A method for esterification of alkyl aromatics and amides via benzylic radical polarity reversal

Abstract

This invention relates to a method for esterifying alkyl aromatics and amides via benzylic radical polarity reversal, belonging to the field of compound preparation technology. This invention leverages the advantages of electrochemical anodic oxidation to anolylate benzylic C(sp) groups. 3 The amide attacks the carbocation to form an imine intermediate, which is then hydrolyzed to break the C–N bond, thus achieving the synthesis of benzyl esters. This invention avoids the use of transition metals, high temperatures, high pressures, and stoichiometric amounts of hazardous oxidizing and reducing agents, and establishes good functional group tolerance, expanding the range of substrates and providing a supplementary approach for the synthesis of benzyl esters under mild conditions.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of compound preparation, and relates to a method for esterification of alkylarene and amide by polarity reversal of benzyl radical free radicals. BACKGROUND

[0002] Synthesizing high-value-added compounds from cheap and easily available raw materials through environmentally friendly means has always been the focus of the chemical field. Benzyl ester structures are widely present in natural products and commercially available drugs. The most common method for preparing benzyl esters is traditional esterification and transesterification, which usually requires heating and acid catalysis (for example, the synthesis of benzyl formate requires benzyl alcohol as a starting material for esterification with formic acid, which is highly corrosive and strongly irritating; or transesterification using formate salt (basically prepared from formic acid) for esterification), which undoubtedly limits its application. In view of the importance of the benzyl ester skeleton, it is extremely important to develop a more environmentally friendly and traditional esterification or transesterification synthesis method that is not limited to benzyl alcohol.

[0003] Amide bonds are stable due to the resonance between the lone pair of electrons of the nitrogen atom and the carbonyl group, so there are few studies on breaking amide bonds compared to synthesizing amide bonds. In 2015, Garg's group developed a method based on nickel-catalyzed activation of amide C–N bonds, which can convert various aromatic amides into esters in the presence of alcohols; in 2016, the same group successfully achieved the esterification of aliphatic amides with alcohols; in 2019, Qin's group used the toxic and corrosive gas sulfur fluoride (SO2F2) as a catalyst to achieve the esterification of amides with alcohols. DMF (N,N-dimethylformamide) is not only a commonly used organic solvent, but also can be used as a cheap and readily available raw material for the synthesis of benzyl esters. For example, Xiao's group developed a visible light-induced photocatalytic formyloxylation reaction of 3-bromoindole with water and DMF; König's group reported the use of diazonium salts and DMF to perform formyloxylation of olefins through a photo-oxidative Meerwein reaction. Hu's group used DMF as a formyloxylation reagent to achieve the electrochemical radical formyloxylation-bromination, chlorination and trifluoromethylation of olefins; recently, Kim's group reported an electrochemically driven stereoselective method for cis-1,2-diol derivatives from vinylarenes and DMF. These methods contribute greatly to the synthesis of benzyl esters by breaking the amide C–N bond. However, these methods require benzyl alcohol, benzyl halide or vinylarene as a starting material.

[0004] There is no report on the direct construction of benzyl ester compounds from unactivated benzyl C(sp 3 )–H and DMF. If unactivated benzyl C(sp 3) -H does not need to be pre-functionalized with the direct construction of benzyl formate compounds with cheap and readily available DMF, which is a very economical and direct synthesis method, so it is necessary to carry out related research.

[0005] SUMMARY

[0006] Therefore, the purpose of the present application is to provide a method for esterification of alkyl aromatic hydrocarbons and amides by benzyl radical polarity reversal.

[0007] To achieve the above purpose, the present application provides the following technical solutions:

[0008] 1. A method for esterification of alkyl aromatic hydrocarbons and amides by benzyl radical polarity reversal, the reaction general formula of the method is as follows:

[0009] ,

[0010] wherein R 1 is any one of hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, formaldehyde group, acetyl group, carboxyl group or ester group, R 2 is any one of hydrogen, methyl, ethyl, n-propyl, n-butyl or n-hexyl, R 3 is any one of hydrogen or methyl, R 4 is any one of methyl or ethyl;

[0011] The electrolyte is any one of n-tetrabutylammonium tetrafluoroborate, n-tetrabutylammonium hexafluorophosphate or n-tetrabutylammonium perchlorate;

[0012] The additive is any one of trifluoroacetic acid, copper acetate, nickel diacetylacetone, silver carbonate, copper sulfate, copper triflate or copper tetraacetonitrile tetrafluoroborate.

