Search

CN-122010709-A - Preparation method and application of fluorine-containing aryl ketone compound

CN122010709ACN 122010709 ACN122010709 ACN 122010709ACN-122010709-A

Abstract

The invention discloses a preparation method and application of a fluorine-containing aryl ketone compound, and relates to the technical field of organic synthesis, comprising the following steps of taking fluorine-containing olefin, benzoyl cyanide compound and boric acid compound as raw materials, and carrying out visible light irradiation reaction in the presence of a photocatalyst, alkali and an organic solvent to prepare the fluorine-containing aryl ketone compound; the invention uses fluoroolefin as a key fluorosubstrate, realizes multi-component synergistic reaction through visible light catalysis, solves the problems of substrate limitation, poor selectivity, low yield and the like in the existing method, and the prepared fluoroaryl ketone compound can be used for preparing antibacterial, anti-inflammatory and anticancer drugs and has higher economic benefit.

Inventors

  • SHEN YONGMIAO
  • JI ZHENGKAI
  • YU JIAKAI
  • WU ZHIXIONG
  • XI ZIWEI

Assignees

  • 浙江理工大学
  • 浙江巍华新材料股份有限公司

Dates

Publication Date
20260512
Application Date
20260414

Claims (10)

  1. 1. A fluorine-containing aryl ketone compound is characterized by having the following structural formula: ; Wherein R 1 is selected from aryl or substituted aryl, alkyl or substituted alkyl, R 2 is selected from aryl or substituted aryl, and R 3 is selected from hydrogen, fluorine or methyl.
  2. 2. A fluorine-containing aryl ketone compound according to claim 1, wherein R 1 is selected from one of p-tolyl, phenethyl and n-butyl, and R 2 is selected from one of phenyl, p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-trifluoromethylphenyl, p-tert-butylphenyl and p-methoxyphenyl.
  3. 3. The method according to claim 1, wherein the fluorinated aryl ketone compound is any one of the following structural formulas: 。
  4. 4. A process for preparing fluorine-containing aryl ketone compound, as claimed in claim 1, characterized in that fluorine-containing olefin, benzoyl cyanide compound and boric acid compound are used as raw materials, and the fluorine-containing aryl ketone compound is prepared by irradiation reaction of visible light in the presence of photocatalyst, alkali and organic solvent.
  5. 5. The method for preparing a fluorine-containing aryl ketone compound according to claim 4, wherein the fluorine-containing olefin is alpha-trifluoromethyl olefin, the benzoyl cyanide compound is any one of benzoyl cyanide, o-methyl benzoyl cyanide and o-fluorobenzoyl cyanide, and the boric acid compound is aryl boric acid or alkyl boric acid.
  6. 6. The method for preparing a fluorine-containing aryl ketone compound according to claim 5, wherein: the alpha-trifluoromethyl olefin is (3, 3-trifluoro-1-en-2-yl) benzene, 1-chloro-4- (3, 3-trifluoro-1-en-2-yl) benzene, 1-fluoro-4- (3, 3-trifluoro-1-en-2-yl) benzene, 1-bromo-4- (3, 3-trifluoro-1-en-2-yl) benzene 1- (trifluoromethyl) -4- (3, 3-trifluoroprop-1-en-2-yl) benzene, 1- (tert-butyl) -4- (3, 3-trifluoroprop-1-enyl) benzene, or 1- (methoxy) -4- (3, 3-trifluoroprop-1-enyl) benzene.
  7. 7. The method for preparing a fluorine-containing aryl ketone compound according to claim 4, wherein the organic solvent is any one of acetonitrile, dimethyl sulfoxide, tetrahydrofuran, ethanol, N-dimethylformamide, acetone, methylene chloride, ethyl toluate, N-methylpyrrolidone, 1, 4-dioxane, cyclohexane, methyl tert-butyl ether and chlorobenzene, and the base is any one of cesium carbonate, cesium acetate, potassium carbonate, potassium phosphate, potassium acetate, potassium hydroxide, sodium carbonate, sodium hydroxide and potassium benzoate.
  8. 8. The method for preparing a fluorine-containing aryl ketone compound according to claim 4, wherein the photocatalyst is any one of Ir[dF(Me)ppy] 2 (dtbbpy)PF 6 、[Ir(dtbbpy)(ppy) 2 ]PF 6 、Ir[dF(CF 3 )ppy] 2 (bpy)PF 6 、4CzIPN、3DPA2FBN%, and the amount of the photocatalyst is 1-5% mol% of benzoyl cyanide.
  9. 9. The method for preparing a fluorine-containing aryl ketone compound according to claim 4, wherein the visible light is blue light with a wavelength of 420-460 nm, the temperature of the visible light irradiation reaction is 20-30 ℃, and the reaction time is 12-36 hours.
  10. 10. Use of the fluorine-containing aryl ketone compound according to claim 1 in the synthesis of antibacterial drugs.

