Method for photocatalytic synthesis of acyl pyrrole

Abstract

The invention relates to the field of organic chemical synthesis, in particular to a method for synthesizing acyl pyrrole through photocatalysis. N-arylglycine and a 3-alkyne chromone compound are used as reactants and react under nitrogen protection and blue light irradiation, after the reaction is stopped, a reaction mixture is washed with water, ethyl acetate is used for extraction, a solvent is removed under reduced pressure, and the acyl pyrrole compound is obtained through column chromatography elution. According to the method, the acyl pyrrole compound can be simply and efficiently prepared, raw materials are easy to obtain, operation is easy, reaction conditions are mild, the yield is excellent, the substrate application range is wide, and the method has very high popularization potential.

Description

Technical Field

[0001] The present invention relates to the field of organic chemical synthesis, and particularly to a method for photocatalytic synthesis of acylpyrroles. Background Art

[0002] Pyrrole is a class of important nitrogen-containing heterocyclic compounds, which are widely present in natural products, bioactive substances and drugs. The structure of pyrrole compounds is easy to be chemically modified and can be used for synthesizing derivatives with different biological activities. Acylpyrrole compounds have a wide range of biological and medical activities and have been applied in the fields of anti-tumor, antibacterial and anti-inflammatory. Therefore, it is of great significance to develop an effective synthesis method to obtain acylpyrrole compounds.

[0003] Visible light catalysis is a powerful tool in organic synthesis because it uses low-cost, renewable and widely available light as an energy source. The reaction conditions of photocatalytic organic synthesis are milder, the reaction yield is higher, and the production cost can be effectively reduced.

[0004] Glycine is a chemically raw material with rich natural yield and easy availability. In the field of photocatalysis, N-aryl glycine and its derivatives can be converted into α-aminoalkyl radicals through photo-redox catalyzed excitation and decarboxylation, and radical addition or radical coupling reactions can be carried out under green and mild conditions. Compared with structurally similar carbon-centered radicals, α-aminoalkyl has unique reactivity and can be applied to the synthesis of nitrogen-containing heterocyclic compounds.

[0005] Therefore, it is very important to invent a method for photocatalytic and efficient synthesis of acylpyrroles with mild conditions, high reaction efficiency and wide applicability. Summary of the Invention

[0006] The object of the present invention is to provide a method for photocatalytic synthesis of acylpyrroles. This method realizes the green and efficient synthesis of acylpyrrole compounds from N-aryl glycine and 3-alkynyl chromone as starting materials under light irradiation and room temperature conditions.

[0007] The technical solution of the present invention is as follows:

[0008] A method for photocatalytic synthesis of acylpyrroles, the general structural formula of acylpyrroles is shown in Formula I:

[0009]

[0010] In the formula: the R 1 is a hydrogen atom, a methyl group, a methoxy group or a halogen atom; R 2 is a phenyl group or a substituted phenyl group; wherein: the R 1 halogen atom includes a fluorine atom or a chlorine atom; the R 2The substituted phenyl group includes 4-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 3-methylphenyl or 2-methylphenyl;

[0011] The preparation method is as follows:

[0012]

[0013] Preparation method of the target compound I: Dissolve compounds II and III in methanol, protect by nitrogen, and react under blue light irradiation. After stopping the reaction, wash the reaction mixture with water, extract with ethyl acetate, remove the solvent under reduced pressure, and elute by column chromatography to obtain the target compound I.

[0014] As a further option of the preparation method, a photocatalyst is added when compounds II and III are dissolved in methanol. The photocatalyst is tetrakis(carbazolyl) isophthalonitrile, eosin B, eosin Y or iridium(III) tris(2-phenylpyridine).

[0015] As a further option of the preparation method, the methanol substitute is acetonitrile, dichloromethane, tetrahydrofuran or dimethyl sulfoxide.

[0016] As a further option of the preparation method, the molar ratio of compounds II and III is II:III = 1:1.5 to 1:2.

[0017] As a further option of the preparation method, the eluent used in the silica gel column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio V 石油醚 :V 乙酸乙酯 = 40:1 to 10:1.

[0018] As a further option of the preparation method, the reaction temperature of compounds II and III is room temperature.

[0019] The beneficial effects brought by the technical solutions provided in the embodiments of the present application at least include the following

[0020] Beneficial effects:

[0021] The method involved in the present invention uses visible light of 10W 455nm to catalyze the reaction at room temperature. The method involved in the present invention can easily prepare acylpyrrole compounds, with easily available raw materials, simple operation, mild reaction conditions and excellent yields. Description of the Drawings

[0022] Figure 1 It is the hydrogen spectrum of product I-1 obtained in the embodiment of the present invention;

[0023] Figure 2 It is the carbon spectrum of product I-1 obtained in the embodiment of the present invention. Detailed implementation mode

[0024] Next, the technical solutions in the embodiments of the present application will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present application.

[0025] Example 1

[0026] The reaction formula of Example 1. The specific compounds II and III used and the structure of the product I-1 are shown in Formula 1. Experiments show that the organic solvent used in the present invention is methanol, the highest yield of its reaction product is 92%, and the optimal molar ratio of raw materials is Compound II-1:Compound III-1 = 1:1.5. The optimal reaction concentration is 0.1M.

