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CN-116041241-B - Method for synthesizing pyrrole compound by solid acid catalysis

CN116041241BCN 116041241 BCN116041241 BCN 116041241BCN-116041241-B

Abstract

The invention discloses a method for synthesizing pyrrole compounds by solid acid catalysis. The method comprises the steps of carrying out one-pot reaction on a beta-nitrostyrene compound shown in a formula (1), acetyl acetate shown in a formula (2) and primary amine shown in a formula (3) in a solvent in the presence of a carbon-based solid acid catalyst, and carrying out post-treatment on a reaction solution after the reaction is finished to obtain a polysubstituted pyrrole compound shown in a formula (4), wherein in the preparation of the polysubstituted pyrrole compound, the preparation can be carried out smoothly under the catalysis of the carbon-based solid acid without other additives, and the method is safe and environment-friendly, has mild reaction conditions, and has the following reaction formula: in the formula (1) to the formula (4), the substituent R 1 is H, C-C5 straight-chain or branched-chain alkyl or alkoxy, halogen, nitro and the like, the substituent R 2 is C1-C10 straight-chain or branched-chain alkyl, C5-C6 cycloalkyl, benzyl and the like, and the substituent R 3 is selected from C1-C5 straight-chain or branched-chain alkyl, phenyl, benzyl or substituted benzyl.

Inventors

  • LI YUJIN
  • HUANG CHENXI
  • WEI JIE
  • YE QING
  • HAN LIANG
  • LI XINYUE

Assignees

  • 浙江工业大学

Dates

Publication Date
20260505
Application Date
20221226

Claims (7)

  1. 1. A method for synthesizing pyrrole compounds by solid acid catalysis is characterized in that beta-nitrostyrene compounds shown in a formula (1), acetyl acetate shown in a formula (2) and primary amine shown in a formula (3) are taken as raw materials, carbon-based solid acid is taken as a catalyst, the raw materials and the catalyst are added into a solvent for one-pot reaction, and after the reaction is finished, a reaction solution is subjected to post-treatment to obtain a polysubstituted pyrrole compound shown in a formula (4) as a target product; the reaction formula is as follows: , in the formula (1) and the formula (4), the substituent R 1 is H, C-C5 straight-chain or branched-chain alkyl or alkoxy, halogen or nitro; In the formulas (2) and (4), the substituent R 3 is selected from C1-C5 straight-chain or branched-chain alkyl, phenyl and benzyl; In the formulas (3) and (4), the substituent R 2 is C1-C10 straight-chain or branched-chain alkyl, C5-C6 cycloalkyl, benzyl and phenyl; the carbon-based solid acid has carbon-based white sugar, glucose, starch or furfural, and the acid source is trifluoromethanesulfonic acid, sulfuric acid, p-toluenesulfonic acid or hydroxyethanesulfonic acid.
  2. 2. The method for synthesizing pyrrole compounds by using solid acid as catalyst according to claim 1, wherein carbon in the carbon-based solid acid is furfural, the acid source is trifluoromethanesulfonic acid, the mass of the carbon-based solid acid is 1% -5% of the molar amount of beta-nitrostyrene compounds shown in formula (1), the mass unit is g, and the molar unit is mmoL.
  3. 3. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, wherein the solvent is a protic solvent which is methanol, ethanol or water, the ratio of the amount of the substance of the beta-nitrostyrene compound shown in the formula (1) to the volume of the solvent is 1:2-10, the amount of the substance is mmol, and the volume unit is mL.
  4. 4. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, wherein the reaction temperature of the one-pot reaction is 20-80 ℃.
  5. 5. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, wherein the reaction time is 2-10 hours.
  6. 6. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, wherein the feeding molar ratio of the beta-nitrostyrene compounds shown in the formula (1), the acetoacetate shown in the formula (2) and the primary amine shown in the formula (3) is 1:1-1.5:1-3.
  7. 7. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, wherein the post-treatment step of the reaction solution is characterized in that 10 mL saturated sodium chloride aqueous solution and ethyl acetate are added into the reaction solution for extraction, organic layers are combined, the solvent is removed by rotary evaporation after drying through anhydrous sodium sulfate, and finally the para-substituted pyrrole compounds shown in the formula (4) are obtained by column chromatography separation, wherein a developing agent adopted by a column laminate is a petroleum ether/ethyl acetate mixed solvent with the volume ratio of 5-20:1.

