Method for 2-pyridyl thienyl alkoxycarbonyl methylation by using vinyl acetate through one-pot multi-component reaction

Abstract

The application discloses a method for realizing 2-pyridyl thiophene alkoxycarbonylmethylation through one-pot multi-component reaction of vinyl acetate, which uses 2-pyridyl thiophene, vinyl acetate and alcohol compounds as raw materials, uses a rhodium catalyst to catalyze the C3 position alkoxycarbonylmethylation reaction of 2-pyridyl thiophene under the condition of copper salt oxidant, and prepares 2-pyridyl thiophene alkoxycarbonylmethyl compounds at the C3 position. The preparation method has the advantages of simple reaction design, convenient operation, wide substrate application range, good functional group compatibility and the like, provides a reliable technical scheme for rapid preparation of 2-pyridyl thiophene alkoxycarbonylmethyl compounds, provides a new path for synthesis and construction of drug intermediates, coordination ligands and organic functional material related N, S-heterocyclic derivatives, and has both academic research value and industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology and relates to a method for achieving 2-pyridylthiophene oxycarbonyl methylation of vinyl acetate via a one-pot multi-component reaction. Background Technology

[0002] 2-Pyridylthiophene is an important N,S-heteroaromatic conjugated skeleton, possessing both metal coordination directing ability and heteroaromatic ring reactivity, making it crucial for applications in bioactive molecules, coordination chemistry, organic functional materials, and fine chemical intermediates. Selective functionalization of its skeleton can expand structural diversity and regulate electronic and coordination properties, representing a core strategy for constructing high-value-added N,S-heterocyclic derivatives. Alkoxycarbonylmethyl (–CH₂COOR) is a key structural unit in ester drug intermediates and functional heterocyclic molecules. Precise introduction of this fragment can enhance molecular polarity and modifiability, providing multiple transformation sites. Efficient and controllable introduction methods are of great significance for the construction of complex heterocyclic molecules.

[0003] Currently, my country's vinyl acetate production capacity exceeds 4.5 million tons per year, significantly higher than the demand of approximately 2.7 million tons per year, resulting in a prominent overcapacity problem. Its traditional downstream applications are concentrated in polyvinyl alcohol and EVA resin, accounting for over 80% of consumption, but the added value is relatively low, and the industry faces pressure from low-price competition. Converting surplus vinyl acetate into high-value-added fine chemical products has become an industry consensus and development trend.

[0004] Existing methods for preparing heteroaryl acetates rely on prefunctionalized substrate cross-coupling, metallization capture, or multi-step transformation, which have drawbacks such as cumbersome steps, difficulty in controlling regioselectivity, poor functional group compatibility, and complex operation. Directly achieving C3-position selective alkoxycarbonyl methylation is even more challenging due to the multi-reaction site characteristics of 2-pyridylthiophene. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a method for achieving 2-pyridylthiophene alkyloxycarbonyl methylation of vinyl acetate via a one-pot multi-component reaction.

[0006] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0007] A method for methylating 2-pyridylthiophene alkoxycarbonylation via a one-pot, multi-component reaction using vinyl acetate is described. Using 2-pyridylthiophene compounds, vinyl acetate, and alcohols as raw materials, the C3-alkoxycarbonylation of 2-pyridylthiophene is catalyzed by a rhodium catalyst under copper salt oxidant conditions to obtain C3-alkoxycarbonylmethylated 2-pyridylthiophene compounds.

[0008] In the above method, compound 1, compound 2, compound 3, rhodium catalyst, copper salt oxidant and solvent are added to a reactor and stirred under air atmosphere. After the reaction is completed, the mixture is cooled to room temperature and concentrated. The crude mixture is purified by silica gel column chromatography to obtain C3-alkoxycarbonylmethylated 2-pyridylthiophene compounds. Among them, compound 1 is a 2-pyridylthiophene compound, compound 2 is vinyl acetate and compound 3 is an alcohol compound.

[0009] The reaction conforms to the following reaction formula:

[0010] .

[0011] The rhodium catalyst is one or more of the following: dichloro(pentamethylcyclopentadienyl)rhodium polymer, tri(acetylacetonate)rhodium, rhodium trichloride hydrate, dichlorobis(acetonitrile)(pentamethylcyclopentadienyl)rhodium, diiodo(pentamethylcyclopentadienyl)rhodium polymer, chlorobis(ethylene)(pentamethylcyclopentadienyl)rhodium, and dichlorobis(triphenylphosphine)rhodium; the copper salt oxidant is copper acetate, copper chloride, copper bromide, cuprous iodide, copper trifluoromethanesulfonate, copper acetylacetonate, copper oxide, cuprous oxide, etc. One or more of copper nitrate, copper carbonate, and copper sulfate; one or more of the following alcohols: methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, benzyl alcohol, substituted benzyl alcohol, allyl alcohol, propargyl alcohol, and cyclohexanol; and one or more of the following solvents: toluene, trifluorotoluene, chlorobenzene, 1,2-dichloroethane, dichloromethane, acetonitrile, 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, hexafluoroisopropanol, methanol, ethanol, and isopropanol.