Description

Preparation method and application of fluorine-containing aryl ketone compound Technical Field The invention relates to the technical field of organic synthesis, in particular to a preparation method and application of a fluorine-containing aryl ketone compound. Background The fluorine-containing organic compound has irreplaceable application value in the fields of medicines, pesticides, functional materials and the like due to the unique physicochemical properties and biological activities. The alpha-branched fluorine-containing aryl ketone compound is taken as an important fluorine-containing synthetic building block, and trifluoromethyl (-CF 3) in the molecular structure of the building block not only can obviously improve the fat solubility, metabolic stability and bioavailability of the compound, but also can derive various high-value functional molecules through structural modification, thereby having wide prospect in the research and development of medicines, antitumor preparations and high-performance materials. At present, the method for synthesizing the alpha-branched fluorine-containing aryl ketone compound has a plurality of limitations that the traditional method relies on cross coupling reaction catalyzed by transition metal (such as palladium and rhodium), expensive noble metal catalyst, complex ligand and harsh reaction conditions (high temperature and strong alkali) are needed, the atom economy is low, and the partial photocatalysis method has mild conditions but is limited by specific fluorine-containing substrates, cannot be efficiently compatible with fluorine-containing olefin with high steric hindrance such as alpha-trifluoromethyl olefin, and has the problems of poor product regioselectivity, low functional group tolerance and the like. In addition, the prior art is difficult to accurately control the position of trifluoromethyl in molecules, so that the yield of target products is low, and the industrial production requirement is difficult to meet. Alpha-trifluoromethyl olefin is taken as an important fluorine-containing synthon, and the synergic action of C=C double bond and trifluoromethyl makes the alpha-trifluoromethyl olefin have unique reactivity, but the difunctional reaction participated by the alpha-trifluoromethyl olefin faces the challenges of difficult control of regioselectivity, multiple side reactions and the like due to the strong electron withdrawing effect and the steric hindrance effect of the trifluoromethyl. Therefore, the development of a mild, efficient and high-selectivity alpha-branched fluorine-containing aryl ketone synthesis method with alpha-trifluoromethyl olefin as a core substrate has important significance for promoting the synthesis innovation and industrial application of fluorine-containing organic compounds. Disclosure of Invention In view of the shortcomings in the prior art, a first aspect of the present invention is to provide a fluorine-containing aryl ketone compound. The technical scheme adopted by the invention is as follows: A fluorine-containing aryl ketone compound has the structural formula as follows: ; Wherein R 1 is selected from aryl or substituted aryl, alkyl or substituted alkyl, R 2 is selected from aryl or substituted aryl, and R 3 is selected from hydrogen, fluorine or methyl. Further, R 1 is selected from one of p-tolyl, phenethyl and n-butyl, and R 2 is selected from one of phenyl, p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-trifluoromethylphenyl, p-tert-butylphenyl, p-methoxyphenyl and the like. Still further, the fluorine-containing aryl ketone compound is any one of the following structural formulas: 。 the second aspect of the invention aims to provide a preparation method of the fluorine-containing aryl ketone compound, which has the advantages of easily available raw materials, mild conditions and high regioselectivity. The technical scheme adopted by the invention is as follows: A process for preparing fluorine-contained aryl ketone compound includes such steps as preparing fluorine-contained aryl ketone compound from fluorine-contained olefin, benzoyl cyanide compound and boric acid compound, and irradiation reaction by visible light in the presence of photocatalyst, alkali and organic solvent. The invention uses fluorine-containing olefin as a key fluorine-containing substrate, realizes multi-component synergistic reaction through visible light catalysis, solves the problems of substrate limitation, poor selectivity, low yield and the like in the existing method, and simultaneously expands the application scene of the fluorine-containing compound. The further arrangement is that: The fluorine-containing olefin is alpha-trifluoromethyl olefin; it is particularly preferred that the composition, the alpha-trifluoromethyl olefin is (3, 3-trifluoro-1-en-2-yl) benzene, 1-chloro-4- (3, 3-trifluoro-1-en-2-yl) benzene, 1-fluoro-4- (3, 3-trifluoro-1-en-2-yl) benzene, 1-bromo-4- (3, 3-trifluoro-1-en-2-yl) benzene 1- (triflu