Process for the catalytic conversion of lignin to pyrimidine derivatives using rhodium-based catalysts

Abstract

The application discloses a method for preparing a pyrimidine derivative by catalyzing lignin conversion through a rhodium-based catalyst. The method takes real lignin as a substrate, takes amidine hydrochloride and a primary alcohol as reaction raw materials, and utilizes the rhodium-based catalyst to prepare the pyrimidine derivative in an air atmosphere through a one-pot two-step method under alkaline conditions. The method for preparing the pyrimidine derivative from the real lignin is realized, and the method has the advantages of simplicity, high product selectivity, mild reaction conditions and the like.

Description

Technical Field

[0001] This invention relates to a method for preparing pyrimidine derivatives by catalytic conversion of lignin using a rhodium-based catalyst. Background Technology

[0002] Pyrimidine compounds are an important class of nitrogen-containing six-membered heterocyclic compounds with wide applications in medicine, pesticides, antibacterial agents, and insecticides (J.Med.Chem.2016,59,10564-10576). Currently, the one-step synthesis of pyrimidine derivatives from secondary alcohols, amidines, and benzyl alcohols using transition metal catalysts such as Re, Ru, Mn, Ni, and Ir is the most direct and efficient method (J.Am.Chem.Soc.2015,137,12804-12807; Angew.Chem.Int.Ed.2017,56,1663-1666). However, the raw materials for these methods are all derived from fossil resources. With increasing emphasis on environmental and energy issues, developing simple, efficient, environmentally friendly, and atom-economical synthetic methods for pyrimidine derivatives has become a hot topic in pyrimidine preparation, but it is also extremely challenging. Based on this, the present invention utilizes real lignin as raw material to prepare pyrimidine derivatives in a one-pot two-step process under alkaline conditions using a rhodium-based catalyst in an air atmosphere. Summary of the Invention

[0003] To address the problems existing in the prior art, the present invention aims to provide a method for preparing pyrimidine derivatives by catalytic conversion of lignin using a rhodium-based catalyst. This method realizes the preparation of pyrimidine derivatives from real lignin and has advantages such as simplicity, high product selectivity, and mild reaction conditions.

[0004] To achieve the above objectives, the technical solution adopted in this invention is as follows: using lignin raw materials as substrates and amidine hydrochloride and primary alcohol as reactants, pyrimidine derivatives are prepared in a one-pot, two-step process under alkaline conditions using a rhodium-based catalyst in air. The general reaction formula is:

[0005]

[0006] Furthermore, in the above technical solution, the lignin raw material is one or more of organic lignin, lignin sulfonate, alkali lignin, ground wood lignin, and enzymatically hydrolyzed lignin.

[0007] Furthermore, in the above technical solution, the rhodium-based catalyst is rhodium trichloride. The R is an alkyl, alkoxy, halogen, nitro, ester, aryl, amino, hydroxyl, or hydrogen atom.

[0008] Furthermore, in the above technical solution, the amidine hydrochloride is... The primary alcohol is The pyrimidine derivative is

[0009] Furthermore, in the above technical solution, the molar concentration ratio of amidine hydrochloride I to primary alcohol II is 1:1 to 1:5; the mass ratio of amidine hydrochloride to lignin is 1:5 to 1:0.1.

[0010] Furthermore, in the above technical solution, the R 1 and R 2 It is an alkyl, alkoxy, halogen, nitro, ester, aryl, amino, hydroxyl, or hydrogen atom; R 3 It is one or more of a methoxy group, a hydroxyl group, or a hydrogen atom.

[0011] Furthermore, in the above technical solution, the alkali is one or more of NaOH, KOH, CsCO3, t-BuOK, and CH3CHONa.

[0012] Furthermore, in the above technical solution, the one-pot two-step process involves first adding lignin raw materials and rhodium-based catalysts to a solvent, heating them to 25-150°C under air conditions, and reacting for 0.5-48 hours. Then, amidine hydrochloride and primary alcohol are added, and the reaction continues for the same amount of time to prepare pyrimidine derivatives.

[0013] Furthermore, in the above technical solution, preferably, the temperature is heated to 90-140°C under air conditions, and the reaction time is 20-30 hours.

[0014] Furthermore, in the above technical solution, the solvent is one or more of toluene, tert-amyl alcohol, water, 1,4-dioxane, acetonitrile, methanol, ethanol, isopropanol, dimethyl sulfoxide, and dimethylformamide.

[0015] The method provided by this invention is a method for preparing pyrimidine derivatives by catalytic conversion of real lignin using a rhodium-based catalyst, and has the following advantages:

[0016] 1) This invention realizes a method for preparing pyrimidine derivatives from real lignin;

[0017] 2) Mild conditions and simple operation;

[0018] 3) Pyrimidine derivatives have high selectivity, few byproducts, and high atom economy;

[0019] In summary, the method for preparing pyrimidine derivatives by catalytic conversion of lignin using a rhodium-based catalyst provided by this invention is a very practical and inventive method. Attached Figure Description

[0020] To more clearly illustrate the embodiments of the present invention, the accompanying drawings involved in the embodiments will be briefly described below.

