Method for electrochemical synthesis of gamma-aryl ester compound

Abstract

The invention provides a method for electrochemical synthesis of a gamma-aryl ester compound, which is characterized in that a diazo compound and olefin are subjected to an addition reaction through an efficient electrochemical reduction strategy to generate the gamma-aryl ester compound. The method disclosed by the invention is carried out under mild reaction conditions, does not need a metal catalyst and a chemical redox reagent, has high functional group tolerance and good synthesis practicability, and has industrial potential.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for electrochemically synthesizing gamma-aryl ester compounds. Background Art

[0002] γ-Aryl ester compounds are chemical substances with multiple application values. As solvents, these compounds are widely used in the coatings, inks and adhesives industries, significantly improving the flow and adhesion properties of these products. In addition, γ-Aryl ester compounds can be added to various daily chemicals and foods as a fragrance ingredient to enhance the flavor of the products. In addition, these compounds are also important intermediates in drug synthesis. They can be converted into γ-aryl acids through hydrolysis, which have shown broad application prospects in the field of anti-cancer treatment and digestive system disease drug development; asymmetric reduction of ethyl 4-phenylbutyrate can also be efficiently converted into bioactive chiral compounds (ACS Catal. 2022, 12(9), 5136–5144).

[0003] The traditional method for synthesizing 4-phenylbutyrate requires the use of strong acids (such as concentrated sulfuric acid) to react olefins with cis addition, which has harsh reaction conditions and produces by-products. At present, although the use of diazo compounds to generate alkyl radicals under the action of photocatalysts and then add to olefins has become a new approach to synthesize a series of γ-aryl ester compounds, this strategy still faces challenges such as limited substrate applicability and high cost. For example, when using a photoenzymatic strategy for the selective hydroalkylation of olefins, diazo compounds are limited to 2-diazoacetic acid benzyl ester substrates (Angew. Chem. Int. Ed. 2022, 62, e202214135); Ru(bpy)3Cl2·6H2O is used as a photocatalyst to undergo a proton-coupled electron transfer (PCET) process with diazo compounds to form alkyl radicals, which then add to olefins, and the synthesis of γ-aryl ester compounds is also achieved. However, the catalyst is expensive and the reaction is difficult to scale up, which limits its promotion in practical applications. (J.Am.Chem.Soc.2020,142,32,13846–13855). Therefore, exploring a method for synthesizing γ-aryl ester compounds with mild reaction conditions, low production cost and wide substrate applicability remains an important issue to be solved. Summary of the invention

[0004] In order to solve the problems in the prior art, the present invention provides a method for electrochemically synthesizing γ-aryl ester compounds. The present invention uses a diazo compound and an olefin as reaction substrates to generate γ-aryl ester compounds.

[0005] To achieve the above object, the technical solution of the present invention is:

[0006] A method for electrochemically synthesizing γ-aryl ester compounds, using compound 1 and compound 2 as raw materials to electrochemically synthesize γ-ester derivative compound 3; the reaction formula is as follows:

[0007]

[0008] Among them, R 1 is selected from alkyl, alkoxy, halogen or alkyl substituted with multiple halogens, and aryl; R 2 Selected from ester group and amide group.

[0009] According to one embodiment of the present invention, the alkyl group is selected from methyl and tert-butyl; the alkoxy group is selected from methoxy; the halogen is selected from fluorine, chlorine and bromine; the alkyl group substituted by multiple halogens is selected from trifluoromethyl; the aryl group is selected from phenyl, 2-naphthyl, 2-thienyl, 2-pyridyl and 5-(4-methylthiazole); the ester group is selected from ethyl formate, tert-butyl formate and 2-methoxyethyl formate; and the amide group is selected from N,N-diethylformamide.

[0010] According to one embodiment of the present invention, the compound 3 is selected from:

[0011]

[0012]

[0013] According to one embodiment of the present invention, the electrolytic cell used in the electrochemical synthesis method is an undivided electrolytic cell; the electrode is one or more of stainless steel, Fe, Ni, Cu, Ag, Zn, foamed stainless steel, graphite sheet, graphite felt, carbon paper or meshed glassy carbon; the electrolyte is one or more of tetra-n-butylammonium hexafluorophosphate, tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium acetate, tetra-n-butylammonium perchlorate and tetraethylammonium tetrafluoroborate; the current is 3 to 10 mA; and the reaction temperature is 0 to 50°C.

