The invention discloses a method for synthesizing 4, 4apos; process for preparing-difluorobenzophenone
By using modified zeolite catalysts and green solvents, the synthesis process of 4,4'-difluorobenzophenone was optimized, solving the problems of expensive raw materials, high reaction risk, and poor selectivity, and achieving high yield and high purity product production.
Patent Information
- Application Number
- CN202610168550.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-02-05
- Publication Date
- 2026-05-15
AI Technical Summary
The existing synthesis process for 4,4'-difluorobenzophenone suffers from problems such as expensive raw materials, high reaction risk, poor regioselectivity, and low intermediate yield, making it difficult to meet the demand of high-tech industries for high-purity products.
By employing modified zeolite catalysts, organic photosensitive catalysts, solid acid catalysts, and quaternary phosphonium salt catalysts, and through steps such as electrophilic substitution, free radical chain reaction, hydrolysis, and nucleophilic substitution, combined with visible light photo-oxidation-reduction technology and green solvents, the reaction conditions are optimized to improve selectivity and safety.
The synthesis of 4,4'-difluorobenzophenone, which features high para-selectivity, high safety, and good environmental protection, has been achieved with high intermediate yield, reducing production costs and minimizing environmental impact.
Smart Images
Figure SMS_1
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic fine chemical synthesis technology, specifically relating to a method for synthesizing 4,4'-difluorobenzophenone. Background Technology
[0002] 4,4'-Difluorobenzophenone (4,4'-DFBP) is an indispensable key monomer for the preparation of specialty engineering plastics such as polyetheretherketone (PEEK). With the rapid development of high-tech industries such as aerospace, electronics, and medical devices, the demand for PEEK materials is increasing, and the demand for 4,4'-DFBP, the core monomer for synthesizing PEEK materials, is also rising. Therefore, there is an urgent need in this field for a green and efficient method for synthesizing 4,4'-difluorobenzophenone.
[0003] Currently, the industrial synthesis route for 4,4'-difluorobenzophenone has the following main drawbacks: 1. Friedel-Crafts acylation: This is the mainstream process, typically using fluorobenzene and p-fluorobenzoyl chloride as raw materials, reacting them under Lewis acid catalysis such as aluminum trichloride. The p-fluorobenzoyl chloride used in this process is expensive, leading to high production costs. Furthermore, the reaction requires superstoichiometric catalysts, generating large amounts of aluminum-containing acidic wastewater, resulting in high environmental treatment costs.
[0004] 2. Diazotization-oxidation method: This route uses relatively inexpensive 4,4'-diaminodiphenylmethane as a raw material, and prepares it through diazotization, fluorination, and oxidation steps. However, the production process is extremely dangerous, such as the use of highly toxic and corrosive hydrofluoric acid, and the risk of explosion when the intermediate azo salt is dried.
[0005] Currently, relevant technologies disclose a route for synthesizing 4,4'-difluorobenzophenone from inexpensive diphenylmethane via chlorination, hydrolysis, and fluorination. However, in practice, this method suffers from poor regioselectivity and low intermediate yields. Summary of the Invention
[0006] This invention provides a method for synthesizing 4,4'-difluorobenzophenone, which has high regioselectivity and yields high intermediates.
[0007] To achieve the above objectives, the present invention provides the following technical solution: A method for synthesizing 4,4'-difluorobenzophenone includes the following steps: Diphenylmethane, a modified zeolite catalyst, a chlorinating agent, and a first solvent were mixed and subjected to an electrophilic substitution reaction to obtain 4,4'-dichlorodiphenylmethane. The 4,4'-dichlorodiphenylmethane, chlorine source, organic photosensitive catalyst, and second solvent were mixed and subjected to a free radical chain reaction to obtain 4,4'-dichloro-α,α-dichlorodiphenylmethane; The 4,4'-dichloro-α,α-dichlorodiphenylmethane, a solid acid catalyst, and a third solvent were mixed and hydrolyzed to obtain 4,4'-dichlorobenzophenone. The 4,4'-dichlorobenzophenone, fluorine source, phase transfer catalyst and fourth solvent were mixed and subjected to nucleophilic substitution reaction to obtain 4,4'-difluorobenzophenone. The phase transfer catalyst is a quaternary phosphonium salt catalyst.
