One-pot synthesis of lignin-based carbazole derivatives

Abstract

The application discloses a one-pot synthesis method of a lignin-based carbazole derivative, and belongs to the technical field of organic compound synthesis. The method uses a lignin beta-O-4 model compound and an N-substituted indole vinyl ketone compound as reaction raw materials, and reacts under the action of a vanadium-based catalyst in a solvent for a certain time under an air atmosphere; finally, a carbazole derivative is obtained. The synthesis method for preparing the carbazole derivative has the advantages of simple operation, mild reaction conditions, high product selectivity and the like, and provides a green new way for preparation of carbazole compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, specifically relating to a one-pot synthesis method for lignin-based carbazole derivatives. Background Technology

[0002] Carbazole and its derivatives are a special class of nitrogen-containing aromatic heterocyclic molecules with unique physicochemical properties and diverse structures, finding wide applications in natural products, pharmaceuticals, and functional materials. Their synthetic methods have always attracted considerable attention. Indole belongs to an electron-rich heterocyclic system, widely found in natural products and pharmaceuticals, and is abundant and inexpensive. Indole has high electron cloud density at its C2 and C3 positions, exhibiting nucleophilicity. Using indole-like substances as raw materials, it is relatively easy to construct carbazole rings through cyclization reactions by extending their π electrons. The synthetic method from indole to carbazole is simple, efficient, and offers advantages such as inexpensive and readily available raw materials and diverse products. However, these methods are limited by the fact that most of the raw materials are non-renewable, resulting in relatively low yields and complex operations. Therefore, researching and developing a novel, efficient, low-energy, environmentally friendly, convenient, and green synthetic method for carbazole derivatives is of great significance. Summary of the Invention

[0003] To address the problems existing in the prior art, the purpose of this invention is to provide a one-pot method for preparing carbazole derivatives from lignin model compounds. This method has advantages such as simple operation, mild reaction conditions, and high product selectivity, providing a green new route for the preparation of carbazole compounds.

[0004] The objective of this invention is achieved through the following means:

[0005] A one-pot synthesis method for lignin-based carbazole derivatives mainly includes the following steps: adding lignin β-O-4 model compound 1, N-substituted indole vinyl ketone compound 2, and vanadium-based catalyst to a solvent and stirring the mixture under air atmosphere for a certain time; followed by separation and purification to obtain carbazole derivative 3; the general reaction formula is:

[0006]

[0007] The R 1 R 2 R 4 Or R 5 It is an alkyl, alkoxy, halogen, nitro, ester, benzyl, aryl, amino, hydroxyl or hydrogen with 1-10 carbon atoms;

[0008] The R 3 It is 1-10 alkyl or benzyl.

[0009] Furthermore, the vanadium-based catalyst is One or more of them.

[0010] Furthermore, the R 6 R 7 R 8 R 9 Or R 10 It is an alkyl, alkoxy, halogen, nitro, ester, benzyl, aryl, amino, hydroxyl or hydrogen with 1-10 carbon atoms.

[0011] Furthermore, the solvent is one or more of toluene, tert-amyl alcohol, water, 1,4-dioxane, acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, and dimethylformamide.

[0012] Furthermore, the reaction conditions are as follows: the temperature is controlled at 20-150℃, and the reaction time is 0.5-48h.

[0013] Furthermore, the molar ratio of the lignin β-O-4 model compound 1 and the N-substituted indole vinyl ketone compound 2 is 1 to 10:1, and the mass of the catalyst is 0.1-10 mmol.

[0014] The synthetic method for preparing carbazole compounds described in this invention has the advantages of simple operation, mild reaction conditions, and high product selectivity, providing a green new route for the preparation of carbazole compounds. Attached Figure Description

[0015] To more clearly illustrate the embodiments of the present invention, the accompanying drawings involved in the embodiments will be briefly described below.

[0016] Figure 1 ((3-benzoyl-9-methyl)carbazole)(3,4-dimethoxyphenyl) methyl ketone prepared in Example 1 1 H-NMR spectrum.

[0017] Figure 2 ((3-benzoyl-9-methyl)carbazole)(4-methoxyphenyl) methyl ketone prepared in Example 21 1 H-NMR spectrum.

[0018] Figure 3 ((3-benzoyl-9-methyl)carbazole)(3-hydroxy-4-methoxyphenyl) methyl ketone prepared in Example 22 1 H-NMR spectrum.

[0019] Figure 4 ((3-benzoyl-9-benzyl)carbazole)(3,4-dimethoxyphenyl) methyl ketone prepared in Example 24 1H-NMR spectrum.

[0020] Figure 5 ((3-benzoyl-7,9-dimethyl)carbazole)(3,4-dimethoxyphenyl) methyl ketone prepared in Example 25 1 H-NMR spectrum.

[0021] Figure 6 ((3-benzoyl-6-methoxy-9-methyl)carbazole)(3,4-dimethoxyphenyl) methyl ketone prepared in Example 26 1 H-NMR spectrum. Detailed Implementation

[0022] The present invention will be described in detail below with reference to the embodiments. However, the implementation of the present invention is not limited thereto. Obviously, the embodiments described below are only some embodiments of the present invention. For those skilled in the art, other similar embodiments can be obtained without creative effort and all fall within the protection scope of the present invention.