[0021] Figure 1 The 4-(4-methoxyphenyl)-2,6-diphenylpyrimidine (compound 2) prepared in Example 1 1 H-NMR spectrum.

[0022] Figure 2 The 4-(3,4-dimethoxyphenyl)-2,6-diphenylpyrimidine (compound 3) prepared in Example 1 1 H-NMR spectrum.

[0023] Figure 3 The 4,6-diphenyl-2-(p-tolyl)pyrimidine prepared in Example 34 1 H-NMR spectrum.

[0024] Figure 4 The 2-(4-p-methoxyphenyl)-4,6-diphenylpyrimidine prepared in Example 35 1 H-NMR spectrum.

[0025] Figure 5 The 2-(4-p-chlorophenyl)-4,6-diphenylpyrimidine prepared in Example 36 1 H-NMR spectrum.

[0026] Figure 6 The 2,4-diphenyl-6-(p-tolyl)pyrimidine prepared in Example 40 1 H-NMR spectrum. Detailed Implementation

[0027] The present invention will be described below with specific embodiments, but the scope of protection of the present invention is not limited to these examples.

[0028] Example 1:

[0029] Organic lignin (100 mg), NaOH (60 mg), and RhCl3 (20 mg) were added to 5 mL of toluene. The mixture was heated to 140 °C and stirred for 20 h under air. Then, benzoamide hydrochloride (0.2 mmol) and benzyl alcohol (0.2 mmol) were added to the reaction tube and stirred for 20 h. After cooling to room temperature, HCl was added to adjust the pH to 1. The organic phase was extracted three times with ethyl acetate to obtain an organic mixture. The mixture was filtered, and the solvent was evaporated. 2 mL of methanol containing an internal standard was added. The yields of compound 1, compound 2, and compound 3 were determined by gas chromatography with internal standard method: 1.5 wt%, 1.3 wt%, and 0.3 wt%.

[0030]

[0031] Examples 2-7:

[0032] Other process conditions and experimental steps are the same as in Example 1, but the reaction temperature is different. The results are shown in Table 1.

[0033] Table 1. Results of synthesis of pyrimidine derivatives under different reaction temperatures

[0034]

[0035] Examples 8-16:

[0036] Other process conditions and experimental steps are the same as in Example 1, but different solvents are used. The results are shown in Table 2.

[0037] Table 2. Results of synthesis of pyrimidine derivatives under different solvent conditions.

[0038] reaction solvent Yield of Compound 1 (wt%) Yield of Compound 2 (wt%) Example 8 tert-amyl alcohol 1.3 1.2 Example 9 water 0.9 1.1 Example 10 methanol 1.8 1.3 Example 11 ethanol 1.7 1.2 Example 12 Isopropanol 1.4 1.3 Example 13 1,4-Dioxane 1.9 1.8 Example 14 Acetonitrile 1.4 1.6 Example 15 dimethyl sulfoxide 1.8 2.1 Example 16 dimethylformamide 2.0 1.9

[0039] Examples 17-22:

[0040] Other process conditions and experimental steps are the same as in Example 1, but different reaction times are used. The results are shown in Table 3.

[0041] Table 3. Results of synthesis of pyrimidine derivatives under different reaction time conditions

[0042]

[0043]

[0044] Examples 22-25:

[0045] Other process conditions and experimental steps are the same as in Example 1, but different alkalis are used. The results are shown in Table 4.

[0046] Table 4. Results of synthesis of pyrimidine derivatives under different alkaline conditions

[0047] project alkali Compound 1 (yield wt%) Yield of Compound 2 (wt%) Example 22 KOH 1.6 1.8 Example 23 <![CDATA[CsCO3]]> 1.7 1.9 Example 24 t-BuOK 1.3 1.6 Example 25 <![CDATA[CH3CHONa]]> 2.0 2.5

[0048] Examples 26-29:

[0049] Other process conditions and experimental steps are the same as in Example 1, but different lignin raw materials are used. The results are shown in Table 5.

[0050] Table 5. Results of synthesis of pyrimidine derivatives under different lignin raw material conditions

[0051] project Lignin raw materials Yield of Compound 1 (wt%) Yield of Compound 2 (wt%) Example 26 lignin sulfonates 1.6 1.5 Example 27 Alkali lignin 1.8 1.8 Example 28 Grinding wood lignin 1.5 1.2 Example 29 Enzymatic hydrolysis of lignin 1.6 0.9

[0052] Examples 30-31:

[0053] Other process conditions and experimental steps are the same as in Example 1, but different I:II molar concentration ratios are used. The results are shown in Table 6.

[0054] Table 6. Results of synthesis of pyrimidine derivatives under different I:II molar concentration ratios

[0055]

[0056]

[0057] Examples 32-33:

[0058] Other process conditions and experimental steps are the same as in Example 1, but different mass ratios of lignin to I are used. The results are shown in Table 7.

[0059] Table 7. Results of synthesis of pyrimidine derivatives under different mass ratios of lignin to I.

