Method for synthesizing pyrrole compounds by using solid acid catalyst

Abstract

This invention discloses a method for synthesizing pyrrole compounds using solid acid catalysis. The method is as follows: in the presence of a carbon-based solid acid catalyst, β-nitrostyrene compounds represented by formula (1), acetyl acetate represented by formula (2), and primary amine represented by formula (3) are reacted in a solvent in a one-pot reaction. After the reaction is completed, the reaction solution is post-treated to obtain polysubstituted pyrrole compounds represented by formula (4). In the preparation of polysubstituted pyrrole compounds by this invention, the reaction can proceed smoothly under carbon-based solid acid catalysis without the need for other additives, making it safe, environmentally friendly, and with mild reaction conditions. The reaction formulas are as follows: in formulas (1) to (4), substituent R1 is H, C1-C5 straight-chain or branched alkyl or alkoxy, halogen, nitro, etc.; substituent R2 is C1-C10 straight-chain or branched alkyl, C5-C6 cycloalkyl, benzyl, etc.; substituent R3 is selected from C1-C5 straight-chain or branched alkyl, phenyl, benzyl, or substituted benzyl.

Description

Technical Field

[0001] This invention relates to a method for synthesizing pyrrole compounds using solid acid catalysis, specifically a one-pot method for synthesizing polysubstituted pyrrole compounds using β-nitrostyrene compounds, ethyl acetoacetate, and primary amines as raw materials and carbon-based solid acids as catalysts. Background Technology

[0002] Pyrroles, as an important class of nitrogen-containing five-membered heterocyclic aromatic compounds, are found in many natural products and are key structural units in many bioactive derivatives. Polysubstituted pyrrole compounds are widely used in materials science, bioorganic chemistry, supramolecular chemistry, and play a vital role in medicine, pesticides, and food. Especially in the pharmaceutical field, they exhibit anticancer, antibacterial, antitumor, antimicrobial, and cholesterol-lowering effects. Therefore, developing simple and green synthetic methods for pyrroles is of great significance. Summary of the Invention

[0003] In view of the above-mentioned technical problems existing in the prior art, the purpose of this invention is to develop a simple, efficient, economical, environmentally friendly and easy-to-operate method for the synthesis of pyrrole compounds by solid acid catalysis. Specifically, it uses β-nitrostyrene compounds, acetoacetate and primary amine as raw materials, and carbon-based solid acid as catalyst to synthesize polysubstituted pyrrole compounds in a one-pot process.

[0004] This invention defines a method for synthesizing pyrrole compounds by solid acid catalysis, specifically: using β-nitrostyrene compounds as shown in formula (1), acetylacetate as shown in formula (2), and primary amine as shown in formula (3) as raw materials, and using carbon-based solid acid as catalyst, the raw materials and catalyst are added to a solvent for a one-pot reaction. After the reaction is completed, the reaction solution is post-treated to obtain the target product as shown in formula (4) of the polysubstituted pyrrole compound.

[0005] The reaction formula is as follows:

[0006]

[0007] In formulas (1) and (4), the substituent R1 is H, C1-C5 straight-chain or branched alkyl or alkoxy, halogen or nitro;

[0008] In formulas (2) and (4), the substituent R3 is selected from C1-C5 straight-chain or branched alkyl, phenyl, benzyl or substituted benzyl;

[0009] In formulas (3) and (4), the substituent R2 is a C1-C10 straight-chain or branched alkyl group, a C5-C6 cycloalkyl group, a benzyl group, a phenyl group, or a substituted phenyl group.

[0010] Furthermore, the present invention further specifies that the carbon group in 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% to 5% of the molar amount of the β-nitrostyrene compound shown in formula (1), preferably 2%, the mass unit is g, and the molar unit is mmol.

[0011] Furthermore, the present invention further specifies that the solvent is methanol, ethanol or water, preferably water; the ratio of the amount of β-nitrostyrene compound represented by formula (1) to the volume of the solvent is 1:2 to 10, preferably 1:5, the amount of substance is in mmol and the volume is in mL.