[0014] According to one embodiment of the present invention, the solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, acetonitrile and methanol.

[0015] According to one embodiment of the present invention, the electrode foam stainless steel is the anode and the carbon paper is the cathode; the electrolyte is tetra-n-butylammonium acetate with an electrolyte concentration of 0.05M; the current is 5mA; and the solvent is a mixed solution of N,N-dimethylacetamide and methanol (volume ratio of 3:1).

[0016] According to one embodiment of the present invention, the reaction temperature is 25°C.

[0017] According to one embodiment of the present invention, the molar ratio of 4-phenylstyrene compounds to diazoacetic acid ester compounds is 1:1-1:10; and the concentration of 4-phenylstyrene is 0.05M-0.2M.

[0018] According to one embodiment of the present invention, the molar ratio of the 4-phenylstyrene compound to the diazoacetic acid ester compound is 1:8; and the concentration of 4-phenylstyrene is 0.05M.

[0019] According to one embodiment of the present invention, the endpoint of the reaction is that thin layer chromatography shows that the starting material completely disappears.

[0020] According to one embodiment of the present invention, after the reaction is completed, water is added to quench, extracted three times with ethyl acetate, the organic phases are combined, and the organic phases are washed once with a saturated sodium chloride aqueous solution to obtain an organic phase, the solvent is concentrated under reduced pressure, and purified by silica gel column chromatography, using a mixture of ethyl acetate and petroleum ether as an eluent during purification to obtain a product.

[0021] Beneficial effects:

[0022] The present invention provides a method for electrochemically synthesizing γ-aryl ester compounds, wherein a diazo compound and an olefin undergo an addition reaction through an efficient electrochemical reduction strategy to generate γ-aryl ester compounds. The method of the present invention is carried out under mild reaction conditions, does not require a metal catalyst and a chemical redox reagent, has high functional group tolerance and good synthetic practicality, and has the potential for industrialization. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present application will be clearly and completely described below in conjunction with the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Unless otherwise specified, the raw materials used in this application can be obtained by commercial purchase, and any range recorded in the present invention includes any value between the end values ​​and the end values, and any sub-range composed of any value between the end values ​​or the end values.

[0024] The present invention is further described below with reference to examples, but is not intended to be limiting of the present invention.

[0025] Embodiment 1:

[0026] Preparation of ethyl 4-([1,1'-biphenyl]-4-yl)butyrate 3

[0027]

[0028] Specific operation steps: 0.2mmol of 4-phenylstyrene and 0.2mmol of tetra-n-butylammonium acetate were weighed in a 10mL electrolytic cell, in which a 1.0cm×1.2cm×0.1cm stainless steel foam sheet was set as an anode and a 1.0cm×1.2cm×0.01cm carbon paper was set as a cathode, 3.0mL of N,N-dimethylformamide and 1.0mL of methanol were added as solvents, 144μL of water and 1.6mmol of ethyl diazoacetate were added, and the reaction was energized for 12h at room temperature, wherein the current was 5mA, and TLC was used for monitoring until the substrate was completely consumed. After the reaction was completed, water was added to quench, and ethyl acetate was used for extraction three times, and the organic phases were combined, and the organic phases were washed once with a saturated sodium chloride aqueous solution to obtain an organic phase, and the solvent was concentrated under reduced pressure, and purified by silica gel column chromatography, and the product was obtained by using ethyl acetate and petroleum ether in a ratio of 1:80 as eluents.

[0029] Table 1. Effect of different anode materials on the preparation of compound 3

[0030]

[0031] It can be seen from Table 1 that when the anode material is foamed stainless steel, the yield of the product can achieve relatively good results.

[0032] Table 2. Effect of different cathode materials on the preparation of compound 3

[0033]

[0034] It can be seen from Table 2 that when the cathode material is carbon paper, the yield of the product can achieve relatively good results.