[0060] project Mass ratio of lignin to I Yield of Compound 1 (wt%) Yield of Compound 2 (wt%) Example 32 1：1 1.0 0.9 Example 33 1：5 1.2 0.8

[0061] Examples 34-43:

[0062] Other process conditions and experimental steps are the same as in Example 1, but different substituents I and II are used. The results are shown in Table 8.

[0063] Table 8. Results of synthesis of pyrimidine derivatives under different substituent I and II conditions

[0064]

[0065]

[0066] Example 44:

[0067] Organic lignin (100 mg), NaOH (60 mg), and RhCl3 (20 mg) were added to 5 mL of toluene. The mixture was heated to 140 °C and stirred for 20 h under air. Then, p-methylbenzoamide hydrochloride (0.2 mmol) and benzyl alcohol (0.2 mmol) were added to the reaction tube and stirred for 20 h. After cooling to room temperature, HCl was added to adjust the pH to 1. The organic phase was extracted three times with ethyl acetate to obtain an organic mixture. The mixture was filtered, and the solvent was evaporated. 2 mL of methanol containing the internal standard was added. The yield of compound 4 was 1.3 wt% and the yield of compound 5 was 1.2 wt% by gas chromatography with internal standard method.

[0068]

[0069] Example 45:

[0070] Organic lignin (100 mg), NaOH (60 mg), and RhCl3 (20 mg) were added to 10 mL of toluene. The mixture was heated to 140 °C and stirred for 20 h under air. Then, benzoamidine hydrochloride (0.2 mmol) and p-methylbenzyl alcohol (0.2 mmol) were added to the reaction tube and stirred for 20 h. After cooling to room temperature, HCl was added to adjust the pH to 1. The organic phase was extracted three times with ethyl acetate to obtain an organic mixture. The mixture was filtered, and the solvent was evaporated. 2 mL of methanol containing the internal standard was added. The yield of compound 6 was 0.8 wt%, and the yield of compound 7 was 0.5 wt%.

[0071]

[0072] Example 46:

[0073] Organic lignin (100mg), NaOH (60mg), 20 mg of compound 1 was added to 10 mL of toluene. The mixture was heated to 140 °C and stirred for 20 h under air. Then, 0.2 mmol of benzidine hydrochloride and 0.2 mmol of p-methylbenzyl alcohol were added to the reaction tube and stirred for 20 h. After cooling to room temperature, the pH was adjusted to 1 with HCl. The organic phase was extracted three times with ethyl acetate to obtain an organic mixture. The mixture was filtered and the solvent was evaporated. 2 mL of methanol containing the internal standard was added. The yields of compound 1, compound 2, and compound 3 were determined by gas chromatography with internal standard method to be 1.5 wt%, 1.3 wt%, and 0.8 wt%, respectively.

[0074] Example 47:

[0075] Organic lignin (100mg), NaOH (60mg), 20 mg of compound 1 was added to 10 mL of toluene. The mixture was heated to 140 °C and stirred for 20 h under air. Then, 0.2 mmol of benzidine hydrochloride and 0.2 mmol of p-methylbenzyl alcohol were added to the reaction tube and stirred for 20 h. After cooling to room temperature, the pH was adjusted to 1 with HCl. The organic phase was extracted three times with ethyl acetate to obtain an organic mixture. The mixture was filtered and the solvent was evaporated. 2 mL of methanol containing the internal standard was added. The yields of compound 1, compound 2, and compound 3 were determined by gas chromatography with internal standard method to be 1.7 wt%, 1.8 wt%, and 1.2 wt%, respectively.

Claims

1. A process for the catalytic conversion of real lignin to pyrimidine derivatives catalyzed by a rhodium-based catalyst, characterized in that, A pyrimidine derivative III is prepared by one-pot two-step method under air atmosphere using a lignin raw material as a substrate and using amidine hydrochloride I and a primary alcohol II as reaction raw materials under alkaline conditions using a rhodium-based catalyst R1 and R2 are each independently selected from an aryl group; R3 is selected from a methoxy group or a hydrogen atom; The rhodium-based catalyst is rhodium trichloride, or ; The base is one or two or more of NaOH, KOH, Cs2CO3, t-BuOK, CH3CH2ONa; The lignin raw material is one or two or more of organic lignin, lignin sulfonate, alkali lignin, groundwood lignin, and enzymatic hydrolysis lignin.

2. The method of claim 1, wherein, The molar concentration ratio of amidine hydrochloride I to primary alcohol II is 1:1-1:5, and the mass ratio of amidine hydrochloride to lignin is 1:5-1:0.

1.

3. The method of claim 1, wherein, The one-pot two-step method is to first add the lignin raw material and the rhodium-based catalyst to a solvent, heat to 25-150 DEG C under air conditions, and react for 0.5-48 h, then add amidine hydrochloride and a primary alcohol, and continue to react for the same time to prepare the pyrimidine derivative.

4. The method of claim 3, wherein, The solvent is one or two or more of toluene, t-amyl alcohol, water, 1,4-dioxane, acetonitrile, methanol, ethanol, isopropyl alcohol, dimethyl sulfoxide, and dimethyl formamide.

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