A method for preparing a β,γ-unsaturated carboxylic acid benzyl ester compound

Abstract

The present invention belongs to the technical field of C-N bond activation, activation and transformation of CO2, and related chemistry, and provides a method for preparing β,γ-unsaturated carboxylic acid benzyl ester compounds. A palladium catalyst, an additive, benzylsulfonamide, tributylallyltin, and a solvent are sequentially added to a reaction kettle, and carbon dioxide is filled to 0.5 MPa to 3.0 MPa; then the reaction kettle is placed in an oil bath at 50 to 100 °C for reaction for 12 to 36 h. After the reaction is completed, it is cooled to room temperature, and the remaining carbon dioxide is released. The obtained reaction solution is separated by column chromatography to obtain β,γ-unsaturated carboxylic acid benzyl ester compounds. This method has the advantages of mild reaction conditions, simple experimental operation, good substrate compatibility, and easy industrialization. Therefore, the present invention has great application value and social and economic benefits.

Description

Technical Field

[0001] The present invention belongs to the technical field of C-N bond activation, activation and transformation of CO2, and related chemistry, and relates to the three-component coupling reaction of benzylsulfonamide compounds and carbon dioxide. Background Art

[0002] Transition metal-catalyzed C-N bond reactions have been widely explored and have become powerful tools for the synthesis of amines, amides, and some other nitrogen-containing molecules, in which key C-M and N-M species usually participate in the catalytic cycle [see: (a) J. Bariwal, E. Vander Eycken, Chem. Soc. Rev. 2013, 42, 9283-9933.]. In principle, these active nucleophiles can react to form new C-C and C-N bonds with other coupling partners under suitable reaction conditions. In addition, the rich sources of C-N bonds increase the attractiveness of this strategy and pave the way for its large-scale application. However, the inertness of the C-N bond and the requirements for corresponding selective functionalization make this process extremely challenging. Compared with the well-developed C-H activation reaction, the similar coupling reaction through C-N bond activation is still in the development stage. Therefore, this research topic has attracted more and more attention.

[0003] As one of the main greenhouse gases, carbon dioxide (CO2) plays a crucial role in global warming and climate change. On the other hand, CO2 can be used as a green, non-toxic, abundant, and renewable C1 source for organic synthesis. Especially for the construction of valuable carboxylic acids, which are key components of various natural products and drugs. Therefore, the chemical fixation and utilization of carbon dioxide have attracted more and more attention. [see: (a) Q. Liu, L. Wu, R. Jackstell, M. Beller, Nat. Commun. 2015, 6, 5933; (b) J.-H. Ye, T. Ju, H. Huang, L.-L. Liao, D.-G. Yu, Acc. Chem. Res. 2021, 54, 2518-253].

[0004] In 2011, the research group of Ming Bao reported a three-component carboxylation reaction using benzyl halides, carbon dioxide and tributylallyltin. However, due to the high reactivity of halides, they are difficult to preserve and can hardly exist stably in some structures [See: (a) X. Feng, A. Sun, S. Zhang, X. Yu, M. Bao, Org. Lett. 2013, 15, 108 - 111.]. Therefore, it becomes very important to find a class of stable electrophilic reagents for such reactions. At the same time, C-N bonds are widely present in natural products in nature, but due to the high bond energy of C-N bonds, it is difficult to convert them into high-value-added products. Therefore, this patent uses two inert substances, inert benzyl sulfonamide and carbon dioxide, to convert them into high-value-added products. Summary of the Invention

[0005] The present invention provides a method for the three-component coupling of C-N bond activation and CO2, which uses Pd(II) as a catalyst and realizes the conversion of carbon dioxide catalyzed by an in-situ generated nano-catalyst. This method has the advantages of mild reaction conditions, simple experimental operation, good substrate compatibility, easy industrialization, etc. Therefore, the present invention has great application value and social and economic benefits.

[0006] Technical solution of the present invention:

[0007] A method for preparing a β,γ-unsaturated carboxylic acid benzyl ester compound, adding a palladium catalyst, an additive, benzyl sulfonamide, tributylallyltin, and a solvent into a reaction kettle in sequence, filling carbon dioxide to 0.5 MPa - 1.0 MPa; then placing the reaction kettle in an oil bath at 70 - 90 °C for reaction for 16 - 24 h, cooling to room temperature after the reaction is completed, discharging the remaining carbon dioxide, and obtaining the reaction solution through column separation to obtain the β,γ-unsaturated carboxylic acid benzyl ester compound;

[0008] The synthesis route is as follows:

[0009]

[0010] In the formula, R on the benzyl sulfonamide is selected from fluorine, chlorine, bromine, nitro, ester group, methyl or methoxy; R is in the ortho, meta or para position of the aromatic ring; the aromatic ring is a benzene ring or a naphthalene ring;

[0011] The molar ratio of benzyl sulfonamide to tributylallyltin is 1:1 - 1:2;

[0012] The molar ratio of benzyl sulfonamide to the palladium catalyst is 1:0.01 - 1:0.5;

[0013] The molar ratio of benzyl sulfonamide to the additive is 1:2 - 1:4;

[0014] The reaction temperature range is 70 - 90 °C;

[0015] The reaction time ranges from 18 to 24 h;

[0016] The molar concentration of benzylsulfonamide in the reaction system is 0.1 mol / L.

