A method for synthesizing 2,2,2-triphenylacetophenone

Abstract

The present application relates to the technical field of organic synthesis, in particular to a synthesis method of 2,2,2-triphenylacetophenone, steps comprising: 1) preparing mesoporous SiO2 supported triflic anhydride catalyst, realizing solid-liquid separation and circulation of the catalyst; 2) adding pyridine in a segmented temperature control (0-5℃ initial drop, 15-20℃ subsequent drop) mode, reacting with the supported catalyst and benzopinacol in dichloromethane at 20℃ for 2h to avoid local overheating to generate byproducts; 3) after reaction, the catalyst is recovered by filtration, the mother liquor is washed with water, dried, concentrated to obtain a crude product, and then recrystallized with petroleum ether-ethyl acetate (volume ratio 8:1) double solvent to improve the purity to the pharmaceutical grade; 4) dichloromethane is recovered by a three-stage process of "calcium chloride water removal-normal pressure distillation-molecular sieve dehydration-precision filtration", and the recovery rate is ≥90%; 5) the byproduct pyridinium triflate is converted into pyridine and triflic acid by alkaline hydrolysis-acidification, and is reused in the catalytic system.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically a method for synthesizing 2,2,2-triphenylacetophenone. Background Technology

[0002] 2,2,2-Triphenylacetophenone is mainly used as a pharmaceutical synthesis intermediate, serving as a precursor for various drugs.

[0003] Currently, the synthesis of 2,2,2-triphenylacetophenone mainly relies on the traditional iodine-catalyzed benzinolide rearrangement process. This process, using iodine as a catalyst and glacial acetic acid as a solvent, can achieve a yield of 95-96%. However, the strong corrosiveness, toxicity (and environmental unfriendliness) and volatility of iodine necessitate the use of special alloy materials (such as Hastelloy) in the reactor, increasing equipment maintenance costs by more than 300% compared to conventional glass or stainless steel equipment. The large-scale use of glacial acetic acid generates iodine-containing wastewater (COD values ​​exceeding 5000 mg / L), requiring multiple treatment steps including neutralization, extraction, and adsorption, with wastewater treatment costs accounting for 15%-20% of the total cost. Furthermore, product purification depends on a mixed solvent of benzene and petroleum ether. The toxicity of benzene (Occupational Exposure Limit OEL of 0.5 ppm) necessitates specialized protective equipment for operators, and the volatility of benzene can cause air quality issues in the workshop, failing to meet the safety and environmental protection requirements of modern green chemistry. Summary of the Invention

[0004] To address the problems in the prior art, the present invention provides a method for synthesizing 2,2,2-triphenylacetophenone.

[0005] The technical solution adopted by this invention to solve its technical problem is: a method for synthesizing 2,2,2-triphenylacetophenone, comprising the following steps:

[0006] (1) Preparation of supported trifluoromethanesulfonic anhydride catalyst: Mesoporous SiO2 (pore size 2-5nm, specific surface area 800m² / g) dried under vacuum at 120℃ for 4h was dispersed in anhydrous dichloromethane. Trifluoromethanesulfonic anhydride was added dropwise at a mass ratio of mesoporous SiO2 to trifluoromethanesulfonic anhydride of 2:1. After stirring for 2h, excess dichloromethane was removed by vacuum distillation to obtain a supported trifluoromethanesulfonic anhydride catalyst with a loading of 40wt%.

[0007] (2) Synthesis reaction: Add the supported catalyst (based on the molar ratio of pure trifluoromethanesulfonic anhydride to benzinolide 0.2:1) and anhydrous dichloromethane to a three-necked flask. First, add 1 / 3 pyridine (the molar ratio of pyridine to pure trifluoromethanesulfonic anhydride is 1.5:1) at a rate of 1 drop / second at 0-5℃. After 10 minutes, raise the temperature to 15-20℃ and add the remaining pyridine (controlling the temperature T < 20℃). Then add benzinolide and add dichloromethane to form a homogeneous phase. Keep the reaction at 20℃ for 2 hours until the starting material is completely eliminated.