[0012] Furthermore, the present invention also limits the reaction temperature of the one-pot reaction to 20°C to 80°C, preferably 50°C.

[0013] Furthermore, the present invention also limits the reaction time to 2 to 10 hours, preferably 5 to 6 hours.

[0014] Furthermore, the present invention also specifies that the molar ratio of the β-nitrostyrene compound represented by formula (1), the acetoacetate represented by formula (2), and the primary amine represented by formula (3) is 1:1 to 1.5:1 to 3, preferably 1:1:2.

[0015] Furthermore, the present invention further specifies the post-treatment steps of the reaction solution as follows: 10 mL of saturated sodium chloride aqueous solution and ethyl acetate are added to the reaction solution for extraction, the organic layers are combined, dried with anhydrous sodium sulfate, the solvent is removed by rotary evaporation, and finally column chromatography is performed to obtain the para-substituted pyrrole compounds shown in formula (4). The developing solvent used in the column chromatography is a petroleum ether / ethyl acetate mixed solvent with a volume ratio of 5-20:1.

[0016] By employing the above-described technology, the advantages of this invention compared to existing technologies are as follows:

[0017] This invention utilizes commercially available acetoacetate, primary amines, and easily prepared β-nitrostyrene compounds in a one-pot reaction system. Through cyclization oxidation catalyzed by inexpensive and efficient carbon-based solid acids, polysubstituted pyrrole compounds are synthesized using water or similar solvents. The reaction, as defined in this invention, can proceed smoothly in air in the presence of a solid acid, requiring no other additives or oxidants. It boasts high yields of target compounds, good substrate applicability, and the ability to construct corresponding polysubstituted pyrrole compounds from various substituents. Furthermore, it offers advantages such as readily available and inexpensive raw materials, fewer reaction steps, and simple post-processing, opening up a new, green, environmentally friendly, economical, and efficient strategy for synthesizing potentially biologically active polysubstituted pyrrole compounds. Detailed Implementation

[0018] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0019] The synthesis processes of different carbon-based solid acids (cc) used in the embodiments of this invention are as follows:

[0020] cc-a: 0.520g of p-aminobenzenesulfonic acid and 2.054g of glucose were placed in a muffle furnace at 200℃ and carbonized for 8 hours to obtain a black solid, which was then ground and used.

[0021] cc-b: 0.571g of p-toluenesulfonic acid and 2.054g of sucrose were placed in a muffle furnace at 200℃ and carbonized for 8 hours to obtain a black solid, which was then ground and used.

[0022] cc-c: 0.294g of sulfuric acid and 2.054g of starch were placed in a muffle furnace at 200℃ and carbonized for 8 hours to obtain a black solid, which was then ground and used.

[0023] cc-d: 0.294g of trifluoromethanesulfonic acid and 2.054g of glucose were placed in a muffle furnace at 200℃ and carbonized for 8 hours to obtain a black solid, which was then ground and used.

[0024] CC-E: A mixture of 10 g of furfural, 5 g of hydroxyethyl sulfuric acid, and 80 mL of deionized water was placed in a 100 mL hydrothermal reactor and reacted at 180 °C for 4 hours in a muffle furnace. The resulting crude product was washed with water and methanol, dried in a vacuum oven, and then ground into powder granules for use.

[0025] Example 1

[0026] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and propylamine 3 (0.012 g, 0.2 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid cc-a (0.004 g) and 1 mL of water were also added. The reaction was carried out at 60 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 48% yield. Its chemical structure is as follows: Characterization data of the target compound: 1H NMR (500MHz, CDCl3) δ7.38 (dd, J=8.2, 1.3Hz, 2H), 7.32 (dd, J=8.2, 6.8Hz, 2H), 7.27-7.23 (m, 1H), 6.55 (s, 1H), 4.1 6(q,J=7.1Hz,2H),3.84-3.80(m,2H),2.55(s,3H),1.83-1.74(m,2H),1.13(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0027] Example 2

[0028] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.039 g, 0.3 mmol), and propylamine 3 (0.012 g, 0.2 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid cc-b (0.006 g) and 0.5 mL of water were then added. The reaction was carried out at 70 °C for 8 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 62% yield. Its chemical structural formula is [insert chemical formula here].