[0017] The solvent is one or a mixture of two or more of toluene, n-hexane, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethyl sulfoxide, chloroform, acetone, and acetonitrile, preferably toluene, tetrahydrofuran, and 1,4-dioxane.

[0018] The palladium catalyst is tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium acetate, palladium acetylacetonate, or palladium bromide, preferably palladium chloride, palladium acetate, and palladium acetylacetonate.

[0019] The additive is tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, or tetrabutylammonium acetate, preferably tetrabutylammonium fluoride, tetrabutylammonium chloride, and tetrabutylammonium bromide.

[0020] Advantages of the present invention: The method for catalytically converting CO2 to produce benzyl β,γ-unsaturated carboxylate according to the present invention has the advantages of mild reaction conditions, simple experimental operation, good substrate compatibility, etc., and shows good application prospects. Description of the drawings

[0021] Figure 1 1H-NMR of compound 2a 1 1H-NMR.

[0022] Figure 2 13C-NMR of compound 2a 13 13C-NMR.

[0023] Figure 3 1H-NMR of compound 2b 1 1H-NMR.

[0024] Figure 4 13C-NMR of compound 2b 13 13C-NMR.

[0025] Figure 5 1H-NMR of compound 2c 1 1H-NMR.

[0026] Figure 6 13C-NMR of compound 2c 13 13C-NMR.

[0027] Figure 7 1H-NMR of compound 2d 1 1H-NMR.

[0028] Figure 8 13C-NMR of compound 2d 13C-NMR.

[0029] Figure 9 For the 1 H-NMR of compound 2e.

[0030] Figure 10 For the 13 C-NMR of compound 2e.

[0031] Figure 11 For the 1 H-NMR of compound 2f.

[0032] Figure 12 For the 13 C-NMR of compound 2f.

[0033] Figure 13 For the 1 H-NMR of compound 2g.

[0034] Figure 14 For the 13 C-NMR of compound 2g.

[0035] Figure 15 For the 1 H-NMR of compound 2h.

[0036] Figure 16 For the 13 C-NMR of compound 2h. Detailed implementation manners

[0037] The present invention will be further described below in conjunction with specific embodiments. These embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. Any simple substitution or improvement made by those skilled in the art to the present invention falls within the scope of the technical solutions protected by the present invention.

[0038] Example 1: Synthesis of Benzyl but-2-enoate (2a)

[0039]

[0040] Accurately weigh tris(dibenzylideneacetone)dipalladium (22.8 mg, 0.025 mmol) and tetrabutylammonium bromide (664.7 mg, 2 mmol), and sequentially add them to a 25 mL reaction kettle. Then add tetrahydrofuran (5.0 mL), N-(benzyl)dimethylsulfoximide (131.5 mg, 0.5 mmol), and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of benzyl 2-butenoate is 75%. 1 H NMR (400 MHz, CDCl3) δ 7.43 - 7.27 (m, 5H), 7.02 (m, 1H), 5.89 (dt, J = 15.5, 1.6 Hz, 1H), 5.17 (s, 2H), 1.87 (dd, J = 7.0, 1.7 Hz, 3H).; 13 C NMR (101 MHz, CDCl3) δ 166.3, 145.1, 136.2, 128.5, 128.1, 122.5, 65.9, 17.9.

[0041] Example 2: Synthesis of 4-Chlorobenzyl but-2-enoate (2b)

[0042]

[0043] Accurately weigh palladium chloride (4.4 mg, 0.025 mmol) and tetrabutylammonium chloride (555.8 mg, 2 mmol), and sequentially add them to a 25 mL reaction kettle. Then add toluene (5.0 mL), N-(4-chlorobenzyl)dimethylsulfoximide (148.5 mg, 0.5 mmol), and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of 4-chlorobenzyl 2-butenoate is 60%. 1 H NMR (400 MHz, CDCl3) δ 7.38 - 7.27 (m, 4H), 7.07 - 6.98 (m, 1H), 5.88 (dd, J = 15.5, 1.8 Hz, 1H), 5.13 (s, 2H), 1.89 (dd, J = 7.0, 1.7 Hz, 3H). 1313C NMR (101 MHz, CDCl3) δ 166.1, 145.5, 134.7, 134.0, 129.5, 128.7, 122.3, 65.1, 18.0.

