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CN-122010702-A - Synthesis method for preparing 4,4' -difluorobenzophenone by one-pot domino reaction

CN122010702ACN 122010702 ACN122010702 ACN 122010702ACN-122010702-A

Abstract

The invention relates to the technical field of fluorine-containing intermediate preparation, and discloses a synthetic method for preparing 4,4' -difluorobenzophenone by one-pot domino reaction. The invention aims to solve the problems of expensive raw materials, complex process, large pollution, low yield and purity and the like in the prior art. The method takes 4-fluorobenzoic acid and fluorobenzene as raw materials, and takes any one or more of trifluoromethanesulfonic anhydride, phosphorus pentoxide, trifluoroacetic anhydride or paraformaldehyde as an acid catalyst under the condition of no solvent, and the target product is directly prepared through one-pot reaction. And (3) recovering excessive fluorobenzene after the reaction is finished, extracting, alkaline washing, drying and concentrating to obtain a high-purity product, and acidifying the water phase to recover unreacted 4-fluorobenzoic acid. The method has the advantages of simple process, easily obtained raw materials, mild conditions and environment friendliness, realizes excellent effects of the 4-fluorobenzoic acid conversion rate of more than 99%, the product yield of more than 95% and the purity of more than 99%, and is suitable for industrial production.

Inventors

  • SHI YONGSEN
  • HE ZHENGBIAO

Assignees

  • 江苏三吉利化工股份有限公司

Dates

Publication Date
20260512
Application Date
20260109

Claims (9)

  1. 1. The synthesis method for preparing 4,4 '-difluorobenzophenone by one-pot domino reaction is characterized by taking 4-fluorobenzoic acid and fluorobenzene as raw materials, carrying out one-pot reaction under the condition of no solvent under the action of an acid catalyst, and carrying out post-treatment after the reaction is finished to obtain the 4,4' -difluorobenzophenone, wherein the specific steps are as follows: Step 1, in the reaction stage, adding an acid catalyst and fluorobenzene into a reaction bottle at a low temperature, stirring 1-10 min, adding 4-fluorobenzoic acid, stirring 5-20 min, and reacting 4-15 h at 50-90 ℃; the acid catalyst is any one or more of trifluoro methanesulfonic anhydride, phosphorus pentoxide, trifluoro acetic anhydride and paraformaldehyde; the molar ratio of the 4-fluorobenzoic acid to the fluorobenzene to the acid catalyst is 1 (6-18) (0.1-10.0); Step 2, after finishing the reaction, firstly recovering unreacted fluorobenzene, then pouring reaction residues into a first solvent with the volume of 6-18 times, stirring for 10-30 minutes, adding a second solvent with the volume of 0.1-0.5 time of the reaction residues for extraction, separating to obtain an organic phase containing a product, washing the organic phase with a third solvent with the volume of 0.1-0.5 time of the organic phase, separating, drying by inorganic salt, filtering, and concentrating to obtain 4,4' -difluorobenzophenone; adjusting the pH value of the washed alkaline aqueous phase to 1-6 by using a fourth solvent, and recovering unreacted 4-fluorobenzoic acid after extraction; The first solvent is one or more of 1, 2-dichloroethane, ethylene glycol dimethyl ether, tributyl phosphate, water, n-hexane, n-heptane or petroleum ether; The second solvent is one or more of ethyl acetate, dichloromethane and butyl acetate; the third solvent is one or more of saturated sodium carbonate, saturated potassium carbonate, saturated sodium bicarbonate and 10% sodium hydroxide; The fourth solvent is an acidic solution.
  2. 2. The synthesis method according to claim 1, wherein the low temperature of step 1 is 0-10 ℃, the stirring time of adding the acid catalyst and fluorobenzene in the reaction bottle in step 1 is 5-8min, the stirring time of adding 4-fluorobenzoic acid is 10-15 min, the reaction temperature of step 1 is 60-85 ℃, and the reaction time is 6-10 h.
  3. 3. The synthesis method according to claim 1, wherein the molar ratio of 4-fluorobenzoic acid, fluorobenzene and acid catalyst in the step 1 is 1 (8-12) (0.5-4.0).
  4. 4. The synthesis method according to claim 1, wherein the fluorobenzene is recovered in the step 2 by vacuum distillation or atmospheric distillation, the first solvent in the step 2 is water, the first solvent is 8-15 times the volume of the reaction residue, and the stirring time in the step 2 is 15-20 min.
  5. 5. The method of claim 1, wherein the second solvent in the step 2 is 0.15 to 0.3 times the volume of the reaction residue.
  6. 6. The method of claim 1, wherein the third solvent in the step 2 is 0.15 to 0.3 times the volume of the organic phase.
  7. 7. The method of claim 1, wherein the inorganic salt in step 2 is a conventional water-removing inorganic salt, including, but not limited to, anhydrous sodium sulfate, anhydrous potassium sulfate, and anhydrous calcium chloride.
  8. 8. The method according to claim 1, wherein the acidic solution is glacial acetic acid, 10% dilute hydrochloric acid or 10% dilute sulfuric acid.
  9. 9. The synthesis method according to claim 1, wherein the pH in the step 2 is 2 to 3.

