A method for the preparation of 2-cyclic ether substituted acrylamides by ether alpha-c-h functionalization under visible light conditions

Abstract

The application discloses a method for preparing 2-cyclic ether substituted acrylamide by ether alpha-C-H functionalization under visible light conditions, and the synthesis process of the method is as follows: in a glass reaction container, different kinds of substrates N-methyl-3-aryl propynylamide are added in proportion, N,N-diisopropyl ethylamine is used as an additive, 4CzIPN is used as a photocatalyst, tetrahydrofuran or 1,4-dioxane is used as a solvent, and the reaction is irradiated under air atmosphere and at 45 o C conditions for 8 hours by two blue LED (450-460 nm) lamps, and 2-cyclic ether substituted acrylamide derivatives are prepared after crude products are separated and purified by column chromatography. The application uses a metal-free photocatalyst 4CzIPN, and avoids the use of noble metal catalysts and external oxidants. In addition, the reaction operation is simple, raw materials are easy to obtain, the reaction conditions are mild, and the substrate application range is wide.

Description

Technical Field

[0001] This invention belongs to the field of organic synthetic chemistry, and specifically relates to a new method for preparing 2-cyclic ether-substituted acrylamides by α-CH functionalization of ethers under visible light conditions. Background Technology

[0002] Simple ethers are important organic synthons and widely used solvents. Due to their inert nature, direct α-functionalization is a very challenging task. However, α-functionalized ether derivatives are abundant in many bioactive molecules and natural products (J. Org. Chem. 2004, 69, 20, 6874-6882.). Therefore, the direct functionalization of simple ethers is of great significance.

[0003] Currently, there are three main methods for the α-CH functionalization of ethers to prepare ether compounds that replace acrylamides. The first method involves activating the relatively inert CH bond in the presence of metal catalysts such as [Cu], [Fe], [Ir], [Pd], and [Ni] to form a new C-C bond through a coupling reaction, thereby generating the target product (Chem. Commun., 2014, 50, 3623; Angew. Chem. Int. Ed. 2019, 58, 1823-1827; Adv. Synth. Catal. 2013, 355, 1971-1976; Org. Lett. 2015, 17, 4726-4729; Org. Lett. 2013, 15, 4600-4603). The second method involves iron-catalyzed α-position deprotonation of the ether, followed by direct α-arylation with azoles to generate the target product (Chem. Commun., 2015, 51, 13365.). The third method involves direct α-arylation of the ether through a combination of photoredox-mediated CH functionalization and the Minisci reaction to generate the target product (Angew. Chem. Int. Ed. 2015, 54, 1565-1569). Although these reported methods demonstrate that ethers can be activated under various metal catalysts and oxidant systems to obtain α-oxoalkyl radical intermediates, the formation of these intermediates and oxidative couplings requires harsh conditions such as high temperatures, excess oxidants, and transition metal catalysts, limiting these reactions. Therefore, developing a mild, simple, and environmentally friendly method to synthesize ethers to replace acrylamides has both theoretical and practical significance. Summary of the Invention

[0004] The purpose of this invention is to overcome the limitations of current methods for preparing 2-cyclic ether-substituted acrylamides and to develop a method for preparing 2-cyclic ether-substituted acrylamides by α-CH functionalization of ethers under visible light conditions. This method involves inducing the photocatalyst 4CzIPN to transform into an excited state 4CzIPN under visible light. * It undergoes a single-electron transfer (SET) with DIPEA to generate the long-lived radical anion 4CzIPN. ·- and free radicals DIPEA · Meanwhile, free radical DIPEA · The activation of ethers forms α-oxoalkyl radicals, which are then added to N-methyl-3-arylpropynamide. Following the 5-exo-trig process and the strategy of aryl migration to form aryl radicals, 2-cyclic ether-substituted acrylamide derivatives are prepared by α-CH functionalization of ethers under visible light conditions.

