Synthetic method of lignin-based triazole compound

Abstract

The invention discloses a synthesis method of a lignin-based triazole compound, and belongs to the technical field of synthesis of organic compounds. According to the method, a lignin beta-O-4 model compound containing gamma-OH and an azide compound are used as reaction raw materials, and the triazole compound is prepared by a one-pot method in an air atmosphere under the action of a vanadium-based catalyst. The synthetic method for preparing the triazole compound has the advantages of simplicity in operation, mild reaction conditions, high product selectivity and the like, and a new way is provided for preparation of the triazole compound.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for synthesizing a lignin-based triazole compound. Background Art

[0002] Triazole compounds are important nitrogen-containing heterocyclic compounds with good antibacterial and antitumor biological activities, and are widely used in drug development, bioconjugation and material science (Chem.Soc.Rev.2016,45,3766). At present, the classical synthesis method of triazole compounds is a "click reaction" of azide and alkyne ring addition or alkene ring addition under the action of a metal catalyst. However, most of the classical synthesis methods use non-renewable raw materials as substrates. With the increasing attention paid to environmental and energy issues, it is urgent to develop a synthesis method of triazole compounds that is simple to operate, efficient, environmentally friendly, and highly atom-economical. 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 object, the technical solution adopted by the present invention is:

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

[0006]

[0007] in,

[0008] The R 1 is selected from an alkyl group having 1 to 10 carbon atoms, R 2 is selected from an alkoxy group having 1 to 10 carbon atoms, R 3 is selected from an alkyl group having 5 to 10 carbon atoms, an aromatic group, an ester group, a nitrile group, a halogen group or naphthalene. 1 is an alkoxy group having 1 to 10 carbon atoms, R 2 is an aromatic group, R 3 is a halogen or naphthalene.

[0009] Further, the catalyst is triethoxyvanadium oxide, vanadium acetylacetonate, vanadium chloride, ammonium metavanadate, sodium metavanadate and Schiff base ligand vanadium catalyst (Angew. Chem. Int. Ed. 2010, 49, 3791-3794). Preferably, the catalyst is a Schiff base ligand vanadium catalyst.

[0010]

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

[0012] Furthermore, the reaction conditions are: the temperature is controlled at 20-200°C, and the reaction time is 0.5-24h. The preferred temperature is 80-150°C, and the preferred time is 6-12h.

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

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

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

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

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

[0018] The beneficial effects of the present invention compared with 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 the present invention have high selectivity, few by-products and high atom economy.

[0021] 3. The present invention utilizes green biomass as raw material, provides a sustainable and green method for synthesizing triazole compounds, and provides a new way to fully utilize biomass. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention, the drawings related to the embodiments are briefly introduced below.

[0023] Figure 1 The triazole product 3d prepared in Example 1 1 H-NMR nuclear magnetic spectrum.

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

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

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

[0027] Figure 5 The triazole product 31 prepared in Example 40 1 H-NMR nuclear magnetic spectrum.

[0028] Figure 6 The triazole product 31 prepared in Example 40 13 C-NMR spectrum.

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

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

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

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

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

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

[0035] Fig.13 The triazole product 3t prepared in Example 48 1 H-NMR nuclear magnetic spectrum.

[0036] Fig.14 The triazole product 3t prepared in Example 48 13 C-NMR spectrum.

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

[0038] Fig.16 The triazole product 3u prepared in Example 49 13 C-NMR spectrum. DETAILED DESCRIPTION

[0039] The present invention is described in detail below with reference to the embodiments, but the embodiments of the present invention are not limited thereto. Obviously, the embodiments described below are only partial embodiments of the present invention. For those skilled in the art, other similar embodiments obtained without creative labor all fall within the protection scope of the present invention.