[0029] Example 3

[0030] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and propylamine 3 (0.024 g, 0.4 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid (cc-c) (0.002 g) and 2 mL of ethanol were also added. The reaction was carried out at 20 °C for 10 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 32% yield. Its chemical structural formula is [insert chemical structure here].

[0031] Example 4

[0032] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and propylamine 3 (0.024 g, 0.4 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid cc-d (0.010 g) and 1 mL of water were also added. The reaction was carried out at 80 °C for 4 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 73% yield. Its chemical structural formula is [insert chemical structure here].

[0033] Example 5

[0034] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and propylamine 3 (0.024 g, 0.4 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid (cc-e) (0.004 g) and 1 mL of water were also added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 83% yield. Its chemical structural formula is [insert chemical structure here].

[0035] Example 6

[0036] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and n-butylamine 3 (0.028 g, 0.4 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid cc-d (0.004 g) and 1 mL of water were also added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 73% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.39-7.37(m,2H),7.33(t,J=7.6Hz,2H),7.25(t,J=7.3Hz,1H),6.55(s,1H),4.16(q,J=7 .1Hz,2H),3.85(t,J=7.3Hz,2H),2.55(s,3H),1.42-1.39(m,2H),1.14(t,J=7.1Hz,2H),0.98(t,J=7.5Hz,3H).

[0037] Example 7

[0038] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and benzylamine 3 (0.042 g, 0.4 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid (cc-e) (0.004 g) and 1 mL of water were also added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 52% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR(600MHz, CDCl3)δ7.40(d,J=7.3Hz,2H),7.36-7.31(m,7H),7.10(d,J=7.4H z,2H),6.61(s,2H),4.18(q,J=7.1Hz,2H),2.50(s,3H),1.15(t,J=7.1Hz,3H).

[0039] Example 8

[0040] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and n-hexylamine 3 (0.045 g, 0.4 mmol) were added to a 15 mL reaction tube. Carbon-based solid sulfonic acid (cc-e) (0.004 g) and 1 mL of water were also added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 52% yield.

[0041] Its chemical structural formula is Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.40-7.37(m,2H),7.33(t,J=7.6Hz,2H),7.27-7.24(m,1H),6.55(s,1H),4.16(q,J=7.1Hz,2H),3. 84(t,J=7.3Hz,2H),2.55(s,3H),1.75(q,J=7.4Hz,2H),1.39–1.30(m,6H),1.14(t,J=7.1Hz,3H),0.92(t,J=6.6Hz,3H).

[0042] Example 9

[0043] In a 15 mL reaction tube, 4-methyl-β-nitrostyrene 1 (0.032 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), and propylamine 3 (0.036 g, 0.6 mmol) were added, along with carbon-based solid sulfonic acid cc-e (0.004 g) and 1 mL of water. The reaction was carried out at 50 °C for 6 hours. After the reaction was complete, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 63% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.29 (d, J = 3.0Hz, 2H), 7.14 (d, J = 8.0Hz, 2H), 6.53 (s, 1H), 4.18 (q, J = 7.1Hz, 2H), 3.81 (t,J=7.3Hz,2H),2.54(s,3H),2.38(s,3H),1.80-1.76(m,2H),1.17(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0044] Example 10

[0045] In a 15 mL reaction tube, 2-methoxyβ-nitrostyrene 1 (0.036 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), propylamine 3 (0.024 g, 0.4 mmol), carbon-based solid sulfonic acid (cc-e) (0.004 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 70% yield. Its chemical structural formula is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.24(t,J=7.9Hz,1H),6.98(d,J=7.6Hz,1H),6.96-6.93(m,1H),6.83-6.80(m,1H),6.56(s,1H),4.17(q, J=7.1Hz,2H),3.83(s,3H),3.79(t,J=7.3Hz,2H),2.54(s,3H),1.81-1.77(m,2H),1.15(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0046] Example 11