[0008] Preferably, the mass ratio of diphenylmethane to modified zeolite catalyst is 1:0.05~0.2; the molar ratio of diphenylmethane to chlorinating agent is 1:2~2.4; the mass ratio of diphenylmethane to first solvent is 1:2~10; the modified zeolite catalyst includes modified KL type zeolite catalyst; the chlorinating agent includes thioyl chloride; and the first solvent includes 1,2-dichloroethane or chlorobenzene.
[0009] Preferably, the preparation method of the modified KL-type zeolite catalyst includes the following steps: KL-type zeolite catalyst was dealuminized by acid treatment to obtain dealuminized zeolite catalyst; The dealuminolite catalyst was mixed with a potassium salt solution and subjected to ion exchange to obtain the modified KL-type zeolite catalyst. The silicon-to-aluminum ratio of the dealuminolite catalyst is 15-22; the potassium exchange rate of the ion exchange is >95%.
[0010] Preferably, the electrophilic substitution reaction is carried out at a temperature of 70-90°C for 4-8 hours.
[0011] Preferably, the molar ratio of 4,4'-dichlorodiphenylmethane to the chlorine source is 1:2.1~2.5; the molar ratio of 4,4'-dichlorodiphenylmethane to the organic photosensitive catalyst is 100:0.1~2; the chlorine source includes N-chlorosuccinimide; the organic photosensitive catalyst includes ruthenium(II) tris(2,2'-bipyridine)chloride or eosin Y; and the second solvent includes acetonitrile.
[0012] Preferably, the free radical chain reaction is carried out at a temperature of 25~40℃ for 4~10h, and the free radical chain reaction is carried out under a protective atmosphere and visible light irradiation.
[0013] Preferably, the mass ratio of 4,4'-dichloro-α,α-dichlorodiphenylmethane to the solid acid catalyst is 1:0.05~0.15; the solid acid catalyst includes Amberlyst-15 catalyst or Nafion NR50 perfluorosulfonic acid resin; the third solvent includes toluene and water, and the volume ratio of toluene to water is 1:0.3~1.
[0014] Preferably, the hydrolysis reaction is carried out at a temperature of 80-110°C for 4-8 hours.
[0015] Preferably, the molar ratio of 4,4'-dichlorobenzophenone to the fluorine source is 1:2.5~4; the molar ratio of 4,4'-dichlorobenzophenone to the quaternary phosphonium salt catalyst is 1:0.03~0.08; the fluorine source includes anhydrous potassium fluoride; the quaternary phosphonium salt catalyst includes tetraphenylphosphonium bromide or tetraphenylphosphonium chloride; and the fourth solvent includes propylene carbonate or sulfolane.
[0016] Preferably, the nucleophilic substitution reaction is carried out at a temperature of 170~195℃ for a time of 6~12h.
[0017] This invention provides a method for synthesizing 4,4'-difluorobenzophenone, comprising the following steps: mixing diphenylmethane, a zeolite catalyst, a chlorinating agent, and a first solvent to perform an electrophilic substitution reaction to obtain 4,4'-dichlorodiphenylmethane; mixing the 4,4'-dichlorodiphenylmethane, a chlorine source, an organic photosensitive catalyst, and a second solvent to perform a free radical chain reaction to obtain 4,4'-dichloro-α,α-dichlorodiphenylmethane; mixing the 4,4'-dichloro-α,α-dichlorodiphenylmethane, a solid acid catalyst, and a third solvent to perform a hydrolysis reaction to obtain 4,4'-dichlorobenzophenone; and mixing the 4,4'-dichlorobenzophenone, a fluorine source, a phase transfer catalyst, and a fourth solvent to perform a nucleophilic substitution reaction to obtain 4,4'-difluorobenzophenone; wherein the phase transfer catalyst is a quaternary phosphonium salt catalyst. The beneficial effects of this invention include: High para-selectivity: Step (1) uses a specially modified L-type zeolite catalyst, which utilizes its unique pore structure to spatially restrict the reaction transition state, which can significantly improve the para- (4,4'-) selectivity of the aromatic ring chlorination reaction, greatly reduce the generation of isomer impurities from the source, and lay the foundation for obtaining high-purity products in the future.