[0005] The present invention utilizes N-methyl-3-arylpropynamide as a raw material, 4CzIPN as a photocatalyst, N,N-diisopropylethylamine as an additive, and tetrahydrofuran or 1,4-dioxane as a solvent. Under air atmosphere and irradiation by two blue LEDs, an α-CH functionalization reaction of the ether occurs at room temperature, efficiently achieving the synthesis of 2-cyclic ether-substituted acrylamide compounds. This invention uses the non-metallic photocatalyst 4CzIPN, avoiding the use of precious metal catalysts and external oxidants. Furthermore, the reaction raw materials are readily available, the operation is simple, the conditions are mild, and the separation yield is excellent, with a wide range of applicable substrates.

[0006] The objective of this invention is achieved through the following technical solution.

[0007] A method for preparing 2-cyclic ether-substituted acrylamides by α-CH functionalization of ethers under visible light conditions includes the following steps: In a glass reaction vessel, N-methyl-3-arylpropyne amide, catalyst, and additives were added in proportion. Using an organic solvent, the mixture was magnetically stirred at room temperature for 8 hours under two blue LED irradiation conditions. The reaction mixture was then concentrated under reduced pressure and purified by column chromatography to obtain the 2-cyclic ether substituted acrylamide derivative.

[0008] Furthermore, the chemical reaction equation for the preparation of 2-cyclic ether-substituted acrylamides by α-CH functionalization of ethers under visible light conditions is shown below:

[0009] In the formula, R 1 R 2 R 3 It is selected from one or more of fluorine, chlorine, bromine, methyl, methoxy, and thiophene-2-yl; Further, the additive is one or more of N,N-diisopropylethylamine, NaHCO3, EtONa, Na2CO3, and triethylamine, preferably N,N-diisopropylethylamine.

[0010] Furthermore, the molar ratio of the additive to the N-methyl-3-arylpropynamide derivative is 1 to 5:1, preferably 4:1.

[0011] Furthermore, the organic solvent is one or more of acetonitrile, DMSO, methanol, 1,4-dioxane, and tetrahydrofuran, preferably tetrahydrofuran or 1,4-dioxane.

[0012] Furthermore, the reaction time for the α-CH functionalization of the ether to prepare 2-cyclic ether-substituted acrylamide is between 2 and 12 hours, preferably 8 hours.

[0013] Further, the catalyst is one or more of 4-DPAIPN, Rhodamine B, Indole Y, 9-Mesityl-10-methylacridinium, 3CzEPAIPN, p-Cl-3CzPAIPN, m-Me-3CzEPAIPN, p-Me-3CzEPAIPN, and 2,4,5,6-tetracarbazole isophthalonitrile (4CzIPN), preferably 4CzIPN.

[0014] Furthermore, the molar ratio of the catalyst to the N-methyl-3-arylpropyne amide compound is 0.01 to 1:1, preferably 0.06:1.

[0015] Furthermore, the target product, the 2-cyclic ether-substituted acrylamide derivative, is separated and purified by column chromatography. The eluent can be a mixed solvent of petroleum ether and ethyl acetate, with a volume ratio of ethyl acetate to petroleum ether between 1:3 and 10. Preferably, the developing solvent is petroleum ether:ethyl acetate = 5:1.

[0016] The principle of this invention is as follows: Under visible light irradiation, the photocatalyst (PC) transforms into an excited state (PC). * Excited-state photocatalyst (PC) * ) undergoes a single-electron transfer (SET) with DIPEA to generate a long-lived free radical anion (PC). ·- ), then PC ·- Losing an electron, the ground-state PC is regenerated to enter the next catalytic cycle. After the SET process, DIPEA is converted into a radical cation (DIPEA). ·+ ), and further lose a proton to generate a free radical (DIPEA). · Tetrahydrofuran and DIPEA· The reaction generates an α-oxoalkyl radical, which adds to N-methyl-3-phenylpropynamide to form a vinyl radical. The vinyl radical is then converted to a spiro radical via a 5-exo-trig process, and the spiro radical subsequently undergoes aryl migration to generate a new radical. This radical reacts with PC... ·- The SET process occurs, ultimately generating the target product, a 2-cyclic ether-substituted acrylamide compound.

