A method for preparing 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone using TS-1 molecular sieve
By using the oxidation and desulfurization method of TS-1 molecular sieve and hydrogen peroxide system in the preparation of 4-methylsulfone acetophenone and 4-methylsulfone acetophenone, the problems of low product yield and high production cost in the prior art are solved, and an efficient and environmentally friendly preparation process is achieved.
Patent Information
- Application Number
- CN202411063782.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-05
- Publication Date
- 2025-04-29
- Estimated Expiration
- 2044-08-05
AI Technical Summary
The existing preparation methods of 4-methylsulfone acetophenone and 4-methylsulfone acetophenone have problems such as low product yield, harsh reaction conditions, high production costs and complex post-treatment.
4-methylsulfone acetophenone and/or 4-methylsulfone acetophenone are prepared by oxidative desulfurization by TS-1 molecular sieve and hydrogen peroxide system, and the catalytic action of TS-1 molecular sieve is used to achieve efficient oxidative desulfurization reaction under mild conditions.
The yields of 4-methylsulfone acetophenone and 4-methylsulfone acetophenone are improved, the post-treatment process is simplified, the production cost is reduced, and the process is more environmentally friendly and safe.
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Figure CN119100958B_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the field of intermediate synthesis, and in particular to a method for synthesizing important pharmaceutical intermediates 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone, and belongs to the field of fine chemical compound preparation. Background Art
[0002]
[0003] 4-Methylsulfonylacetophenone is also known as 4-(methylsulfonyl)acetophenone or p-(methylsulfonyl)acetophenone, 4-methylsulfoxyacetophenone is also known as p-methylsulfinylacetophenone, 1-(4-methylsulfinylphenyl)ethanone, which are widely used in the synthesis of antibiotics, antibacterial drugs and anticancer drugs, such as lidocaine, amphetamines and non-steroidal anti-inflammatory drugs (NSAIDs).
[0004] The following are some commonly used methods for preparing 4-methylsulfonylacetophenone / 4-methylsulfoxideacetophenone. For example, in a diethylene glycol dibutyl ether system, 4-methylsulfonylacetophenone is prepared using acetylanisole as a reactant and oxygen as an oxidant (Chinese Chemical Letters, 2020). Since the oxidation reaction product selectivity of oxygen as an oxidant is low, and oxygen as an oxidant is potentially dangerous at high concentrations, which may cause explosion or fire risks, strict safety measures need to be taken during the operation. In addition, diethylene glycol dibutyl ether itself may have certain toxicity and environmental pollution risks, so the method faces problems such as reaction selectivity, reaction rate, environmental and safety issues. In addition, in a methanol and acetic acid system, magnesium monoperoxyphthalate is used as an oxidant to prepare 4-methylsulfonylacetophenone / 4-methylsulfoxideacetophenone ( ChemInform , 2010, 33(4)). Magnesium monoperoxyphthalate, as a strong oxidant, has the problems of instability and easy decomposition. Especially in high temperature or strong acid environment, acetic acid, as an acidic solvent, may react with magnesium monoperoxide phthalate, resulting in low selectivity of reaction products. In recent years, Su Yuan et al. used sodium tungstate dihydrate and sodium perborate tetrahydrate as catalysts in an acetone system to prepare 4-methylsulfonylacetophenone / 4-methylsulfoxide acetophenone. However, acetone as a solvent has certain volatility and flammability, which increases the operational risk and safety hazard in the reaction process. In addition, sodium perborate as an oxidant will generate boron-containing waste liquid in the reaction process, which increases the burden of environmental governance and reduces economic benefits. In addition, Saeedi et al. used acetyl thioanisole as a reactant and hydrogen peroxide as an oxidant in an acetic acid aqueous solution system to prepare 4-methylsulfonylacetophenone / 4-methylsulfoxide acetophenone ( Applied Organometallic Chemistry, 2019,33(3).). The reaction needs to be carried out under specific acidic conditions, the selectivity of the reaction products is low, and the participation of acetic acid in the reaction may produce by-products such as peracetic acid, which increases the difficulty and cost of subsequent treatment. Summary of the invention
[0005] The purpose of the present invention is to solve at least one of the technical problems existing in the prior art, and to provide a green and efficient synthesis method of 4-methylsulfonylacetophenone / 4-methylsulfoxideacetophenone. In view of the shortcomings of low product yield, harsh reaction conditions, high production cost and complicated post-processing in the existing preparation process of 4-methylsulfonylacetophenone / 4-methylsulfoxideacetophenone, the present invention develops a TS-1 molecular sieve / hydrogen peroxide system to selectively produce high-purity 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone by oxidative desulfurization. The preparation process is green and environmentally friendly, the post-processing is simple, the reaction is more stable, and the efficiency is high. Provided.