[0035] Table 3. Effect of different currents (same charge Q = I·t) on the preparation of compound 3

[0036]

[0037] It can be seen from Table 3 that when the current is 5 mA and the reaction time is 10 h, the yield of the product can achieve relatively good results.

[0038] Table 4. Effects of different solvents on the preparation of compound 3

[0039]

[0040] It can be seen from Table 4 that when the solvent is a mixed solvent with a volume ratio of N,N-dimethylacetamide and methanol of 3:1, the yield of the product can achieve relatively good results.

[0041] Table 5. Effect of different electrolytes on the preparation of compound 3

[0042]

[0043] It can be seen from Table 5 that when the electrolyte is tetra-n-butylammonium acetate, the yield of the product can achieve relatively good results.

[0044] Table 6. Effect of different electrolyte concentrations on the preparation of compound 3

[0045]

[0046] It can be seen from Table 6 that when the electrolyte concentration is 0.05 M, the yield of the product can achieve relatively good results.

[0047] Table 7. Effect of different temperatures on the preparation of compound 3

[0048]

[0049] It can be seen from Table 7 that when the reaction temperature is room temperature (25°C), the yield of the product can achieve relatively good results.

[0050] Investigation of substrate universality

[0051]

[0052] In summary, the present invention starts from readily available and inexpensive aryl vinyl compounds and diazo compounds, and uses an efficient electrochemical reduction strategy to generate γ-aryl ester compounds by reacting diazo compounds with olefins. The reaction of the present invention does not require metal catalysts and chemical redox reagents, and the reaction conditions are mild, with high functional group tolerance and good synthetic practicality.

[0053] The specific structure and structural analysis data of compound 3-31 are as follows.

[0054] Compound 3: 4-([1,1'-biphenyl]-4-yl)butyric acid ethyl ester, colorless oily liquid, isolated yield 71% (38 mg), 1 H NMR(600MHz,Chloroform-d)δ7.60(d,J=7.8Hz,2H),7.54(d,J=7.2Hz,2H),7.44(t,J=7.2Hz,2H),7.34(t,J=7.2Hz,1H),7.27( d,J=7.8Hz,2H),4.15(q,J=7.2Hz,2H),2.71(t,J=7.2Hz,2H),2.37(t,J=7.2Hz,2H),2.04-1.99(m,2H),1.28(t,J=6.6Hz,3H).

[0055] Compound 4: 4-(4'-methyl-[1,1'-biphenyl]-4-yl)butyric acid ethyl ester, colorless oily liquid, isolated yield 59% (34 mg), 1 H NMR(600MHz,Chloroform-d)δ7.40(dd,J=14.4,7.8Hz,4H),7.14(dd,J=7.8,2.4Hz,4H),4.04(q,J=7.2Hz ,2H),2.59(t,J=7.2Hz,2H),2.29(s,3H),2.26(t,J=7.2Hz,2H),1.92-1.87(m,2H),1.16(t,J=7.2Hz,3H).

[0056] Compound 5: 4-(4'-chloro-[1,1'-biphenyl]-4-yl)butyric acid ethyl ester. Colorless oily liquid, isolated yield 78% (47 mg), 1 H NMR(600MHz,Chloroform-d)δ7.39(dd,J=13.8,8.4Hz,4H),7.29(d,J=9.0Hz,2H),7.16(d,J=7.8Hz,2H),4. 02(q,J=7.2Hz,2H),2.57(t,J=7.8Hz,2H),2.23(t,J=7.2Hz,2H),1.90-1.85(m,2H),1.14(t,J=7.2Hz,3H).

[0057] Compound 6: 4-(3',5'-dimethyl-[1,1'-biphenyl]-4-yl)butanoic acid ethyl ester, colorless oily liquid, isolated yield of 82% (49 mg), 1 H NMR(600MHz,Chloroform-d)δ7.43(d,J=7.8Hz,2H),7.16(d,J=8.4Hz,2H),7.12(s,2H),6.90(s,1H),4.06(q,J= 7.2Hz,2H),2.62(t,J=7.8Hz,2H),2.30(s,6H),2.28(t,J=7.2Hz,2H),1.94-1.89(m,2H),1.19(t,J=7.2Hz,3H).