[0018] Improved process safety and selectivity: Step (2) uses N-chlorosuccinimide as the chlorine source and utilizes visible light photo-oxidation-reduction catalysis, avoiding the use of highly toxic chlorine gas and high-energy ultraviolet light. This method provides mild reaction conditions, more precise control over the selectivity of geminal dichlorination products, and effectively inhibits the formation of overchlorination byproducts.
[0019] Green and environmentally friendly with simple operation: Step (3) uses a recyclable solid acid catalyst to replace the liquid strong acid or strong alkali that requires neutralization in the traditional process, simplifying the post-treatment process and reducing the generation of waste liquid. Step (4) uses biodegradable green solvents such as propylene carbonate to replace traditional highly toxic solvents such as DMSO and DMF. At the same time, a quaternary phosphonium salt phase transfer catalyst with better thermal stability is used to ensure the stability and efficiency of the high-temperature fluorination reaction.
[0020] The synthesis method provided by this invention achieves a high selectivity of over 95% for the intermediate 4,4'-dichlorodiphenylmethane by introducing specific catalyst systems, reaction reagents and reaction media in key steps. The yield of each step is superior to that of existing traditional processes, the starting raw material cost is low, and the process is safer, more selective and has less environmental impact. Detailed Implementation
[0021] This invention provides a method for synthesizing 4,4'-difluorobenzophenone, comprising the following steps: Diphenylmethane, a modified zeolite catalyst, a chlorinating agent, and a first solvent were mixed and subjected to an electrophilic substitution reaction to obtain 4,4'-dichlorodiphenylmethane. The 4,4'-dichlorodiphenylmethane, chlorine source, organic photosensitive catalyst, and second solvent were mixed and subjected to a free radical chain reaction to obtain 4,4'-dichloro-α,α-dichlorodiphenylmethane; The 4,4'-dichloro-α,α-dichlorodiphenylmethane, a solid acid catalyst, and a third solvent were mixed and hydrolyzed to obtain 4,4'-dichlorobenzophenone. The 4,4'-dichlorobenzophenone, fluorine source, phase transfer catalyst and fourth solvent were mixed and subjected to nucleophilic substitution reaction to obtain 4,4'-difluorobenzophenone. The phase transfer catalyst is a quaternary phosphonium salt catalyst.
[0022] In this invention, unless otherwise specified, all raw materials used in the preparation are preferably commercially available products well known to those skilled in the art.
[0023] This invention involves mixing diphenylmethane, a modified zeolite catalyst, a chlorinating agent, and a first solvent to perform an electrophilic substitution reaction, yielding 4,4'-dichlorodiphenylmethane. In one embodiment of this invention, the mass ratio of diphenylmethane to the modified zeolite catalyst can be 1:0.05~0.2, specifically 1:0.1; the molar ratio of diphenylmethane to the chlorinating agent is 1:2~2.4, specifically 1:2.25; and the mass ratio of diphenylmethane to the first solvent is 1:2~10, specifically 1:5. The chlorinating agent includes thioyl chloride; the first solvent includes 1,2-dichloroethane or chlorobenzene; the modified zeolite catalyst includes a modified KL-type zeolite catalyst. In another embodiment of this invention, the preparation method of the modified KL-type zeolite catalyst includes the following steps: KL-type zeolite catalyst was dealuminized by acid treatment to obtain dealuminized zeolite catalyst; The dealuminolite catalyst was mixed with a potassium salt solution and subjected to ion exchange to obtain the modified KL-type zeolite catalyst. The silicon-to-aluminum ratio of the dealuminolite catalyst is 15-22; the potassium exchange rate of the ion exchange is >95%.
[0024] In one embodiment of the present invention, the KL-type zeolite catalyst was purchased from the catalyst factory of Nankai University; the acid used for the acid treatment to remove aluminum can be hydrochloric acid, with a concentration of 1.5~2.5 mol / L, specifically 2.0 mol / L; the acid treatment temperature for the aluminum removal can be 70~90℃, specifically 80℃; and the time can be 3~5h, specifically 4h; the silicon-to-aluminum ratio of the aluminum removal catalyst can be specifically 18; the potassium salt solution includes potassium chloride solution, with a concentration of 0.5~1.5 mol / L, specifically 1.0 mol / L; and the ion exchange temperature can be 50~70℃, specifically 60℃; and the time can be 3~5h, specifically 4h.
