(E)-alkoxycarbonyl derivative containing alkenyl amide skeleton and preparation method of (E)-alkoxycarbonyl derivative

Abstract

The invention discloses (E)-alkoxycarbonyl derivatives containing an alkenyl amide skeleton and a preparation method of the (E)-alkoxycarbonyl derivatives. The molecular structures of the (E)-alkoxycarbonyl derivatives are shown in the specification; wherein R1 is phenyl, alkyl, alkoxy, halogen or thiomethyl; r2 is benzyl, methyl, acyl or t-butyloxycarbonyl; and R3 is alkyl. The preparation method comprises the following steps: in a reactor equipped with an electrode plate, mixing a non-cycloolefin amide compound, carbazate, an additive, an electrolyte and a solvent, and carrying out beta-C (sp2) H alkoxycarbonylation reaction under an electrochemical condition to highly selectively obtain the series of E-type beta-alkoxycarbonyl olefin amide derivatives. According to the method, current is used as an oxidant, and various metal catalysts and chemical oxidants do not need to be added; reaction conditions are mild, and the obtained product has good stereoselectivity; the whole process is simple and easy to implement, the reaction system is simple, pollution is small, the green chemistry concept is met, and good application potential is achieved.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a derivative containing an enamide skeleton (E)-alkoxycarbonyl and its preparation method. Background Technology

[0002] Among various methods for constructing C–C bonds, carbonylation is a powerful synthetic tool. In particular, alkoxycarbonylation is highly valuable due to its ability to directly introduce ester groups into organic molecules. Compared to classic carboxylic acid esterification, directly inserting ester functional groups into the organic framework provides a more efficient and direct strategy. On the other hand, enamides, as an important class of synthetic building blocks in organic synthesis, are widely used in the synthesis of many chiral amines and nitrogen-containing heterocyclic compounds. The β–C(sp) of enamides… 2 Direct functionalization of β-alkoxycarbonylated enamides using the β-H-H reaction is an effective strategy for constructing functionalized enamide derivatives, and significant research results have been achieved to date. However, reports on the synthesis of β-alkoxycarbonylated enamide derivatives are relatively few. In 2014, Loh's research group reported the first iron-catalyzed β-C(sp)-H functionalization of enamides. 2 The alkoxycarbonylation reaction of β-H exhibits good stereoselectivity, primarily yielding Z-type β-alkoxycarbonylated enamide derivatives. However, this reaction requires the use of additional peroxides and metal catalysts. Therefore, developing an environmentally friendly and efficient method to synthesize E-type β-alkoxycarbonylated enamide derivatives has significant scientific and practical value.

[0003] In recent years, electrochemical organic synthesis, as a highly efficient and green synthetic method, uses a weak electric current to replace the use of traditional chemical oxidizing or reducing reagents. This effectively avoids the use of toxic or expensive metal reagents and reduces environmental pollution during the synthesis process, highlighting its advantages in the field of green chemistry. It has been widely used in organic synthesis reactions. However, literature review indicates that methods for synthesizing β-alkoxycarbonylated enamide derivatives based on electrochemical oxidation have not yet been reported. Summary of the Invention

[0004] This invention proposes a derivative containing an enamide skeleton (E)-alkoxycarbonyl and its preparation method. The method utilizes electrocatalysis of noncyclic enamides and methyl hydrazine formate β-C(sp) 2 Synthesis of alkoxycarbonylation reaction containing amide skeleton E Type β-alkoxycarbonyl derivatives.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows: A derivative containing an enamide skeleton (E)-alkoxycarbonyl group has the following molecular structures: ; Among them, R1 It is phenyl, alkyl, alkoxy, halogen, or thiomethyl; R 2 It is benzyl, methyl, acyl, or tert-butyloxycarbonyl; R 3 It is an alkyl group.

[0006] As an improvement to the above technical solution, the enamide skeleton (E)-alkoxycarbonyl derivative includes: .

