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CN-121991014-A - Method for preparing polyfluoroalkyl coumarin derivative

CN121991014ACN 121991014 ACN121991014 ACN 121991014ACN-121991014-A

Abstract

The application discloses a method for preparing a polyfluoroalkyl coumarin derivative, and belongs to the field of organic synthesis. The method utilizes the cheap and easily available polyfluorocarboxylic anhydride as a polyfluoroalkylating reagent and combines the in-situ activation of NHPI to prepare the coumarin derivative substituted by the C3-polyfluoroalkyl. Under the condition of visible light catalysis, using polyfluoroalkyl carboxylic anhydride as polyfluoroalkylating reagent, generating polyfluoroalkyl free radical through NHPI in-situ activation, and carrying out free radical cyclization rearrangement reaction on the free radical and aromatic propiolate, thus finally realizing the preparation of the C3-polyfluoroalkyl substituted coumarin derivative. The polyfluoroalkyl carboxylic anhydride used by the method has stable property, is cheap and easy to obtain, and reduces the synthesis cost. The application range of the substrate is wide, a plurality of polyfluoroalkyl carboxylic acid anhydrides can be applied, and the tolerance of the functional group of the reaction is good.

Inventors

  • ZHANG MIN
  • SHEN LUJIE
  • LIANG PINGPING
  • Kan jian
  • REN YUXI
  • SU WEIPING

Assignees

  • 闽都创新实验室
  • 中国科学院福建物质结构研究所

Dates

Publication Date
20260508
Application Date
20241105

Claims (10)

  1. 1. A method for preparing a polyfluoroalkyl coumarin derivative, which is characterized in that a mixture containing a compound I, polyfluoroalkyl carboxylic anhydride, an activating reagent, a photocatalyst and a solvent is subjected to illumination reaction in an inactive atmosphere to obtain the polyfluoroalkyl coumarin derivative; the compound I has a structural formula shown as a formula (I): The polyfluoroalkyl carboxylic anhydride has a structural formula shown in a formula (II): The polyfluoroalkyl coumarin derivative has a structural formula shown in a formula (III): wherein R 1 is selected from one of hydrogen, alkyl, alkoxy, halogen, cyano, trifluoromethyl, trifluoromethoxy and ester group; R 2 is one of aryl and substituted aryl; Rf is selected from one of CF 2 H、CF 3 、C 2 F 5 、CF 2 Cl; the activating reagent is selected from N-hydroxyphthalimide.
  2. 2. The method according to claim 1, wherein the alkyl group has 1 to 6 carbon atoms; the carbon number of the alkoxy is 1-6; The aryl is selected from one of phenyl and biphenyl; the substituent of the substituted aryl is selected from one of alkyl, alkoxy and halogen.
  3. 3. The method according to claim 1, wherein the molar ratio of the compound I to the polyfluoroalkyl carboxylic anhydride is 1:1-5.
  4. 4. The method according to claim 1, wherein the molar ratio of the compound I to the activating reagent is 1:1-5.
  5. 5. The method of claim 1, wherein the photocatalyst is selected from at least one of Ru (bpy) 3 Cl 2 、Ir(ppy) 3 、Ru(bpy) 3 (PF 6 ) 2 .
  6. 6. The method according to claim 1, wherein the amount of photocatalyst is 0.5 to 5mol%, based on the molar equivalent of compound I.
  7. 7. The method according to claim 1, wherein the solvent is selected from at least one of 1, 2-dichloroethane, dichloromethane, acetonitrile.
  8. 8. The method according to claim 1, wherein the photoreaction is a stirred reaction under blue light irradiation of 3W x 3450 nm.
  9. 9. The method according to claim 1, wherein the reaction temperature is 20-35 ℃, and the reaction time is 1-72 hours.
  10. 10. The method of claim 1, further comprising the steps of suction filtration, spin drying, and column purification with petroleum ether and ethyl acetate after the illumination reaction.

