Preparation method of 4, 4 '-difluorobenzophenone

Abstract

The invention relates to the field of organic synthesis, and particularly discloses a preparation method of 4, 4 '-difluorobenzophenone, which comprises the following steps: mixing benzophenone, KCoF4, CsCoF4 and a first solvent, and reacting at 100-250 DEG C to obtain a crude product 4, 4'-difluorobenzophenone; wherein the molar ratio of the benzophenone to the KCoF4 to the CsCoF4 is 1: (0.6 to 0.8): (0.3 to 0.6), and the molar ratio of the benzophenone to the KCoF4 to the CsCoF4 is 1: (0.6 to 0.8) The first solvent is an aprotic polar solvent, and the weight ratio of the first solvent to the benzophenone is (1-20): 1. The preparation method is simple, the yield of three wastes is low, reaction conditions are mild, operation is easy, the purity of the obtained crude product 4, 4 '-difluorobenzophenone can reach 85% or above, and by-products are few.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and particularly to a method for preparing 4,4'-difluorobenzophenone. Background Art

[0002] 4,4'-Difluorobenzophenone is a key raw material for synthesizing polyetheretherketone (PEEK for short). PEEK is a semi-crystalline, thermoplastic special engineering plastic, which has excellent comprehensive properties such as high temperature resistance, self-lubrication, corrosion resistance, flame retardancy, hydrolysis resistance, wear resistance, and fatigue resistance, and is widely used in the fields of aerospace, automotive industry, electronic and electrical, and medical devices.

[0003] There are several methods for synthesizing 4,4'-difluorobenzophenone as follows: (1)

[0004] This method uses fluorobenzene and p-chlorobenzoyl chloride as raw materials. Through the Friedel-Crafts reaction, 4-fluoro-4'-chlorobenzophenone is obtained, and then through high-temperature substitution with potassium fluoride, 4,4'-difluorobenzophenone is obtained. First, the Friedel-Crafts reaction is used in the first step, generating a large amount of Al-containing wastewater. In the second step of potassium fluoride substitution, the reaction is not complete, resulting in difficult separation of the intermediate. (2)

[0006] This method is that fluorobenzene and p-fluorobenzoyl chloride undergo the Friedel-Crafts reaction to obtain 4,4'-difluorobenzophenone. It is also the same Friedel-Crafts reaction, generating a large amount of aluminum trichloride wastewater. There are a small amount of chlorinated products in the product, which are difficult to separate, and the product needs to be rectified multiple times to reach 99.99% of the product. (3)

[0008] This method uses fluorobenzene and carbon tetrachloride as raw materials, catalyzed by anhydrous aluminum trichloride. First, 4,4'-difluorophenyl dichloromethane is generated, and then the unreacted carbon tetrachloride and fluorobenzene are recovered by distillation. The crude product is obtained by hydrolysis at low temperature, and then the finished product is obtained through distillation and recrystallization. However, CCl4 is restricted in use, and aluminum trichloride as a catalyst will also generate a large amount of Al-containing wastewater. (4)

[0010] This method uses fluorobenzene and phosgene as raw materials and conducts a high-temperature and high-pressure reaction with boron trifluoride as a catalyst. However, it will produce about 25% of isomers, which are difficult to separate, and phosgene is highly toxic, making production control more difficult. (5)

[0012] This method dissolves 4,4'-diamino-diphenylmethane in HF, and sodium nitrite is added dropwise at low temperature to form a diazonium salt; then, the intermediate 4,4'-difluorodiphenylmethane is obtained through thermal decomposition, and finally, 4,4'-difluorobenzophenone is formed through oxidation with dilute nitric acid. The overall yield of this method reaches about 80%, with a high yield, and it is one of the common industrialization routes. However, the diazonium salt is explosive and corrosive to equipment seriously. (6)

[0014] This method uses diphenylmethane as a raw material. After two-step chlorination, 4,4'-dichlorophenyl dichloromethane is obtained, and then dechlorination hydrolysis and fluorination reaction are carried out to obtain the product. Although its yield is relatively high, the reaction steps are long and the industrialization difficulty is high.