[0012] The rhodium catalyst is a dichloro(pentamethylcyclopentadienyl) rhodium polymer; the copper salt oxidant is copper acetate; and the solvent is toluene.

[0013] The molar ratio of compound 1, compound 2, and compound 3 is 1:(1-6):(1-50).

[0014] The reaction temperature is 0–150 °C, and the reaction time is 0–48 h.

[0015] The molar ratio of compound 1, compound 2, and compound 3 was 1:2:10, the reaction temperature was 120 °C, and the reaction time was 12 h.

[0016] The reactor is a Schlenk tube.

[0017] To address the technical problems in existing 2-pyridylthiophene heterocyclic alkoxycarbonyl methylation reactions, such as strong substrate prefunctionalization dependence, cumbersome reaction steps, difficulty in controlling regioselectivity, and challenges in matching multi-component systems, the inventors have established a method for achieving 2-pyridylthiophene alkoxycarbonyl methylation via a one-pot multi-component reaction using vinyl acetate. Using 2-pyridylthiophene compounds, vinyl acetate, and alcohols as raw materials, under copper salt oxidant conditions, a rhodium catalyst is used to catalyze the C3-alkoxycarbonyl methylation reaction of 2-pyridylthiophene, yielding C3-alkoxycarbonyl methylated 2-pyridylthiophene compounds.

[0018] This invention relies on a pyridine-guided rhodium-catalyzed C–H activation strategy. By rationally combining rhodium catalysts, copper salt oxidants, alcohol components, and solvent systems, it effectively controls the migration insertion and subsequent oxidative esterification processes involving vinyl acetate, achieving the directional introduction of –CH2COOR structural units with high regioselectivity. This preparation method possesses advantages such as simple reaction design, convenient operation, wide substrate applicability, and good functional group compatibility. It provides a reliable technical solution for the rapid preparation of C3-alkoxycarbonyl methylated 2-pyridylthiophene compounds, and also offers a new pathway for the synthesis and construction of N,S-heterocyclic derivatives related to pharmaceutical intermediates, coordinating ligands, and organic functional materials. Furthermore, it provides a new direction for the high-value utilization of vinyl acetate, possessing both academic research value and promising industrial application prospects. Attached Figure Description

[0019] Figure 1 The image shows the hydrogen spectrum of the product obtained in Example 1.

[0020] Figure 2 The image shows the carbon spectrum of the product obtained in Example 1.

[0021] Figure 3 The image shows the hydrogen spectrum of the product obtained in Example 2.

[0022] Figure 4 The image shows the carbon spectrum of the product obtained in Example 2.

[0023] Figure 5 The image shows the hydrogen spectrum of the product obtained in Example 3.

[0024] Figure 6 The image shows the carbon spectrum of the product obtained in Example 3.

[0025] Figure 7 The fluorine spectrum of the product obtained in Example 3 is shown.

[0026] Figure 8 The image shows the hydrogen spectrum of the product obtained in Example 4.

[0027] Figure 9 The image shows the carbon spectrum of the product obtained in Example 4.

[0028] Figure 10 The image shows the hydrogen spectrum of the product obtained in Example 5.

[0029] Figure 11 The image shows the carbon spectrum of the product obtained in Example 5.

[0030] Figure 12 The fluorine spectrum of the product obtained in Example 5 is shown.

[0031] Figure 13 The image shows the hydrogen spectrum of the product obtained in Example 6.

[0032] Figure 14 The image shows the carbon spectrum of the product obtained in Example 6.

[0033] Figure 15 The image shows the hydrogen spectrum of the product obtained in Example 7.

[0034] Figure 16 The image shows the carbon spectrum of the product obtained in Example 7.

[0035] Figure 17 The image shows the hydrogen spectrum of the product obtained in Example 8.

[0036] Figure 18 The carbon spectrum of the product obtained in Example 8 is shown below. Detailed Implementation

[0037] Example 1

[0038] 2-pyridylthiophene (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), methanol (81 μL, 2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the mixture was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to give the desired yellow liquid C3-alkoxycarbonyl methylated product Methyl 2-(2-(pyridin-2-yl)thiophen-3-yl)acetate (38.2 mg, 82%).