[0017] Compared with the prior art, the present invention has the following advantages and beneficial effects: (1) This invention realizes the photocatalytic α-CH functionalization of ethers to prepare 2-cyclic ether-substituted acrylamide compounds under metal-free conditions. In addition, the main features of this reaction are that it does not require metallizing agents, does not require external oxidizing agents, the reaction raw materials are readily available, the conditions are mild, the substrates are widely applicable, and the operation is simple; (2) This invention utilizes visible light to induce the formation of a strongly reducing species in a 4CzIPN photocatalyst to activate ethers and form α-oxoalkyl radicals, which then react with readily available raw materials to efficiently achieve α-CH functionalization of ethers and prepare 2-cyclic ether-substituted acrylamide compounds. Compared with existing methods, this method has higher step economy and avoids the use of precious metal catalysts and external oxidants. Attached Figure Description

[0018] Figure 1 , Figure 2 These are the proton and carbon spectra of the target product obtained in Example 1; Figure 3 , Figure 4 These are the proton and carbon spectra of the target product obtained in Example 2; Figure 5 , Figure 6 These are the proton and carbon spectra of the target product obtained in Example 3; Figure 7 , Figure 8 These are the proton and carbon spectra of the target product obtained in Example 4. Detailed Implementation

[0019] The present invention will be further described below through specific embodiments, but the scope of protection and implementation of the present invention are not limited thereto.

[0020] Example 1

[0021] Prepare a quartz reaction tube and add the weighed N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate with two blue LEDs at 45°C. oThe reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product N-methyl-3,3-diphenyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 75%.

[0022] The proton and carbon spectra of the obtained target product are as follows: Figure 1 and Figure 2 As shown, the structural characterization data is as follows: 1 H NMR (500 MHz, CDCl3) δ 7.36 (dd, J = 8.1, 6.2 Hz, 2H), 7.31 (dd, J= 14.7, 7.1 Hz, 3H), 7.28 (s, 2H), 7.24 - 7.19 (m, 3H), 6.05 (d, J = 5.1 Hz,1H), 4.56 (dd, J = 9.0, 6.6 Hz, 1H), 3.89 (p, J = 7.8 Hz, 1H), 3.80 - 3.68(m, 1H), 2.74 (d, J = 4.9 Hz, 3H), 2.28 (dq, J = 13.1, 9.0 Hz, 1H), 2.01(dddt, J = 15.4, 11.9, 8.6, 4.1 Hz, 2H), 1.84 (dd, J = 7.0, 1.5 Hz, 1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.8, 144.6, 141.5, 141.0, 140.1,136.2, 129.3, 129.2, 128.6, 128.4, 128.2, 128.0, 127.7, 127.5, 126.6, 78.1,68.7, 30.7, 26.6, 26.3, 26.1 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 21 NO2 308.1645; found 308.1641. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0023] Example 2

[0024] Prepare a quartz reaction tube and add the weighed N-(2-fluorophenyl)-N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3-(2-fluorophenyl)-N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 61.8%.

[0025] The proton and carbon spectra of the obtained target product are as follows: Figure 3 and Figure 4 As shown, the structural characterization data is as follows: 1 H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 7.4 Hz, 2H), 7.28 (s, 2H), 7.25(s, 3H), 7.08 (t, J = 7.4 Hz, 1H), 6.99 (t, J = 9.1 Hz, 1H), 6.36 - 6.17 (m,1H), 4.61 (dd, J = 9.0, 6.7 Hz, 1H), 3.89 (q, J = 7.5 Hz, 1H), 3.76 (td, J =8.0, 5.0 Hz, 1H), 2.67 (d, J = 5.0 Hz, 3H), 2.23 - 2.17 (m, 1H), 2.07 (dtd, J= 12.2, 7.3, 3.7 Hz, 1H), 1.99 (tq, J = 7.5, 3.9 Hz, 1H), 1.86 (ddd, J =17.2, 8.6, 4.2 Hz, 1H) ppm. 13 C{ 1H} NMR (125 MHz, CDCl3) δ 168.8, 159.15 (d, J = 245.8 Hz), 139.3,139.0, 138.6, 130.77 (d, J = 3.4 Hz), 129.57 (d, J = 8.1 Hz), 128.8, 128.22,128.16, 127.7, 123.9 (d, J = 3.6 Hz), 115.46 (d, J = 21.9 Hz), 77.2, 68.8,30.9, 26.7, 26.1 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 20 FNO2 326.1551; found 326.1559. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0026] Example 3

[0027] Prepare a quartz reaction tube and add the weighed N-(4-chlorophenyl)-N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3-(4-chlorophenyl)-N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 57.5%.