[0013] Preferably, the compound I is any one of I-1~I-24 compounds, the corresponding chemical structural formula of which is shown as follows:

[0014] .

[0015] Preferably, the compound II includes any one of II-1~II-4 compounds, the corresponding chemical structural formula of which is shown as follows:

[0016] .

[0017] Preferably, the compound III includes any one of III-1~III-27 compounds, the corresponding chemical structural formula of which is shown as follows:

[0018]

[0019]

[0020] Preferably, the anode material in the electrochemical device comprises any one of graphite sheet, platinum sheet (Pt), carbon felt or glassy carbon electrode;

[0021] The cathode material in the electrochemical device comprises any one of graphite sheet, platinum sheet, stainless steel sheet or nickel foam.

[0022] Preferably, the current during the power-on process of the electrochemical device is 1-16 mA.

[0023] Preferably, the method specifically comprises the following steps: adding compound I and compound II as reaction substrates into the electrochemical device, adding an additive, an electrolyte, stirring to dissolve, powering on to react, and separating the target product compound III after the reaction is completed, so as to perform esterification on the benzyl position of compound I.

[0024] Further preferably, the volume of the added compound II is greater than or equal to the volume of compound II capable of dissolving all of the added compound I, the additive and the electrolyte.

[0025] Further preferably, the molar ratio of the compound I, the additive and the electrolyte is 1:1-4:1-4.

[0026] 2. The benzyl ester compound prepared according to the above method.

[0027] The method disclosed by the present application has the beneficial effects that: the present application discloses a method for esterification of alkylarene and amide by polarity reversal of benzyl radical, and the main process is as follows: firstly, by the advantage of electrochemistry, a transient radical is constructed on the anode oxidation of the benzyl C(sp 3 )–H bond, and then by further oxidation of the radical, a carbon cation is constructed with high atom economy; then the carbon cation is attacked by amide, and after hydrolysis, a benzyl ester compound with high added value is obtained. The method of the present application avoids the use of transition metals, high temperature, high pressure and chemical equivalent dangerous oxidants and reductants, establishes good functional group tolerance, expands various substrates, provides a supplementary scheme for the synthesis of benzyl ester compounds, and has good application prospect. In addition, the method of the present application uses clean energy electricity as the power source of the reaction, which is green and environmentally friendly and has high atom economy; the method of electrochemical benzyl esterification of alkylarene has not been reported in the prior art, so the development of the method of the present application fills the gap in this field.

[0028] Additional advantages, objects, and features of the application will be apparent to those skilled in the art upon examination of the following detailed description, it being understood that each of the foregoing general statements are true of the particular embodiments of the application. Additionally, it is to be understood that the objects of the application can be practiced otherwise than as set forth in the following detailed description and that the claims can be amended to encompass variations and modifications obvious to the skilled worker. BRIEF DESCRIPTION OF DRAWINGS

[0029] In order to make the objects, technical solutions and advantages of the present application clearer, the preferred embodiments of the present application will be described in detail below with reference to the drawings, in which:

[0030] Figure 1 Radical trapping experiment for mechanism research in the method of the present application for esterification of alkylarenes and amides by polarity reversal of benzyl radicals;

[0031] Figure 2 Isotope labeling experiment for mechanism research in the method of the present application for esterification of alkylarenes and amides by polarity reversal of benzyl radicals;

[0032] Figure 3 Reaction mechanism of the method of the present application for esterification of alkylarenes and amides by polarity reversal of benzyl radicals. DETAILED DESCRIPTION

[0033] The above embodiments of the present application are described with reference to specific examples. Other advantages and effects of the present application will be readily appreciated by skilled in the art from the above disclosure. The present application can be carried out or applied in other different embodiments, and the details in the present disclosure can be modified or changed based on different views and applications without departing from the spirit of the present application. It should be noted that the figures provided in the following examples only schematically illustrate the basic concept of the present application, and the following examples and features in the examples can be combined with each other without conflict.