[0039] The proton and carbon spectra of the obtained products are as follows: Figure 1 and Figure 2 As shown, the structural characterization data are as follows:

[0040] 1 H NMR (600 MHz, CDCl3) δ 8.61 (d, J = 4.3 Hz, 1H), 7.70 (td, J =7.7, 1.8 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.32 (d, J = 5.1 Hz, 1H), 7.17(dd, J = 7.1, 5.3 Hz, 1H), 7.06 (d, J = 5.1 Hz, 1H), 4.03 (s, 2H), 3.70 (s,3H).

[0041] 13 C NMR (151 MHz, CDCl3) δ 171.8, 152.3, 149.4, 139.4, 136.6, 131.8,131.3, 125.4, 122.0, 121.7, 52.0, 35.2.

[0042] HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 12 NO2S 234.0583; Found 234.0579.

[0043] Based on the above data, the structure of the product is inferred as follows:

[0044]

[0045] Example 2

[0046] 5-Methyl-2-(thiophen-2-yl)pyridine (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), methanol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the product was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the desired yellow liquid C3 alkoxycarbonyl methylated product Methyl 2-(2-(5-methylpyridin-2-yl)thiophen-3-yl)acetate (38.7 mg, 78%).

[0047] The proton and carbon spectra of the obtained products are as follows: Figure 3 and Figure 4 As shown, the structural characterization data are as follows:

[0048] 1 H NMR (600 MHz, CDCl3) δ 8.44 (s, 1H), 7.50 (d, J = 5.6 Hz, 2H), 7.29 (d, J = 5.1 Hz, 1H), 7.04 (d, J = 5.1 Hz, 1H), 4.00 (s, 2H), 3.69 (s, 3H),2.34 (s, 3H).

[0049] 13 C NMR (151 MHz, CDCl3) δ 171.9, 150.2, 149.8, 139.6, 137.2, 131.4,131.19, 131.16, 124.9, 121.6, 52.0, 35.1, 18.2.

[0050] HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 14 NO2S 248.0667; Found 248.0674.

[0051] Based on the above data, the structure of the product is inferred as follows:

[0052]

[0053] Example 3

[0054] 5-Fluoro-2-(thiophene-2-yl)pyridine (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), methanol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the mixture was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the desired brown liquid C3 alkoxycarbonyl methylated product Methyl 2-(2-(5-fluoropyridin-2-yl)thiophen-3-yl)acetate (32.6 mg, 65%).

[0055] The proton, carbon, and fluorine spectra of the obtained product are as follows: Figure 5 , Figure 6 and Figure 7 As shown, the structural characterization data are as follows:

[0056] 1 H NMR (600 MHz, CDCl3) δ 8.46 (d, J = 2.9 Hz, 1H), 7.61 (dd, J = 8.7,4.3 Hz, 1H), 7.44 – 7.41 (m, 1H), 7.31 (d, J = 5.1 Hz, 1H), 7.05 (d, J = 5.1Hz, 1H), 3.98 (s, 2H), 3.70 (s, 3H).

[0057] 13 C NMR (151 MHz, CDCl3) δ 171.8, 157.3, 149.3, 138.2, 137.5, 131.8,131.4, 126.9, 126.2, 125.3, 124.6, 123.6, 123.5, 122.9, 52.1, 35.1.

[0058] 19 F NMR (565 MHz, CDCl3) δ -129.06 (s).

[0059] HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 11 FNO2S 252.0489; Found 252.0483.

[0060] Based on the above data, the structure of the product is inferred as follows:

[0061]

[0062] Example 4

[0063] 5-Chloro-2-(thien-2-yl)pyridine (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), methanol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the mixture was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the desired yellow solid C3-alkoxycarbonyl methylated product Methyl 2-(2-(5-chloropyridin-2-yl)thiophen-3-yl)acetate (33.1 mg, 62%).

[0064] The proton and carbon spectra of the obtained products are as follows: Figure 8 and Figure 9 As shown, the structural characterization data are as follows:

[0065] 1 H NMR (600 MHz, CDCl3) δ 8.54 (d, J = 2.5 Hz, 1H), 7.66 (dd, J = 8.5,2.5 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.32 (d, J = 5.1 Hz, 1H), 7.04 (d, J =5.1 Hz, 1H), 4.00 (s, 2H), 3.69 (s, 3H).

[0066] 13C NMR (151 MHz, CDCl3) δ 171.7, 151.1, 148.2, 138.0, 136.4, 132.5,131.7, 129.9, 125.7, 122.5, 52.1, 35.2.

[0067] HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 11 ClNO2S 268.0194; Found 268.0188.