[0015] As can be seen from the above, the existing synthesis methods of 4,4'-difluorobenzophenone have problems such as low yield, difficult separation, a large amount of wastewater production, and serious equipment corrosion, so it is necessary to improve. Summary of the Invention

[0016] The technical problem to be solved by the present invention is to provide a preparation method of 4,4'-difluorobenzophenone, which has a simple process, a high yield, and less generation of three wastes.

[0017] To solve the technical problem of the present invention, the present invention provides a preparation method of 4,4'-difluorobenzophenone, which includes: Mix benzophenone, KCoF4, CsCoF4, and a first solvent, and react at 100-250 °C to obtain crude 4,4'-difluorobenzophenone; Among them, the molar ratio of benzophenone, KCoF4, and CsCoF4 is 1:(0.6-0.8):(0.3-0.6); The first solvent is an aprotic polar solvent, and the weight ratio of the first solvent to benzophenone is (1-20):1.

[0018] As an improvement of the above technical solution, the molar ratio of benzophenone, KCoF4, and CsCoF4 is 1:(0.62-0.75):(0.4-0.5); and / or The weight ratio of the first solvent to benzophenone is (3-10):1; As an improvement of the above technical solution, the molar ratio of benzophenone, KCoF4, and CsCoF4 is 1:(0.65-0.7):(0.4-0.48); and / or The weight ratio of the first solvent to the benzophenone is (3 - 8):1.

[0019] As an improvement to the above technical solution, the reaction temperature is 120 - 200 °C, and the reaction duration is 5 - 15 h.

[0020] As an improvement to the above technical solution, the reaction temperature is 150 - 200 °C, and the reaction duration is 8 - 12 h.

[0021] As an improvement to the above technical solution, the first solvent is selected from one or more of N,N - dimethylformamide, N,N - dimethylacetamide, N - methylpyrrolidone, dimethyl sulfoxide, dimethyl sulfone, and sulfolane.

[0022] As an improvement to the above technical solution, the first solvent is selected from N,N - dimethylformamide or dimethyl sulfone.

[0023] As an improvement to the above technical solution, it further includes: Dissolving the crude 4,4'-difluorobenzophenone in a second solvent, cooling to a first preset temperature, and holding for a first preset time; then cooling to a second preset temperature, holding for a second preset time, and performing solid - liquid separation to obtain an intermediate product; Dissolving the intermediate product in a third solvent, cooling to a third preset temperature, holding for a third preset time, and performing solid - liquid separation to obtain 4,4'-difluorobenzophenone; Among them, the second solvent is selected from one or more of methanol, ethanol, isopropanol, tert - butanol, butanone, and methyl isobutyl ketone; the weight ratio of the second solvent to the crude 4,4'-difluorobenzophenone is (2 - 10):1; The third solvent is selected from one or more of benzene, toluene, chloroform, and carbon tetrachloride; the weight ratio of the third solvent to the crude 4,4'-difluorobenzophenone is (1 - 5):1.

[0024] As an improvement to the above technical solution, the second solvent is selected from methanol or ethanol, and the weight ratio of the second solvent to the crude 4,4'-difluorobenzophenone is (3 - 8):1; and / or The third solvent is selected from benzene, and the weight ratio of the third solvent to the crude 4,4'-difluorobenzophenone is (1.5 - 5):1; and / or The first preset temperature is 25 - 35 °C, and the first preset time is 0.8 - 2.5 h; and / or The second preset temperature is 0 - 10 °C, and the second preset time is 0.8 - 2.5 h; and / or The third preset temperature is 0 - 8 °C, and the third preset time is 0.8 - 2.5 h.

[0025] As an improvement of the above technical solution, the first preset temperature is 30 - 35 °C, and the first preset time is 1 - 2 h; and / or the second preset temperature is 0 - 5 °C, and the second preset time is 1 - 2 h; and / or the third preset temperature is 0 - 5 °C, and the third preset time is 1 - 2 h.