[0028] The proton and carbon spectra of the obtained target product are as follows: Figure 5 and Figure 6 As shown, the structural characterization data is as follows: 1H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 8.2 Hz, 3H), 7.29 (s, 1H), 7.23(s, 2H), 7.15 (d, J = 8.3 Hz, 3H), 6.03 (s, 1H), 4.52 (dt, J = 15.2, 7.9 Hz,1H), 3.88 (q, J = 7.6 Hz, 1H), 3.76 (dt, J = 8.8, 4.4 Hz, 1H), 2.70 (dd, J =25.2, 5.2 Hz, 3H), 2.25 (d, J = 3.7 Hz, 1H), 2.05 - 1.96 (m, 2H), 1.87 - 1.80 (m, 1H) ppm. 13 C{ 1 H NMR (125 MHz, CDCl3) δ 169.5, 143.7, 143.5, 140.7, 139.7,139.6, 138.5, 136.7, 136.5, 133.7, 133.7, 130.8, 130.1, 129.4, 128.7, 128.5,128.4, 128.3, 128.1, 128.0, 127.9, 78.4, 68.8, 30.7, 27.1, 26.3 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 20 NO2Cl 342.1255; found 342.1261. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0029] Example 4

[0030] Prepare a quartz reaction tube and add the weighed N-(3-chlorophenyl)-N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. oThe reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)-3-(o-tolyl)acrylamide, with a yield of 68.9%.

[0031] The proton and carbon spectra of the obtained target product are as follows: Figure 7 and Figure 8 As shown, the structural characterization data is as follows: 1 H NMR (500 MHz, CDCl3) δ 7.35 - 7.29 (m, 3H), 7.16 (td, J = 8.4, 6.9,4.2 Hz, 6H), 6.22 (s, 1H), 4.50 (dd, J = 8.9, 6.7 Hz, 1H), 3.85 (q, J = 7.4Hz, 1H), 3.72 (td, J = 7.8, 5.0 Hz, 1H), 2.69 (d, J = 4.9 Hz, 3H), 2.24 -2.09 (m, 1H), 1.98 (dddd, J = 19.3, 11.4, 7.6, 3.7 Hz, 2H), 1.87 - 1.76 (m,1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.4 169.3, 143.4 143.0, 142.9, 141.9140.4 139.4 137.2, 137.1, 134.2, 133.9, 129.6 129.3, 129.3, 129.2, 128.7,128.6, 128.4, 128.2 128.0, 127.90, 127.88, 127.8, 127.6 126.9, 77.9, 68.8,30.7, 26.7, 26.4 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 20 NO2Cl 342.1255; found 342.1261. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0032] Example 5

[0033] Prepare a quartz reaction tube and add the weighed N-(4-bromophenyl)-N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3-(4-bromophenyl)-N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 89%.

[0034] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.47 - 7.41 (m, 1H), 7.37 - 7.31 (m, 3H), 7.22 - 7.05 (m, 5H), 6.19 (s, 1H), 4.51 (dd, J = 9.0, 6.7 Hz, 1H), 3.86 (q, J= 7.5 Hz, 1H), 3.77 - 3.66 (m, 1H), 2.71 (d, J = 4.9 Hz, 2H), 2.65 (d, J =5.0 Hz, 1H), 2.28 - 2.08 (m, 1H), 2.00 (ddt, J = 20.1, 11.1, 6.1 Hz, 2H),1.83 (dd, J = 7.9, 4.6 Hz, 1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.5, 143.7, 140.1, 139.6, 136.6,131.6, 131.5, 131.2, 131.1, 130.4, 129.4, 129.3, 128.8, 128.74, 128.68,128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 78.0, 68.8, 30.7, 26.7, 26.4 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 20 BrNO2 386.0750; found 386.0748. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0035] Example 6

[0036] Prepare a quartz reaction tube and add the weighed N-methyl-N-phenyl-3-(o-tolyl)propynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product (Z)-N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)-3-(o-tolyl)acrylamide was purified by silica gel column chromatography with a yield of 64%.