[0006] The technical solution of the present invention is as follows:
[0007] A method for preparing 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone by using TS-1 molecular sieve comprises fully mixing 4-methylthioacetophenone, a hydrogen peroxide solution and the TS-1 molecular sieve with an organic solvent, preheating the mixture to a reaction temperature, and synthesizing 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone in one step.
[0008] Preferably, the molar ratio of the 4-methylthioacetophenone to the hydrogen peroxide solution is 1:0.5-1:5, and the added amount of the TS-1 molecular sieve is 0.5-20 wt % of the total mass of the 4-methylthioacetophenone and the hydrogen peroxide solution.
[0009] Furthermore, the molar ratio of the 4-methylthioacetophenone to the hydrogen peroxide solution is 1:1-1:4, and the added amount of the TS-1 molecular sieve is 0.5-15 wt% of the total mass of the 4-methylthioacetophenone and the hydrogen peroxide solution.
[0010] Furthermore, the molar ratio of the 4-methylthioacetophenone to the hydrogen peroxide solution is 1:2-1:3, and the added amount of the TS-1 molecular sieve is 1-10 wt% of the total mass of the 4-methylthioacetophenone and the hydrogen peroxide solution.
[0011] Preferably, the size of the TS-1 molecular sieve is 100 nm~1.5 µm, and the SiO2 / TiO2 is 25~200.
[0012] Furthermore, the size of the TS-1 molecular sieve is 100 nm~1 µm, and the SiO2 / TiO2 is 25~150.
[0013] Furthermore, the size of the TS-1 molecular sieve is 100 nm~0.5 µm, and the SiO2 / TiO2 is 25~100.
[0014] Preferably, the preparation method of the TS-1 molecular sieve comprises:
[0015] Under stirring, tetraethyl orthosilicate is added to water and tetrapropylammonium hydroxide aqueous solution, and aged at room temperature of 20-30° C. for 0.5-1.5 hours; then, a mixture of tetrabutyl titanate and hydrogen peroxide aqueous solution is dripped into the aged solution, and then aged for 0.5-1.5 hours to form a final precursor solution;
[0016] The final precursor solution is transferred to the liner, and then the liner is placed in a high-pressure reactor and crystallized at 140~160℃ for 20~28 hours; after the crystallization is completed, the obtained mother liquor is washed with deionized water, boiled, cooled and then centrifuged to neutrality; dried overnight at 80~120℃, and finally the obtained powder is placed in a muffle furnace at 500~600℃ and a heating rate of 2.5~3.0℃ / min and calcined for 8~12 hours to obtain TS-1 molecular sieve powder; its sol molar ratio is 0.5~1.5 SiO2: 0.03~0.04 TiO2: 0.3~0.4 H2O2: 0.2~0.4 TPAOH: 25~35H2O.
[0017] Preferably, the volume ratio of the total volume of the 4-methylthioacetophenone and the hydrogen peroxide solution to the organic solvent is 1:5-1:40, and the organic solvent is at least one of methanol, ethanol, acetonitrile, chloroform and dichlorotoluene.
[0018] Furthermore, the volume ratio of the total volume of the 4-methylthioacetophenone and the hydrogen peroxide solution to the organic solvent is 1:10 to 1:40.
[0019] Furthermore, the volume ratio of the total volume of the 4-methylthioacetophenone and the hydrogen peroxide solution to the volume of the organic solvent is 1:10-1:30.
[0020] Preferably, the reaction temperature is 0-100 °C, and the reaction time is 5 minutes to 6 hours.
[0021] Further, at 10-90 °C, the reaction time is 10 minutes to 2 hours
[0022] Furthermore, the reaction temperature is 20-80 °C, and the reaction time is 20 minutes-1.5 hours.
