixture was rinsed twice with 50g of acetone and dried under reduced pressure to obtain 170.6g of trimethylsulfonium bromide. The yield was about 86.89% and the content was about 99.6%.

[0031] Example 7 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 225.20g (about 3.88mol) of acetone were added and stirred, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 171.11g of trimethylsulfonium bromide. The yield was about 87.15% and the content was about 99.5%.

[0032] Example 8 In a 500mL four-necked reaction flask, 97.66g (about 1.25mol) of DMSO, 120.12g (about 2.0mol) of isopropanol and 73.76g (about 1.27mol) of acetone were added and stirred, and the mixture was heated to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed with 50g of acetone twice and dried under reduced pressure to obtain 179.6g of trimethylsulfonium bromide. The yield was about 91.47% and the content was about 99.3%.

[0033] Example 9 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 150.52g (about 3.27mol) of formic acid were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for testing. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 135.26g of trimethylsulfonium bromide. The yield was about 68.89% and the content was about 96.6%.

[0034] Example 10 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 207.14g (about 4.50mol) of formic acid were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for testing. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 152.73g of trimethylsulfonium bromide. The yield was about 77.79% and the content was about 97.8%.

[0035] Embodiment 11 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 75.08g (about 1.25mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 125.42g of trimethylsulfonium bromide. The yield was about 63.88% and the content was about 96.1%.

[0036] Example 12 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 750.75g (about 12.5mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for testing. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 182.30g of trimethylsulfonium bromide. The yield was about 92.85% and the content was about 98.3%.

[0037] Embodiment 13 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 1501.50g (about 25mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 118.69g (about 1.25mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed twice with 50g of isopropanol and dried under reduced pressure to obtain 188.22g of trimethylsulfonium bromide. The yield was about 94.34% and the content was about 95.8%.

[0038] Embodiment 14 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 106.82g (about 1.125mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed with 50g of acetone twice and dried under reduced pressure to obtain 176.62g of trimethylsulfonium bromide. The yield was about 89.96% and the content was about 98.2%.

[0039] Embodiment 15 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 154.29g (about 1.625mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed with 50g of acetone twice and dried under reduced pressure to obtain 178.70g of trimethylsulfonium bromide. The yield was about 91.02% and the content was about 99.2%.

[0040] Example 16 In a 500mL reaction bottle, 97.66g (about 1.25mol) of DMSO and 196.40g (about 3.27mol) of isopropanol were added, stirred and mixed, and the temperature was raised to 62°C. The mixture was kept warm and 237.38g (about 2.5mol) of methyl bromide was introduced to react for 70h. Samples were taken for detection. The residual DMSO content was ≤0.5%. The mixture was cooled to 18°C ​​and filtered. The mixture was rinsed with 50g of acetone twice and dried under reduced pressure to obtain 177.12g of trimethylsulfonium bromide. The yield was about 90.21% and the content was about 98.7%.

[0041] The test results of Examples 1 to 16 are summarized in Table 1 below.

[0042] Table 1 Performance test table of Examples 1-16 In summary, the trimethylsulfonium bromide prepared by DMSO, isopropanol or acetone and methyl bromide in this application can have a yield of 63.88% or more and a content of 95.8% or more. On the premise of eliminating dimethyl sulfide to reduce the impact on the environment, it has a relatively high yield and content and has a high application prospect.

[0043] Further analyzing the results of the above examples, only the reaction temperature was adjusted in Examples 1 to 5, and the yield and content of trimethylsulfonium bromide obtained in Examples 1, 4 and 5 were significantly higher than those in Examples 2 and 3. Therefore, the present application further prefers 60-65°C at a reaction temperature of 30-80°C.

[0044] Examples 6 to 10 adjust the reducing solvent based on the method of Example 1. Combined with the test results, it can be obtained that the reducing solvent in the present application can be one or more of alcohol solvents and aldehyde-ketone solvents with reducing properties, and one or more of isopropanol and acetone are further preferred.

[0045] In Examples 11 to 13, the amount of isopropanol is adjusted based on the method of Example 1. Combined with the test results, it can be obtained that the molar ratio of DMSO to the reducing solvent in the present application can be adjusted within the range of 1:1-20. Combined with the test results of Examples 6-10, the molar ratio of DMSO to the reducing solvent is further preferably 1:1-10.

[0046] Examples 14 to 16 adjust the amount of methyl bromide based on the method of Example 1. Combined with the test results, it can be obtained that the molar ratio of DMSO to methyl bromide in the present application can be adjusted within the range of 1:0.9-2, and more preferably 1:1-1.3.

[0047] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A method for preparing trimethylsulfonium bromide by synthesizing trimethylsulfonium bromide from DMSO, characterized in that: The steps include: mixing DMSO and a reducing solvent, heating to 30-80°C, keeping the temperature and introducing methyl bromide to react, and waiting for the residual DMSO to be ≤ 0.5%, cool and filter, then wash and dry to obtain trimethylsulfonium bromide.

2. The preparation method according to claim 1, characterized in that: After the temperature is raised to 60-65° C., the temperature is maintained and methyl bromide is introduced for reaction.

3. The preparation method according to claim 1, characterized in that: The reducing solvent is one or more of an alcohol solvent and an aldehyde-ketone solvent having reducing properties.

4. The preparation method according to claim 3, characterized in that: The reducing solvent is selected from one or more of isopropanol and acetone.

5. The preparation method according to claim 1, characterized in that: The molar ratio of the DMSO to the reducing solvent is 1:1-20.

6. The preparation method according to claim 1, characterized in that: The molar ratio of DMSO to methyl bromide is 1:0.9-2.

7. The preparation method according to claim 1, characterized in that: In the cleaning step, a reducing solvent is used for elution 1-5 times.

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