[0037] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.27 (s, 1H), 7.27 - 7.20 (m, 5H), 7.12 (d,J = 7.6 Hz, 1H), 7.04 - 6.98 (m, 2H), 6.04 - 6.01 (m, 1H), 4.54 (dd, J = 9.0,6.5 Hz, 1H), 3.88 (q, J = 7.5 Hz, 1H), 3.75 (td, J = 7.9, 4.9 Hz, 1H), 2.68(t, J = 4.3 Hz, 3H), 2.33 (s, 3H), 2.28 - 2.22 (m, 1H), 2.00 (qt, J = 8.3,3.6 Hz, 2H), 1.83 (dt, J = 11.9, 8.4 Hz, 1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.9, 144.7, 141.1, 140.0, 137.9,136.1, 129.8, 128.5, 128.3, 128.04, 127.98, 127.7, 126.3, 78.1, 68.7, 30.7,27.2, 27.0, 21.4 ppm. HRMS (ESI-TOF) [M+Na] +calcd. for C 21 H 23 NO2 344.1621; found 344.1626. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0038] Example 7

[0039] Prepare a quartz reaction tube and add the weighed N-methyl-3-phenyl-N-(m-tolyl)propynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product (E)-N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)-3-(m-tolyl)acrylamide was purified by silica gel column chromatography with a yield of 62%.

[0040] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.31 (dt, J = 14.4, 7.1 Hz, 3H), 7.22 (d, J= 4.6 Hz, 1H), 7.18 (d, J = 6.7 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 7.06 -6.90 (m, 3H), 6.06 - 6.02 (m, 1H), 4.52 (dt, J = 9.3, 5.2 Hz, 1H), 3.86 (q, J= 7.4 Hz, 1H), 3.72 (td, J = 7.8, 4.7 Hz, 1H), 2.65 (t, J = 4.4 Hz, 3H), 2.31(s, 1H), 2.25 (s, 3H), 1.97 (s, 2H), 1.86 - 1.74 (m, 1H) ppm. 13 C{ 1H} NMR (125 MHz, CDCl3) δ 170.7, 144.9, 141.1, 140.2, 137.6,136.1, 129.3, 128.6, 128.2, 127.9, 127.5, 126.4, 125.7, 78.1, 68.7, 30.7,26.7, 26.3, 21.4 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 21 H 23 NO2 322.1802; found 322.1802. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0041] Example 8

[0042] Prepare a quartz reaction tube and add the weighed N,3-bis(4-bromophenyl)-N-methylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3,3-bis(4-bromophenyl)-N-methyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 50.8%.

[0043] The structural characterization data of the obtained target product are shown below: 1H NMR (500 MHz, CDCl3) δ 7.46 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.4Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.07 (d, J = 8.5 Hz, 2H), 7.02 (t, J = 4.2Hz, 2H), 6.16 (d, J = 5.0 Hz, 1H), 4.45 (dd, J = 8.9, 6.6 Hz, 1H), 3.85 (q, J= 7.4 Hz, 1H), 3.73 (td, J = 7.9, 4.9 Hz, 1H), 2.73 - 2.67 (m, 3H), 2.17 -2.08 (m, 1H), 2.01 - 1.90 (m, 2H), 1.86 - 1.81 (m, 1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.1, 142.4, 139.4, 138.4, 136.9,131.5, 131.2, 131.0, 130.3, 122.2, 122.1, 77.7, 68.7, 30.5, 26.6, 26.3ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 19 Br2NO2 463.9855; found 463.9858. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0044] Example 9

[0045] Prepare a quartz reaction tube and add the weighed N-(4-bromophenyl)-3-(4-chlorophenyl)-N-methylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3-(4-bromophenyl)-3-(4-chlorophenyl)-N-methyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 61.1%.