[0058] Compound 7: 4-(3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)butanoic acid ethyl ester, colorless oily liquid, isolated yield of 86% (70 mg), 1H NMR(600MHz,Chloroform-d)δ8.00(s,2H),7.84(s,1H),7.54(d,J=7.8Hz,2H),7.33(d,J=7.8Hz,2H), 4.15(q,J=6.6Hz,2H),2.73(t,J=7.8Hz,2H),2.36(t,J=7.2Hz,2H),2.0(m,2H),1.27(t,J=7.2Hz,3H).

[0059] Compound 8: ethyl 4-(4-(naphthalen-2-yl)phenyl)butanoate, colorless oily liquid, isolated yield 86% (55 mg), 1 H NMR(600MHz,Chloroform-d)δ8.07(s,1H),7.93(t,J=6.6Hz,2H),7.89(d,J=7.8Hz,1H),7.78(dd,J=8.4,1.8Hz,1H),7.69(d,J=8.4Hz,2H),7.56- 7.48(m,2H),7.34(d,J=7.8Hz,2H),4.19(q,J=7.2Hz,2H),2.76(t,J=7.8 Hz,2H),2.41(t,J=7.2Hz,2H),2.08-2.03(m,2H),1.31(t,J=7.2Hz,3H). 13 C NMR (150MHz, CDCl3) δ172.41,139.62,137.73,137.28,132.64,131.46,127.96,127.30,12 7.08,126.56,126.31,125.17,124.74,124.44,124.43,59.23,33.73,32.63,25.48,13.22.

[0060] Compound 9: 4-phenylbutyric acid ethyl ester, colorless oily liquid, isolated yield 58% (67 mg). 1 HNMR(600MHz,Chloroform-d)δ7.29(t,J=7.2Hz,2H),7.20(t,J=7.8Hz,3H),4.13(q,J=6.6Hz ,2H),2.66(t,J=7.2Hz,2H),2.33(t,J=7.2Hz,2H),1.99-1.94(m,2H),1.26(t,J=6.6Hz,3H).

[0061] Compound 10: 4-(p-tolyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 30% (37 mg). 1HNMR(600MHz,Chloroform-d)δ7.10(d,J=7.8Hz,2H),7.07(d,J=7.8Hz,2H),4.13(q,J=6.6 Hz,2H),2.62(t,J=7.2Hz,2H),2.34-2.31(m,5H),1.96-1.91(m,2H),1.26(t,J=7.2Hz,3H).

[0062] Compound 11: 4-(4-(tert-butyl)phenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 50% (75 mg). 1 H NMR(600MHz,Chloroform-d)δ7.32(d,J=8.4Hz,2H),7.13(d,J=8.4Hz,2H),4.13(q,J=7.2Hz,2H),2 .63(t,J=7.8Hz,2H),2.34(t,J=7.2Hz,2H),1.99-1.94(m,2H),1.32(s,9H),1.26(t,J=7.2Hz,3H).

[0063] Compound 12: 4-(4-fluorophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 30% (38 mg). 1 HNMR (600MHz, Chloroform-d) δ7.13 (dd, J=8.4, 5.4Hz, 2H), 6.96 (t, J=8.4Hz, 2H), 4.12 (q, J=7. 2Hz,2H),2.62(t,J=7.2Hz,2H),2.30(t,J=7.2Hz,2H),1.95-1.90(m,2H),1.25(t,J=7.2Hz,3H).

[0064] Compound 13: 4-(4-chlorophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 52% (71 mg). 1 HNMR(600MHz,Chloroform-d)δ7.26-7.23(m,2H),7.10(d,J=8.4Hz,2H),4.12(q,J=7.2Hz, 2H),2.62(t,J=7.8Hz,2H),2.30(t,J=7.2Hz,2H),1.95-1.90(m,2H),1.25(t,J=7.2Hz,3H).

[0065] Compound 14: 4-(4-bromophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 50% (81 mg). 1HNMR(600MHz,Chloroform-d)δ7.41-7.38(dt,J=9.0,2.4Hz,2H),7.06-7.04(dt,J=9.0,2.4Hz,2H),4.12 (q,J=7.2Hz,2H),2.60(t,J=7.8Hz,2H),2.30(t,J=7.2Hz,2H),1.95-1.90(m,2H),1.25(t,J=7.2Hz,3H).

