Synthesis method of lignin-based triazole compounds

Abstract

The application discloses a synthesis method of a lignin-based triazole compound and belongs to the technical field of organic compound synthesis. The method uses a gamma-OH-containing lignin beta-O-4 model compound and an azide compound as reaction raw materials, and one-pot preparation of a triazole compound is carried out under the action of a vanadium-based catalyst in an air atmosphere. The synthesis method for preparing the triazole compound has the advantages of simple operation, mild reaction conditions and high product selectivity, and provides a new approach for preparation of the triazole compound.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, and specifically relates to a method for synthesizing lignin-based triazole compounds. Background Technology

[0002] Triazole compounds are important nitrogen-containing heterocyclic compounds with excellent antibacterial and antitumor biological activities, and have wide applications in drug development, bioconjugation, and materials science (Chem. Soc. Rev. 2016, 45, 3766). Currently, the classic synthetic method for triazole compounds involves a "click reaction" of azides with alkynes or alkenes under the action of a metal catalyst. However, most classic synthetic methods use non-renewable raw materials as substrates. With increasing attention to environmental and energy issues, there is an urgent need to develop a simple, efficient, environmentally friendly, and atom-economical synthetic method for triazole compounds. Summary of the Invention

[0003] In order to solve the problems existing in the prior art, the present invention aims to provide a method for synthesizing lignin-based triazole compounds, which has the advantages of simple operation, mild reaction conditions and high product selectivity.

[0004] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0005] A method for synthesizing lignin-based triazole compounds mainly includes the following steps: adding lignin β-O-4 model compound 1, azide compound 2, and a vanadium-based catalyst to a solvent, stirring the mixture under air atmosphere to obtain a reaction mixture, and then separating and purifying it to obtain triazole compound 3; the general reaction formula is:

[0006]

[0007] in,

[0008] The R 1 Selected from alkyl groups having 1-10 carbon atoms, R 2 Selected from alkoxy groups with 1-10 carbon atoms, R 3 Selected from alkyl, aromatic, ester, nitrile, halogen, or naphthalene groups having 5-10 carbon atoms. R is preferred. 1 It is an alkoxy group with 1-10 carbon atoms, R 2 It is an aromatic group, R 3 It is either halogen or naphthalene.

[0009] Furthermore, the catalyst is vanadium triethoxy, vanadium acetylacetonate, vanadium chloride, ammonium metavanadate, sodium metavanadate, and Schiff base ligand vanadium catalyst (Angew. Chem. Int. Ed. 2010, 49, 3791-3794). The preferred catalyst is a Schiff base ligand vanadium catalyst.

[0010]

[0011] Furthermore, the solvent is one or more of the following: n-butanol, water, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, n-hexane, dimethyl carbonate, dimethyl sulfoxide, dimethylformamide, benzene, toluene, and chlorobenzene. Preferably, it is one or more of the following: 1,4-dioxane, dimethyl carbonate, benzene, toluene, and chlorobenzene.

[0012] Furthermore, the reaction conditions are as follows: temperature controlled at 20-200℃, reaction time at 0.5-24h. Preferably, the temperature is 80-150℃, and preferably the time is 6-12h.

[0013] Further, the molar ratio of the lignin model compound 1 to the azide compound 2 is 1–10:1; the molar ratio of the lignin model compound 1 to the vanadium-based catalyst is 1:0.05–0.1. Preferably, the molar ratio of the lignin model compound 1 to the azide compound 2 is 5–10:1, and more preferably, the molar ratio of the lignin model compound 1 to the vanadium-based catalyst is 1:0.07–0.1.

[0014] Furthermore, the concentration of the lignin model compound 1 in the mixture is 0.01–0.5 mol / L.

[0015] Furthermore, the specific steps of the separation and purification are as follows: after the reaction mixture is cooled to room temperature, it is loaded onto a silica gel chromatography column, eluted with elution buffer, and the elution buffer containing triazole compound 3 is collected.

[0016] Furthermore, the eluent is any two selected from petroleum ether, n-hexane, n-pentane, ethyl acetate, and dichloromethane, with a volume ratio of 1:1 to 10. Preferably, it is any two selected from petroleum ether, ethyl acetate, and dichloromethane, with a volume ratio of 1:3 to 10.

[0017] Another aspect of the present invention is to provide triazole compounds prepared by the above method.

[0018] The advantages of this invention over the prior art are as follows:

[0019] 1. The preparation method of the present invention has mild reaction conditions, short reaction time, and simple operation.

[0020] 2. The triazole compounds prepared by this invention have high selectivity, few byproducts, and high atom economy.