[0046] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.51 - 7.28 (m, 4H), 7.07 (q, J = 18.7, 13.4Hz, 4H), 6.17 - 6.14 (m, 1H), 4.46 (t, J = 7.8 Hz, 1H), 3.79 (dd, J = 61.1,7.1 Hz, 2H), 2.69 (s, 3H), 2.14 (d, J = 10.0 Hz, 1H), 1.97 (s, 2H), 1.86 -1.79 (m, 1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.1, 142.4, 139.5, 137.9, 137.0,133.9, 131.53, 131.49, 131.2, 131.0, 130.8, 130.7, 130.4, 130.3, 130.1,129.6, 128.6, 128.5, 128.3, 122.2, 122.1, 77.7, 68.7, 30.5, 26.6, 26.3 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 19 BrClNO2 420.0360; found420.0364. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0047] Example 10

[0048] Prepare a quartz reaction tube and add the weighed N,3-bis(4-methoxyphenyl)-N-methylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. oThe reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3,3-bis(4-methoxyphenyl)-N-methyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 44.8%.

[0049] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.14 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.5Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 6.76 (d, J = 8.4 Hz, 2H), 6.10 (d, J = 5.3Hz, 1H), 4.59 - 4.52 (m, 1H), 3.86 (q, J = 7.2 Hz, 2H), 3.80 (s, 3H), 3.76(s, 3H), 2.69 (d, J = 5.0 Hz, 3H), 2.20 (dd, J = 12.6, 8.7 Hz, 1H), 2.01 -1.95 (m, 2H), 1.84 (d, J = 6.3 Hz, 1H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 170.3, 159.1, 159.0, 144.5, 134.4,133.9, 132.7, 130.8, 130.2, 113.5, 113.3, 78.3, 68.5, 55.2, 55.1, 30.5, 26.7,26.3 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 22 H 25 NO4 368.1856; found 368.1856. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0050] Example 11

[0051] Prepare a quartz reaction tube and add the weighed N-(2-bromophenyl)-N-methyl-3-(o-tolyl)propynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate the tube with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3-(2-bromophenyl)-N-methyl-2-(tetrahydrofuran-2-yl)-3-(o-tolyl)acrylamide, with a yield of 55%.

[0052] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.70 - 7.58 (m, 2H), 7.44 - 7.33 (m, 3H), 7.30 (d, J = 5.7 Hz, 2H), 7.15 (dd, J = 7.6, 1.7 Hz, 1H), 6.04 (q, J = 4.9Hz, 0.5H), 5.73 (q, J = 5.0 Hz, 0.5H), 4.28 (ddd, J = 24.1, 8.9, 6.9 Hz, 1H), 3.82 (td, J = 7.9, 4.3 Hz, 1H), 3.73 (dt, J = 8.0, 3.9 Hz, 1H), 2.77 (d, J =5.0 Hz, 3H), 2.68 (dd, J = 19.2, 4.9 Hz, 3H), 2.46 - 2.32 (m, 1H), 2.32 -2.23 (m, 1H), 2.09 (dpd, J = 15.9, 8.5, 4.0 Hz, 1H), 1.91 (dt, J = 8.0, 3.5Hz, 1H) ppm. 13 C{ 1H} NMR (125 MHz, CDCl3) δ 169.2, 169.0, 140.4, 140.3, 140.1,139.5, 139.4, 139.2, 137.1, 137.1, 133.9, 133.8, 133.2, 133.1, 130.9, 130.3,129.9, 129.7, 129.4, 129.3, 128.3, 128.2, 127.7, 127.6, 124.2, 122.8, 78.7,78.5, 69.2, 68.9, 31.1, 30.6, 26.5, 26.4, 26.3 ppm. HRMS (ESI-TOF) [M+Na] + calcd. for C 21 H 22 BrNO2 422.0726; found 422.0366. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0053] Example 12

[0054] Prepare a quartz reaction tube. Add the weighed N,3-bis(2-chlorophenyl)-N-methylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) sequentially. Irradiate with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product 3,3-bis(2-chlorophenyl)-N-methyl-2-(tetrahydrofuran-2-yl)acrylamide, with a yield of 57%.