[0025] This invention employs a specially modified L-type zeolite catalyst, which utilizes its unique pore structure to spatially restrict the reaction transition state, significantly improving the para- (4,4'-) selectivity of the aromatic ring chlorination reaction. This greatly reduces the generation of isomer impurities at the source, laying the foundation for obtaining high-purity products in the future.
[0026] In one embodiment of the present invention, the temperature of the electrophilic substitution reaction can be 70~90℃, specifically 70℃, 80℃ or 90℃, and the time is 4~8h, specifically 4h, 5h, 6h, 7h or 8h; the HCl and SO2 gases generated during the electrophilic substitution reaction are treated by a tail gas absorption device, which includes a 15wt% sodium hydroxide solution; after the electrophilic substitution reaction is completed, filtration is also included to recover the zeolite catalyst solid obtained by filtration, and the obtained filtrate is successively washed with water, dried to remove water, and distilled under reduced pressure to remove solvent and a small amount of low-boiling point impurities to obtain 4,4'-dichlorodiphenylmethane.
[0027] After obtaining 4,4'-dichlorodiphenylmethane, the present invention mixes the 4,4'-dichlorodiphenylmethane, a chlorine source, an organic photosensitive catalyst, and a second solvent to carry out a free radical chain reaction to obtain 4,4'-dichloro-α,α-dichlorodiphenylmethane. In one embodiment of the present invention, the molar ratio of 4,4'-dichlorodiphenylmethane to the chlorine source is 1:2.1~2.5, specifically 1:2.35; the molar ratio of 4,4'-dichlorodiphenylmethane to the organic photosensitive catalyst is 100:0.1~2, specifically 100:0.5; the mass ratio of 4,4'-dichlorodiphenylmethane to the volume ratio of the second solvent is 100g:300~500mL, specifically 100g:400mL; the chlorine source includes N-chlorosuccinimide (NCS); the organic photosensitive catalyst includes ruthenium(II) tris(2,2'-bipyridine)chloride or eosin Y; and the second solvent includes acetonitrile.
[0028] In one embodiment of the present invention, the temperature of the free radical chain reaction can be 25~40℃, specifically 30℃, and the time can be 4~10h, specifically 6~8h. The free radical chain reaction is carried out under a protective atmosphere and visible light irradiation. The protective atmosphere can be nitrogen, and the visible light is blue or green light with a wavelength of 455nm or 520nm. After the free radical chain reaction, filtration is performed to remove the generated byproduct succinimide. The obtained filtrate is then subjected to vacuum distillation to remove the solvent, yielding a crude product. The crude product is then separated by high-vacuum distillation to collect the 4,4'-dichloro-α,α-dichlorodiphenylmethane fraction. The vacuum degree of the high-vacuum distillation is -0.09~-0.1MPa. Unreacted raw materials and monochloro intermediates are recovered and recycled through the high-vacuum distillation.
[0029] This invention uses N-chlorosuccinimide as the chlorine source and employs visible light photo-oxidation-reduction catalysis, avoiding the use of highly toxic chlorine gas and high-energy ultraviolet light. The method offers mild reaction conditions, more precise selective control over geminal dichlorination products, and effectively inhibits the formation of over-chlorination byproducts.
[0030] After obtaining 4,4'-dichloro-α,α-dichlorodiphenylmethane, the present invention mixes the 4,4'-dichloro-α,α-dichlorodiphenylmethane, a solid acid catalyst, and a third solvent to carry out a hydrolysis reaction to obtain 4,4'-dichlorobenzophenone. In one embodiment of the present invention, the mass ratio of the 4,4'-dichloro-α,α-dichlorodiphenylmethane to the solid acid catalyst can be 1:0.05~0.15, specifically 1:0.1; the mass ratio of the 4,4'-dichloro-α,α-dichlorodiphenylmethane to the volume ratio of the third solvent is 120g:400~500mL, specifically 120g:450mL; the solid acid catalyst includes Amberlyst-15 catalyst or Nafion NR50 perfluorosulfonic acid resin; the third solvent includes toluene and water, and the volume ratio of toluene to water can be 1:0.3~1, specifically 1:0.5.
[0031] This invention uses a recyclable solid acid catalyst to replace the liquid strong acid or strong alkali that requires neutralization in traditional processes, simplifying the post-treatment process and reducing the generation of waste liquid.