[0007] As an improvement to the above technical solution, the present invention provides a method for preparing the above-mentioned derivatives containing an enamide skeleton (E)-alkoxycarbonyl group, the steps of which are: In a reactor equipped with electrode plates, a noncyclic enamide compound, hydrazine carbamate, additives, electrolyte, and solvent are mixed, and β-C(sp) oxidation is carried out under electrochemical conditions. 2 The )−H alkoxycarbonylation reaction yields a series of highly selective products. E Type β-alkoxycarbonyl amide derivatives.

[0008] As an improvement to the above technical solution, the reactor equipped with electrode plates is a non-separate electrolytic cell, the power supply is a DC regulated power supply, and the reaction is carried out under constant current conditions, with a current of 5 to 15 mA. More preferably, it is 10 mA.

[0009] As an improvement to the above technical solution, the positive electrode of the reactor equipped with electrode plates is selected from any one of carbon sheets, carbon cloth, graphite felt, platinum sheets, and carbon rods; the negative electrode is selected from any one of platinum sheets, stainless steel sheets, nickel sheets, and carbon sheets. Preferably, graphite felt is used as the positive electrode, and platinum sheets are used as the negative electrode.

[0010] As an improvement to the above technical solution, the noncyclic enamide compound has the following structure: .

[0011] As an improvement to the above technical solution, the hydrazine carbamate has the following structure: .

[0012] As an improvement to the above technical solution, the additive is selected from any one or more of nitric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, potassium carbonate, potassium bicarbonate, and sodium acetate in any ratio. Trifluoroacetic acid is preferred as the additive.

[0013] As an improvement to the above technical solution, the electrolyte is selected from... n Bu4NBF4, n Bu4NClO4, n Bu4NI, n Bu4NH2PO4,n Bu4NPF6,Et3N·3HF,Et4NBF4,Me4NOAc, n Any one or more of Bu4NOAc. More preferably... n Bu4NOAc is used as an electrolyte.

[0014] As an improvement to the above technical solution, the solvent is selected from any one or a mixture of several of water, dichloroethane, methanol, ethanol, tetrahydrofuran, and dichloromethane. Preferably, H₂O / dichloroethane = 4 / 1 is used as the reaction solvent.

[0015] As an improvement to the above technical solution, the molar ratio of the noncyclic enamide compound, methyl hydrazine carbamate, electrolyte, and additive is 1.0:(1.0-5.0):(0.5-5.0):(1.0-5.0); the initial concentration of the noncyclic enamide compound is 0.02-0.2 mol / L. A more preferred molar ratio is 1.0:3.0:3.0:3.0. H₂O / dichloroethane = 4 / 1 is preferably used as the reaction solvent.

[0016] As an improvement to the above technical solution, the alkoxycarbonylation reaction temperature is 20–100 °C. 0 C. The reaction time is 2-10 hours. The preferred temperature is 80°C. o C, the time is 5 hours.

[0017] As an improvement to the above technical solution, the alkoxycarbonylation reaction further includes separation and purification; the separation and purification method is selected from any one or more of column chromatography, liquid chromatography, distillation and recrystallization.

[0018] As an improvement to the above technical solution, the reaction equation for the alkoxycarbonylation reaction is as follows:

[0019] Or: .