[0023] Preferably, the method specifically comprises the following steps:
[0024] (1) After 4-methylthioacetophenone, hydrogen peroxide solution and TS-1 molecular sieve are fully mixed with an organic solvent, the mixture is added into a reaction vessel, stirred and mixed, and preheated to the reaction temperature;
[0025] (2) intermittently taking out the reaction liquid in step (1), separating the reaction mixture and the TS-1 molecular sieve, analyzing the components of the separated mixture by gas chromatography, calculating the conversion rate of the product 4-methylsulfonylacetophenone and / or 4-methylsulfoxyacetophenone, and determining the time when the oxidative desulfurization reaction is complete;
[0026] (3) According to the reaction endpoint determined in step (2), the reaction product after the reaction is completed and the TS-1 molecular sieve are separated, the acetonitrile solvent and water in the reaction product are removed by distillation or reduced pressure distillation, and the final product 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone is collected, and the yield is calculated.
[0027] Preferably, in step (3), the temperature and pressure of the distillation or reduced pressure distillation are 40-130° C. and 25-760 mmHg, respectively.
[0028] Furthermore, in step (3), the temperature and pressure of the distillation or reduced pressure distillation are 60-130°C and 50-760 mm Hg, respectively.
[0029] Furthermore, in step (3), the temperature and pressure of the distillation or reduced pressure distillation are 70-120°C and 100-760 mm Hg, respectively.
[0030] The present invention has at least one of the following beneficial effects:
[0031] As an efficient, selective and environmentally friendly catalyst, TS-1 molecular sieve can react with hydrogen peroxide to generate active oxygen species with strong oxidizing ability, and can achieve efficient catalytic oxidation of specific functional groups under mild conditions, such as epoxidation of olefins, oxidation of alcohols, oxidation of amines and oxidative desulfurization. The TS-1 molecular sieve / hydrogen peroxide system is not only conducive to the preparation of high-purity and high-yield target products, but also the other reaction product is only water, the product post-processing is simple, and it is environmentally friendly.
[0032] The method of the present invention adopts TS-1 molecular sieve and hydrogen peroxide system to prepare 4-methylsulfonyl acetophenone and / or 4-methylsulfonyl acetophenone by oxidative desulfurization, which solves the defects of harsh reaction conditions and high production cost of the traditional preparation method, more by-products, low yield, complex purification process and waste residue discharge pollution, and greatly improves the yield of 4-methylsulfonyl acetophenone and / or 4-methylsulfoxide acetophenone and simplifies the post-treatment process. It is a truly green production process, is very likely to replace the traditional production process of 4-methylsulfonyl acetophenone and 4-methylsulfoxide acetophenone, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0033] Figure 1 Schematic diagram of the device for preparing 4-methylsulfonylacetophenone using TS-1 molecular sieve, wherein a: condenser; b: round-bottom flask; c: constant temperature water bath;
[0034] Figure 2 XRD pattern and SEM photo of TS-1 molecular sieve, where (a) XRD pattern, (b) SEM photo;
[0035] Figure 3 The 4-methylsulfonyl acetophenone sample separated after the reaction is complete in Example 1 1 H NMR spectrum;
[0036] Figure 4 is the gas chromatogram of the reaction product in Example 1;
[0037] Figure 5 is the gas chromatogram of the reaction product in Example 2;
[0038] Figure 6 is the gas chromatogram of the reaction product in Example 3;
[0039] Figure 7 is the gas chromatogram of the reaction product in Example 4;
[0040] Figure 8 is the gas chromatogram of the reaction product in Example 5;
[0041] Fig. 9 is the gas chromatogram of the reaction product in Example 6;
[0042] Fig.10 is the gas chromatogram of the reaction product in Example 7;
[0043] Fig.11 is the gas chromatogram of the reaction product in Example 8;
[0044] Fig.12 is the gas chromatogram of the reaction product in Example 9;
[0045] Fig.13 is the gas chromatogram of the reaction product in Example 10;
[0046] Fig.14 is the gas chromatogram of the reaction product in Example 11;
[0047] Fig.15 is the gas chromatogram of the reaction product in Example 12;
[0048] Fig.16is the gas chromatogram of the reaction product in Example 13; DETAILED DESCRIPTION
[0049] In order to make the technical means, features and functions achieved by the present invention easier to understand, the technical solutions in the embodiments of the present invention are clearly and completely described below in combination with the specific implementation methods and the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.