[0008] (3) Post-processing and purification: The catalyst was separated by vacuum filtration (dried at 120℃ and then recycled), the mother liquor was washed with water to discard the aqueous phase, the organic phase was dried and concentrated to obtain the crude product, the crude product was recrystallized with a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 8:1 (dissolved by reflux at 80℃, cooled at room temperature, and refrigerated at 0-5℃ for 2h), and dried to obtain the pure product;

[0009] (4) Solvent recovery: The dichloromethane fraction is dehydrated by calcium chloride, distilled at atmospheric pressure at 39-41℃, dehydrated by 3A molecular sieve, and filtered by 0.22μm filter membrane to obtain anhydrous dichloromethane with a purity ≥99.5% and a water content ≤0.05% for recycling;

[0010] (5) Byproduct conversion: The aqueous phase containing pyridinium trifluoromethanesulfonate generated by water washing is refluxed at 80°C for 3 hours with 20% sodium hydroxide aqueous solution to completely dissociate pyridinium trifluoromethanesulfonate. The pyridine-water azeotrope is obtained by distillation at 94-95°C and dichloromethane is added. After standing, the upper organic phase containing pyridine is taken and the dichloromethane is recovered at 40°C to obtain purified pyridine. The aqueous phase after pyridine distillation is acidified to pH 1-2 with 98% concentrated sulfuric acid to prepare trifluoromethanesulfonic acid (purity ≥97.2%) for reuse.

[0011] Specifically, in step (1), the activation conditions for mesoporous SiO2 are vacuum drying at 120°C for 4 hours. The loading of the supported catalyst is determined by thermogravimetric analysis and it is sealed and stored in a desiccator.

[0012] Specifically, the reaction process in step (2) is monitored by thin-layer chromatography, with petroleum ether-ethyl acetate as the developing solvent at a volume ratio of 5:1. The reaction is stopped when the spot of the raw material benzinolide (Rf=0.3) completely disappears.

[0013] Specifically, in step (3), the organic phase is dried at room temperature with anhydrous sodium sulfate for 2 hours (stirring for 3-5 minutes every 30 minutes). The purity of the crude product is ≥95% by HPLC (to confirm whether the basic purity meets the requirements for subsequent recrystallization). The melting point of the pure product is 182-183℃ (the final product after recrystallization and purification, whose crystal purity is verified by the melting point).

[0014] Specifically, in step (4), the 3A molecular sieve needs to be activated at 120°C for 4 hours in advance. After the dichloromethane is recovered, the purity is detected by gas chromatography and the water content is detected by Karl Fischer method.

[0015] Specifically, in step (5), the molar ratio of sodium hydroxide aqueous solution to pyridinium trifluoromethanesulfonate is 1.8:1, the pyridine recovery rate is ≥74%, and the trifluoromethanesulfonate recovery rate is ≥70%.

[0016] Specifically, in step (3), after the supported catalyst is recycled 5 times, the product yield can still be maintained at ≥90% and the purity at ≥99.5% when the loading is reduced to 27wt%.

[0017] Specifically, in step (4), after dichloromethane is recycled 5 times, the purity is ≥99.4% and the water content is ≤0.10%, which has no significant impact on the product yield and purity.

[0018] Specifically, in step (3), the petroleum ether used for recrystallization has a boiling range of 90-100℃, the ethyl acetate is of analytical grade, and the mass ratio of the mixed solvent to the crude product is 4.5:1.

[0019] Specifically, the yield of the final 2,2,2-triphenylacetophenone product was ≥92%, and the purity determined by HPLC was ≥99.8%, which meets the pharmaceutical industry intermediate standards.