[0020] Compared with the prior art, the technical effects of the present invention are as follows: This invention provides a framework containing an amide ( E )-Alkoxycarbonyl derivatives and their preparation methods: In a reactor equipped with electrode plates, a noncyclic enamide compound, hydrazine carbamate, additives, electrolyte, and solvent are mixed, and under electrochemical conditions, β-C(sp...) 2 The )−H alkoxycarbonylation reaction yielded a series of highly selective products. E Type β-alkoxycarbonyl amide derivatives. Furthermore, the presence of olefin esters as a crucial core framework is of significant value for the research and development of natural products, drug molecules, and functional materials. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is the 1H NMR spectrum of the product prepared in Example 1; Figure 2 This is the carbon spectrum of the product prepared in Example 1; Figure 3 This is the 1H NMR spectrum of the product prepared in Example 2; Figure 4 This is the carbon spectrum of the product prepared in Example 2; Figure 5 This is the 1H NMR spectrum of the product prepared in Example 3; Figure 6 This is the carbon spectrum of the product prepared in Example 3; Figure 7 This is the 1H NMR spectrum of the product prepared in Example 4; Figure 8 This is the carbon spectrum of the product prepared in Example 4; Figure 9 This is the 1H NMR spectrum of the product prepared in Example 5; Figure 10 This is the carbon spectrum of the product prepared in Example 5; Figure 11 This is the 1H NMR spectrum of the product prepared in Example 6; Figure 12 This is the carbon spectrum of the product prepared in Example 6; Figure 13 This is the 1H NMR spectrum of the product prepared in Example 7; Figure 14 This is the carbon spectrum of the product prepared in Example 7; Figure 15 This is the 1H NMR spectrum of the product prepared in Example 8; Figure 16 This is the carbon spectrum of the product prepared in Example 8; Figure 17 This is the 1H NMR spectrum of the product prepared in Example 9; Figure 18 This is the carbon spectrum of the product prepared in Example 9; Figure 19 This is the 1H NMR spectrum of the product prepared in Example 10; Figure 20This is the carbon spectrum of the product prepared in Example 10; Figure 21 This is the 1H NMR spectrum of the product prepared in Example 11; Figure 22 This is the carbon spectrum of the product prepared in Example 11; Figure 23 This is the 1H NMR spectrum of the product prepared in Example 12; Figure 24 This is the carbon spectrum of the product prepared in Example 12. Detailed Implementation

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, any modifications, equivalent substitutions, improvements, etc., made by those skilled in the art to all other embodiments obtained without creative effort should be included within the protection scope of the present invention.

[0024] The following examples illustrate the enamide-containing skeleton provided by the present invention. E The preparation method of type β-alkoxycarbonyl derivatives is described in detail, but it should not be construed as limiting the scope of protection of this invention.

[0025] Example 1 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of (-benzylacetamido)-3-phenylacrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benZyl- N 1-(1-phenylvinyl)acetamide, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid were added, along with 5.0 mL of a mixed solvent of H2O and DCE in a volume ratio of 4:1. The mixture was then inserted into a graphite felt electrode and a platinum negative electrode and energized with 10 mA. The mixture was then reacted in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 52.9 mg of the target product, with a yield of 85%.

[0026] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 1 and Figure 2 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.49–7.45(m,1H),7.45–7.41(m,2H),7.35–7.27(m,5H),7 .18(dd,J=7.9,1.7Hz,2H),5.70(s,1H),4.58(s,2H),3.60(s,3H),2.28(s,3H)..

[0027] 13 CNMR(101MHZ,CDCl3)δ170.53,165.64,153.56,136.78,133.76,130.51,129.19,128.55,128.52,128.40,127.54,117.73,51.54,49.80,22.82.

[0028] HRMS(ESI)m / Z: [M+H] + CalcdforC 19 H 20 NO3310.1438; found310.1441.

[0029] The product prepared in this embodiment is methyl( E )-3-( N The structural formula of (-benzylacetamido)-3-phenylacrylate is: .

[0030] Example 2 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of (-benzylacetamido)-3-(p-tolyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N -(1-(p-tolyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the mixture into the graphite felt positive electrode and the platinum sheet negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 48.8 mg of the target product, with a yield of 75%.

[0031] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 7 and Figure 8 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.31–7.22(m,3H),7.21(s,4H),7.16(dd,J=7.9,1. 7Hz,2H),5.62(s,1H),4.55(s,2H),3.59(s,3H),2.40(s,3H),2.23(s,3H).

[0032] 13 CNMR(101MHZ,CDCl3)δ170.6,165.8,153.8,141.0,136.9,130.7,129.20,129.16,128.6,128.5,127.5,117.1,51.5,49.8,22.9,21.5.

[0033] HRMS(ESI)m / Z: [M+H] + CalcdforC 20 H 22 NO3324.1594; found324.1592.

[0034] The product prepared in this embodiment is methyl( E )-3-( N The structural formula of 3-benzylacetamido)-3-(p-tolyl)acrylate is: .

[0035] Example 3 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of (-benzylacetamido)-3-(4-fluorophenyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N-(1-(4-fluorophenyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the mixture into the graphite felt positive electrode and the platinum sheet negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 40.4 mg of the target product, with a yield of 61%.