[0032] In one embodiment of the present invention, the hydrolysis reaction temperature can be 80~110℃, specifically 92℃, and the time can be 4~8h, specifically 5~6h. The HCl gas generated during the hydrolysis reaction is distilled off with the toluene-water azeotrope, and the tail gas is absorbed by an alkaline solution using a tail gas absorption device. After the hydrolysis reaction, the reaction system is further cooled to room temperature, filtered, the obtained solid acid catalyst is recovered, the obtained organic phase is washed with water and dried to remove water, cooled to precipitate crystals, the crystallization system is subjected to solid-liquid separation, and the obtained crystalline solid is dried to obtain a white solid, 4,4'-dichlorobenzophenone. The cooling temperature for crystallization is 0~5℃.
[0033] After obtaining 4,4'-dichlorobenzophenone, the present invention mixes the 4,4'-dichlorobenzophenone, a fluorine source, a phase transfer catalyst and a fourth solvent to carry out a nucleophilic substitution reaction to obtain 4,4'-difluorobenzophenone. In one embodiment of the present invention, the molar ratio of 4,4'-dichlorobenzophenone to the fluorine source is 1:2.5~4, specifically 1:3; the molar ratio of 4,4'-dichlorobenzophenone to the phase transfer catalyst is 1:0.03~0.08, specifically 1:0.05; the mass ratio of 4,4'-dichlorobenzophenone to the volume ratio of the fourth solvent is 25.1g:50~80mL, specifically 25.1g:60mL; the fluorine source includes anhydrous potassium fluoride, which is spray-dried; the phase transfer catalyst is a quaternary phosphonium salt catalyst, which includes tetraphenylphosphonium bromide or tetraphenylphosphonium chloride; the fourth solvent includes propylene carbonate or sulfolane.
[0034] This invention uses biodegradable green solvents such as propylene carbonate to replace traditional highly toxic solvents such as DMSO and DMF. Simultaneously, it employs a quaternary phosphonium salt phase-transfer catalyst with superior thermal stability to ensure a stable and efficient high-temperature fluorination reaction.
[0035] In one embodiment of the present invention, the temperature of the nucleophilic substitution reaction can be 170~195℃, specifically 185℃ or 190℃, and the time can be 6~12h, specifically 6h, 8h or 10h; the nucleophilic substitution reaction is carried out under a protective atmosphere, namely nitrogen protection; after the nucleophilic substitution reaction, the resulting reaction mixture is further cooled to room temperature, filtered to remove the solid byproduct potassium chloride, and the resulting filtrate is subjected to vacuum distillation to obtain a crude product; the crude product is recrystallized in ethanol to obtain 4,4'-difluorobenzophenone.
[0036] To further illustrate the present invention, the technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments thereof. Obviously, the described embodiments are merely some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.
[0037] Example 1 Step 1: Preparation of 4,4'-dichlorodiphenylmethane KL-type zeolite catalyst (purchased from Nankai University Catalyst Factory) was acid-treated with 2.0 mol / L hydrochloric acid at 80°C for 4 hours to remove aluminum, yielding a dealuminized catalyst with a silicon-to-aluminum ratio of 18. The dealuminized catalyst was then subjected to ion exchange with 1.0 mol / L potassium chloride solution at 60°C for 4 hours (potassium exchange rate >95%) to obtain a modified KL-type zeolite catalyst. 10 g of the modified KL-type zeolite catalyst was added to 500 mL of 1,2-dichloroethane solution containing 100 g of diphenylmethane (0.59 mol), heated to 80°C under stirring, and then 180 g of sulfuryl chloride (1.33 mol) was slowly added dropwise. The reaction was allowed to proceed for 4 hours. HCl and SO2 gases generated during the reaction were treated by a tail gas absorption device. After the reaction was completed, the zeolite catalyst was recovered by filtration. The resulting filtrate was then washed with water, dried to remove water, and subjected to vacuum distillation to remove the solvent and a small amount of low-boiling-point impurities, yielding 4,4'-dichlorodiphenylmethane.
[0038] Gas chromatography (GC) analysis showed that the conversion rate of the raw material diphenylmethane was 99.1%, and the selectivity of the intermediate 4,4'-dichlorodiphenylmethane was 96.8%.