[0050] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative work shall fall within the scope of protection of the present invention.
[0051] The present invention is further described in detail below with specific examples, but the present invention is not limited to the following specific examples.
[0052] Example 1
[0053] like Figure 1 As shown, a proper amount of 4-methylthioacetophenone, hydrogen peroxide solution and TS-1 molecular sieve are fully mixed with an organic solvent in a certain proportion and added to a three-necked flask (b), stirred, mixed and preheated to the reaction temperature. The reaction liquid is intermittently taken out, the reaction mixture and TS-1 molecular sieve are separated by a high-speed centrifuge, the components of the separated mixed liquid are analyzed by gas chromatography, the conversion rate of the product 4-methylsulfonylacetophenone / 4-methylsulfoxideacetophenone of the reactant 4-methylthioacetophenone is calculated, and the time for the oxidative desulfurization reaction to be completed is determined; after the reaction, the reaction product and TS-1 molecular sieve are separated by a high-speed centrifuge, the acetonitrile solvent and water in the reaction product are removed by atmospheric distillation, the final product 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone is collected, and the yield is calculated.
[0054] The TS-1 molecular sieve used in this embodiment is prepared by hydrothermal synthesis, and the preparation method is as follows:
[0055] Under stirring, tetraethyl orthosilicate was added to water and tetrapropylammonium hydroxide aqueous solution and aged at room temperature for 1 hour at 25°C. Subsequently, a mixture of tetrabutyl titanate and hydrogen peroxide aqueous solution was dripped into the solution aged for 1 hour and aged for another 1 hour to form the final precursor solution. The final precursor solution was transferred to a 150ml para-polyphenylene (PPL) liner, which was then placed in an autoclave and crystallized at 150°C for 24 hours. After crystallization, the resulting mother liquor was washed with deionized water, boiled, cooled, and then centrifuged to neutrality. After drying at 100°C overnight, the resulting powder was finally calcined in a muffle furnace at 550°C with a heating rate of 2.8°C / min for 10 hours to obtain TS-1 molecular sieve powder with a sol molar ratio of 1.0 SiO2: 0.035 TiO2: 0.35 H2O2: 0.25 TPAOH: 30H2O.
[0056] Figure 2 The XRD pattern of the catalyst TS-1 molecular sieve used in the present invention is ( Figure 2 a) and SEM images ( Figure 2 b). XRD spectrum shows that TS-1 molecular sieve has a typical MFI topological structure (2θ = 7.9°, 8.8°, 23.1°, 23.9° and 24.4°), and electron microscopy shows that the size of TS-1 molecular sieve is ca. 300nm.
[0057] In this example, the initial molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution is 1:2, the organic solvent is acetonitrile, the volume ratio of the reaction raw materials (4-methylthioacetophenone and hydrogen peroxide) to the solvent is 1:20, the reaction temperature is 80 ° C, and the ratio of TS-1 molecular sieve to the reactant (4-methylthioacetophenone and hydrogen peroxide) is 5 wt%. The size of the TS-1 molecular sieve and SiO2 / TiO2 are ca.300 nm and 45, respectively, the reaction time is 1 hour, and the temperature of atmospheric distillation is 120 ° C to separate the product.
[0058] The conversion rate of 4-methylthioacetophenone was 100%, and the selectivity of 4-methylsulfonylacetophenone was 100%.
[0059] Figure 3 The 4-methylsulfonyl acetophenone sample separated after the reaction is complete in Example 1 1 H NMR spectrum. Figure 3 It can be seen that the sample synthesized in this example is pure 4-methylsulfonylacetophenone.
[0060] Figure 4 is the gas chromatogram of the reaction product in Example 1, Figure 4It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile, and the retention time 9.8 min is attributed to the response of the product 4-methylsulfonylacetophenone, indicating that the final product of this example is 4-methylsulfonylacetophenone.
[0061] Example 2
[0062] Provided is a method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone by using TS-1 molecular sieve, which is different from Example 1 in that: the molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution in the raw material liquid is 1:1.2, and after reacting for 10 minutes, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 19%, and the selectivity of 4-methylsulfonylacetophenone is 81%.