[0036] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 13 and Figure 14 As shown, the structural characterization data is as follows: 1 HNMR (400MHZ, CDCl3) δ7.34–7.22(m,5H),7.17–7.10(m,2H),7.09(t,J=8.6Hz,2H),5.67(s,1H),4.55(s,2H),3.59(s,3H),2.24(s,3H).

[0037] 13 CNMR(101MHZ,CDCl3)δ170.45,165.51,163.91(d, 1 J C-F =251.7Hz),152.70,136.61,131.37(d, 3 J C-F =8.7Hz), 129.68(d, 4 J C-F =3.4Hz),128.57,128.51,127.63,117.60,115.60(d, 2 J C-F =22.0Hz), 51.60, 49.81, 22.83.

[0038] HRMS(ESI)m / Z: [M+H] + CalcdforC 19 H 19 NO3F328.1344;found328.1344.

[0039] The product prepared in this embodiment is methyl( E )-3-( NThe structural formula of 3-benzylacetamido)-3-(4-fluorophenyl)acrylate is: .

[0040] Example 4 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of 3-benzylacetamido)-3-(4-(trifluoromethyl)phenyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N -(1-(4-(trifluoromethyl)phenyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the mixture into the graphite felt positive electrode and the platinum sheet negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 52.5 mg of the target product, with a yield of 69%.

[0041] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 15 and Figure 16 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.65(d,J=8.0Hz,2H),7.40(d,J=8.0Hz,2H),7.28(d,J=7. 7Hz,3H),7.16–7.09(m,2H),5.78(s,1H),4.54(s,2H),3.59(s,3H),2.26(s,3H).

[0042] 13 CNMR(101MHZ,CDCl3)δ170.33,165.17,152.19,137.45,136.41,132.14(d, 2 J C-F=32.7Hz),129.61,128.65,128.43,127.74,125.35(q, 3 J C-F =3.8Hz), 123.70(d, 1 J C-F =272.5Hz),118.90,51.74,49.88,22.83.

[0043] HRMS(ESI)m / Z: [M+H] + CalcdforC 20 H 19 NO3F3378.1312;found378.1304.

[0044] The product prepared in this embodiment is methyl( E )-3-( N The structural formula of 3-benzylacetamido)-3-(4-(trifluoromethyl)phenyl)acrylate is: .

[0045] Example 5 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of (-benzylacetamido)-3-(4-chlorophenyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N -(1-(4-chlorophenyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the mixture into the graphite felt positive electrode and the platinum sheet negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 42.2 mg of the target product, with a yield of 61%.

[0046] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 17 and Figure 18As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.35(d,J=8.5Hz,2H),7.28–7.21(m,3H),7.20(d,J=8.5Hz,2 H),7.10(dd,J=7.7,1.8Hz,2H),5.66(s,1H),4.52(s,2H),3.56(s,3H),2.21(s,3H).

[0047] 13 CNMR(101MHZ,CDCl3)δ170.4,165.4,152.5,136.6,136.5,132.2,130.6,128.7,128.6,128.5,127.7,118.0,51.7,49.83,22.8.

[0048] HRMS(ESI)m / Z: [M+H] + CalcdforC 19 H 19 NO3Cl344.1048; found344.1046.

[0049] The product prepared in this embodiment is methyl( E )-3-( N The structural formula of 3-benzylacetamido)-3-(4-chlorophenyl)acrylate is: .

[0050] Example 6 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3- (N The preparation method of 3-benzylacetamido)-3-(4-iodophenyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N -(1-(4-iodophenyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine carbamate, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the mixture into the graphite felt positive electrode and the platinum sheet negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 41.3 mg of the target product, with a yield of 47%.

[0051] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 19 and Figure 20 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.74(d,J=8.5Hz,2H),7.30–7.24(m,3H),7.12(dd,J=7.7,1. 8Hz,2H),7.02(d,J=8.4Hz,2H),5.68(s,1H),4.54(s,2H),3.59(s,3H),2.23(s,3H).

[0052] 13 CNMR(101MHZ,CDCl3)δ170.4,165.4,152.8,137.6,136.5,133.2,130.8,128.6,128.5,128.5,127.7,118.0,97.2,51.7,49.8,22.8.