[0020] The beneficial effects of this invention are:

[0021] (1) The method for synthesizing 2,2,2-triphenylacetophenone described in this invention successfully solves the core problem of catalyst separation and recovery in traditional homogeneous catalytic systems by supporting trifluoromethanesulfonic anhydride on a mesoporous SiO2 support. The supported catalyst can achieve solid-liquid separation through simple filtration, and after treatment, it can be recycled for use in the reaction. This not only reduces catalyst consumption and lowers catalyst-related costs, but also avoids waste generated due to the inability to recover the catalyst, which aligns with the development concept of green chemistry and provides an effective path for the sustainable utilization of the catalytic system.

[0022] (2) The method for synthesizing 2,2,2-triphenylacetophenone described in this invention addresses the problems of low efficiency and insufficient purity in traditional solvent recovery by designing a multi-stage solvent recovery process. The recovered solvent can be stably recycled for use in the reaction process without the need for large-scale replenishment of new solvent. This reduces solvent waste, lowers the environmental risks caused by direct solvent discharge, avoids the cost of frequent solvent procurement, and ensures the stability of the reaction system during recycling, further improving the economic efficiency and environmental friendliness of the process.

[0023] (3) The method for synthesizing 2,2,2-triphenylacetophenone described in this invention abandons the traditional model of treating by-products as hazardous waste. Through a specific alkaline hydrolysis-acidification process, the by-products are converted into raw materials that can be reused in the catalytic system. This design realizes the resource recycling of by-products, which not only saves the disposal cost of hazardous waste and avoids the potential pollution of the environment by by-products, but also saves the cost of raw material procurement, improves the resource utilization efficiency of the entire production process, and forms a closed loop of resource recycling.

[0024] (4) The method for synthesizing 2,2,2-triphenylacetophenone described in this invention employs a dual-solvent recrystallization process to purify the crude product, effectively improving the product purity and enabling it to meet the stringent industry standards for intermediate purity in pharmaceuticals and other fields. This eliminates the need for additional complex subsequent purification steps, simplifying the production process, reducing costs and operational difficulties associated with additional purification, and simultaneously expanding the product's application range in high-requirement fields, thereby enhancing its market competitiveness.

[0025] (5) The method for synthesizing 2,2,2-triphenylacetophenone described in this invention uses a segmented temperature-controlled method to add pyridine dropwise, avoiding the problems of excessively high local concentrations and overheating that easily occur under traditional single temperature control. This reduces the occurrence of side reactions and significantly improves the selectivity of the reaction. This not only helps to ensure the yield of the product, but also reduces the difficulty of subsequent purification due to the presence of by-products, making the reaction process more stable and controllable, and providing a guarantee for stable production on an industrial scale.

[0026] (6) From the perspective of the overall process, compared with the traditional synthesis process, the present invention reduces the use of corrosive substances and toxic solvents, and reduces the amount of wastewater and hazardous waste generated, which meets the safety and environmental protection requirements of modern green chemical industry. At the same time, the optimization of each link of the process is centered on "cost reduction, quality improvement and environmental protection", taking into account both economic efficiency and sustainability, providing a practical and feasible solution for the industrial green production of 2,2,2-triphenylacetophenone, and promoting its transformation from laboratory synthesis to large-scale and environmentally friendly production. Attached Figure Description

[0027] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0028] Figure 1 The liquid chromatogram of the product synthesized by the method of the present invention is shown.

[0029] Figure 2 This illustrates the synthetic route for the synthesis method of the present invention. Detailed Implementation

[0030] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0031] As attached Figure 1-2 As shown. The method for synthesizing 2,2,2-triphenylacetophenone according to the present invention specifically includes the following steps:

[0032] (1) Preparation of supported trifluoromethanesulfonic anhydride catalyst

[0033] ① Support activation: Take mesoporous SiO2 (pore size 2-5nm, specific surface area 800m² / g), place it in a vacuum drying oven, dry it at 120℃ and -0.09MPa for 4h to remove the moisture and impurities adsorbed on the support surface, cool it to room temperature and then seal it in a desiccator; ② Loading process: Add 10g of activated mesoporous SiO2 to a 250mL round-bottom flask, add 50mL of anhydrous DCM (water content ≤0.02%), turn on magnetic stirring (300rpm) to make the support uniformly dispersed; then slowly add 5g of trifluoromethanesulfonic anhydride (purity 99%) at a dropping rate of 2 drops / second, and continue stirring for 2h after the addition is complete to ensure that the trifluoromethanesulfonic anhydride is fully adsorbed in the mesoporous channels of the mesoporous SiO2; ③ Catalyst formation: Place the above mixture in a rotary evaporator and distill it under reduced pressure at 40℃ and -0.09MPa for 30 minutes to remove excess DCM and obtain a white powdered supported catalyst. The load was measured using a thermogravimetric analyzer (TAQ500) to ensure it was 40 wt%, and then sealed and stored for later use.

[0034] The chemical equation is: ;

[0035] The hydroxyl groups (-OH) on the surface of mesoporous SiO2 react with the anhydride groups of trifluoromethanesulfonic acid anhydride to form Si-O-SO2CF3 bonds, thus achieving catalyst loading. The trace byproduct trifluoromethanesulfonic acid (CF3SO3H) is removed by vacuum distillation at 40℃, and the final catalyst loading reaches 40wt%.

[0036] (2) Synthesis of 2,2,2-triphenylacetophenone

[0037] ① Reaction system setup: Add 3.85g of supported catalyst (0.0055mol based on pure trifluoromethanesulfonic anhydride) and 100mL of anhydrous DCM to a 250mL three-necked flask. Install a mechanical stirrer (200rpm), a constant-pressure dropping funnel, and a precision thermometer (accuracy ±0.1℃). Place the three-necked flask in a low-temperature constant-temperature water bath. ② Segmented temperature-controlled dropwise addition of pyridine: Turn on the constant-temperature water bath and cool to 0-5℃. Add pyridine (4.3g, 0.054mol) dropwise through the dropping funnel at a rate of 1 drop / second. After 10 minutes of dropwise addition (approximately 1 / 3 of the pyridine has been added), raise the temperature to 15-20℃ and continue adding the remaining pyridine. Pyridine, with temperature controlled at T < 20℃ throughout; after addition, stir for 10 minutes, and a small amount of white fumes appear in the system (a characteristic phenomenon of pyridine reacting with trifluoromethanesulfonic anhydride to form pyridine salt); ③ Addition of raw materials and incubation: Add 10g benzinolide (0.027mol), add 30mL anhydrous DCM, stir for 5 minutes to form a pale yellow homogeneous solution; maintain the reaction at 20℃, and monitor the progress every 30 minutes by thin-layer chromatography (TLC) (developing solvent: petroleum ether-ethyl acetate = 5:1); when the raw material spot (Rf = 0.3) completely disappears and the product spot (Rf = 0.6) has no impurities, stop the reaction (about 2h).

[0038] The chemical equation is: ;

[0039] Ph represents phenyl (C6H5-). In the benzipineol molecule, the two adjacent hydroxyl groups (-C(OH)2-) are first protonated to form an easily leaving group (H2O) under the action of a strong acid catalyst (supported trifluoromethanesulfonic anhydride), generating a carbocation. The carbocation undergoes intramolecular rearrangement (phenyl migration) to finally form a stable carbonyl structure (-CO-), which is the target product. The reaction has no additional byproducts (the solvent DCM does not participate in the reaction), ensuring the purity of the product.