[0026] Implementing the present invention has the following beneficial effects: In the preparation method of 4,4'-difluorobenzophenone in an embodiment of the present invention, benzophenone, KCoF4, and CsCoF4 are reacted in a polar protic solvent at 100 - 250 °C to obtain crude 4,4'-difluorobenzophenone. The purity of the crude 4,4'-difluorobenzophenone reaches more than 85%, with few by-products. Subsequently, a 4,4'-difluorobenzophenone product with extremely high purity can be obtained through simple purification. This preparation process is simple, with less industrial waste production, and the reaction conditions are relatively mild, the operation is simple, and the industrial feasibility is high. Detailed implementation manners

[0027] To facilitate the understanding of the present invention, the present invention will be described in more detail below. However, it should be understood that the present invention can be implemented in many different forms and is not limited to the embodiments or examples described herein. On the contrary, the purpose of providing these embodiments or examples is to make the understanding of the disclosure content of the present invention more thorough and comprehensive.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention in this specification are only for the purpose of describing specific embodiments or examples and are not intended to limit the present invention. The optional range of the term "and / or" used herein includes any one of two or more related listed items, and also includes any and all combinations of the related listed items. The any and all combinations include any two related listed items, any more related listed items, or all related listed items.

[0029] For the present invention. Those skilled in the art will understand that the changes and other uses thereof, as defined by the scope of the claims, are included within the spirit of the present invention. The materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0030] In the present invention, among the technical features described in an open-ended manner, a closed technical solution composed of the listed features is included, and an open technical solution including the listed features is also included.

[0031] In the present invention, unless otherwise specified, the percentage content for solid-liquid mixing and solid-solid mixing refers to the mass percentage, and for liquid-liquid mixing, it refers to the volume percentage.

[0032] In the present invention, unless otherwise specified, the percentage concentration refers to the final concentration. The final concentration refers to the proportion of the added component in the system after adding the component.

[0033] In the present invention, unless otherwise specified, the temperature parameter allows both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument.

[0034] The present invention discloses a preparation method of 4,4'-difluorobenzophenone, which includes mixing benzophenone, KCoF4, CsCoF4, and a first solvent and reacting them to obtain crude 4,4'-difluorobenzophenone;

[0035] Among them, the molar ratio of benzophenone, KCoF4, and CsCoF4 is 1:(0.6 - 0.8):(0.3 - 0.6); exemplarily, it is 1:0.62:0.57, 1:0.65:0.52, 1:0.69:0.49, 1:0.74:0.43, 1:0.77:0.36, 1:0.79:0.38, but not limited thereto.

[0036] Among them, the first solvent is an aprotic polar solvent, exemplarily one or more of tetrahydrofuran (THF), acetone, acetonitrile, dichloromethane, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-methylpyrrolidone (NMP), dimethyl sulfoxide (DMSO), dimethyl sulfone (MSM), and sulfolane (DMS). Preferably, in some embodiments, the first solvent is selected from one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, dimethyl sulfone, and sulfolane. Among these first solvents, the fluoride anions generated by the fluorination reagent have higher nucleophilicity, which can further reduce the probability of side reactions and improve the purity of the crude 4,4'-difluorobenzophenone. More preferably, the first solvent is selected from N,N-dimethylformamide or dimethyl sulfone. The above first solvent can further accelerate the reaction rate and improve the purity and yield of the crude 4,4'-difluorobenzophenone.

[0037] Among them, the weight ratio of the first solvent to benzophenone is (1 - 20):1, exemplarily 2:1, 5:1, 8:1, 11:1, 14:1, 16:1, or 19:1, but not limited thereto.

[0038] Among them, the reaction temperature is 100 to 250 °C, and exemplarily it is 110 °C, 130 °C, 150 °C, 170 °C, 190 °C, 210 °C, 230 °C or 240 °C, but not limited thereto.