[0053] HRMS(ESI)m / Z: [M+H] + CalcdforC 19 H 19 NO3I436.0404;found436.0404.

[0054] The product prepared in this embodiment is methyl( E )-3- (N The structural formula of 3-benzylacetamido)-3-(4-iodophenyl)acrylate is: .

[0055] Example 7 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of 3-benzylacetamido)-3-(4-bromophenyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N-(1-(4-bromophenyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine carbamate, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the graphite felt electrode and the platinum negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 39.1 mg of the target product, with a yield of 50%.

[0056] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 23 and Figure 24 As shown, the structural characterization data is as follows: 1 HNMR (400MHZ, CDCl3) δ7.53(d,J=8.5Hz,2H),7.31–7.24(m,3H),7.20–7.09(m,4H),5.69(s,1H),4.54(s,2H),3.59(s,3H),2.23(s,3H).

[0057] 13 CNMR(101MHZ,CDCl3)δ170.4,165.4,152.6,136.5,132.6,131.7,130.8,128.6,128.5,127.7,125.0,118.0,51.7,49.8,22.8.

[0058] HRMS(ESI)m / Z: [M+H] + CalcdforC 19 H 19 NO3Br388.0543;found388.0540.

[0059] The product prepared in this embodiment is methyl( E )-3-( N The structural formula of 3-benzylacetamido)-3-(4-bromophenyl)acrylate is: .

[0060] Example 8 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-([1,1'-biphenyl]-4-yl)-3-(N The preparation method of β-benzylacetamido)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -(1-([1,1'-biphenyl]-4-yl)vinyl)- N 0.6 mmol of benzyl lactone, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid were added, along with 5.0 mL of a mixed solvent of H2O and DCE in a volume ratio of 4:1. The mixture was inserted into a graphite felt positive electrode and a platinum sheet negative electrode and energized with 10 mA. The mixture was then reacted in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 43.4 mg of the target product, with a yield of 56%.

[0061] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 23 and Figure 24 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.64(d,J=8.1Hz,4H),7.47(t,J=7.5Hz,2H),7.40(d,J=8.0Hz,3H), 7.33–7.24(m,3H),7.22–7.15(m,2H),5.70(s,1H),4.61(s,2H),3.62(s,3H),2.28(s,3H).

[0062] 13 CNMR(101MHZ,CDCl3)δ170.6,165.7,153.4,143.3,140.0,136.8,132.5,129. 8,128.9,128.6,128.6,128.0,127.6,127.2,127.0,117.7,51.6,49.9,22.9.

[0063] HRMS(ESI)m / Z[M+H] + CalcdforC 25 H 24 NO3386.1751; found386.1743.

[0064] The product prepared in this embodiment is methyl( E )-3-([1,1'-biphenyl]-4-yl)-3-( NThe structural formula of acrylate (-benzylacetamido) is: .

[0065] Example 9 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-(benzo[d][1,3]dioxol-5-yl)-3-( N The preparation method of β-benzylacetamido)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -(1-(benzo[d][1,3]dioxol-5-yl)vinyl)- N 0.6 mmol of benzyl lactone, 0.6 mmol of methyl hydrazine, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid were added, along with 5.0 mL of a mixed solvent of H2O and DCE in a volume ratio of 4:1. The mixture was inserted into a graphite felt positive electrode and a platinum sheet negative electrode and energized with 10 mA. The mixture was then reacted in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 44.8 mg of the target product, with a yield of 63%.

[0066] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 23 and Figure 24 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ, CDCl3)δ7.31–7.22(m,3H),7.20–7.12(m,2H),6.83(d,J=2.2Hz,2H),6. 77(d,J=0.9Hz,1H),6.03(s,2H),5.57(s,1H),4.56(s,2H),3.60(s,3H),2.22(s,3H).

[0067] 13 CNMR(101MHZ,CDCl3)δ170.6,165.8,153.1,149.7,147.8,136.8,128.6,1 28.5,127.6,127.3,124.1,116.75,109.4,108.3,101.7,51.6,49.9,22.8.

[0068] HRMS(ESI)m / Z: [M+H] + CalcdforC 20 H 20 NO5354.1336; found354.1333.