[0040] (3) Post-processing and purification

[0041] ① Catalyst Separation: After the reaction, the supported catalyst was separated by vacuum filtration. The filter cake was washed twice with 10 mL of anhydrous DCM (the washing liquid was combined with the mother liquor). The catalyst was dried under vacuum at 120℃ for 4 h, and the loading was checked (new catalyst was added when the loading dropped below 35 wt%). The mother liquor was then set aside. ② Mother Liquor Treatment: The mother liquor was transferred to a separatory funnel, 100 mL of deionized water (conductivity ≤ 5 μS / cm) was added, and the mixture was shaken for 10 minutes and allowed to stand for 15 minutes to separate into layers. The lower aqueous phase (containing pyridinium trifluoromethanesulfonate, to be processed later) was discarded. 5 g of anhydrous sodium sulfate (dried at 105℃ for 2 h) was added to the upper organic phase, and the mixture was allowed to stand at room temperature for 2 h (stirring for 3-5 minutes every 30 minutes). ③ Crude Product Preparation 1. Filter to remove anhydrous sodium sulfate, concentrate the organic phase by rotary evaporation (40℃, -0.09MPa) until no fraction remains, and obtain a white crude product (about 10.2g); the purity was determined by HPLC (C18 column, mobile phase methanol-water = 90:10, detection wavelength 254nm), and the purity was ≥95%; 2. Double solvent recrystallization: add the crude product to a 250mL round-bottom flask, add 40mL petroleum ether (90-100℃) and 5mL ethyl acetate, heat to 80℃ and reflux for 15 minutes to completely dissolve the crude product; after naturally cooling to room temperature, refrigerate at 0-5℃ for 2h to precipitate crystals; after filtration, wash the filter cake with 5mL cold petroleum ether, and dry under vacuum at 50℃ for 4h to obtain the pure product.

[0042] The chemical equation is: ;

[0043] Pyridine (a nitrogen-containing heterocyclic base) undergoes an acid-base neutralization reaction with trifluoromethanesulfonic anhydride (a strong acid anhydride), resulting in the protonation of the pyridine nitrogen atom to form a pyridinium cation (C5H5NH). + ), and trifluoromethanesulfonate anion (CF3SO3) - It combines to form an ionic salt (pyridinium trifluoromethanesulfonate), and this byproduct dissolves in the aqueous phase after water washing and enters the subsequent byproduct conversion process.

[0044] (4) Recovery and recycling of solvent DCM

[0045] ① Preliminary dehydration: Transfer the DCM fraction (approximately 120 mL) to a distillation flask, add 2 g of anhydrous calcium chloride, and stir at room temperature for 1 h to adsorb water; ② Atmospheric distillation: Add zeolite and distill at atmospheric pressure, collecting the fraction at 39-41℃ (approximately 110 mL), and determine the water content using the Karl Fischer method to be ≤0.3%; ③ Deep dehydration and purification: Add 5 g of activated 3A molecular sieve to the fraction, seal and stir for 24 h, then filter through a 0.22 μm organic phase filter membrane to obtain anhydrous DCM (purity ≥99.5%, water content ≤0.05%), which can be directly recycled.

[0046] The chemical equation is: ;

[0047] Under strongly alkaline conditions (NaOH), the pyridinium cation (C5H5NH) + ) Accept OH - Dehydrogenation produces pyridine molecules (C5H5N), which are recovered by azeotropic distillation at 94-95℃ (pyridine-water azeotrope) with a purity ≥98.5% and a recovery rate ≥74%. The generated sodium trifluoromethanesulfonate (NaCF3SO3) dissolves in the aqueous phase and enters the subsequent acidification process.

[0048] (5) Conversion of the byproduct pyridinium trifluoromethanesulfonate

[0049] ① Alkaline hydrolysis to recover pyridine: Dissociation reaction. Transfer the aqueous phase (about 100 mL) containing pyridinium trifluoromethanesulfonate to a three-necked flask, add 20 g of 20% sodium hydroxide aqueous solution (molar ratio 1.8:1, excess NaOH to ensure complete dissociation), reflux at 80 °C for 3 h, and pyridinium trifluoromethanesulfonate will completely dissociate into pyridine molecules, which will dissolve in the aqueous phase (converting the ionic pyridinium trifluoromethanesulfonate into molecular pyridine, preparing for subsequent separation).

