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CN-118420536-B - Preparation method and application of o-pyrazolyl propiophenone derivatives

CN118420536BCN 118420536 BCN118420536 BCN 118420536BCN-118420536-B

Abstract

The invention discloses a preparation method and application of an o-pyrazolyl propiophenone derivative; according to the invention, an o-pyrazolyl phenylketonurine derivative is obtained by dispersing an o-pyrazolyl phenylpropenol compound, an aryl aldehyde compound and a catalyst in an organic solvent for reaction. The synthesis method of the o-pyrazolyl propiophenone derivatives has the advantages of low raw material cost, simplicity, convenience, high efficiency, mild reaction conditions, high atom economy, easy purification of products, green economy and the like, and the obtained products can be directly applied to the field of medicines as potential medicines, and have wide application prospects.

Inventors

  • ZENG WEI
  • Xuan Yanshuo

Assignees

  • 华南理工大学

Dates

Publication Date
20260505
Application Date
20240318

Claims (9)

  1. 1. The preparation method of the o-pyrazolyl propiophenone derivatives is characterized by comprising the following steps of: Dispersing an o-pyrazolyl phenylpyryl alcohol compound, an aryl aldehyde compound and a catalyst in an organic solvent for reaction to obtain an o-pyrazolyl phenylpyryl ketone derivative, wherein the structural formula of the o-pyrazolyl phenylpyryl alcohol compound is shown as a formula A, the structural formula of the aryl aldehyde compound is CHO-R 6 , and the structural formula of the o-pyrazolyl phenylpyryl ketone derivative is shown as a formula B: R 1 is selected from one of methyl and H, R 2 is selected from one of-H, methoxy and methyl, R 3 is selected from one of-H, methyl, halogen and-CF 3 , R 4 is selected from one of-H and methyl, R 5 is selected from one of-H and methyl, R 6 is selected from one of 4-methylphenyl, phenyl, 4-halogenophenyl, 4-CF 3 phenyl, 2-fluoro-5-CF 3 phenyl, 4-methoxyphenyl, 2-methylphenyl, 2-fluorophenyl, 3-methylphenyl, 3-bromo-4-methylphenyl, 4-tert-butylphenyl, 2-naphthyl, 2-thienyl, 2-furyl and 2-fluoro-5-methylphenyl, the catalyst is manganese (I) pentacarbonyl bromide, the reaction is further added with Lewis acid, the Lewis acid comprises zinc bromide, magnesium oxide and dimethyl zinc, and the molar ratio of the zinc bromide, the magnesium oxide, the dimethyl zinc to the o-pyrazolyl propenol compound is 0.8:1.1-2.8:1.1.
  2. 2. The method for synthesizing an o-pyrazolyl propiophenone derivatives according to claim 1, wherein the organic solvent is diethylene glycol dimethyl ether.
  3. 3. The method for synthesizing o-pyrazolyl propiophenone derivatives according to claim 1, wherein the molar ratio of the o-pyrazolyl propiophenone alcohol compound to the catalyst is 1:0.1-0.2.
  4. 4. The method for synthesizing the o-pyrazolyl propiophenone derivatives according to claim 1, wherein the molar ratio of the o-pyrazolyl propiophenone alcohol compound to the organic solvent is 1:6-8.
  5. 5. The method for synthesizing the o-pyrazolyl propiophenone derivatives according to claim 1, wherein the molar ratio of the o-pyrazolyl propiophenone alcohol compounds to the aryl aldehyde compounds is 1:2-3.
  6. 6. The method for synthesizing the o-pyrazolyl propiophenone derivatives according to claim 1, wherein the reaction temperature is 90-110 ℃, and the reaction time is 4-12 hours.
  7. 7. The method for synthesizing an O-pyrazolyl propiophenone derivative according to claim 1, wherein the O-pyrazolyl propiophenone derivative is separated and purified by column chromatography.
  8. 8. The method for synthesizing an O-pyrazolyl propiophenone derivatives according to claim 7, wherein the eluent used in the column chromatography consists of petroleum ether and ethyl acetate.
  9. 9. Use of the preparation method according to any one of claims 1 to 8 for preparing 1, 5-diphenyl-3-carbonyl-1-pentene compounds, characterized in that the o-pyrazolyl-phenylpropanone derivatives prepared by the preparation method according to any one of claims 1 to 8 are subjected to pyrazolyl removal to obtain 1, 5-diphenyl-3-carbonyl-1-pentene compounds.