[0069] The product prepared in this embodiment is methyl( E )-3-(benzo[d][1,3]dioxol-5-yl)-3-( N The structural formula of acrylate (-benzylacetamido) is: .

[0070] Example 10 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives methyl( E )-3-( N The preparation method of 3-benzylacetamido)-3-(4-(methylthio)phenyl)acrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benzyl- N -(1-(4-(methylthio)phenyl)vinyl)acetamide, 0.6 mmol of methyl hydrazine carbamate, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid, and then add 5.0 mL of a mixed solvent of H2O and DCE with a volume ratio of 4:1. Insert the mixture into the graphite felt positive electrode and the platinum sheet negative electrode and apply an electric current of 10 mA. React in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 43.6 mg of the target product, with a yield of 61%.

[0071] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 23 and Figure 24 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.32–7.25(m,1H),7.26(d,J=2.1Hz,2H),7.22(s,4H),7.15(dd ,J=7.8,1.8Hz,2H),5.62(s,1H),4.56(s,2H),3.59(s,3H),2.51(s,3H),2.22(s,3H).

[0072] 13 CNMR(101MHZ,CDCl3)δ170.6,165.7,153.3,142.5,136.8,129.7,129.7,128.6,128.5,127.6,125.3,117.1,51.6,49.9,22.9,15.0.

[0073] HRMS(ESI)m / Z: [M+H] + CalcdforC 20 H 22 NO3S356.1315;found356.1310.

[0074] The product prepared in this embodiment is methyl( E )-3-( N The structural formula of 3-benzylacetamido)-3-(4-(methylthio)phenyl)acrylate is: .

[0075] Example 11 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives ethyl ( E )-3-( N The preparation method of (-benzylacetamido)-3-phenylacrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benZyl- N 1-(1-phenylvinyl)acetamide, 0.6 mmol of ethyl hydrazine carboxylate, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid were added, along with 5.0 mL of a mixed solvent of H2O and DCE in a volume ratio of 4:1. The mixture was inserted into a graphite felt positive electrode and a platinum sheet negative electrode, and an electric current of 10 mA was applied. The mixture was then reacted in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 43.7 mg of the target product, with a yield of 67%.

[0076] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 21 and Figure 22 As shown, the structural characterization data is as follows: 1HNMR(400MHZ, CDCl3)δ7.47–7.41(m,2H),7.40–7.38(m,1H),7.33–7.25(m,5H),7.18–7.12( m,2H),5.67(s,1H),4.54(s,2H),4.03(q,J=7.1Hz,2H),2.26(s,3H),1.09(t,J=7.1Hz,3H).

[0077] 13 CNMR(101MHZ,CDCl3)δ170.6,165.3,153.2,136.8,133.9,130.4,129.2,128.5,128.4,127.5,118.3,60.6,49.7,22.9,13.9.

[0078] HRMS(ESI)m / Z: [M+H] + CalcdforC 20 H 22 NO3324.1594; found324.1596.

[0079] The product prepared in this embodiment is ethyl( E )-3-( N The structural formula of (-benzylacetamido)-3-phenylacrylate is: .

[0080] Example 12 This embodiment provides a specific enamide-containing skeleton. E Type β-alkoxycarbonyl derivatives 3-phenylpropyl ( E )-3-( N The preparation method of (-benzylacetamido)-3-phenylacrylate includes the following steps: Add 0.2 mmol of [agent] to the three-necked flask. N -benZyl- N 1-(1-phenylvinyl)acetamide, 0.6 mmol of 3-phenylpropylhydrazine carboxylate, 0.6 mmol of tetrabutylammonium acetate and 0.6 mmol of trifluoroacetic acid were added, along with 5.0 mL of a mixed solvent of H2O and DCE in a volume ratio of 4:1. The mixture was inserted into a graphite felt positive electrode and a platinum sheet negative electrode, and an electric current of 10 mA was applied. The mixture was then reacted in an oil bath at 80 °C for 5 h. After the reaction was completed, the product was cooled, dried, and separated by column chromatography using a petroleum ether and ethyl acetate eluent in a ratio of 3:1 to obtain 47.4 mg of the target product, with a yield of 57%.