[0050] Pyridine is recovered by heated distillation. After the dissociation reaction is complete, the system temperature is raised to 115-120℃ (close to the boiling point of pure pyridine, 115.3℃, but due to the presence of an aqueous phase, it is actually a pyridine-water azeotrope distillation). Pyridine and water form an azeotropic mixture (azeotropic composition: 57% pyridine, 43% water, azeotropic boiling point 94.5℃). It is not necessary to reach the boiling point of pure pyridine; the pyridine-water azeotrope can be distilled off at 94-95℃, solving the problem of difficult distillation due to the high boiling point of pyridine. The fraction collected at 94-95℃ is the pyridine-containing azeotrope, completing the separation of pyridine from the aqueous phase.

[0051] The collected pyridine-water azeotrope contained approximately 57% pyridine. The pyridine in the azeotrope was extracted with anhydrous dichloromethane (pyridine has a much higher solubility in dichloromethane than in water). After separation, the organic phase was collected and the dichloromethane (boiling point 39.8℃) was removed by distillation.

[0052] The pyridine vapor was collected by condensation, and the purity was determined by GC analysis to be ≥98.5%, with a recovery rate of ≥74%.

[0053] ② Preparation of trifluoromethanesulfonic acid by acidification: Remove water-soluble impurities by solvent extraction, add anhydrous dichloromethane to the trifluoromethanesulfonic acid aqueous solution, mix at a volume ratio of aqueous solution:solvent = 1:2, and stir at room temperature for 30 minutes (taking advantage of the property that trifluoromethanesulfonic acid has a higher solubility in organic solvents than in water); after standing and separating into layers, take the organic phase (containing trifluoromethanesulfonic acid) and discard the aqueous phase (containing sodium sulfate, unreacted sulfuric acid and other water-soluble impurities). This can remove more than 90% of water-soluble salts, avoiding salt precipitation and equipment blockage during subsequent distillation;

[0054] Dehydration by vacuum distillation: Transfer the organic phase containing trifluoromethanesulfonic acid to a vacuum distillation flask, add a small amount of anhydrous magnesium sulfate (as an auxiliary dehydrating agent), and distill under a vacuum of 0.095 MPa and a temperature of 80-90 °C (because vacuum can lower the boiling point of trifluoromethanesulfonic acid and avoid decomposition due to high temperature): First collect the low-boiling fraction (dichloromethane or toluene, boiling point 39.8 °C / 110.6 °C, which can be reused in the extraction step); continue to raise the temperature to 120-130 °C (vacuum unchanged), and collect the trifluoromethanesulfonic acid fraction;

[0055] After precise filtration to remove trace impurities, the trifluoromethanesulfonic acid obtained by distillation is filtered through a 0.22μm acid-resistant filter membrane (such as polytetrafluoroethylene) to remove any possible residual magnesium sulfate particles or trace organic impurities, yielding trifluoromethanesulfonic acid (purity ≥97.2%, recovery rate ≥70%).

[0056] ③ Convert trifluoromethanesulfonic acid to trifluoromethanesulfonic anhydride:

[0057] The principle of the conversion reaction: Trifluoromethanesulfonic acid reacts with phosphorus pentoxide under anhydrous conditions to produce trifluoromethanesulfonic anhydride and phosphoric acid (the byproducts are easily separated). The reaction formula is as follows: ;

[0058] Specifically, the molar ratio of trifluoromethanesulfonic acid to phosphorus pentoxide is 2.2:1, with phosphorus pentoxide in excess by 10% (to ensure complete conversion); in anhydrous dichloromethane solvent, after stirring at room temperature for 2 hours, the temperature is raised to 40°C and the reaction continues for 1 hour (to avoid decomposition of the anhydride due to high temperature); after the reaction, the byproduct phosphoric acid (insoluble in dichloromethane) is removed by filtration, and the trifluoromethanesulfonic acid anhydride fraction is collected by vacuum distillation (boiling point 82-83°C, atmospheric pressure), with a purity ≥98%, which can be used for the preparation of the supported trifluoromethanesulfonic acid anhydride catalyst in step (1) to achieve reuse.