[0066] Compound 15: 4-(4-(trifluoromethyl)phenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 63% (98 mg). 1 H NMR(600MHz,Chloroform-d)δ7.54(d,J=8.4Hz,2H),7.29(d,J=8.4Hz,2H),4.13(q,J=7.2Hz ,2H),2.71(t,J=7.2Hz,2H),2.32(t,J=7.2Hz,2H),1.99-1.94(m,2H),1.25(t,J=7.2Hz,3H).

[0067] Compound 16: 4-(2-methoxyphenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 40% (36 mg). 1 HNMR(600MHz,Chloroform-d)δ7.18(td,J=7.8,1.8Hz,1H),7.12(dd,J=7.2,1.8Hz,1H),6.88(td,J=7.8,1.2Hz,1H),6.84(d,J=8. 4Hz, 1H), 4.12 (q, J = 7.2Hz, 2H), 3.81 (s, 3H), 2.66 (t, J = 7.2, 2H), 2.32 (t, J = 7.8Hz, 2H), 1.95-1.90 (m, 2H), 1.25 (t, J = 6.6Hz, 3H).

[0068] Compound 17: 4-(2-chlorophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 60% (82 mg). 1HNMR(600MHz,Chloroform-d)δ7.33(dd,J=7.8,1.2Hz,1H),7.21(dd,J=7.8,1.8Hz,1H),7.18(td,J=7.2,1.2Hz,1H),7.14(td,J =7.2,1.8Hz,1H),4.13(q,J=7.2Hz,2H),2.78(t,J=7.8Hz,2H),2.35(t,J=7.2Hz,2H),1.99-1.94(m,2H),1.26(t,J=7.2Hz,3H).

[0069] Compound 18: 4-(2-bromophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 70% (114 mg). 1 HNMR(600MHz,Chloroform-d)δ7.52(d,J=8.4Hz,1H),7.25-7.20(m,2H),7.06(ddd,J=7.8,6.6,2.4Hz,1H),4 .13(q,J=7.2Hz,2H),2.78(t,J=7.8Hz,2H),2.36(t,J=7.2Hz,2H),1.99-1.94(m,2H),1.26(t,J=7.2Hz,3H).

[0070] Compound 19: 4-(3-fluorophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 62% (78 mg). 1 HNMR(600MHz,Chloroform-d)δ7.25-7.21(m,1H),6.95(d,J=7.8Hz,1H),6.90–6.86(m,1H),4.13(q, J=6.6Hz,2H),2.65(t,J=7.2Hz,2H),2.31(t,J=7.2Hz,2H),1.97-1.92(m,2H),1.25(t,J=7.2Hz,3H).

[0071] Compound 20: 4-(3-chlorophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 57% (78 mg). 1 HNMR(600MHz,Chloroform-d)δ7.22-7.14(m,3H),7.05(d,J=7.2Hz,1H),4.12(q,J=7.2Hz, 2H), 2.63 (t, J=7.8Hz, 2H), 2.31 (t, J=7.2Hz, 2H), 1.96-1.91 (m, 2H), 1.25 (t, J=7.2Hz, 3H).

[0072] Compound 21: 4-(3-bromophenyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 56% (91 mg). 1 HNMR(600MHz,Chloroform-d)δ7.34-7.31(m,2H),7.15(t,J=7.8Hz,1H),7.10(dt,J=7.2,1.2Hz,1H),4.1 3(q,J=7.2Hz,2H),2.62(t,J=7.2Hz,2H),2.31(t,J=7.2Hz,2H),1.96-1.91(m,2H),1.26(t,J=7.2Hz,3H).

[0073] Compound 22: 4-(2-naphthyl)butyric acid ethyl ester, colorless oily liquid, isolated yield 50% (73 mg). 1 H NMR(600MHz,Chloroform-d)δ7.83(d,J=7.8Hz,1H),7.80(d,J=8.4Hz,2H),7.64(s,1H),7.51-7.43(m,2H),7.36(dd,J=8.4 ,1.2Hz,1H),4.16(q,J=7.2Hz,2H),2.85(t,J=7.2Hz,2H),2.38(t,J=7.2Hz,2H),2.11-2.06(m,2H),1.28(t,J=7.2Hz,3H).