[0063] Figure 5 The gas chromatogram and analysis results of the reaction products in Example 2 are as follows: Figure 5 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile; the retention time 9.4 min is attributed to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.7 min is attributed to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0064] Example 3
[0065] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the reaction temperature is 60° C. After 20 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 73%, and the selectivity of 4-methylsulfonylacetophenone is 21%.
[0066] Figure 6 The gas chromatogram and analysis results of the reaction products in Example 3 are as follows: Figure 6 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile; the retention time 9.4 min is attributed to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.7 min is attributed to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0067] Example 4
[0068] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the reaction temperature is 40° C. After 20 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 87%, and the selectivity of 4-methylsulfonylacetophenone is 13%.
[0069] Figure 7 The gas chromatogram and analysis results of the reaction products in Example 4 are as follows: Figure 7 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile; the retention time 9.3 min is attributed to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.5 min is attributed to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0070] Example 5
[0071] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the reaction temperature is 25° C. After reacting for 1 hour, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 10%, and the selectivity of 4-methylsulfonylacetophenone is 90%.
[0072] Figure 8 The gas chromatogram and analysis results of the reaction products in Example 5 are as follows: Figure 8 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile; the retention time 9.4 min is attributed to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.6 min is attributed to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0073] Example 6
[0074] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the reaction temperature is 0° C. After reacting for 3 hours, the conversion rate of 4-methylthioacetophenone is 23%, the selectivity of 4-methylsulfoxideacetophenone is 79%, and the selectivity of 4-methylsulfonylacetophenone is 21%.
[0075] Fig. 9 The gas chromatogram and analysis results of the reaction products in Example 6 are as follows: Fig. 9 It can be seen that the retention time 2.0min belongs to the response of the solvent acetonitrile; the retention time 7.2min belongs to the response of the reactant 4-thioacetophenone; the retention time 9.4min belongs to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.6min belongs to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0076] Example 7
[0077] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the reaction temperature is 70° C. After reacting for 1 hour, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 6%, and the selectivity of 4-methylsulfonylacetophenone is 94%.
[0078] Fig.10 The gas chromatogram and analysis results of the reaction products in Example 7 are as follows: Fig.10 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile; the retention time 9.3 min is attributed to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.9 min is attributed to the response of the product 4-methylsulfonylacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0079] Example 8
[0080] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution in the raw material solution is 1:3, and the reaction temperature is 70°C. After reacting for 1 hour, the conversion rate of 4-methylthioacetophenone is 100%, and the selectivity of 4-methylsulfonylacetophenone is 100%.
[0081] Fig.11 The gas chromatogram and analysis results of the reaction products in Example 8 are as follows: Fig.11 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile, and the retention time 9.8 min is attributed to the response of the product 4-methylsulfonylacetophenone, indicating that the final product of this example is 4-methylsulfonylacetophenone.
[0082] Example 9
[0083] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution in the raw material liquid is 1:1.2, and the reaction temperature is 70°C. After 20 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 77%, and the selectivity of 4-methylsulfonylacetophenone is 23%.
[0084] Fig.12 The gas chromatogram and analysis results of the reaction products in Example 9 are as follows: Fig.12It can be seen that the retention time 1.9min belongs to the response of the solvent acetonitrile; the retention time 9.3min belongs to the response of the product 4-methylsulfoxyacetophenone; the retention time 9.6min belongs to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0085] Example 10
[0086] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution in the raw material solution is 1:1, and the reaction temperature is 70°C. After reacting for 1 hour, the conversion rate of 4-methylthioacetophenone is 77%, the selectivity of 4-methylsulfoxideacetophenone is 82%, and the selectivity of 4-methylsulfonylacetophenone is 18%.
[0087] Fig.13 The gas chromatogram and analysis results of the reaction products in Example 10 are as follows: Fig.13 It can be seen that the retention time 1.9 min belongs to the response of the solvent acetonitrile; the retention time 7.2 min belongs to the response of the reactant 4-thioacetophenone; the retention time 9.5 min belongs to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.7 min belongs to the response of the product 4-methylsulfonylacetophenone. This shows that the final product of this example is 4-methylsulfonylacetophenone.
[0088] Embodiment 11
[0089] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution in the raw material liquid is 1:0.5, and the reaction temperature is 70° C. After 30 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 37%, the selectivity of 4-methylsulfoxideacetophenone is 87%, and the selectivity of 4-methylsulfonylacetophenone is 13%.