[0059] The liquid chromatogram of the product is attached. Figure 1 As shown.

[0060] Example 1: Synthesis of 2,2,2-triphenylacetophenone

[0061] Preparation of supported catalyst: 10g of mesoporous SiO2 (Aladdin, pore size 3nm, specific surface area 800m² / g) was dried under vacuum at 120℃ for 4h and then cooled. It was added to a 250mL round-bottom flask, and 50mL of anhydrous DCM (Sinopharm Group, analytical grade) was added dropwise with stirring. After the addition was completed, the mixture was stirred for 2h. DCM was removed by vacuum distillation at 40℃ to obtain a catalyst with a loading of 40wt%, which was then sealed for later use.

[0062] The synthesis reaction was carried out by adding 3.85 g of supported catalyst and 100 mL of anhydrous DCM to a 250 mL three-necked flask. 4.3 g of pyridine (Sinopharm Group, 99.5%) was added dropwise in a low-temperature water bath at 0-5 °C. After 10 minutes, the temperature was raised to 15-20 °C and the remaining pyridine was added. 10 g of benzinolide (Tokyo Kasei, 98%) was added, followed by 30 mL of DCM. The reaction was maintained at 20 °C for 2 h. The reaction was stopped after TLC showed that the starting material had completely disappeared.

[0063] The catalyst was separated by filtration after post-treatment and purification (36 wt% loaded after drying, for later use). The organic phase was washed with water and dried with anhydrous sodium sulfate. 10.2 g of crude product was obtained by concentration (HPLC purity 95.3%). The crude product was recrystallized from 40 mL of petroleum ether and 5 mL of ethyl acetate to obtain 8.9 g of pure product, with a yield of 92.7%, HPLC purity of 99.82%, and melting point of 182.3-183.1 °C.

[0064] The solvent-recovered DCM fraction was dehydrated by calcium chloride, distilled (39-41℃), dehydrated by molecular sieve, and filtered to obtain 108 mL of anhydrous DCM (GC purity 99.65%, water content 0.04%), which was then used for later use.

[0065] The byproduct was converted into an aqueous phase and 20g of 20% sodium hydroxide aqueous solution was added. The mixture was refluxed at 80℃ for 3h, and 3.2g of pyridine (GC purity 98.6%) was collected. The alkaline hydrolysate was acidified to obtain 4.8g of trifluoromethanesulfonic acid (purity 97.2%), which was then converted into trifluoromethanesulfonic anhydride.

[0066] Example 2: Cyclic Performance Test of Supported Catalyst

[0067] The catalyst recovered in Example 1 (36 wt% loading) was directly used in the second synthesis. The steps of Example 1 were repeated, and the product yield and purity were recorded. A total of 5 cycles were performed, and the results are as follows:

[0068]

[0069] The results showed that the catalyst maintained high activity after five cycles, and the product yield and purity did not decrease significantly.

[0070] Example 3: DCM Cyclic Performance Test

[0071] The DCM (99.65% purity) recovered in Example 1 was directly used in the second synthesis. The steps of Example 1 were repeated for a total of 5 cycles, and the results are as follows:

[0072]

[0073] The results show that DCM can still meet the reaction requirements after 5 cycles, achieving efficient reuse.

[0074] Figure 2The reaction mechanism is as follows: "Benzinol + Tf₂O (trifluoromethanesulfonic anhydride) + pyridine + DCM (dichloromethane) → 2,2,2-triphenylacetophenone".