[0039] Among them, the reaction duration is 5 to 20 h, and exemplarily it is 6 h, 8 h, 10 h, 12 h, 14 h, 16 h or 18 h, but not limited thereto.

[0040] Specifically, during the research process, the inventors unexpectedly found that when KCoF4 and CsCoF4 are mixed as the fluorination reagent, 4,4'-difluorobenzophenone can be directly prepared from benzophenone via a fluorination reaction, and the purity of the crude 4,4'-difluorobenzophenone reaches more than 85%, with few by-products. Subsequently, a high-purity 4,4'-difluorobenzophenone product can be obtained through simple purification. This preparation process is simple, with less industrial waste, and the reaction conditions are relatively mild and the operation is simple. It should be noted that when only KCoF4 or CsCoF4 is used as the fluorination reagent, the purity of the obtained crude 4,4'-difluorobenzophenone is relatively low (≤60%), and the crude product yield is also relatively low.

[0041] Preferably, in some embodiments, the molar ratio of benzophenone, KCoF4, and CsCoF4 is 1:(0.62 to 0.75):(0.4 to 0.5); the weight ratio of the first solvent to benzophenone is (3 to 10):1; the reaction temperature is 120 to 200 °C, and the reaction duration is 5 to 15 h. Based on the above conditions, the purity of the crude 4,4'-difluorobenzophenone can reach more than 90%, and the crude product yield can reach more than 90%.

[0042] Preferably, in some embodiments, the molar ratio of benzophenone, KCoF4, and CsCoF4 is 1:(0.65 to 0.7):(0.4 to 0.48); the weight ratio of the first solvent to benzophenone is (3 to 8):1; the reaction temperature is 150 to 200 °C, and the reaction duration is 8 to 12 h. Based on the above conditions, the purity of the crude 4,4'-difluorobenzophenone can reach more than 91.5%, and the crude product yield can reach more than 94%.

[0043] Specifically, the crude 4,4'-difluorobenzophenone obtained in the present invention can be purified by dissolving it in a polar solvent for recrystallization. The polar solvent can be selected from one or more of methanol, ethanol, isopropanol, tert-butanol, butanone, methyl isobutyl ketone, and benzene, but not limited thereto.

[0044] Preferably, in some embodiments, the purification of the crude 4,4'-difluorobenzophenone includes: (1) Dissolve the crude 4,4'-difluorobenzophenone in a second solvent, cool down to a first preset temperature, and keep the temperature for a first preset time; then cool down to a second preset temperature, keep the temperature for a second preset time, and perform solid-liquid separation to obtain an intermediate product; (2) Dissolve the intermediate product in a third solvent, cool down to a third preset temperature, keep the temperature for a third preset time, and perform solid-liquid separation to obtain 4,4'-difluorobenzophenone; Among them, the second solvent is selected from one or more of methanol, ethanol, isopropanol, tert-butanol, methyl ethyl ketone, and methyl isobutyl ketone, but not limited thereto. The weight ratio of the second solvent to the crude 4,4'-difluorobenzophenone is 3:1, 4.5:1, 6:1, 7.5:1, or 9:1, but not limited thereto.

[0045] Among them, the third solvent is selected from one or more of benzene, toluene, chloroform, and carbon tetrachloride. The weight ratio of the third solvent to the crude 4,4'-difluorobenzophenone is (1-5):1, and exemplarily 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, or 4.5:1, but not limited thereto.

[0046] Among them, the first preset temperature is 20-35°C, and exemplarily 22°C, 24°C, 26°C, 28°C, 30°C, 32°C, or 34°C, but not limited thereto. The first preset time is 0.5-2.5 h, and exemplarily 0.8 h, 1.1 h, 1.4 h, 1.7 h, 2.0 h, or 2.3 h, but not limited thereto.

[0047] Among them, the second preset temperature is -5-10°C, and exemplarily -3°C, 0°C, 3°C, 6°C, or 9°C, but not limited thereto. The second preset time is 0.5-2.5 h, and exemplarily 0.8 h, 1.1 h, 1.4 h, 1.7 h, 2.0 h, or 2.3 h, but not limited thereto.