[0021] 3. This invention utilizes green biomass as raw material to provide a sustainable and green method for synthesizing triazole compounds, offering a new approach for the full utilization of biomass. Attached Figure Description

[0022] To more clearly illustrate the embodiments of the present invention, the accompanying drawings involved in the embodiments will be briefly described below.

[0023] Figure 1 The triazole product prepared in Example 1 was 3 days old. 1 H-NMR spectrum.

[0024] Figure 2 The triazole product prepared in Example 1 was 3 days old. 13 C-NMR spectrum.

[0025] Figure 3 The triazole product 3e prepared in Example 33 1 H-NMR spectrum.

[0026] Figure 4 The triazole product 3e prepared in Example 33 13 C-NMR spectrum.

[0027] Figure 5 The triazole product 3l prepared in Example 40 1 H-NMR spectrum.

[0028] Figure 6 The triazole product 3l prepared in Example 40 13 C-NMR spectrum.

[0029] Figure 7 The triazole product 3p prepared in Example 44 1 H-NMR spectrum.

[0030] Figure 8 The triazole product 3p prepared in Example 44 13 C-NMR spectrum.

[0031] Figure 9 The triazole product 3r prepared in Example 46 1 H-NMR spectrum.

[0032] Figure 10 The triazole product 3r prepared in Example 46 13 C-NMR spectrum.

[0033] Figure 11 The triazole product 3s prepared in Example 47 1 H-NMR spectrum.

[0034] Figure 12 The triazole product 3s prepared in Example 47 13 C-NMR spectrum.

[0035] Figure 13 3t of the triazole product prepared in Example 48 1 H-NMR spectrum.

[0036] Figure 14 3t of the triazole product prepared in Example 48 13 C-NMR spectrum.

[0037] Figure 15 The triazole product 3u prepared in Example 49 1 H-NMR spectrum.

[0038] Figure 16 The triazole product 3u prepared in Example 49 13 C-NMR spectrum. Detailed Implementation

[0039] 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.

[0040] Example 1:

[0041] 0.3 mmol of 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenyl)-propane-1,3-diol (synthesized in the literature, Green. Chem. 2020, 22, 248-255), benzyl azide (0.2 mmol), and a Schiff base ligand vanadium catalyst (0.03 mmol) were added to 2 mL of toluene. The mixture was heated to 110 °C in air and stirred for 10 h. After the reaction was complete, the mixture was cooled to room temperature and loaded onto a silica gel chromatography column. Elution was performed using petroleum ether and ethyl acetate in a 1:9 volume ratio. The eluent containing the target product was collected, yielding the triazole product 1-benzyl-1H-1,2,3-triazole-4-benzophenone (d3), with a yield of 82%, and guaiacol (87%). 1 H-NMR characterization is attached. Figure 1 ; Triazole product 3d13 C-NMR characterization is attached. Figure 2 .

[0042] Examples 2-7:

[0043] Except for the different reaction temperature, the other process conditions and experimental steps of Examples 2-7 are the same as those of Example 1, and the results are shown in Table 1.

[0044] Table 1. Effect of different reaction temperatures on the synthesis of triazole compounds

[0045] Reaction temperature (°C) Triazole product yield (%) 3 days Guaiacin yield (%) Example 2 30 39 61 Example 3 50 58 73 Example 4 70 69 78 Example 5 90 75 84 Example 6 110 82 87 Example 7 130 80 85

[0046] As shown in Table 1, initially, the yields of both triazole product 3d and guaiacol increased significantly with increasing reaction temperature, reaching over 80% at a reaction temperature of 110℃. With further increases in temperature, the yields of both triazole product 3d and guaiacol began to decrease; however, at a reaction temperature of 130℃, the yields of triazole product 3d and guaiacol still reached 80% and 85%, respectively.

[0047] Examples 8-17:

[0048] Except for the use of different solvents, the other process conditions and experimental steps of Examples 8-17 are the same as those of Example 1, and the results are shown in Table 2.

[0049] Table 2. Effects of different solvents on the synthesis of triazole compounds

[0050]

[0051]

[0052] As shown in Table 2, when n-butanol, ethanol, 1,4-dioxane, dimethyl carbonate, dimethylformamide, and dimethyl sulfoxide are used as solvents, the yields of triazole product 3d and guaiacol are both above 70%.

[0053] Examples 18-23:

[0054] Except for the reaction time, the other process conditions and experimental steps of Examples 18-23 are the same as those of Example 1, and the results are shown in Table 3.