Description

Method for synthesizing pyrrole compound by solid acid catalysis Technical Field The invention relates to a method for synthesizing pyrrole compounds by solid acid catalysis, in particular to a method for synthesizing polysubstituted pyrrole compounds by a one-pot method by taking beta-nitrostyrene compounds, ethyl acetoacetate and primary amine as raw materials and adopting carbon-based solid acid as a catalyst. Background Pyrrole is an important class of nitrogen-containing five-membered heterocyclic aromatic compounds that exist in many natural products and are important building blocks for many biologically active derivatives. The polysubstituted pyrrole compound is widely applied to the fields of material science, bio-organic chemistry, supermolecular chemistry and the like, and plays an important role in the fields of medicines, pesticides, foods and the like. Especially in the medicine field, the medicine has the functions of resisting cancer, resisting bacteria, resisting tumor, resisting bacteria, reducing cholesterol, etc. Therefore, the development of a simple and green synthesis method is of great significance. Disclosure of Invention Aiming at the technical problems existing in the prior art, the invention aims to develop a method for synthesizing pyrrole compounds by using solid acid catalysis, which is simple, efficient, economical and environment-friendly and is simple and convenient to operate, specifically, the method is to synthesize polysubstituted pyrrole compounds by using beta-nitrostyrene compounds, acetoacetate and primary amine as raw materials and adopting carbon-based solid acid as a catalyst by a one-pot method. The invention provides a method for synthesizing pyrrole compounds by solid acid catalysis, which comprises the steps of taking beta-nitrostyrene compounds shown in a formula (1), acetyl acetate shown in a formula (2) and primary amine shown in a formula (3) as raw materials, taking carbon-based solid acid as a catalyst, adding the raw materials and the catalyst into a solvent to perform one-pot reaction, and after the reaction, performing post-treatment on a reaction solution to obtain a target product of polysubstituted pyrrole compounds shown in a formula (4); the reaction formula is as follows: In the formula (1) and the formula (4), the substituent R 1 is H, C-C5 straight-chain or branched-chain alkyl or alkoxy, halogen or nitro; in the formula (2) and the formula (4), the substituent R 3 is selected from C1-C5 straight-chain or branched-chain alkyl, phenyl, benzyl or substituted benzyl; in the formulas (3) and (4), the substituent R 2 is C1-C10 straight-chain or branched-chain alkyl, C5-C6 cycloalkyl, benzyl, phenyl or substituted phenyl. The invention further provides that the carbon-based solid acid is white sugar, glucose, starch or furfural, preferably furfural, the acid source is trifluoromethanesulfonic acid, sulfuric acid, p-toluenesulfonic acid or hydroxyethanesulfonic acid, preferably hydroxyethanesulfonic acid, the mass of the carbon-based solid acid is 1% -5%, preferably 2%, of the molar amount of the beta-nitrostyrene compound shown in the formula (1), the mass unit is g, and the molar unit is mmoL. The invention further provides a method for preparing the beta-nitrostyrene compound, which comprises the steps of preparing the beta-nitrostyrene compound, wherein the solvent is methanol, ethanol or water, preferably water, the ratio of the amount of the beta-nitrostyrene compound shown in the formula (1) to the volume of the solvent is 1:2-10, preferably 1:5, the amount of the substance is mmol, and the volume unit is mL. Further, the invention also defines that the reaction temperature of the one-pot reaction is 20-80 ℃, preferably 50 ℃. Further, the invention also defines a reaction time of 2 to 10 hours, preferably 5 to 6 hours. Furthermore, the invention also defines the feeding mole ratio of the beta-nitrostyrene compound shown in the formula (1), the acetoacetate shown in the formula (2) and the primary amine shown in the formula (3) to be 1:1-1.5:1-3, preferably 1:1:2. The invention further defines the post-treatment step of the reaction liquid, wherein 10mL of saturated sodium chloride aqueous solution and ethyl acetate are added into the reaction liquid for extraction, the organic layers are combined, the solvent is removed by rotary evaporation after the reaction liquid is dried by anhydrous sodium sulfate, and finally the p-substituted pyrrole compound shown in the formula (4) is obtained by column chromatography separation, wherein the developing agent adopted by a column layer plate is a petroleum ether/ethyl acetate mixed solvent with the volume ratio of 5-20:1. By adopting the technology, compared with the prior art, the invention has the advantages that: The invention adopts commercially available acetoacetate, primary amine and easily prepared beta-nitrostyrene compounds to synthesize the polysubstituted pyrrole compounds by cyclization o