[0048] Among them, the third preset temperature is -5-10°C, and exemplarily -3°C, 0°C, 3°C, 6°C, or 9°C, but not limited thereto. The third preset time is 0.5-2.5 h, and exemplarily 0.8 h, 1.1 h, 1.4 h, 1.7 h, 2.0 h, or 2.3 h, but not limited thereto.

[0049] Based on the above purification steps, the by-product dicyclohexylmethanone in the crude product can be removed, and the product purity can be increased to more than 99.5%. It should be noted that the process of dissolving with a common polar solvent and then gradually cooling the temperature can only increase the purity to about 99%.

[0050] Preferably, in some embodiments, the second solvent is selected from methanol or ethanol, and the weight ratio of the second solvent to the crude 4,4'-difluorobenzophenone is (3-8):1; the third solvent is selected from benzene, and the weight ratio of the third solvent to the crude 4,4'-difluorobenzophenone is (1.5-4):1; the first preset temperature is 25-35°C, the first preset time is 0.8-2.5 h; the second preset temperature is 0-10°C, the second preset time is 0.8-2.5 h; the third preset temperature is 0-8°C, the third preset time is 0.8-2.5 h. Based on the above conditions, the purity of the product can be increased to more than 99.8%.

[0051] More preferably, in some embodiments, the first preset temperature is 30-35°C, the first preset time is 1-2 h; the second preset temperature is 0-5°C, the second preset time is 1-2 h; the third preset temperature is 0-5°C, the third preset time is 1-2 h.

[0052] The following further illustrates the present invention with specific examples: Example 1 This example provides a method for preparing 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 1000 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 750 g of DMF, add 29 g of KCoF4 and 32.3 g of CsCoF4, heat up to 110-115°C, keep the temperature for reaction for 18 h, cool down to room temperature, add the system to water, then extract with 200 mL of dichloroethane, and dry the obtained organic phase with anhydrous sodium sulfate to obtain 56.3 g of solid, and the crude product yield is 94.0%.

[0053] Add 150 g of methanol to the above solid, heat up to reflux until it becomes clear, cool down to 30-32°C and keep the temperature for 2 h, then cool down to 0-5°C and keep the temperature for 2 h, and filter to obtain 48 g of white solid, with a purity of 98.92% and a total yield of 80.5%.

[0054] Example 2 This example provides a method for preparing 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 500 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 150 g of DMSO, add 30.2 g of KCoF4 and 29.4 g of CsCoF4, heat up to 120-130°C, keep the temperature for reaction for 15 h, cool down to room temperature, add the system to water, then extract with 200 mL of dichloroethane, and dry the obtained organic phase with anhydrous sodium sulfate to obtain 57.4 g of solid, and the crude product yield is 95.8%.

[0055] Add 150 g of methanol to the above solid, heat it to reflux until clear, cool it to 30 - 32 °C and keep it warm for 2 h, then cool it to 0 - 5 °C, keep it warm for 2 h, and filter by suction to obtain a white solid; dissolve the white solid in 150 g of benzene, heat it to reflux until clear, then cool it to 0 - 5 °C, keep it warm for 2 h, and filter by suction to obtain the finished product, with a purity of 99.91% and a total yield of 87.0%.

[0056] Example 3 This example provides a preparation method of 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 500 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 150 g of DMSO, add 32.5 g of KCoF4 and 26.5 g of CsCoF4, heat it to 160 - 170 °C, keep it warm for reaction for 10 h, cool it to room temperature, add the system to water, then extract with 200 mL of dichloroethane, and dry the obtained organic phase with anhydrous sodium sulfate to obtain 58.2 g of solid, with a crude product yield of 97.2%.