[0055] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.62 (s, 1H), 7.34 (d, J = 29.9 Hz, 3H), 7.21 (d, J = 19.2 Hz, 4H), 6.21 (s, 1H), 4.36 (s, 1H), 3.80 (d, J = 66.5 Hz, 2H), 2.61 (s, 3H), 2.18 (d, J = 39.6 Hz, 2H), 1.96 (s, 2H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 168.1, 141.4, 139.1, 139.0, 138.8,137.0, 132.11, 132.10, 131.3, 130.8, 129.7, 129.4, 129.1, 129.0, 126.7,126.5, 77.6, 68.8, 29.7, 26.4, 26.0 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 19 Cl2NO2 376.0866; found 376.0865. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0056] Example 13

[0057] Prepare a quartz reaction tube and add the weighed N-methyl-N-phenyl-3-(thiophen-2-yl)propynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and tetrahydrofuran (2 mL) in sequence. Irradiate with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product was purified by silica gel column chromatography to obtain the final product N-methyl-3-phenyl-2-(tetrahydrofuran-2-yl)-3-(thiophen-2-yl)acrylamide, with a yield of 59%.

[0058] The structural characterization data of the obtained target product are shown below: 1H NMR (500 MHz, CDCl3) δ 7.37 - 7.29 (m, 2H), 7.24 (d, J = 8.8 Hz,4H), 6.99 - 6.87 (m, 2H), 5.98 (s, 1H), 4.89 - 4.83 (m, 1H), 3.79 (s, 2H), 2.84 (dd, J = 5.1, 2.7 Hz, 1H), 2.60 (dd, J = 5.1, 2.7 Hz, 2H), 2.26 - 2.17(m, 1H), 2.14 - 2.08 (m, 1H), 1.95 (ddd, J = 42.6, 13.7, 7.6 Hz, 2H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.7, 169.2, 142.8, 141.5, 141.0,139.7, 137.9, 137.5, 135.9, 134.9, 129.2, 128.5, 128.4, 128.2, 127.99,127.97, 127.1, 126.7, 78.0, 77.7, 68.7, 30.9, 30.5, 26.6, 26.6, 26.2 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 18 H 19 NO2S 314.1209; found 314.1210. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0059] Example 14

[0060] Prepare a quartz reaction tube and add the weighed N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and 1,4-dioxane (2 mL) in sequence. Irradiate with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product 2-(1,4-dioxane-2-yl)-N-methyl-3,3-diphenylacrylamide was purified by silica gel column chromatography with a yield of 55.6%.

[0061] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.34 (d, J = 7.4 Hz, 3H), 7.24 (d, J = 6.9Hz, 3H), 7.18 (d, J = 6.9 Hz, 4H), 5.64 (s, 1H), 4.35 (d, J = 10.2 Hz, 1H), 4.00 (t, J = 10.9 Hz, 1H), 3.74 (dd, J = 19.5, 10.0 Hz, 2H), 3.67 - 3.57 (m,3H), 2.58 (d, J = 4.9 Hz, 3H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 169.1, 146.4, 140.4, 139.7, 133.3,128.8, 128.5, 128.4, 128.1, 128.0, 127.9, 75.8, 69.1, 66.5, 65.8, 26.3 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 21 NO3 324.1594; found 324.1589. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0062] Example 15

[0063] Prepare a quartz reaction tube and add the weighed N-methyl-3-phenylpropynamide (0.2 mmol), N,N-diisopropylethylamine (0.8 mmol), 4CzIPN (0.0012 mmol), and 1,4-dioxane (2 mL) in sequence. Irradiate with two blue LEDs at 45°C. o The reaction was carried out at C for 8 hours under TCL monitoring. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain the crude product. Finally, the crude product 3-(4-bromophenyl)-2-(1,4-dioxane-2-yl)-N-methyl-3-phenylacrylamide was purified by silica gel column chromatography with a yield of 55%.