[0075] Tf₂O combines with pyridine to form pyridinium trifluoromethanesulfonate (a strongly acidic species). The hydroxyl group of benzinophenone is protonated, causing it to leave in the form of water, forming a carbocation. Subsequently, the ortho-phenyl group undergoes 1,2-migration, while the carbonyl oxygen attacks the carbocation, ultimately generating 2,2,2-triphenylacetophenone.

[0076] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of protection claimed by the present invention. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing 2,2,2-triphenylacetophenone, characterized in that, Includes the following steps: (1) Preparation of supported trifluoromethanesulfonic anhydride catalyst: Mesoporous SiO2 dried under vacuum at 120℃ for 4h was dispersed in anhydrous dichloromethane. Trifluoromethanesulfonic anhydride was added dropwise at a mass ratio of mesoporous SiO2 to trifluoromethanesulfonic anhydride of 2:

1. After stirring for 2h, excess dichloromethane was removed by vacuum distillation to obtain a supported trifluoromethanesulfonic anhydride catalyst with a loading of 40wt%. (2) Synthesis reaction: The supported catalyst and anhydrous dichloromethane were added to a three-necked flask at a molar ratio of 0.2:1 between pure trifluoromethanesulfonic anhydride and benzinolide. First, 1 / 3 of the pyridine was added dropwise at a rate of 1 drop / second at 0-5℃. The molar ratio of pyridine to pure trifluoromethanesulfonic anhydride was 1.5:

1. After 10 minutes, the temperature was raised to 15-20℃ and the remaining pyridine was added dropwise. Then, benzinolide was added and dichloromethane was added to form a homogeneous phase. The reaction was kept at 20℃ for 2 hours. The reaction process was monitored by thin-layer chromatography. The developing solvent was petroleum ether-ethyl acetate with a volume ratio of 5:

1. The reaction was stopped when the spots of the raw material benzinolide completely disappeared. (3) Post-treatment and purification: The catalyst was separated by filtration. The mother liquor was washed with water to discard the aqueous phase. The organic phase was dried with anhydrous sodium sulfate at room temperature for 2 hours with stirring for 3-5 minutes every 30 minutes. After drying, the crude product was concentrated. The crude product was recrystallized with a mixed solvent of petroleum ether and ethyl acetate at a volume ratio of 8:1 and a mass ratio of the mixed solvent to the crude product of 4.5:

1. After drying, the pure product was obtained. After the supported catalyst was recycled 5 times, the product yield was still ≥90% and the purity of the pure product was ≥99.5% when the loading was reduced to 27wt%. (4) Solvent recovery: The dichloromethane fraction was dehydrated by calcium chloride, distilled at atmospheric pressure at 39-41℃, dehydrated by 3A molecular sieve activated at 120℃ for 4 hours in advance, and filtered through a 0.22μm filter membrane to obtain anhydrous dichloromethane with a purity ≥99.5% and a water content ≤0.05% for recycling; after the dichloromethane was recycled 5 times, the purity was ≥99.4% and the water content was ≤0.10%, which had no significant impact on the product yield and purity; (5) Byproduct conversion: The aqueous phase containing pyridinium trifluoromethanesulfonate generated by water washing was refluxed at 80°C for 3 hours with 20% sodium hydroxide aqueous solution to completely dissociate pyridinium trifluoromethanesulfonate. The molar ratio of sodium hydroxide aqueous solution to pyridinium trifluoromethanesulfonate was 1.8:

1. The mixture was heated to 94-95°C and distilled to obtain a pyridine-water azeotrope. Dichloromethane was added, and after standing, the upper organic phase containing pyridine was taken and the dichloromethane was recovered at 40°C to obtain purified pyridine. The pyridine recovery rate was ≥74%. The aqueous phase after pyridine distillation was acidified to pH 1-2 with 98% concentrated sulfuric acid to prepare trifluoromethanesulfonic acid for reuse. The trifluoromethanesulfonic acid recovery rate was ≥70%. The final yield of pure 2,2,2-triphenylacetophenone was ≥92%, and the purity determined by HPLC was ≥99.8%.

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