[0074] Compound 23: 4,4-diphenylbutyric acid ethyl ester, colorless oily liquid, isolated yield 67% (72 mg). 1 H NMR(600MHz,Chloroform-d)δ7.28-7.19(m,8H),7.14(t,J=7.2Hz,2H),4.06(q,J=6.6Hz,2H ),3.89(t,J=7.8Hz,1H),2.35(q,J=7.8Hz,2H),2.23(t,J=7.2Hz,2H),1.19(t,J=7.2Hz,3H).

[0075] Compound 24: 4-phenylpentanoic acid ethyl ester, colorless oily liquid, isolated yield 37% (31 mg). 1 HNMR(600MHz,Chloroform-d)δ7.31-7.27(m,2H),7.21-7.16(m,3H),4.08(qd,J=7.2,2.4Hz,2H),2. 76-2.66(m,1H),2.24-2.13(m,2H),1.99-1.84(m,2H),1.27(d,J=7.2Hz,3H),1.22(t,J=7.2Hz,3H).

[0076] Compound 25: (R)-3,4-diphenylbutyric acid ethyl ester, colorless oily liquid, isolated yield 22% (24 mg). 1 HNMR(600MHz,Chloroform-d)δ7.28-7.12(m,8H),7.05(d,J=7.2Hz,2H),3.98(qd,J=7.2,1 .8Hz,2H),3.44-3.39(m,1H),2.95-2.88(m,2H),2.71-2.54(m,2H),1.10(t,J=7.2Hz,3H).

[0077] Compound 26: 4-(thiophen-2-yl)butanoic acid ethyl ester, colorless oily liquid, isolated yield 20% (16 mg). 1 HNMR(600MHz,Chloroform-d)δ7.12(dd,J=4.8,1.2Hz,1H),6.92(dd,J=4.8,2.4Hz,1H),6.80(dd,J=2.4,1.2Hz,1 H), 4.13 (q, J = 6.6Hz, 2H), 2.88 (t, J = 7.2Hz, 2H), 2.36 (t, J = 7.2Hz, 2H), 2.03-1.98 (m, 2H), 1.26 (t, J = 7.2Hz, 3H).

[0078] Compound 27: 4-(4-methylthiazol-5-yl)butyric acid methyl ester, colorless oily liquid, isolated yield 45% (36 mg). 1 HNMR(600MHz,Chloroform-d)δ8.55(s,1H),3.67(s,3H),2.80(t,J=7.2Hz,2H),2.37(s,3H),2.35(t,J=7.2Hz,2H),1.96-1.92(m,2H).The spectral data were inaccordance with those reported in the literature.

[0079] Compound 28: 4-(pyridin-2-yl)butanoic acid ethyl ester, colorless oily liquid, isolated yield 40% (31 mg). 1HNMR(600MHz,Chloroform-d)δ8.58-8.44(m,1H),7.60(td,J=7.2,1.8Hz,1H),7.16(d,J=7.8Hz,1H),7.11(dd,J=7.2,5 .4Hz,1H),4.12(q,J=6.6Hz,2H),2.83(t,J=7.2Hz,2H),2.36(t,J=7.2Hz,2H),2.10-2.05(m,2H),1.25(t,J=7.2Hz,2H).

[0080] Compound 29: tert-butyl 4-([1,1'-biphenyl]-4-yl)butanoate, colorless oily liquid, isolated yield 63% (37 mg). 1 H NMR(600MHz,Chloroform-d)δ7.62-7.58(m,2H),7.56-7.52(m,2H),7.47-7.41(m,2H),7.37-7.31(m,1 H),7.28(d,J=8.4Hz,2H),2.70(t,J=7.2Hz,2H),2.29(t,J=7.2Hz,2H),2.00-1.95(m,2H),1.48(s,9H). 13 C NMR (150MHz, CDCl3) δ171.85,140.02,139.73,137.85,127.89,127.67,126.06,125.98,125.95,79.12,33.93,33.74,27.11,25.70.