[0039] Step 2: Preparation of 4,4'-dichloro-α,α-dichlorodiphenylmethane 100 g of 4,4'-dichlorodiphenylmethane, 125 g of N-chlorosuccinimide (NCS), and 0.15 g of tris(2,2'-bipyridine)ruthenium(II) chloride were dissolved in 400 mL of acetonitrile. The reaction mixture was continuously irradiated with a 455 nm blue LED strip for 6 h under nitrogen protection and at 30 °C. The reaction progress was monitored by gas chromatography (GC), and the reaction was stopped when the raw materials no longer transformed. The resulting reaction solution was filtered to remove the solid byproduct succinimide. The filtrate was then subjected to vacuum distillation to remove the solvent, yielding a crude product. The crude product was separated by high-vacuum distillation at a vacuum degree of -0.09 to -0.1 MPa. Unreacted raw materials and monochloro intermediates (mainly 4-chlorodiphenylmethane) were recovered and recycled, and the 4,4'-dichloro-α,α-dichlorodiphenylmethane fraction was collected.
[0040] The conversion rate of the 4,4'-dichlorodiphenylmethane was 99.5%, and the selectivity of the 4,4'-dichloro-α,α-dichlorodiphenylmethane was 97.5%.
[0041] Step 3: Preparation of 4,4'-dichlorobenzophenone 120 g of the 4,4'-dichloro-α,α-dichlorodiphenylmethane was mixed with 300 mL of toluene, and 150 mL of water and 12 g of Amberlyst-15 catalyst (purchased from Dow Chemical) were added. The mixture was heated to reflux temperature (92 °C) under stirring and subjected to hydrolysis reaction for 6 h. The HCl gas produced by the reaction was distilled off with the toluene-water azeotrope and absorbed by 15 wt% sodium hydroxide. After the reaction was completed, the mixture was cooled to room temperature, and the Amberlyst-15 catalyst was recovered by filtration. The resulting organic phase was washed with water and dried to remove water. The mixture was cooled to 0-5 °C to precipitate crystals. Solid-liquid separation was performed, and the obtained crystalline solid was dried to obtain a white solid, 4,4'-dichlorobenzophenone.
[0042] The yield of the 4,4'-dichlorobenzophenone was 98.6%, and the purity was >99%.
[0043] Step 4: Preparation of 4,4'-difluorobenzophenone In a strictly anhydrous (water content <0.05%) reactor, 25.1 g of the 4,4'-dichlorobenzophenone, 17.4 g of spray-dried anhydrous potassium fluoride, 2.1 g of tetraphenylphosphonium bromide, and 60 mL of propylene carbonate were added; the mixture was heated to 185 °C under nitrogen protection and reacted for 8 h; after the reaction was completed, the resulting reaction mixture was cooled to room temperature, and the solid byproduct potassium chloride was removed by filtration; the filtrate was subjected to vacuum distillation to obtain a crude product; the crude product was recrystallized in ethanol to obtain 4,4'-difluorobenzophenone.
[0044] The yield of the 4,4'-difluorobenzophenone was 96.8%, and the purity (HPLC) was >99.9%.
[0045] Example 2 Step 1: This step is essentially the same as Step 1 in Example 1, except that 400 mL of chlorobenzene is used instead of 500 mL of 1,2-dichloroethane as the solvent; the heating temperature is changed to 90°C; and the reaction time is changed to 5 hours. GC analysis showed that the conversion rate of the starting material diphenylmethane was 98.5%, and the selectivity of the intermediate 4,4'-dichlorodiphenylmethane was 96.2%.
[0046] Steps two through four are the same as in Example 1.
[0047] As can be seen from Examples 1 and 2, chlorobenzene can replace 1,2-dichloroethane as a high-boiling-point solvent, which can maintain the high conversion rate of the raw material diphenylmethane and the high selectivity of the intermediate 4,4'-dichlorodiphenylmethane.
[0048] Example 3 Step one is the same as in Example 1; Step 2: This step is essentially the same as Step 2 in Example 1, except that the organic photosensitive dye Eosin Y (Eosin Y) is used instead of ruthenium(II) tris(2,2'-bipyridine)chloride as the photocatalyst; a 520nm green LED light source is used; and the reaction time is changed to 8 hours. GC analysis showed that the conversion rate of the 4,4'-dichlorodiphenylmethane was 97.8%, and the selectivity of the 4,4'-dichloro-α,α-dichlorodiphenylmethane was 96.5%.