[0081] The product prepared in this embodiment was characterized, and its proton NMR spectrum and carbon NMR spectrum are shown below. Figure 23 and Figure 24 As shown, the structural characterization data is as follows: 1 HNMR(400MHZ,CDCl3)δ7.47–7.39(m,2H),7.42–7.35(m,1H),7.34–7.26(m,6H),7.24(s,1H),7.22–7.13(m,3H),7.10–7. 03(m,2H),5.68(s,1H),4.55(s,2H),3.99(t,J=6.5Hz,2H),2.46(dd,J=8.7,6.8Hz,2H),2.26(s,3H),1.84–1.72(m,2H).

[0082] 13 CNMR(101MHZ,CDCl3)δ170.5,165.4,153.2,141.1,137.3,130.4,129.2,128.6,1 28.5,128.43,128.39,128.32,127.5,126.0,118.2,64.0,49.8,32.0,29.9,22.9.

[0083] HRMS(ESI)m / Z: [M+H] + CalcdforC 27 H 28 NO3414.2064;found414.2065.

[0084] The product prepared in this embodiment is 3-phenylpropyl( E )-3-( N The structural formula of (-benzylacetamido)-3-phenylacrylate is: .

[0085] The analysis and characterization experimental data are the same as those in Example 1. The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A derivative containing an enamide skeleton (E)-alkoxycarbonyl, characterized in that: The molecular structures are as follows: ； Among them, R 1 It is phenyl, alkyl, alkoxy, halogen, or thiomethyl; R 2 It is benzyl, methyl, acyl, or tert-butyloxycarbonyl; R 3 It is an alkyl group.

2. The enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 1, characterized in that: The enamide skeleton (E)-alkoxycarbonyl derivatives include: 。 3. A method for preparing an enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 1 or 2, characterized in that: The preparation method involves the following steps: In a reactor equipped with electrode sheets, a non-cyclic enamide compound, hydrazine carbamate, additives, electrolyte, and solvent are mixed, and under electrochemical conditions, β-C(sp...) is carried out... 2 The )−H alkoxycarbonylation reaction yields a series of highly selective products. E Type β-alkoxycarbonyl amide derivatives; The noncyclic amide compounds have The structure shown; The hydrazine carbamate has The structure shown; The additive is selected from any one or a mixture of two or more of nitric acid, hydrochloric acid, acetic acid, trifluoroacetic acid, potassium carbonate, potassium bicarbonate and sodium acetate; The electrolyte is selected from n Bu4NBF4, n Bu4NClO4, n Bu4NI, n Bu4NH2PO4, n Bu4NPF6, Et3N·3HF,Et4NBF4, Me4NOAc, n Any one or more mixtures of Bu4NOAc; The solvent is selected from any one or a mixture of two or more of water, dichloroethane, methanol, ethanol, tetrahydrofuran, and dichloromethane.

4. The method for preparing the enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 3, characterized in that: The reaction equation for the alkoxycarbonylation reaction is as follows:

5. The method for preparing the enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 3, characterized in that: The molar ratio of the noncyclic enamide compound, methyl hydrazine carbamate, electrolyte, and additive is 1.0:(1.0~5.0):(0.5~5.0):(1.0~5.0); the initial concentration of the noncyclic enamide compound is 0.02~0.2 mol / L.

6. The method for preparing the enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 3, characterized in that: The reactor in the electrochemical conditions is a non-separated electrolytic cell, the power supply is a DC regulated power supply, and the reaction is carried out under constant current conditions, with a current of 5~15 mA.

7. The method for preparing the enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 3, characterized in that: The positive electrode is selected from any one of carbon sheet, carbon cloth, graphite felt, platinum sheet and carbon rod; the negative electrode is selected from any one of platinum sheet, stainless steel sheet, nickel sheet and carbon sheet.

8. The method for preparing the enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 3, characterized in that: The alkoxycarbonylation reaction temperature is 20–100 °C. 0 C; the reaction time is 2-10 hours.

9. The method for preparing the enamide skeleton (E)-alkoxycarbonyl derivative as described in claim 3, characterized in that: The alkoxycarbonylation reaction is followed by separation and purification; the separation and purification method is selected from any one of column chromatography, liquid chromatography, distillation and recrystallization.

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