[0064] The structural characterization data of the obtained target product are shown below: 1 H NMR (500 MHz, CDCl3) δ 7.49 (d, J = 8.3 Hz, 2H), 7.45 - 7.32 (m,1H), 7.25 - 7.22 (m, 2H), 7.16 (dd, J = 7.2, 2.5 Hz, 2H), 7.07 (dd, J = 8.6,2.4 Hz, 2H), 5.63 (d, J = 5.0 Hz, 1H), 4.30 (ddd, J = 10.1, 7.5, 2.7 Hz, 1H), 3.96 (dd, J = 11.8, 10.2 Hz, 1H), 3.80 - 3.69 (m, 2H), 3.63 (dt, J = 20.1,7.3 Hz, 3H), 2.61 (dd, J = (30.9, 4.9 Hz, 3H) ppm. 13 C{ 1 H} NMR (125 MHz, CDCl3) δ 168.8, 145.3, 139.9, 138.6, 133.7,133.6, 132.03, 131.95, 131.7, 131.2, 130.6, 130.3, 130.3, 129.5, 128.8,128.6, 128.5, 128.3, 128.2, 122.33, 122.29, 75.7, 75.6, 69.04, 68.97, 66.5,66.0, 65.8, 65.5, 26.41, 26.36 ppm. HRMS (ESI-TOF) [M+H] + calcd. for C 20 H 20 NO3Br 402.0699; found 402.0698. Based on the above characterization data, the structure of the target compound is inferred as follows:

[0065] The above embodiments are some examples of the method of the present invention, but they do not limit the specific implementation of the present invention. Any substitution of substituents, changes in the basic skeleton, or simplification of conditions made without departing from the spirit and principle of the present invention should be classified as equivalent substitution methods and are included within the protection scope of the present invention.

Claims

1. A method for preparing 2-cyclic ether-substituted acrylamides by α-CH functionalization of ethers under visible light conditions, characterized in that, It includes the following steps: In a glass reaction vessel, N-methyl-3-arylpropyne amide 1, catalyst, and additives were added in proportion, and organic solvent 2 was used as the solvent. The mixture was magnetically stirred at room temperature for 8 hours under two blue LED irradiation conditions. The reaction mixture was then concentrated under reduced pressure and purified by column chromatography to obtain the 2-cyclic ether substituted acrylamide derivative 3.

2. The synthesis method according to claim 1, characterized in that, The chemical reaction equation for the preparation of 2-cyclic ether-substituted acrylamides by α-CH functionalization of ethers under light conditions is shown below: ； In the formula, R 1 R 2 R 3 It is selected from one or more of fluorine, chlorine, bromine, methyl, methoxy, and thiophene-2-yl.

3. The preparation method according to claim 1 or 2, characterized in that, The additive is one or more of N,N-diisopropylethylamine, NaHCO3, EtONa, Na2CO3, and triethylamine; the molar ratio of the additive to the N-methyl-3-arylpropynamide derivative is 1 to 5:

1.

4. The preparation method according to claim 1 or 2, characterized in that, The organic solvent is one or more of acetonitrile, DMSO, methanol, tetrahydrofuran, and 1,4-dioxane.

5. The preparation method according to claim 1 or 2, characterized in that, The catalyst is one or more of 4-DPAIPN, Rhodamine B, Indole Y, 9-Mesityl-10-methylacridinium, 3CzEPAIPN, p-Cl-3CzPAIPN, m-Me-3CzEPAIPN, p-Me-3CzEPAIPN, and 2,4,5,6-tetracarbazole isophthalonitrile (4CzIPN); the molar ratio of the catalyst to the N-methyl-3-arylpropynamide compound is 0.01 to 1:

1.

6. The preparation method according to claim 1 or 2, characterized in that, The reaction time for the α-CH functionalization of the ether to prepare 2-cyclic ether-substituted acrylamide is 2–12 h.

7. The preparation method according to claim 1 or 2, characterized in that, The target product, a 2-cyclic ether-substituted acrylamide derivative, was purified by column chromatography. The eluent was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1 to 3:1.

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