[0049] Steps three and four are the same as in Example 1.
[0050] As can be seen from Examples 1 and 3, inexpensive organic dyes and visible light sources of different wavelengths can be used to achieve efficient conversion, maintaining the high conversion rate of 4,4'-dichlorodiphenylmethane and the high selectivity of 4,4'-dichloro-α,α-dichlorodiphenylmethane.
[0051] Example 4 Steps one and two are the same as in Example 1; Step three is basically the same as step three in Example 1, except that Nafion NR50 perfluorosulfonic acid resin is used instead of Amberlyst-15 as the solid acid catalyst; and the hydrolysis reaction is changed to 5 hours. The yield of the 4,4'-dichlorobenzophenone is 99.0%.
[0052] Step four is the same as in Example 1.
[0053] As can be seen from Examples 1 and 4, Nafion NR50 perfluorosulfonic acid resin can replace Amberlyst-15 as a solid acid catalyst, and the 4,4'-dichlorobenzophenone has a high yield.
[0054] Example 5 Steps one through three are the same as in Example 1; Step 4: This step is essentially the same as Step 4 in Example 1, except that tetraphenylphosphonium chloride is used instead of tetraphenylphosphonium bromide as the phase transfer catalyst; sulfolane is used instead of propylene carbonate as the solvent; and the reaction temperature and time are changed to 190°C and 6 hours. The results show that the conversion rate of 4,4'-dichlorobenzophenone is 99.3%, and the yield of 4,4'-difluorobenzophenone is 96.5%.
[0055] As can be seen from Examples 1 and 5, the quaternary phosphonium salt and polar aprotic solvent defined in this invention have good interchangeability and process flexibility, and can maintain the high conversion rate and high yield of the 4,4'-dichlorobenzophenone.
[0056] Comparative Example 1 Anhydrous aluminum trichloride was used instead of the modified KL zeolite catalyst in step one of Example 1, and the reaction was carried out at 25°C, with all other conditions remaining the same. The results showed that although the conversion rate of the feedstock diphenylmethane reached 99.8%, the selectivity of the intermediate 4,4'-dichlorodiphenylmethane was only 42.5%, while the selectivity of the byproduct 2,4'-dichlorodiphenylmethane was as high as 48.2%.
[0057] As shown in Example 1 and Comparative Example 1, the anhydrous aluminum trichloride used in Comparative Example 1 is a conventional catalyst. Conventional catalysts have low selectivity for the intermediate 4,4'-dichlorodiphenylmethane, even lower than the selectivity for the byproduct 2,4'-dichlorodiphenylmethane. This indicates that the modified zeolite catalyst provided by the present invention can improve the regioselectivity of the intermediate 4,4'-dichlorodiphenylmethane.
[0058] Comparative Example 2 Tetrabutylammonium bromide (TBAB) was used instead of tetraphenylphosphonium bromide in step four of Example 1, and the reaction was carried out at 185°C, with the other conditions remaining the same. After 4 hours of reaction, the solution turned black and the reaction stopped, and the conversion rate of the 4,4'-dichlorobenzophenone was only 45.2%.
[0059] As shown in Example 1 and Comparative Example 2, the tetrabutylammonium bromide used in Comparative Example 2 is a conventional phase transfer catalyst, which exhibits low conversion rates for the 4,4'-dichlorobenzophenone. This indicates that the quaternary phosphonium salt catalyst selected in this invention possesses irreplaceable thermal stability advantages in high-temperature fluorination reactions.
[0060] Test Example 1 The modified KL zeolite catalyst recovered after the reaction in step one of Example 1 was washed with 1,2-dichloroethane and dried in an oven at 120°C for 2 hours for use in the next batch of reaction. Five consecutive cycles were performed, and the results are shown in Table 1.
[0061] Table 1. Effect of the number of cycles of the modified KL-type zeolite catalyst on the conversion of diphenylmethane and the selectivity of the intermediate 4,4'-dichlorodiphenylmethane. As shown in Table 1, the modified KL-type zeolite catalyst showed no significant decrease in activity and selectivity after 5 cycles, exhibiting excellent stability.
[0062] Test Example 2 The Amberlyst-15 catalyst recovered after the reaction in step three of Example 1 was washed with water and acetone and then air-dried before being used in the next batch of reaction. Five consecutive cycles were conducted.