[0034] In the following examples, the structure correspondence of various compounds used is shown as follows:

[0035] (1) The structural formulae of compounds I-1~I-24 are as follows: .

[0036] (2) The structural formulae of compounds II-1~II-4 are as follows:

[0037] .

[0038] (3) The structural formulae of compounds III-1~III-27 are as follows:

[0039] .

[0040] Example 1

[0041] The benzylic radical polarity reversal method for esterification of alkylarenes and amides to prepare benzylic ester compound 1-([1,1'-biphenyl]-4-yl)ethyl formate (compound III-1) is as follows:

[0042] 0.3 mmol of compound I-1 and 5 mL of compound II-1 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n- butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction was completed, 55 mg (81% yield) of white solid (m.p. 114-117°C) was obtained by silica gel column chromatography, which was compound III-1.

[0043] In addition, 0.3 mmol of compound I-1 and 5 mL of compound II-3 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n-butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 5 h. After the reaction was completed, compound III-1 was separated by silica gel column chromatography with a yield of 30%.

[0044] 1 H NMR (600 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.62 – 7.57 (m, 4H),7.48 – 7.43 (m, 4H), 7.36 (t, J = 7.3 Hz, 1H), 6.07 (q, J = 6.4 Hz, 1H), 1.64(d, J = 6.6 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.37, 141.20, 140.68,139.89, 128.81, 127.44, 127.37, 127.14, 126.65, 72.02, 22.07; HRMS (ESI)calcd for C 15 H14 O2: [M+Na] + 249.0886, found 249.0890.

[0045] Example 2

[0046] The benzyl ester compound 1-([1,1'-biphenyl]-4-yl)propyl formate (compound III-2) was prepared by the method of esterification of alkylarene and amide by benzyl radical polarity reversal, and the specific preparation method is as follows:

[0047] 0.3 mmol of compound I-2 and 5 mL of compound II-1 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n-butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction was completed, 52 mg (72% yield) of white solid (m.p. 48~52℃) was obtained by silica gel column chromatography, which was compound III-2.

[0048] 1 H NMR (600 MHz, Chloroform-d) δ 8.15 (s, 1H), 7.60 (d, J = 7.5 Hz,4H), 7.46 – 7.43 (m, 4H), 7.36 (t, J = 7.3 Hz, 1H), 5.86 (t, J = 6.7 Hz, 1H),2.07 – 2.00 (m, 1H), 1.96 – 1.89 (m, 1H), 0.96 (t, J = 7.3 Hz, 3H); 13 C NMR(151 MHz, Chloroform-d) δ 160.51, 141.11, 140.71, 138.82, 128.81, 127.43,127.27, 127.14, 127.12, 77.09, 29.18, 9.92; HRMS (ESI) calcd for C 16 H 16 O2: [M+Na] + 263.1043, found 263.1039.

[0049] Example 3

[0050] The compound 1-([1,1'-biphenyl]-4-yl)butyl formate (compound III-3) was prepared by the method of esterification of alkylarene and amide through the radical polarity reversal of benzyl, and the specific preparation method is as shown below:

[0051] 0.3 mmol of compound I-3 and 5 mL of compound II-1 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n-butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction was completed, 58 mg (76% yield) of white solid (m.p. 47~49℃) was obtained by silica gel column chromatography, which was compound III-3.

[0052] 1 H NMR (600 MHz, Chloroform-d) δ 8.14 (s, 1H), 7.59 (d, J = 7.9 Hz,4H), 7.47 – 7.41 (m, 4H), 7.36 (t, J = 7.3 Hz, 1H), 5.93 (t, J = 6.9 Hz, 1H),2.04 – 1.96 (m, 1H), 1.87 – 1.81 (m, 1H), 1.47 – 1.39 (m, 1H), 1.38 – 1.32(m, 1H), 0.97 (t, J = 7.4 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.43,141.12, 140.72, 139.11, 128.78, 127.40, 127.26, 127.11, 127.06, 75.60, 38.21,18.74, 13.71; HRMS (ESI) calcd for C 17 H 18 O2: [M+Na] + 277.1199, found 277.1202。

[0053] Example 4

[0054] Benzyl ester compound 1-([1,1'-biphenyl]-4-yl)pentyl formate (III-4) was prepared by a method of esterification of alkylarene and amide by benzyl radical polarity reversal, and the specific preparation method is as shown below:

[0055] 0.3 mmol of compound I-4 and 5 mL of compound II-1 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n-butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction was completed, 58 mg (72% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-4.