[0057] Add 200 g of methanol to the above solid, heat it to reflux until clear, cool it to 30 - 32 °C and keep it warm for 2 h, then cool it to 0 - 5 °C, keep it warm for 2 h, and filter by suction to obtain a white solid; dissolve the white solid in 100 g of benzene, heat it to reflux until clear, then cool it to 0 - 5 °C, keep it warm for 2 h, and filter by suction to obtain the finished product, with a purity of 99.99% and a total yield of 90.8%.

[0058] Comparative Example 1 This example provides a preparation method of 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 1000 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 750 g of DMF, add 54.5 g of KCoF4, heat it to 110 - 115 °C, keep it warm for reaction for 18 h, cool it to room temperature, add the system to water, then extract with 200 mL of dichloroethane, and dry the obtained organic phase with anhydrous sodium sulfate to obtain 52.5 g of solid, with a crude product yield of 87.7%.

[0059] Add 150 g of methanol to the above solid, heat it to reflux until clear, cool it to 30 - 32 °C and keep it warm for 2 h, then cool it to 0 - 5 °C, keep it warm for 2 h, and filter by suction to obtain 26.5 g of white solid, with a purity of 99.11% and a total yield of 44.26%.

[0060] Comparative Example 2 This example provides a preparation method of 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 1000 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 750 g of DMF, add 69 g of CsCoF4, heat up to 110 - 115 °C, keep the temperature for reaction for 18 h, cool down to room temperature, add the system to water, then extract with 200 mL of dichloroethane, dry the obtained organic phase with anhydrous sodium sulfate, and obtain 53.6 g of solid. The crude product yield is 94.0%.

[0061] Add 150 g of methanol to the above solid, heat up to reflux until it becomes clear, cool down to 30 - 32 °C and keep the temperature for 2 h, then cool down to 0 - 5 °C and keep the temperature for 2 h, filter by suction to obtain 30.3 g of white solid, with a purity of 99.11% and a total yield of 50.6%.

[0062] Comparative Example 3 This example provides a preparation method of 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 1000 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 750 g of DMF, add 19.1 g of KCoF4 and 42.3 g of CsCoF4, heat up to 110 - 115 °C, keep the temperature for reaction for 18 h, cool down to room temperature, add the system to water, then extract with 200 mL of dichloroethane, dry the obtained organic phase with anhydrous sodium sulfate, and obtain 58.8 g of solid. The crude product yield is 98.2%.

[0063] Add 150 g of methanol to the above solid, heat up to reflux until it becomes clear, cool down to 30 - 32 °C and keep the temperature for 2 h, then cool down to 0 - 5 °C and keep the temperature for 2 h, filter by suction to obtain 36.2 g of white solid, with a purity of 98.57% and a total yield of 60.5%.

[0064] Comparative Example 4 This example provides a preparation method of 4,4'-difluorobenzophenone, which includes: Insert a thermometer into a 1000 mL three-necked flask, add 50 g of benzophenone to the reaction flask, add 750 g of DMF, add 43 g of KCoF4 and 12.1 g of CsCoF4, heat up to 110 - 115 °C, keep the temperature for reaction for 18 h, cool down to room temperature, add the system to water, then extract with 200 mL of dichloroethane, dry the obtained organic phase with anhydrous sodium sulfate, and obtain 56.8 g of solid. The crude product yield is 94.0%.

[0065] Add 150 g of methanol to the above solid, heat up to reflux until it becomes clear, cool down to 30 - 32 °C and keep the temperature for 2 h, then cool down to 0 - 5 °C and keep the temperature for 2 h, filter by suction to obtain 41.3 g of white solid, with a purity of 99.95% and a total yield of 69%.

[0066] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered to be within the scope described in this specification. The above-described embodiments only express several implementation manners of the present invention, which are convenient for understanding the technical solution of the present invention specifically and in detail, but should not be construed as a limitation on the protection scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention.

[0067] It should be understood that the technical solutions obtained by those skilled in the art based on the technical solutions provided by the present invention through logical analysis, reasoning or limited experiments are all within the protection scope of the appended claims of the present invention. Therefore, the protection scope of this invention patent should be determined by the content of the appended claims, and the specification can be used to explain the content of the claims.