[0090] Fig.14 The gas chromatogram and analysis results of the reaction products in Example 11 are as follows: Fig.14 It can be seen that the retention time 1.9 min belongs to the response of the solvent acetonitrile; the retention time 7.3 min belongs to the response of the reactant 4-thioacetophenone; the retention time 9.4 min belongs to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.6 min belongs to the response of the product 4-methylsulfonylacetophenone. This shows that the final product of this example is 4-methylsulfonylacetophenone.
[0091] Example 12
[0092] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that: the ratio of TS-1 molecular sieve to reactants (4-methylthioacetophenone and hydrogen peroxide) is 3wt%. After 20 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 45%, and the selectivity of 4-methylsulfonylacetophenone is 55%.
[0093] Fig.15 The gas chromatogram and analysis results of the reaction products in Example 12 are as follows: Fig.15 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile, and the retention time 9.8 min is attributed to the response of the product 4-methylsulfonylacetophenone, indicating that the final product of this example is 4-methylsulfonylacetophenone.
[0094] Embodiment 13
[0095] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the ratio of TS-1 molecular sieve to reactants (4-methylthioacetophenone and hydrogen peroxide) is 1wt%. After 40 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 50%, and the selectivity of 4-methylsulfonylacetophenone is 50%.
[0096] Fig.16 The gas chromatogram and analysis results of the reaction products in Example 13 are as follows: Fig.16 It can be seen that the retention time 1.9 min is attributed to the response of the solvent acetonitrile; the retention time 9.4 min is attributed to the response of the product 4-methylsulfoxyacetophenone; and the retention time 9.8 min is attributed to the response of the product 4-methylsulfoxyacetophenone. This shows that the final products of this example are 4-methylsulfoxyacetophenone and 4-methylsulfoxyacetophenone.
[0097] Embodiment 14
[0098] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the organic solvent is methanol. After 40 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 65%, the selectivity of 4-methylsulfoxideacetophenone is 32%, and the selectivity of 4-methylsulfonylacetophenone is 68%.
[0099] Embodiment 15
[0100] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that the size of the TS-1 molecular sieve is 2 μm. After 2 hours of reaction, the conversion rate of 4-methylthioacetophenone is 100%, the selectivity of 4-methylsulfoxideacetophenone is 22%, and the selectivity of 4-methylsulfonylacetophenone is 78%.
[0101] Comparative Example 1
[0102] Provided is a method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone, which is different from Example 1 in that the molar ratio of 4-methylthioacetophenone to the hydrogen peroxide solution in the raw material solution is 1:0.5, no TS-1 molecular sieve is added as a catalyst, the reaction temperature is 80°C, and after 20 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 30%, the selectivity of 4-methylsulfonylacetophenone is 0, and the selectivity of 4-methylsulfoxideacetophenone is 100%
[0103] Comparative Example 2
[0104] A method for preparing 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone using TS-1 molecular sieve is provided, which is different from Example 1 in that: no oxidant hydrogen peroxide solution is added, and after 20 minutes of reaction, the conversion rate of 4-methylthioacetophenone is 0%. No reaction occurs under this condition.
[0105] The amounts of raw materials added, process parameters and catalytic performance results in Examples 1 to 16 and Comparative Examples 1 to 2 are specifically shown in Table 1.
[0106] Table 1
[0107]
[0108] As can be seen from Table 1, the methods in Examples 1 to 15 of the present invention can all prepare 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone, wherein the final products of Examples 1 and 8 are only 4-methylsulfonylacetophenone, while the final products of other Examples are 4-methylsulfonylacetophenone and 4-methylsulfoxideacetophenone.
[0109] Moreover, the conversion rates of 4-methylthioacetophenone in Examples 1 to 9, Examples 12 to 13 and Example 15 were all 100%, while the conversion rates of 4-methylthioacetophenone in other Examples were lower than 100%, indicating that the molar ratio of 4-methylthioacetophenone to hydrogen peroxide and the type of solvent would affect the conversion rate of 4-methylthioacetophenone.