[0081] Compound 30: 2-methoxyethyl 4-([1,1'-biphenyl]-4-yl)butyrate, colorless oily liquid, isolated yield 54% (32 mg). 1 HNMR(600MHz,Chloroform-d)δ7.50(dd,J=7.8,1.8Hz,2H),7.44(d,J=8.4Hz,2H),7.35(t,J=7.2Hz,2H),7.25(t,J=7.2Hz,1H),7.17(d, J=7.8Hz,2H),4.16(t,J=4.8Hz,2H),3.51(t,J=4.8Hz,2H),3.31(s,3H),2.62(t,J=7.2Hz,2H),2.33(t,J=7.2Hz,2H),1.95-1.90(m,2H).

[0082] Compound 31: 4-([1,1'-biphenyl]-4-yl)-N,N-diethylbutyramide, colorless oily liquid, isolated yield 27% (16 mg).1 HNMR(600MHz,Chloroform-d)δ7.43(dd,J=7.2,1.2Hz,2H),7.37(d,J=7.8Hz,2H),7.28(t,J=7.2Hz,2H),7.20-7.15(m,1H),7.14-7.10(m,2H),3.23(q,J=6.6Hz,2H),3.10(q,J=7.2Hz,2H),2.58(t,J=7.2Hz,2H),2.19(t,J=7.2Hz,2H),1.94-1.82(m,2H),1.01-0.88(m,6H)。

Claims

1. A method for electrochemically synthesizing γ-aryl ester compounds, using compound 1 and compound 2 as raw materials to electrochemically synthesize γ-ester derivative compound 3; the reaction formula is as follows: in, R 1 is selected from alkyl, alkoxy, halogen or alkyl substituted with multiple halogens, and aryl; R 2 Selected from ester group and amide group.

2. The method according to claim 1, characterized in that: The alkyl group is selected from methyl and tert-butyl; the alkoxy group is selected from methoxy; the halogen is selected from fluorine, chlorine and bromine; the alkyl group substituted with multiple halogens is selected from trifluoromethyl; the aryl group is selected from phenyl, 2-naphthyl, 2-thienyl, 2-pyridyl and 5-(4-methylthiazole); the ester group is selected from ethyl formate, tert-butyl formate and 2-methoxyethyl formate; and the amide group is selected from N,N-diethylformamide.

3. The method according to claim 1, characterized in that: The compound 3 is selected from:

4. The method according to any one of claims 1 to 3, characterized in that: The electrolytic cell used in the electrochemical synthesis method is an undivided electrolytic cell; the electrode is one or more of stainless steel, Fe, Ni, Cu, Ag, Zn, foamed stainless steel, graphite sheet, graphite felt, carbon paper or meshed glassy carbon; the electrolyte is one or more of tetra-n-butylammonium hexafluorophosphate, tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium acetate, tetra-n-butylammonium perchlorate and tetraethylammonium tetrafluoroborate; the current is 3-10 mA; and the reaction temperature is 0-50° C.

5. The method according to claim 4, characterized in that: The solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, acetonitrile and methanol.

6. The method according to claim 4, characterized in that: The electrode foam stainless steel is the anode and the carbon paper is the cathode; the electrolyte is tetra-n-butylammonium acetate with an electrolyte concentration of 0.05M; the current is 5mA; and the solvent is a mixed solution of N,N-dimethylacetamide and methanol (volume ratio is 3:1).

7. The method according to claim 6, characterized in that The reaction temperature was 25°C.

8. The method according to claim 7, characterized in that The molar ratio of 4-phenylstyrene compounds to diazoacetic acid ester compounds is 1:1-1:10; the concentration of 4-phenylstyrene is 0.05M-0.2M.

9. The method according to claim 8, characterized in that The molar ratio of the 4-phenylstyrene compound to the diazoacetic acid ester compound is 1:8; the concentration of 4-phenylstyrene is 0.05M.

10. The method according to claim 9, characterized in that After the reaction is completed, water is added to quench, and the mixture is extracted three times with ethyl acetate. The organic phases are combined and washed once with a saturated sodium chloride aqueous solution to obtain an organic phase. The solvent is concentrated under reduced pressure and purified by silica gel column chromatography using a mixture of ethyl acetate and petroleum ether as an eluent to obtain the product.

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