[0047] In a 15 mL reaction tube, 4-methoxyβ-nitrostyrene 1 (0.038 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), propylamine 3 (0.024 g, 0.4 mmol), carbon-based solid sulfonic acid CC-E (0.005 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 75% yield. Its chemical structural formula is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.31(d,J=8.6Hz,2H),6.89(d,J=8.7Hz,2H),6.50(s,1H),4.17(q,J=7.1Hz,2H),3.84 (s,3H),3.81(t,J=7.3Hz,2H),2.54(s,3H),1.80-1.76(m,2H),1.17(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0048] Example 12

[0049] In a 15 mL reaction tube, 2,5-dimethoxyβ-nitrostyrene 1 (0.045 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), propylamine 3 (0.024 g, 0.4 mmol), carbon-based solid sulfonic acid (cc-e) (0.004 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 80% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ6.85 (dd, J=7.2, 0.8Hz, 1H), 6.81 (d, J=7.2Hz, 1H), 6.78 (s, 1H), 6.55 (s, 1H), 4.09 (q, J=7.1Hz, 2H), 3. 81(t,J=7.3Hz,,2H),3.80(s,3H),3.72(s,3H),2.52(s,3H),1.70–1.60(m,2H),1.05(t,J=7.1Hz,3H),0.99(t,J=7.4Hz,3H).

[0050] Example 13

[0051] In a 15 mL reaction tube, 4-bromoβ-nitrostyrene 1 (0.046 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), propylamine 3 (0.024 g, 0.4 mmol), carbon-based solid sulfonic acid (cc-e) (0.004 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 67% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.46-7.43(m,2H),7.25(d,J=8.4Hz,2H),6.53(s,1H),4.17(q,J=7.1Hz,2H) ,3.84-3.80(m,2H),2.54(s,3H),1.81-1.77(m,2H),1.17(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0052] Example 14

[0053] In a 15 mL reaction tube, 3-bromo-β-nitrostyrene 1 (0.046 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), propylamine 3 (0.024 g, 0.4 mmol), carbon-based solid sulfonic acid cc-d (0.004 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 73% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.54(s,1H),7.38(d,J=7.9Hz,1H),7.31(d,J=7.7Hz,1H),7.19(t,J=7.8Hz,1H),6.55(s,1H),4.1 8(q,J=7.1Hz,2H),3.82(t,J=7.3Hz,2H),2.55(s,3H),1.81-1.77(m,2H),1.17(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0054] Example 15

[0055] In a 15 mL reaction tube, 4-chloro-β-nitrostyrene 1 (0.039 g, 0.2 mmol), ethyl acetoacetate 2 (0.039 g, 0.3 mmol), propylamine 3 (0.024 g, 0.4 mmol), carbon-based solid sulfonic acid (cc-e) (0.004 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 70% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (600MHz, CDCl3) δ7.32-7.29 (m, 4H), 6.53 (s, 1H), 4.17 (q, J = 7.1Hz, 2H), 3.82 (t, J = 7 .3Hz,2H),2.54(s,3H),1.81-1.77(m,2H),1.17(t,J=7.1Hz,3H),0.98(t,J=7.4Hz,3H).

[0056] Example 16

[0057] In a 15 mL reaction tube, 4-nitro-β-nitrostyrene 1 (0.039 g, 0.2 mmol), methyl acetoacetate 2 (0.024 g, 0.2 mmol), aniline 3 (0.037 g, 0.4 mmol), carbon-based solid sulfonic acid CC-E (0.004 g), and 1 mL of water were added. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 45% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (500MHz, CDCl3) δ (ppm) 8.20 (d, J = 8.8Hz, 2H), 7.59 (d, J = 8.8Hz, 2H), 7.52 (t, J = 7.4Hz ,2H),7.47(t,J=7.4Hz,1H),7.34(d,J=7.4Hz,2H),6.82(s,1H),3.65(s,3H),2.47(s,3H).