[0044] Example 3: Synthesis of 4-Methoxybenzyl but-2-enoate (2c)

[0045]

[0046] Accurately weigh palladium acetate (5.6 mg, 0.025 mmol), tetrabutylammonium fluoride (522.9 mg, 2 mmol), and N-(4-methoxybenzyl) dimethylsulfoximide (192.5 mg, 0.5 mmol) and add them to a 25 mL reaction kettle in sequence. Then add tetrahydrofuran (5.0 mL) and tributylallyltin (198.7 mg, 0.6 mmol). Then charge carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure. Use petroleum ether / ethyl acetate as the eluent and separate by silica gel column. The yield of 4-methoxybenzyl 2-butenoate is 82%. 1 1H NMR (400 MHz, CDCl3) δ 7.36 - 7.27 (m, 2H), 7.06 - 6.93 (m, 1H), 6.92 - 6.83 (m, 2H), 5.86 (dq, J = 15.5, 1.5 Hz, 1H), 5.10 (d, J = 1.7 Hz, 2H), 3.80 (d, J = 1.8 Hz, 3H), 1.86 (dd, J = 7.0, 2.0 Hz, 3H).; 13 13C NMR (101 MHz, CDCl3) δ 166.4, 159.5, 144.9, 130.1, 130.0, 128.3, 122.6, 113.9, 65.8, 55.2, 17.9.

[0047] Example 4: Synthesis of 4-methylbenzyl but-2-enoate (2d)

[0048]

[0049] Accurately weigh palladium(II) bromide (6.6 mg, 0.025 mmol) and tetrabutylammonium chloride (555.8 mg, 2 mmol), and successively add them to a 25 mL reaction kettle. Then add tetrahydrofuran (5.0 mL), N-(4-methylbenzyl) dimethylsulfoxonium methylide (138.5 mg, 0.5 mmol), and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of 4-methylbenzyl 2-butenoate is 64%. 1 H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 7.7 Hz, 2H), 7.15 (d, J = 7.7 Hz, 2H), 7.00 (tdd, J = 13.9, 6.9, 1.4 Hz, 1H), 5.87 (dt, J = 15.7, 1.7 Hz, 1H), 5.12 (s, 2H), 2.34 (s, 3H), 1.86 (dt, J = 7.0, 1.6 Hz, 3H) .13 C NMR (101 MHz, CDCl3) δ 166.3, 144.9, 137.9, 133.2, 129.2, 128.3, 122.6, 65.9, 21.1, 17.9.

[0050] Example 5: Synthesis of 2-Methoxybenzyl but-2-enoate (2e)

[0051]

[0052] Accurately weigh palladium(II) acetylacetonate (7.6 mg, 0.025 mmol) and tetrabutylammonium chloride (555.8 mg, 2 mmol), and successively add them to a 25 mL reaction kettle. Then add 1,4-dioxane (5.0 mL), N-(2-methoxybenzyl) dimethylsulfoxonium methylide (192.5 mg, 0.5 mmol), and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of 2-methoxybenzyl 2-butenoate is 82%. 11H NMR (400 MHz, CDCl3) δ 7.36 - 7.26 (m, 2H), 7.07 - 6.92 (m, 2H), 6.88 (d, J = 8.2 Hz, 1H), 5.90 (dt, J = 15.6, 1.7 Hz, 1H), 5.23 (s, 2H), 3.83 (s, 3H), 1.87 (dt, J = 6.8, 1.6 Hz, 3H).; 13 13C NMR (101 MHz, CDCl3) δ 166.5, 157.4, 144.8, 129.5, 129.4, 124.5, 122.7, 120.4, 110.4, 61.4, 55.4, 17.9.

[0053] Example 6: Synthesis of 4-phenylbenzyl but-3-enoate (2f)

[0054]

[0055] Accurately weigh palladium acetylacetonate (7.6 mg, 0.025 mmol) and tetrabutylammonium bromide (664.7 mg, 2 mmol), and successively add them to a 25 mL reaction kettle. Add toluene (5.0 mL), N-(4-phenylbenzyl) dimethyl disulfonimide (169.5 mg, 0.5 mmol), and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of 4-phenylbenzyl 2-butenoate is 77%. 1 1H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 8.0, 2.2 Hz, 4H), 7.41 (t, J = 7.7 Hz, 4H), 7.32 (t, J = 7.4 Hz, 1H), 7.03 (m, 1H), 5.90 (dt, J = 15.5, 1.9 Hz, 1H), 5.20 (s, 2H), 1.85 (dd, J = 6.9, 1.7 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 166.3, 145.3, 141.1, 140.7, 135.2, 128.8, 128.7, 127.4, 127.3, 127.1, 122.5, 65.7, 18.0