[0110] Comparing the examples with comparative examples 1 and 2, it can be seen that comparative example 1 does not use TS-1 molecular sieve, and not only can only prepare the product 4-methylsulfoxyacetophenone, but also the conversion rate of 4-methylthioacetophenone is only 30%; comparative example 2 does not add the oxidant hydrogen peroxide solution, resulting in no reaction, and 4-methylsulfoxyacetophenone and / or 4-methylsulfoxyacetophenone cannot be prepared. This shows that TS-1 molecular sieve and oxidant hydrogen peroxide solution are the key conditions for preparing 4-methylsulfoxyacetophenone and / or 4-methylsulfoxyacetophenone in the present invention.
[0111] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.
Claims
1. A method for preparing 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone using TS-1 molecular sieve, characterized in that: The 4-methylthioacetophenone, hydrogen peroxide solution and TS-1 molecular sieve are fully mixed with an organic solvent, and preheated to a reaction temperature to synthesize 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone in one step; The molar ratio of 4-methylthioacetophenone to hydrogen peroxide solution is 1:1 to 1:4; The organic solvent is acetonitrile; The preparation method of the TS-1 molecular sieve comprises: Under stirring, tetraethyl orthosilicate is added to water and tetrapropylammonium hydroxide aqueous solution, and aged at room temperature of 20-30° C. for 0.5-1.5 hours; then, a mixture of tetrabutyl titanate and hydrogen peroxide aqueous solution is dripped into the aged solution, and then aged for 0.5-1.5 hours to form a final precursor solution; The final precursor solution is transferred to the liner, and then the liner is placed in a high-pressure reactor and crystallized at 140~160℃ for 20~28 hours; after the crystallization is completed, the obtained mother liquor is washed with deionized water, boiled, cooled and then centrifuged to neutrality; dried overnight at 80~120℃, and finally the obtained powder is placed in a muffle furnace at 500~600℃ and a heating rate of 2.5~3.0℃ / min and calcined for 8~12 hours to obtain TS-1 molecular sieve powder; its sol molar ratio is 0.5~1.5 SiO2: 0.03~0.04TiO2: 0.3~0.4 H2O2: 0.2~0.4 TPAOH: 25~35H2O.
2. The method according to claim 1, characterized in that: The amount of the TS-1 molecular sieve added is 0.5-20 wt % of the total mass of the 4-methylthioacetophenone and the hydrogen peroxide solution.
3. The method according to claim 1, characterized in that The amount of the TS-1 molecular sieve added is 0.5-15 wt % of the total mass of the 4-methylthioacetophenone and the hydrogen peroxide solution.
4. The method according to claim 1, characterized in that: The molar ratio of the 4-methylthioacetophenone to the hydrogen peroxide solution is 1:2-1:3, and the added amount of the TS-1 molecular sieve is 1-10 wt % of the total mass of the 4-methylthioacetophenone and the hydrogen peroxide solution.
5. The method according to claim 1, characterized in that The size of the TS-1 molecular sieve is 100 nm~1.5 µm.
6. The method according to claim 1, characterized in that The volume ratio of the total volume of the 4-methylthioacetophenone and the hydrogen peroxide solution to the volume of the organic solvent is 1:5-1:
40.
7. The method according to claim 1, characterized in that The reaction temperature is 0~100 ℃, and the reaction time is 5 minutes~6 hours.
8. The method according to claim 1, characterized in that: The method specifically comprises the following steps: (1) After 4-methylthioacetophenone, hydrogen peroxide solution and TS-1 molecular sieve are fully mixed with an organic solvent, the mixture is added into a reaction vessel, stirred and mixed, and preheated to the reaction temperature; (2) intermittently taking out the reaction liquid in step (1), separating the reaction mixture and the TS-1 molecular sieve, analyzing the components of the separated mixture by gas chromatography, calculating the conversion rate of the product 4-methylsulfonylacetophenone and / or 4-methylsulfoxyacetophenone, and determining the time when the oxidative desulfurization reaction is complete; (3) According to the reaction endpoint determined in step (2), the reaction product after the reaction is completed and the TS-1 molecular sieve are separated, the acetonitrile solvent and water in the reaction product are removed by vacuum distillation, and the final product 4-methylsulfonylacetophenone and / or 4-methylsulfoxideacetophenone is collected, and the yield is calculated.
9. The method according to claim 8, characterized in that In step (3), the temperature and pressure of the reduced pressure distillation are 40-130° C. and 25-760 mm Hg, respectively.