[0058] Example 17

[0059] β-nitrostyrene 1 (0.030 g, 0.2 mmol), ethyl acetoacetate 2 (0.026 g, 0.2 mmol), cyclohexylamine 3 (0.038 g, 0.4 mmol), carbon-based solid sulfonic acid (cc-e) (0.004 g), and 1 mL of water were added to a 15 mL reaction tube. The reaction was carried out at 50 °C for 6 hours. After the reaction was completed, 10 mL of saturated sodium chloride was added, and the mixture was extracted with ethyl acetate (3 x 10 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was removed by vacuum distillation. Column chromatography was used to separate the target compound in 52% yield. Its chemical structure is as follows: Characterization data of the target compound: 1 H NMR (500MHz, CDCl3) δ (ppm) 7.42-7.36 (m, 2H), 7.33 (t, J = 7.6Hz, 2H), 7.25 (t, J = 7.3Hz, 1H), 6.66 (s, 1H), 4 .16(q,J=7.1Hz,2H),3.91(tt,J=7.5,6.8Hz,1H),2.58(s,3H),2.07-1.20(m,10H),1.13(t,J=7.1Hz,3H).

[0060] The contents described in this specification are merely an enumeration of the implementation forms of the inventive concept, and the scope of protection of this invention should not be regarded as limited to the specific forms described in the embodiments.

Claims

1. A method for synthesizing pyrrole compounds using solid acid catalysis, characterized in that... Using β-nitrostyrene compounds as shown in formula (1), acetylacetate as shown in formula (2), and primary amine as shown in formula (3) as raw materials, and carbon-based solid acid as catalyst, the raw materials and catalyst were added to the solvent for a one-pot reaction. After the reaction was completed, the reaction solution was post-treated to obtain the target product as shown in formula (4) of the polysubstituted pyrrole compound. The reaction formula is as follows: ， In formulas (1) and (4), the substituent R1 is H, C1~C5 straight-chain or branched alkyl or alkoxy, halogen or nitro; In formulas (2) and (4), the substituent R3 is selected from C1~C5 straight-chain or branched alkyl, phenyl, and benzyl groups; In formulas (3) and (4), the substituent R2 is a C1~C10 straight-chain or branched alkyl, a C5~C6 cycloalkyl, benzyl, or phenyl. The carbon group in the carbon-based solid acid is white sugar, glucose, starch or furfural; the acid source is trifluoromethanesulfonic acid, sulfuric acid, p-toluenesulfonic acid or hydroxyethanesulfonic acid.

2. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1, characterized in that... The carbon group in the carbon-based solid acid is furfural; the acid source is trifluoromethanesulfonic acid; the mass of the carbon-based solid acid is 1% to 5% of the molar amount of the β-nitrostyrene compound shown in formula (1), with the mass unit being g and the molar unit being mmol.

3. The method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, characterized in that... The solvent is a protic solvent, such as methanol, ethanol or water; the ratio of the amount of β-nitrostyrene compound shown in formula (1) to the volume of the solvent is 1:2~10, the amount of substance is in mmol and the volume is in mL.

4. A method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, characterized in that... The reaction temperature for the one-pot process is 20℃~80℃.

5. A method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, characterized in that... The reaction time is 2 to 10 hours.

6. A method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, characterized in that... The molar ratio of the β-nitrostyrene compound shown in formula (1), the acetoacetate shown in formula (2), and the primary amine shown in formula (3) is 1:1~1.5:1~3.

7. A method for synthesizing pyrrole compounds by solid acid catalysis according to claim 1 or 2, characterized in that... The post-treatment steps of the reaction solution are as follows: 10 mL of saturated sodium chloride aqueous solution and ethyl acetate are added to the reaction solution for extraction, the organic layers are combined, dried with anhydrous sodium sulfate, the solvent is removed by rotary evaporation, and finally column chromatography is performed to obtain the para-substituted pyrrole compounds shown in formula (4). The developing solvent used in the column chromatography is a mixture of petroleum ether and ethyl acetate with a volume ratio of 5-20:1.

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