[0055] Table 3. Effect of different reaction times on the synthesis of triazole compounds

[0056]

[0057] As shown in Table 3, the yields of triazole product 3d and guaiacol increased significantly with the extension of reaction time. When the reaction time was 8h, the yields of triazole product 3d and guaiacol were both above 80%.

[0058] Examples 24-27:

[0059] Except for the different substrate feeding ratio, the other process conditions and experimental steps of Examples 24-27 are the same as those of Example 1, and the results are shown in Table 4.

[0060] Table 4. Effect of different substrate ratios on the synthesis of triazole compounds

[0061]

[0062] As shown in Table 4, when the molar ratio of lignin model compound to benzyl azide is 3:1, the yields of triazole product 3d and guaiacol are both above 80%.

[0063] Examples 28-49:

[0064] Except for the use of different types of lignin model compounds and azide compounds as raw materials, the other process conditions and experimental procedures in Examples 27-49 are the same as in Example 1, and the results are shown in Table 5. To more clearly illustrate the synthesized triazole compounds, some of the accompanying drawings from the examples will be briefly described; specific NMR spectra are attached. Figure 3-16 .

[0065] Table 5. Effects of different lignin model compounds and different azide compounds on the synthesis of triazole compounds.

[0066]

[0067]

[0068]

[0069] As shown in Table 5, when different types of lignin model compounds and azide compounds are used as substrates, triazole compounds and phenols can be synthesized, and the yields are all above 60%.

[0070] In Example 49, we selected glucose azide. This example provides an all-biomass route, and this strategy has the potential to be applied to the design of new therapeutics.

[0071] 1,2,3-Triazole is often used as a functional heterocyclic compound, intercalating within multiple heterocycles and connecting two molecules. Due to its structure, it readily undergoes non-covalent interactions such as hydrophobic effects, electrostatics, van der Waals forces, and hydrogen bonding, thus possessing biological functions. It participates in the binding of various enzymes and receptors in vivo, exhibiting a variety of pharmacological activities including anticancer, antiviral, anti-inflammatory, antibacterial, and antimalarial effects, and can find wide applications in organic chemistry, materials chemistry, and drug molecule research.

[0072] Examples 50-53:

[0073] Except for using different solvent volumes, the other process conditions and experimental steps of Examples 50-53 are the same as those of Example 1, and the results are shown in Table 6.

[0074] Table 6. Effect of different solvent volumes on the synthesis of triazole compounds

[0075]

[0076]

[0077] As shown in Table 6, the smaller the solvent volume, the higher the yield of triazole product 3d and the yield of guaiacol. At the same time, the solubility of the reaction substrate needs to be considered. According to the results of Example 1, when the solvent volume is 2 mL, the yield of triazole product 3d and the yield of guaiacol are both above 80%.

[0078] 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 method for synthesizing lignin-based triazole compounds, characterized in that, The main steps include: adding lignin β-O-4 model compound 1, azide compound 2, and vanadium-based catalyst to a solvent, stirring the mixture under air atmosphere to obtain a reaction mixture, and then separating and purifying it to obtain triazole compound 3; the general reaction formula is: The R 1 Selected from alkyl groups having 1-10 carbon atoms, R 2 Selected from alkoxy groups with 1-10 carbon atoms, R 3 Selected from alkyl, aromatic, ester, nitrile, halogen, or naphthalene groups having 5-10 carbon atoms; The catalyst used is a Schiff base ligand vanadium catalyst; Schiff base ligand vanadium catalyst.

2. The synthesis method according to claim 1, characterized in that, The solvent is one or more of the following: n-butanol, water, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, n-hexane, dimethyl carbonate, dimethyl sulfoxide, dimethylformamide, benzene, toluene, and chlorobenzene.

3. The synthesis method according to claim 1, characterized in that, The reaction conditions are: temperature controlled at 20-200 ℃, and reaction time of 0.5-24 h.

4. The synthesis method according to claim 1, characterized in that, The molar ratio of the lignin model compound 1 to the azide compound 2 is 1 to 10:1; the molar ratio of the lignin model compound 1 to the vanadium-based catalyst is 1:0.05 to 0.

1.

5. The synthesis method according to claim 1, characterized in that, The concentration of the lignin β-O-4 model compound 1 in the mixture is 0.01–0.5 mol / L.

6. The synthesis method according to claim 1, characterized in that, The specific steps of the separation and purification are as follows: after the reaction mixture is cooled to room temperature, it is loaded onto a silica gel chromatography column, eluted with elution buffer, and the elution buffer containing triazole compound 3 is collected.

7. The synthesis method according to claim 6, characterized in that, The eluent is petroleum ether and ethyl acetate, with a volume ratio of 1:1 to 10.

Images