[0056] Example 7: Synthesis of 4-Phenacetyleneylbenzyl but-2-enoate (2g)

[0057]

[0058] Accurately weigh palladium chloride (4.4 mg, 0.025 mmol) and tetrabutylammonium bromide (664.7 mg, 2 mmol), and add them successively to a 25 mL reaction kettle. Then add tetrahydrofuran (5.0 mL), N-(4-phenylethynylbenzyl) dimethyl disulfonimide (181.5 mg, 0.5 mmol), and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 1.0 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of 4-phenylethynylbenzyl 2-butenoate is 84%. 1 H NMR (400 MHz, CDCl3) δ 7.57 - 7.47 (m, 4H), 7.37 - 7.27 (m, 5H), 7.03 (m, 1H), 5.89 (dt, J = 15.5, 1.8 Hz, 1H), 5.16 (s, 2H), 1.86 (dd, J = 6.9, 1.7 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.2, 145.4, 136.3, 131.7, 131.6, 128.4, 128.3, 128.0, 123.1, 123.1, 122.4, 89.8, 89.1, 65.5, 18.0.

[0059] Example 8: Synthesis of Naphthalen-1-ylmethyl but-2-enoate (2h)

[0060]

[0061] Accurately weigh palladium chloride (4.4 mg, 0.025 mmol), tetrabutylammonium bromide (1.3294 g, 4 mmol), and N-(naphthalenemethyl) dimethyl disulfonimide (152.6 mg, 0.5 mmol), and add them successively to a 50 mL reaction kettle. Then add tetrahydrofuran (5.0 mL) and tributylallyltin (198.7 mg, 0.6 mmol). Then fill with carbon dioxide to 0.5 MPa. Place the reaction kettle in an oil bath at 90 °C and react for 24 h. After the reaction is completed, slowly cool the reaction kettle to room temperature and release the remaining carbon dioxide. Finally, remove the solvent under reduced pressure, use petroleum ether / ethyl acetate as the eluent, and separate by silica gel column. The yield of naphthalenylmethyl 2-butenoate is 86%. 11H NMR (400 MHz, CDCl3) δ 8.05 - 7.99 (m, 1H), 7.91 - 7.81 (m, 2H), 7.57 - 7.47 (m, 3H), 7.44 (dd, J = 8.2, 7.0 Hz, 1H), 7.01 (dd, J = 15.5, 6.9 Hz, 1H), 5.88 (dd, J = 15.5, 1.7 Hz, 1H), 5.62 (s, 2H), 1.84 (dd, J = 6.9, 1.7 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 166.4, 145.3, 133.7, 131.7, 129.2, 128.7, 127.4, 126.5, 125.9, 125.3, 123.6, 122.5, 64.3, 18.0.

Claims

1. A method for preparing a β,γ-unsaturated carboxylic acid benzyl ester compound, characterized in that, A palladium catalyst, an additive, benzylsulfonamide, tributylallyltin, and a solvent were successively added to a reaction kettle, and carbon dioxide was filled to 0.5 MPa to 1.0 MPa; then the reaction kettle was placed in an oil bath at 70 to 90 °C for reaction for 16 to 24 h. After the reaction was completed, it was cooled to room temperature, and the remaining carbon dioxide was released. The obtained reaction solution was separated by column to obtain a β,γ-unsaturated carboxylic acid benzyl ester compound; The synthetic route is as follows: In the formula, R on the benzylsulfonamide is selected from fluorine, chlorine, bromine, nitro, ester group, methyl or methoxy; R is in the ortho, meta or para position of the aromatic ring; the aromatic ring is a benzene ring or a naphthalene ring; The molar ratio of benzylsulfonamide to tributylallyltin is 1:1 to 1:2; The molar ratio of benzylsulfonamide to the palladium catalyst is 1:0.01 to 1:0.5; The molar ratio of benzylsulfonamide to the additive is 1:2 to 1:4; The reaction temperature range is 70 to 90 °C; The reaction time range is 18 to 24 h; The molar concentration of benzylsulfonamide in the reaction system is 0.1 mol / L; The palladium catalyst is tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium acetate, palladium acetylacetonate or palladium bromide; The additive is tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide.

2. The method according to claim 1, wherein The solvent is one or a mixture of two or more of toluene, n-hexane, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethyl sulfoxide, chloroform, acetone, and acetonitrile.

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