Description

Synthesis method for preparing 4,4' -difluorobenzophenone by one-pot domino reaction Technical Field The invention relates to the technical field of preparation of fluorine-containing intermediates, in particular to a synthetic method for preparing 4,4' -difluorobenzophenone by one-pot domino reaction. Background The 4,4' -Difluorobenzophenone (DFBP) has symmetrical molecular structure and high reactivity, and is an important fluorine-containing organic fine chemical intermediate and medical intermediate. The DFBP has relatively concentrated application, and is mainly used as a synthetic monomer for synthesizing high-performance special engineering plastics, such as Polyaryletherketone (PAEK), polyetherketone (PEK) and Polyetheretherketone (PEEK). The high-performance special plastic has excellent mechanical property, chemical corrosion resistance, high temperature resistance and flame retardance, and is widely applied to high-end fields such as aerospace, medical equipment, automobile manufacturing, electronic appliances and the like. In addition, in the field of pharmaceutical intermediates, flunarizine for synthesizing cerebral vasodilation, duloxetine for treating diabetes, amitraz for treating senile dementia and the like are used. DFBP can also be used for synthesizing other fine chemicals such as pesticides, dyes, electronic chemicals, etc. Along with the increasing demand, the synthesis process of DFBP is also valued by scientific researchers, and the innovation and optimization of the preparation process are important research subjects in the field of organic synthesis. The synthesis of DFBP mainly includes the following classes: The main method in China is to take fluorobenzene and 4-fluorobenzoyl chloride as raw materials, and obtain a product after F-C acylation, hydrolysis and rectification under the catalysis of Lewis acid (including anhydrous aluminum trichloride, ferric trichloride, boron trifluoride, trifluoromethanesulfonic acid and the like). The method has better selectivity (the purity is more than or equal to 99.5 percent) and higher yield (85-90 percent), but the used 4-fluorobenzoyl chloride has high price, air sensitivity, and byproducts cannot be directly utilized, and a large amount of aluminum-containing wastewater can be generated, so that the method has the advantages of difficult treatment, high environmental pressure and high comprehensive cost. The DFBP is prepared by using fluorobenzene and carbon tetrachloride as raw materials, generating an intermediate through F-C alkylation, and then hydrolyzing, distilling and recrystallizing. The method has low cost and mild reaction conditions, but the product of the method contains a large amount of ortho-substituted isomers, so that the total yield is about 63.9%, and the carbon tetrachloride has high toxicity and high hazard, the raw materials are difficult to obtain, the equipment is severely corroded, and the method is basically eliminated; 4,4' -dichloro diphenyl ketone is used as a raw material, and reacts with KF or KOH under high temperature and strong alkaline conditions to replace chlorine atoms to generate fluoroketone, the molecular structure of the method accords with atom economy, but the reaction condition is harsh, high temperature (200 ℃) and strong alkaline conditions are needed, the halogen exchange reaction is reversible, the conversion rate and selectivity are difficult to control, and repeated recrystallization is needed; 4,4' -diaminodiphenyl methane is taken as a raw material, diazotized to generate diazonium salt, and then fluorinated reaction and oxidation reaction are carried out to obtain the target product. The method is also one of the mainstream industrial routes at home and abroad at present, can directly introduce fluorine atoms, is simple to operate, has few impurities (purity is more than or equal to 90%), and has high yield (70% -80%), but the diazotization reaction has explosion risk, excessive hazard degree, strong HF corrosiveness and serious equipment corrosion. The method has the advantages that fluorobenzene, phosgene and boron trifluoride are used as raw materials, fluoroketone is generated at high temperature and high pressure, the process is simple, the target product is generated by one-step reaction, but the phosgene is high-toxic gas, the operation is dangerous, 25% of 2,4' -isomer is a byproduct, and the separation is difficult. In recent years, some of the materials are fluoroboric acid and carbon monoxide, and DFBP is prepared under the catalysis of metals such as palladium, nickel, iron and the like, so that the reaction yield is high, the reaction rate is high, but the materials are expensive, the reaction conditions are severe, and the method is not suitable for large-scale production. In summary, the prior reported synthesis method of DFBP has the problems of complex process, long time consumption, high energy consumption, high risk, difficult catalyst recovery, expensive raw ma