Description

Method for preparing polyfluoroalkyl coumarin derivative Technical Field The application relates to a method for preparing a polyfluoroalkyl coumarin derivative, belonging to the field of organic synthesis. Background Coumarin derivatives are organic compounds with important application value, can be used as important structures of natural products and drug molecules, and have special luminescence characteristics after being excited by light due to inherent charge transfer characteristics, so that the coumarin derivatives have wide application in the fields of photoelectrons, dye-sensitized solar cells, cell imaging, fluorescent probes and the like. It is well known that the incorporation of fluorine atoms or fluorine-containing groups in organic functional compounds can enhance their physicochemical, biological and pharmacological properties. Therefore, there has been great interest in the synthesis of polyfluoroalkyl-substituted coumarin derivatives by synthetic chemists. The existing method for synthesizing the 3-fluoroalkyl substituted coumarin derivative by utilizing the visible light catalytic technology comprises the steps of (1) taking difluoromethyl benzothiazole sulfone or [ bis (difluoroacetoxy) iodine ] benzene as a difluoromethylating reagent, and obtaining the C3-difluoromethyl substituted coumarin derivative by the free radical cyclization reaction of aromatic propiolate. These difluoromethylating agents require a preliminary synthesis step, and in particular the synthesis of difluoromethyl benzothiazole sulfones requires a multi-step reaction. (2) Is prepared by the direct functionalization reaction of coumarin compound under the catalysis of Eosin Y by taking CF 2HSO2 Na as a difluoromethylating reagent. The sodium difluoromethylsulfinate used in this process is expensive. (3) CF 3SO2 Cl is used as a trifluoromethylating reagent, and the free radical cyclization reaction of the aromatic propiolate is used for respectively obtaining the coumarin derivative substituted by the trifluoromethyl at the C3-position. The CF 3SO2 Cl used in the reaction is expensive, and the reaction system needs to be heated. These developed methods have the disadvantage of the price of the polyfluoroalkylating agent and the cumbersome pre-preparation steps, and have the general limitation that the system is limited to single trifluoro or difluoromethyl functionalization, and the general system has not been reported. Disclosure of Invention The application provides a visible light catalyzed free radical pathway, which takes phenylpropionate as a substrate, uses simple and easily available polyfluoroalkyl carboxylic anhydride as a polyfluoroalkyl source, generates polyfluoroalkyl free radicals through in-situ activation of N-hydroxyphthalimide (NHPI), and generates free radical cyclization rearrangement reaction with aromatic propiolate to obtain 3-polyfluoroalkyl coumarin derivatives with high yield. The application uses the polyfluoroalkyl carboxylic anhydride as polyfluoroalkyl source, and has the advantages of cheap and easily obtained raw materials and simple and convenient operation. The established conditions are universal and can be suitable for introducing difluoromethyl, trifluoromethyl, pentafluoroethyl and difluorochloromethyl. According to one aspect of the present application, a method of preparing a polyfluoroalkyl coumarin derivative is provided. Under the condition of visible light catalysis, using polyfluoroalkyl carboxylic anhydride as polyfluoroalkylating reagent, generating polyfluoroalkyl free radical through NHPI in-situ activation, and carrying out free radical cyclization rearrangement reaction on the free radical and aromatic propiolate, thus finally realizing the preparation of the C3-polyfluoroalkyl substituted coumarin derivative. A method for preparing polyfluoroalkyl coumarin derivative, comprising the steps of carrying out illumination reaction on a mixture containing a compound I, polyfluoroalkyl carboxylic anhydride, an activating reagent, a photocatalyst and a solvent in an inactive atmosphere to obtain the polyfluoroalkyl coumarin derivative; the compound I has a structural formula shown as a formula (I): The polyfluoroalkyl carboxylic anhydride has a structural formula shown in a formula (II): The polyfluoroalkyl coumarin derivative has a structural formula shown in a formula (III): wherein R 1 is selected from one of hydrogen, alkyl, alkoxy, halogen, cyano, trifluoromethyl, trifluoromethoxy and ester group; R 2 is one of aryl and substituted aryl; Rf is selected from one of CF 2H、CF3、C2F5、CF2 Cl; the activating reagent is selected from N-hydroxyphthalimide. Optionally, the carbon number of the alkyl is 1-6; the carbon number of the alkoxy is 1-6; The aryl is selected from one of phenyl and biphenyl; the substituent of the substituted aryl is selected from one of alkyl, alkoxy and halogen. Wherein alkyl, alkoxy includes a straight, branched or cyclic chain. Optionally, the molar