[0027]

[0028] The specific experimental steps are as follows: Dissolve 25 mg (0.10 mmol, 0.1 equivalent) of Compound II-1 and 23 mg (0.15 mmol, 0.15 equivalent) of Compound III-1 in 1 mL of methanol, protect with nitrogen, and place it under a 10 W 455 nm blue light irradiation at room temperature for reaction for 24 hours. Monitor the reaction by thin layer chromatography. After stopping the reaction, wash the reaction mixture with water, extract with ethyl acetate, and rotary evaporate to remove the solvent under reduced pressure with a water pump. The residue is chromatographed on silica gel with 200-300 mesh, and the eluent (volume ratio V 石油醚 :V 乙酸乙酯 = 40:1 to 20:1) to obtain 32 mg of the compound shown in I-1. The product is identified by nuclear magnetic resonance (proton spectrum, carbon spectrum).

[0029] The product I-1 is a white powder with a yield of 92%; 1 H NMR (400 MHz, CDCl3) δ 12.30 (s, 1H), 8.02 (dd, J = 8.0, 1.7 Hz, 1H), 7.47 (ddd, J = 8.7, 7.2, 1.7 Hz, / 1H), 7.41–7.34 (m, 3H), 7.15–7.08 (m, 5H), 7.04 (dd, J = 8.4, 1.2 Hz, 1H), 6.93 (ddd, J = 8.2, 7.2, 1.2 Hz, 1H), 6.90–6.86 (m, 2H), 6.76 (d, J = 3.1 Hz, 1H), 6.62 (d, J = 3.1 Hz, 1H), 4.29 (s, 2H); 1313C NMR (100 MHz, CDCl3) δ 196.3, 162.7, 139.3, 138.9, 138.4, 135.1, 133.0, 129.3, 128.6, 128.3, 128.3, 126.9, 126.1, 122.3, 121.4, 121.3, 118.5, 118.2, 112.2, 31.2.

[0030] The method used in the preparation examples of other acylpyrrole compounds (Compound I-2 to Compound I-10) involved in the present invention is the same as that in Example 1, and the reaction conditions and operations are as follows: Compound II (0.1 mmol) and Compound III (0.15 equivalents) are dissolved in a mixed solvent of 1 mL of methanol and dimethyl sulfoxide, protected by nitrogen, and reacted under irradiation with 10 W 455 nm blue light at room temperature. The reaction is monitored by thin-layer chromatography. After stopping the reaction, the reaction mixture is washed with water, extracted with ethyl acetate, and the solvent is removed by rotary evaporation under reduced pressure with a water pump. The residue is subjected to column chromatography on silica gel with 200 - 300 mesh, and the eluent (volume ratio V 石油醚 :V 乙酸乙酯 = 40:1 to 20:1) to obtain the indicated compound.

[0031] The structure of the obtained product is as follows:

[0032]

[0033] For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and without departing from the spirit or basic characteristics of the present invention, the present invention can be implemented in other specific forms. Therefore, from any point of view, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, all changes falling within the meaning and scope of the equivalent elements of the claims are intended to be encompassed within the present invention.

[0034] In addition, it should be understood that although this specification is described according to embodiments, not every embodiment only contains an independent technical solution. This narrative manner of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A method for photocatalytic synthesis of acylpyrrole, and the general structural formula of acylpyrrole is Structure I in the following formula: In the formula: the R 1 is a hydrogen atom, a methyl group, a methoxy group or a halogen atom; R 2 is a phenyl group or a substituted phenyl group; wherein: The R 1 The halogen atom includes a fluorine atom or a chlorine atom; the R 2 The substituted phenyl group includes a 4-methylphenyl group, a 4-fluorophenyl group, a 4-cyanophenyl group, a 3-methylphenyl group or a 2-methylphenyl group; It is characterized in that the preparation method is as follows: Preparation method of target compound I: Dissolve compound II and compound III in methanol, protect with nitrogen, and react under blue light irradiation. After stopping the reaction, wash the reaction mixture with water, extract with ethyl acetate, remove the solvent under reduced pressure, and elute by column chromatography to obtain the target compound I.

2. The method for photocatalytic synthesis of acylpyrrole according to claim 1, wherein When compound II and compound III are dissolved in methanol, a photocatalyst is added. The photocatalyst is tetrakazolyl isophthalonitrile, eosin B, eosin Y or iridium tris(2-phenylpyridine).

3. The method for photocatalytic synthesis of acylpyrrole according to claim 1, wherein The methanol substitute is acetonitrile, dichloromethane, tetrahydrofuran or dimethyl sulfoxide.

4. A method for photocatalytic synthesis of acylpyrrole according to claim 1, characterized in that, The molar ratio of compound II to compound III is II:III = 1:1.5 to 1:

2.

5. A method for photocatalytic synthesis of acylpyrrole according to claim 1, characterized in that, The eluent used in the silica gel column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio V 石油醚 :V 乙酸乙酯 = 40:1 to 10:

1.

6. A method for photocatalytic synthesis of acylpyrrole according to any one of claims 1-5, characterized in that, The reaction temperature of compound II and compound III is room temperature.

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