Claims

1. A preparation method of 4,4'-difluorobenzophenone, characterized in that, Comprising: Mix benzophenone, KCoF4, CsCoF4, and a first solvent, and react at 100 - 250 °C to obtain crude 4,4'-difluorobenzophenone; Wherein, the molar ratio of the benzophenone, the KCoF4, and the CsCoF4 is 1:(0.6 - 0.8):(0.3 - 0.6); The first solvent is an aprotic polar solvent, and the weight ratio of the first solvent to the benzophenone is (1 - 20):

1.

2. The preparation method of 4,4'-difluorobenzophenone according to claim 1, characterized in that, The molar ratio of the benzophenone, the KCoF4, and the CsCoF4 is 1:(0.62 - 0.75):(0.4 - 0.5); and / or The weight ratio of the first solvent to the benzophenone is (3 - 10):

1.

3. The preparation method of 4,4'-difluorobenzophenone according to claim 1, characterized in that, The molar ratio of the benzophenone, the KCoF4, and the CsCoF4 is 1:(0.65 - 0.7):(0.4 - 0.48); and / or The weight ratio of the first solvent to the benzophenone is (3 - 8):

1.

4. The preparation method of 4,4'-difluorobenzophenone according to claim 1, characterized in that, The reaction temperature is 120 - 200 °C, and the reaction duration is 5 - 15 h.

5. The preparation method of 4,4'-difluorobenzophenone according to claim 1, characterized in that, The reaction temperature is 150 - 200 °C, and the reaction duration is 8 - 12 h.

6. The preparation method of 4,4'-difluorobenzophenone according to any one of claims 1 to 5, characterized in that, The first solvent is selected from one or more of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, dimethyl sulfone, and sulfolane.

7. The preparation method of 4,4'-difluorobenzophenone according to any one of claims 1 to 5, characterized in that, The first solvent is selected from N,N-dimethylformamide or dimethyl sulfone.

8. The preparation method of 4,4'-difluorobenzophenone according to claim 1, characterized in that, Also comprising: Dissolve the crude 4,4'-difluorobenzophenone in a second solvent, cool down to a first preset temperature, and keep warm for a first preset time; Then cool down to a second preset temperature, keep warm for a second preset time, and perform solid-liquid separation to obtain an intermediate product; Dissolve the intermediate product in a third solvent, cool down to a third preset temperature, keep warm for a third preset time, and perform solid-liquid separation to obtain 4,4'-difluorobenzophenone; Wherein, the second solvent is selected from one or more of methanol, ethanol, isopropanol, tert-butanol, butanone, and methyl isobutyl ketone; the weight ratio of the second solvent to the crude 4,4'-difluorobenzophenone is (2 - 10):1; The third solvent is selected from one or more of benzene, toluene, chloroform, and carbon tetrachloride; the weight ratio of the third solvent to the crude 4,4'-difluorobenzophenone is (1 - 5):

1.

9. The preparation method of 4,4'-difluorobenzophenone according to claim 8, characterized in that, The second solvent is selected from methanol or ethanol, and the weight ratio of the second solvent to the crude 4,4'-difluorobenzophenone is (3 - 8):1; and / or The third solvent is selected from benzene, and the weight ratio of the third solvent to the crude 4,4'-difluorobenzophenone is (1.5 - 4):1; and / or The first preset temperature is 25 - 35 °C, and the first preset time is 0.8 - 2.5 h; and / or The second preset temperature is 0 - 10 °C, and the second preset time is 0.8 - 2.5 h; and / or The third preset temperature is 0 - 8 °C, and the third preset time is 0.8 - 2.5 h.

10. The preparation method of 4,4'-difluorobenzophenone according to claim 8, characterized in that, The first preset temperature is 30 - 35 °C, and the first preset time is 1 - 2 h; and / or The second preset temperature is 0 - 5 °C, and the second preset time is 1 - 2 h; and / or The third preset temperature is 0 to 5 °C, and the third preset time is 1 to 2 h.

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