Description

Preparation method and application of o-pyrazolyl propiophenone derivatives Technical Field The invention relates to the technical field of synthesis of organic compounds, in particular to a preparation method and application of an o-pyrazolyl phenylketonurine derivative. Background The unsaturated bond, carbonyl and other reaction sites contained in the unsaturated ketone compound structural unit can be easily converted by 1, 4-conjugate addition, aldol reaction and the like. Therefore, as an organic synthetic building block with extremely high application potential, the unsaturated ketone compound is widely applied to the fields of perfume, biochemistry, agriculture, food chemistry, polymer material science and the like. Also for this reason, methods for synthesizing unsaturated ketone compounds have been attracting attention in both academia and industry. The traditional method for constructing unsaturated ketone skeleton mainly comprises witig reaction, homer-Wadsworth-Emmons reaction, aldol reaction and Claisen-Schmidt condensation reaction (Kreher,U.;Rosamilia,A.;Raston,C.;Scott,J.;Strauss,C.;Direct Preparation of Monoarylidene Derivatives of Aldehydes and Enolizable Ketones with DIMCARB.[J]Org.Lett.2003,5,17,3107–3110)., and new methods for synthesizing unsaturated ketone by using metal catalysis are developed later (Wu,X.;Neumann,H.;Spannenberg,A.;Schulz,T.;Jiao,H.;Beller,M.Development of aGeneral Palladium-Catalyzed Carbonylative Heck Reaction of Aryl Halides.[J]J.Am.Chem.Soc.2010,132,41,14596–14602). The o-pyrazolyl propiophenone derivatives have good application prospect as potential drug molecular frameworks and natural product framework molecules, and the pyrazole derivatives have the effects of resisting microorganisms, tumors, viruses, tuberculosis, malaria, diabetes, urination, convulsion, depression, obesity, fever and the like. Therefore, the development of the synthesis method of the o-pyrazolyl propiophenone derivatives has the advantages of low raw material cost, simplicity, convenience, high efficiency, mild reaction conditions, high atom economy, easy purification of products, green economy and the like, and has very important significance. Disclosure of Invention Aiming at the defects existing in the prior art, the invention aims to provide a preparation method and application of an o-pyrazolyl phenylketonurine derivative. The technical scheme adopted by the invention is as follows: a preparation method of an o-pyrazolyl propiophenone derivative comprises the following steps: Dispersing an o-pyrazolyl phenylpyryl alcohol compound, an aryl aldehyde compound and a catalyst in an organic solvent for reaction to obtain an o-pyrazolyl phenylpyryl derivative, wherein the structural formula of the o-pyrazolyl phenylpyryl alcohol compound is shown as a formula A, the structural formula of the aryl aldehyde compound is CHO-R 6, and the structural formula of the o-pyrazolyl phenylpyryl derivative is shown as a formula B: Wherein R 1 is selected from one of methyl and H, R 2 is selected from one of-H, methoxy and methyl, R 3 is selected from one of-H, methyl, halogen and-CF 3, R 4 is selected from one of-H and methyl, R 5 is selected from one of-H and methyl, R 6 is selected from one of 4-methylphenyl, phenyl, 4-halogenated phenyl, 4-CF 3 phenyl, 2-fluoro-5-CF 3 phenyl, 4-methoxyphenyl, 2-methylphenyl, 2-fluorophenyl, 3-methylphenyl, 3-bromo-4-methylphenyl, 4-tert-butylphenyl, 2-naphthyl, 2-thienyl, 2-furyl and 2-fluoro-5-methylphenyl, and the catalyst is manganese (I) pentacarbonyl bromide. Preferably, the organic solvent is diethylene glycol dimethyl ether. Preferably, the molar ratio of the o-pyrazolyl phenyl propenol compound to the catalyst is 1:0.1-0.2. Further preferably, the molar ratio of the o-pyrazolyl phenyl propenol compound to the catalyst is 1:0.2. Preferably, the molar ratio of the enol compound to the organic solvent is 1:6-8. Preferably, the molar ratio of the o-pyrazolyl phenyl propenol compound to the aryl aldehyde compound is 1:2-3. Preferably, the reaction also adds a lewis acid; further preferred, the lewis acid comprises zinc bromide, magnesium oxide, and dimethyl zinc; More preferably, the molar ratio of the zinc bromide to the magnesium oxide to the dimethyl zinc to the o-pyrazolyl phenyl propenol compound is 0.8-1.2:0.8-1.2:1. Preferably, the reaction temperature is 90-110 ℃. Preferably, the reaction time is 4-12 hours. Preferably, the o-pyrazolyl propiophenone derivatives are separated and purified by column chromatography. Further preferably, the eluent used in the column chromatography consists of petroleum ether and ethyl acetate. Application of the preparation method in preparation of 1, 5-diphenyl-3-carbonyl-1-pentene compounds, removing pyrazolyl from the o-pyrazolyl phenylketonuri derivative prepared by the preparation method (reference for removing pyrazolyl: CHEM ASIAN J.2020,15,1941-1944; J.am. Chem. Soc.2020,142, 7345-7349) to obtain 1, 5-diphenyl-3-carbon