[0063] The average yield of 4,4'-dichlorobenzophenone remained above 98%, indicating that the Amberlyst-15 catalyst has a good industrial application lifespan.
[0064] This document uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of the above embodiments are only for the purpose of helping to understand the method and core ideas of the present invention. Furthermore, those skilled in the art will recognize that, based on the ideas of the present invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of the present invention.
Claims
1. A method for synthesizing 4,4'-difluorobenzophenone, comprising the following steps: Diphenylmethane, a modified zeolite catalyst, a chlorinating agent, and a first solvent were mixed and subjected to an electrophilic substitution reaction to obtain 4,4'-dichlorodiphenylmethane. The 4,4'-dichlorodiphenylmethane, chlorine source, organic photosensitive catalyst, and second solvent were mixed and subjected to a free radical chain reaction to obtain 4,4'-dichloro-α,α-dichlorodiphenylmethane; The 4,4'-dichloro-α,α-dichlorodiphenylmethane, a solid acid catalyst, and a third solvent were mixed and hydrolyzed to obtain 4,4'-dichlorobenzophenone. The 4,4'-dichlorobenzophenone, fluorine source, phase transfer catalyst and fourth solvent were mixed and subjected to nucleophilic substitution reaction to obtain 4,4'-difluorobenzophenone. The phase transfer catalyst is a quaternary phosphonium salt catalyst.
2. The method according to claim 1, characterized in that, The mass ratio of diphenylmethane to modified zeolite catalyst is 1:0.05~0.2; the molar ratio of diphenylmethane to chlorinating agent is 1:2~2.4; the mass ratio of diphenylmethane to first solvent is 1:2~10; the modified zeolite catalyst includes modified KL type zeolite catalyst; the chlorinating agent includes thioyl chloride; the first solvent includes 1,2-dichloroethane or chlorobenzene.
3. The method according to claim 2, characterized in that, The preparation method of the modified KL-type zeolite catalyst includes the following steps: KL-type zeolite catalyst was dealuminized by acid treatment to obtain dealuminized zeolite catalyst; The dealuminolite catalyst was mixed with a potassium salt solution and subjected to ion exchange to obtain the modified KL-type zeolite catalyst. The silicon-to-aluminum ratio of the dealuminolite catalyst is 15-22; the potassium exchange rate of the ion exchange is >95%.
4. The method according to any one of claims 1 to 3, characterized in that, The electrophilic substitution reaction is carried out at a temperature of 70-90°C for 4-8 hours.
5. The method according to claim 1, characterized in that, The molar ratio of 4,4'-dichlorodiphenylmethane to the chlorine source is 1:2.1~2.5; the molar ratio of 4,4'-dichlorodiphenylmethane to the organic photosensitive catalyst is 100:0.1~2; the chlorine source includes N-chlorosuccinimide; the organic photosensitive catalyst includes ruthenium(II) tris(2,2'-bipyridine)chloride or eosin Y; the second solvent includes acetonitrile.
6. The method according to claim 1 or 5, characterized in that, The free radical chain reaction is carried out at a temperature of 25~40℃ for 4~10h under a protective atmosphere and visible light irradiation.
7. The method according to claim 1, characterized in that, The mass ratio of 4,4'-dichloro-α,α-dichlorodiphenylmethane to the solid acid catalyst is 1:0.05~0.15; the solid acid catalyst includes Amberlyst-15 catalyst or Nafion NR50 perfluorosulfonic acid resin; the third solvent includes toluene and water, and the volume ratio of toluene to water is 1:0.3~1.
8. The method according to claim 1 or 7, characterized in that, The hydrolysis reaction is carried out at a temperature of 80-110℃ for 4-8 hours.
9. The method according to claim 1, characterized in that, The molar ratio of 4,4'-dichlorobenzophenone to a fluorine source is 1:2.5~4; the molar ratio of 4,4'-dichlorobenzophenone to a quaternary phosphonium salt catalyst is 1:0.03~0.08; the fluorine source includes anhydrous potassium fluoride; the quaternary phosphonium salt catalyst includes tetraphenylphosphonium bromide or tetraphenylphosphonium chloride; the fourth solvent includes propylene carbonate or sulfolane.
10. The method according to claim 1 or 9, characterized in that, The nucleophilic substitution reaction is carried out at a temperature of 170-195°C for 6-12 hours.