[0023] Example 1:

[0024] 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenyl)-propane-1,3-diol (1a, 0.4 mmol), N-methylindole-3-phenylvinyl ketone (2a, 0.2 mmol), and a vanadium-based catalyst (10 mol%) were added to 10 mL of toluene. The mixture was heated to 140 °C under air and stirred for 20 h. The general reaction formula is as follows. After the reaction was completed, the mixture was cooled to room temperature, and the resulting solution was loaded onto a silica gel chromatography column. Elution was performed using petroleum ether and ethyl acetate in a volume ratio of 1:9. The eluent containing the target product was collected to obtain ((3-benzoyl-9-methyl)carbazole)(3,4-dimethoxyphenyl)methyl ketone (3a) with a yield of 94%, and guaiacol 4a with a yield of 93%. 1 For H-NMR characterization, please see the appendix. Figure 1 .

[0025]

[0026] Examples 2-6:

[0027] Except for the different reaction temperature, the other process conditions and experimental steps of Examples 2-6 are the same as those of Example 1, and the results are shown in Table 1.

[0028] Table 1. Effect of different reaction temperatures on the synthesis of carbazole derivatives

[0029]

[0030]

[0031] As shown in Table 1, the yields of 3a and guaiacol both increased significantly with increasing reaction temperature.

[0032] Examples 7-15:

[0033] Except for the use of different solvents, the other process conditions and experimental steps of Examples 7-15 are the same as those of Example 1, and the results are shown in Table 2.

[0034] Table 2. Effects of different solvents on the synthesis of carbazole derivatives

[0035] reaction solvent 3a yield (%) Guaiacin yield (%) Example 7 tert-amyl alcohol 78 71 Example 8 water 69 60 Example 9 methanol 75 73 Example 10 ethanol 80 75 Example 11 Isopropanol 89 85 Example 12 1,4-Dioxane 90 92 Example 13 Acetonitrile 93 91 Example 14 Dimethyl sulfoxide 82 81 Example 15 dimethylformamide 86 83

[0036] As shown in Table 2, when ethanol, isopropanol, 1,4-dioxane, acetonitrile, dimethyl sulfoxide, and dimethylformamide are used as solvents, the yields of 3a and guaiacol are both above 80%.

[0037] Examples 16-20:

[0038] Except for using different reaction times, the other process conditions and experimental steps of Examples 16-20 are the same as those of Example 1, and the results are shown in Table 3.

[0039] Table 3. Effect of different reaction times on the synthesis of carbazole derivatives

[0040]

[0041]

[0042] As shown in Table 3, the yields of 3a and guaiacol both increased significantly with the extension of reaction time.

[0043] Examples 21-34:

[0044] Except for the use of different types of lignin model compounds and N-substituted indolevinyl ketones as raw materials, the other process conditions and experimental steps of Examples 21-34 are the same as those of Example 1, and the results are shown in Table 4.

[0045] Table 4. Effects of different lignin model compounds, N-methylindole-3-carboxaldehyde, and 3-chlorophenylacetone compounds on the synthesis of carbazole derivatives.

[0046]

[0047]

[0048] As shown in Table 4, when different types of lignin model compounds and N-substituted indole vinyl ketones are used as substrates, carbazole derivatives and phenols can be synthesized, and the yields are all above 70%.

[0049] Examples 35-59:

[0050] Except for the use of different vanadium-based catalysts, the other process conditions and experimental steps in Examples 35-59 are the same as in Example 1, and the results are shown in Table 5.

[0051] Table 5. Effects of different catalysts on the synthesis of carbazole derivatives

[0052]

[0053]

[0054]

[0055]

[0056] Examples 60-62:

[0057] Except for the use of different catalyst dosages, the other process conditions and experimental steps in Examples 60-62 are the same as in Example 1, and the results are shown in Table 6.

[0058] Table 6. Effect of different catalyst dosages on the synthesis of carbazole derivatives

[0059]

[0060] Examples 63-65

[0061] Except for using different molar ratios of reactants, the other process conditions and experimental steps in Examples 63-65 were the same as in Example 1, and the results are shown in Table 7.

[0062] Table 7 Effect of different reactant molar ratios on the synthesis of carbazole derivatives.

[0063] 1a:2a 3a yield (%) Guaiacin yield (%) Example 63 1:1 55 58 Example 64 5:1 88 84 Example 65 10:1 85 83

[0064] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A one-pot synthesis method for lignin-based carbazole derivative 3, characterized in that, The main steps include: adding lignin β-O-4 model compound 1, N-substituted indole vinyl ketone compound 2, and vanadium-based catalyst to a solvent and stirring the mixture in air for a certain time; then separating and purifying to obtain carbazole derivative 3; the general reaction formula is: The R 1 R 2 R 4 Or R 5 It is an alkyl, alkoxy, halogen, nitro, ester, benzyl, aryl, amino, hydroxyl or hydrogen with 1-10 carbon atoms; The R 3 It is an alkyl or benzyl group with 1-10 carbon atoms; The vanadium-based catalyst is , , One or more of the following; The R 6 R 7 R 8 R 9 Or R 10 It is an alkyl, alkoxy, halogen, nitro, ester, benzyl, aryl, amino, hydroxyl or hydrogen with 1-10 carbon atoms.

2. The synthesis method according to claim 1, characterized in that, The solvent is one or more of toluene, tert-amyl alcohol, water, 1,4-dioxane, acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, and dimethylformamide.

3. The synthesis method according to claim 1, characterized in that, The reaction conditions are: temperature controlled at 20-150 ℃, and reaction time of 0.5-48 h.

4. The synthesis method according to claim 1, characterized in that, The molar ratio of the lignin β-O-4 model compound 1 and the N-substituted indole vinyl ketone compound 2 is 1 to 10:1, and the amount of catalyst used is 0.1 to 20 mmol.

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