[0040] Embodiment 1:

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

[0042] Embodiment 2-7:

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

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

[0045] Reaction temperature (℃) Yield of triazole product 3d (%) Guaiacol 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, with the increase of reaction temperature, the yield of triazole product 3d and the yield of guaiacol both increased significantly. When the reaction temperature was 110°C, the yield of triazole product 3d and the yield of guaiacol were both above 80%. As the temperature increased again, the yield of triazole product 3d and the yield of guaiacol began to decrease; but when the reaction temperature was 130°C, the yield of triazole product 3d and the yield of guaiacol could still reach 80% and 85%.

[0047] Embodiment 8-17:

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

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

[0050]

[0051]

[0052] It can be seen from Table 2 that 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] Embodiment 18-23:

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

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

[0056]

[0057] It can be seen from Table 3 that with the extension of the reaction time, the yield of the triazole product 3d and the yield of guaiacol are significantly improved. When the reaction time is 8h, the yield of the triazole product 3d and the yield of guaiacol are both above 80%.

[0058] Embodiment 24-27:

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

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

[0061]

[0062] It can be seen from Table 4 that when the molar ratio of the lignin model compound to benzyl azide is 3:1, the yield of the triazole product 3d and the yield of guaiacol are both above 80%.

[0063] Embodiment 28-49:

[0064] Except for using different types of lignin model compounds and azide compound raw materials, the other process conditions and experimental steps of Examples 27-49 are the same as those of Example 1, and the results are shown in Table 5. In order to more clearly illustrate the synthesized triazole compounds, the drawings involved in some examples are briefly introduced, and the specific NMR spectra are shown in the attached Figure 3-16 .

[0065] Table 5. Effects of different types of 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 with a yield of more than 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 in the design of new therapeutic drugs.

[0071] 1,2,3-Triazole is often used as a functional heterocyclic compound, embedded in a polycyclic ring and connecting two molecules. Since its structure is prone to non-covalent interactions such as hydrophobic effect, electrostatics, van der Waals force, hydrogen bonding, etc., it has biological functions, participates in the binding of multiple enzymes and receptors in organisms, and exhibits multiple pharmacological activities such as anticancer, antiviral, anti-inflammatory, antibacterial, and antimalarial, and can be widely used in the fields of organic chemistry, material chemistry, and drug molecules.

[0072] Embodiment 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. The results are shown in Table 6.

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

[0075]

[0076]

[0077] It can be seen from Table 6 that when the solvent volume is smaller, the yield of triazole product 3d and the yield of guaiacol are higher. At the same time, the solubility of the synthesis 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, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements 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 a lignin-based triazole compound, characterized in that: The method mainly comprises the following steps: adding a lignin β-O-4 model compound 1, an azide compound 2 and a vanadium-based catalyst into a solvent, stirring the mixture under air atmosphere to obtain a reaction mixture, and separating and purifying the mixture to obtain a triazole compound 3; the general reaction formula is: The R 1 is selected from an alkyl group having 1 to 10 carbon atoms, R 2 is selected from an alkoxy group having 1 to 10 carbon atoms, R 3 It is selected from an alkyl group having 5 to 10 carbon atoms, an aromatic group, an ester group, a nitrile group, a halogen group or naphthalene.

2. The synthesis method according to claim 1, characterized in that The catalysts used are triethoxyvanadium oxide, vanadium acetylacetonate, vanadium chloride, ammonium metavanadate, sodium metavanadate and Schiff base ligand vanadium catalyst; 3. The synthesis method according to claim 1, characterized in that The solvent is one or more of n-butanol, water, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, n-hexane, dimethyl carbonate, dimethyl sulfoxide, dimethylformamide, benzene, toluene and chlorobenzene.

4. The synthesis method according to claim 1, characterized in that The reaction conditions are: the temperature is controlled at 20-200° C., and the reaction time is 0.5-24 h.

5. 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.

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

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

8. The synthesis method according to claim 7, characterized in that The eluent is any two of petroleum ether, n-hexane, n-pentane, ethyl acetate, and dichloromethane, and the volume ratio of the two is 1:1-10.

9. A lignin-based triazole compound, characterized in that: Prepared by the synthesis method according to any one of claims 1 to 8.

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