[0068] Based on the above data, the structure of the product is inferred as follows:

[0069]

[0070] Example 5

[0071] 5-Trifluoromethyl-2-(thiophen-2-yl)pyridine (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), methanol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the product was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the desired yellow liquid C3 alkoxycarbonyl methylated product Methyl 2-(2-(5-(trifluoromethyl)pyridin-2-yl)thiophen-3-yl)acetate (33.7 mg, 56%).

[0072] The proton, carbon, and fluorine spectra of the obtained product are as follows: Figure 10 , Figure 11 and Figure 12 As shown, the structural characterization data are as follows:

[0073] 1H NMR (600 MHz, CDCl3) δ 8.84 (s, 1H), 7.92 (dd, J = 8.4, 2.4 Hz,1H), 7.71 (d, J = 8.3 Hz, 1H), 7.40 (d, J = 5.1 Hz, 1H), 7.08 (d, J = 5.1 Hz,1H), 4.07 (s, 2H), 3.70 (s, 3H).

[0074] 13 C NMR (151 MHz, CDCl3) δ 171.6, 146.2, 146.2, 146.2, 137.6, 134.1,133.91, 133.89, 132.1, 126.8, 121.1, 52.1, 35.4.

[0075] 19 F NMR (565 MHz, CDCl3) δ -62.32 (s).

[0076] HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 11 F3NO2S 302.0457; Found 302.0450.

[0077] Based on the above data, the structure of the product is inferred as follows:

[0078]

[0079] Example 6: 2-(thiophen-2-yl)quinoline (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), methanol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the mixture was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the desired brown solid C3-alkoxycarbonyl methylated product Methyl 2-(2-(quinolin-2-yl)thiophen-3-yl)acetate (44.2 mg, 78%).

[0080] The proton and carbon spectra of the obtained products are as follows: Figure 13 and Figure 14 As shown, the structural characterization data are as follows:

[0081] 1 H NMR (600 MHz, CDCl3) δ 8.12 (dd, J = 8.6, 0.8 Hz, 1H), 8.07 (dd, J= 8.4, 1.1 Hz, 1H), 7.76 (d, J = 8.1 Hz, 1H), 7.71 (d, J = 8.6 Hz, 1H), 7.69(s, 1H), 7.51 – 7.47 (m, 1H), 7.37 (d, J = 5.1 Hz, 1H), 7.11 (d, J = 5.1 Hz,1H), 4.23 (s, 2H), 3.70 (s, 3H).

[0082] 13 C NMR (151 MHz, CDCl3) δ 172.1, 152.8, 147.9, 138.9, 136.6, 133.7,132.1, 129.8, 129.3, 127.4, 126.5, 126.3, 125.6, 120.3, 52.0, 35.9.

[0083] HRMS (ESI) m / z: [M+H] + Calcd for C 16 H 14 NO2S 284.0739; Found 284.0731.

[0084] Based on the above data, the structure of the product is inferred as follows:

[0085]

[0086] Example 7: 2-pyridylthiophene (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), ethanol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the mixture was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to give the desired yellow liquid C3-alkoxycarbonyl methylated product Ethyl 2-(2-(pyridin-2-yl)thiophen-3-yl)acetate (39.5 mg, 80%).

[0087] The proton and carbon spectra of the obtained products are as follows: Figure 15 and Figure 16 As shown, the structural characterization data are as follows:

[0088] 1 H NMR (600 MHz, CDCl3) δ 8.61 (d, J = 4.7 Hz, 1H), 7.70 (t, J = 7.7Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 5.1 Hz, 1H), 7.18 – 7.15 (m,1H), 7.06 (d, J = 5.1 Hz, 1H), 4.15 (q, J = 7.1 Hz, 2H), 4.00 (s, 2H), 1.23(t, J = 7.1 Hz, 3H).

[0089] 13 C NMR (151 MHz, CDCl3) δ 171.5, 152.9, 149.4, 139.5, 136.6, 131.9,131.3, 125.4, 122.0, 121.7, 60.8, 35.4, 14.2.

[0090] HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 14 NO2S 248.0667; Found 248.0676.

[0091] Based on the above data, the structure of the product is inferred as follows:

[0092]

[0093] Example 8: 2-pyridylthiophene (0.2 mmol, 1 equiv), vinyl acetate (0.4 mmol, 2 equiv), [Cp*RhCl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%), Cu(OAc)2 (72.7 mg, 0.4 mmol, 2 equiv), 3-methoxybenzyl alcohol (2.0 mmol, 10 equiv), and toluene (1.5 mL) were sequentially added to a 15 mL dried Schlenk tube. The reaction mixture was stirred at 120 °C in air for 12 h. After the reaction was completed, the mixture was cooled to room temperature and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain the desired yellow solid C3-alkoxycarbonyl methylated product 3-Methoxybenzyl 2-(2-(pyridin-2-yl)thiophen-3-yl)acetate (25.8 mg, 38%).

[0094] The proton and carbon spectra of the obtained products are as follows: Figure 17 and Figure 18 As shown, the structural characterization data are as follows:

[0095] 1 H NMR (600 MHz, CDCl3) δ 8.57 (d, J = 4.3 Hz, 1H), 7.68 (td, J = 7.8,1.8 Hz, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.34 (d, J = 5.1 Hz, 1H), 7.28 – 7.26(m, 1H), 7.16 (dd, J = 7.4, 4.9 Hz, 1H), 7.09 (d, J = 5.1 Hz, 1H), 6.92 (d, J= 7.4 Hz, 1H), 6.87 (d, J = 6.4 Hz, 2H), 5.15 (s, 2H), 4.10 (s, 2H), 3.80 (s,3H).

[0096] 13C NMR (151 MHz, CDCl3) δ 167.2, 155.8, 148.9, 145.5, 135.5, 133.5,132.7, 127.9, 127.5, 125.6, 121.5, 117.9, 117.7, 116.3, 109.9, 109.4, 62.5,51.3, 31.5.

[0097] HRMS (ESI) m / z: [M+H] + Calcd for C 19 H 18 NO3S 340.1002; Found 340.0995.

[0098] Based on the above data, the structure of the product is inferred as follows:

[0099]

Claims

1. A method for achieving 2-pyridylthiophene alkyloxycarbonyl methylation of vinyl acetate via a one-pot, multi-component reaction, characterized in that: Using 2-pyridylthiophene compounds, vinyl acetate, and alcohols as raw materials, and under copper salt oxidant conditions, a rhodium catalyst was used to catalyze the C3-alkoxycarbonyl methylation reaction of 2-pyridylthiophene to obtain C3-alkoxycarbonyl methylated 2-pyridylthiophene compounds.

2. The method according to claim 1, characterized in that: Compound 1, Compound 2, Compound 3, rhodium catalyst, copper salt oxidant, and solvent were added to a reactor and stirred under air atmosphere. After the reaction was completed, the mixture was cooled to room temperature and concentrated. The crude mixture was purified by silica gel column chromatography to obtain C3-alkoxycarbonylmethylated 2-pyridylthiophene compounds. Among them, Compound 1 is a 2-pyridylthiophene compound, Compound 2 is vinyl acetate, and Compound 3 is an alcohol compound.

3. The method according to claim 2, characterized in that... The reaction conforms to the following reaction formula: 。 4. The method according to claim 2, characterized in that: The rhodium catalyst is one or more of the following: dichloro(pentamethylcyclopentadienyl) rhodium polymer, tri(acetylacetonate) rhodium, rhodium trichloride hydrate, dichlorobis(acetonitrile)(pentamethylcyclopentadienyl) rhodium, diiodo(pentamethylcyclopentadienyl) rhodium polymer, chlorobis(ethylene)(pentamethylcyclopentadienyl) rhodium, and dichlorobis(triphenylphosphine) rhodium; the copper salt oxidant is copper acetate, copper chloride, copper bromide, cuprous iodide, copper trifluoromethanesulfonate, copper acetylacetonate, copper oxide, and cuprous oxide. One or more of copper nitrate, copper carbonate, and copper sulfate; the alcohol compound is one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, benzyl alcohol, substituted benzyl alcohol, allyl alcohol, propargyl alcohol, and cyclohexanol; the solvent is one or more of toluene, trifluorotoluene, chlorobenzene, 1,2-dichloroethane, dichloromethane, acetonitrile, 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, hexafluoroisopropanol, methanol, ethanol, and isopropanol.

5. The method according to claim 4, characterized in that: The rhodium catalyst is a dichloro(pentamethylcyclopentadienyl) rhodium polymer; the copper salt oxidant is copper acetate; and the solvent is toluene.

6. The method according to claim 2, characterized in that: The molar ratio of compound 1, compound 2, and compound 3 is 1:(1-6):(1-50).

7. The method according to claim 2, characterized in that: The reaction temperature is 0–150 °C, and the reaction time is 0–48 h.

8. The method according to claim 7, characterized in that: The molar ratio of compound 1, compound 2, and compound 3 is 1:2:10, the reaction temperature is 120 °C, and the reaction time is 12 h.

9. The method according to claim 2, characterized in that: The reactor is a Schlenk tube.

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