[0056] 1 H NMR (600 MHz, Chloroform-d) δ 8.14 (s, 1H), 7.60 (d, J = 7.8 Hz,4H), 7.47 – 7.42 (m, 4H), 7.36 (t, J = 7.3 Hz, 1H), 5.92 (t, J = 6.9 Hz, 1H),2.05 – 1.95 (m, 1H), 1.92 – 1.84 (m, 1H), 1.43 – 1.34 (m, 3H), 1.33 – 1.27(m, 1H), 0.92 (t, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.50,141.10, 140.70, 139.13, 128.80, 127.42, 127.28, 127.13, 127.09, 75.86, 35.85,27.62, 22.40, 13.92; HRMS (ESI) calcd for C 18 H 20 O2: [M+Na] + 291.1356, found291.1346。

[0057] Example 5

[0058] The compound 1-(4'-fluoro-[1,1'-biphenyl]-4-yl)ethyl formate (compound III-5) was prepared by the method of esterification of alkylarene and amide through the radical polarity reversal of benzyl, and the specific preparation method is as follows:

[0059] 0.3 mmol of compound I-5 and 5 mL of compound II-1 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n-butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction was completed, 60 mg (82% yield) of white solid (m.p. 55~59℃) was obtained by silica gel column chromatography, which was compound III-5.

[0060] 1 H NMR (600 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.55 – 7.52 (m, J =7.1 Hz, 4H), 7.45 (d, J = 8.2 Hz, 2H), 7.13 (t, J = 8.7 Hz, 2H), 6.07 (q, J =6.5 Hz, 1H), 1.63 (d, J = 6.6 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 162.60(d, J = 246.7 Hz), 160.27, 140.19, 139.98, 136.80 (d, J = 3.2 Hz), 128.66 (d,J = 8.1 Hz), 127.21, 126.69, 115.66 (d, J = 21.5 Hz), 71.93, 22.03; 19 F NMR(565 MHz, Chloroform-d) δ -115.45. HRMS (ESI) calcd for C 15 H 13 FO2: [M+Na] + 267.0792, found 267.0795。

[0061] Example 6

[0062] Benzyl ester compound 1-(4'-chloro-[1,1'-biphenyl]-4-yl)ethyl formate (compound III-6) was prepared by the method of esterification of alkylarene and amide through the polarity reversal of benzyl radical, and the specific preparation method is as follows:

[0063] 0.3 mmol of compound I-6 and 5 mL of compound II-1 were added as reaction substrates into an electrochemical device (anode: graphite sheet with a size of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet with a size of 52 mm x 8 mm x 2 mm), 0.3 mmol of electrolyte n-butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction was completed, 60 mg (77% yield) of white solid (m.p. 75~80℃) was obtained by silica gel column chromatography, which was compound III-6.

[0064] 1 H NMR (600 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.55 (d, J = 8.2 Hz,2H), 7.50 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.5 Hz,2H), 6.06 (q, J = 6.6 Hz, 1H), 1.63 (d, J = 6.6 Hz, 3H); 13 C NMR (151 MHz,Chloroform-d) (151 MHz, Chloroform-d) δ 160.26, 140.33, 139.91, 139.11,133.61, 128.97, 128.34, 127.19, 126.74, 71.90, 22.05; HRMS (ESI) calcd forC 15 H 13 ClO2: [M+Na] + 283.0496, found 283.0496.

[0065] Example 7

[0066] Benzyl ester compound 1-(4'-chloro-[1,1'-biphenyl]-4-yl)ethyl formate (compound III-6) was prepared by the method of esterification of alkylarene and amide through the polarity reversal of benzyl radical, and the specific preparation method is as follows:

[0067] To an electrochemical device (anode: graphite sheet of 52 mm x 8 mm x 0.2 mm, cathode: graphite sheet of 52 mm x 8 mm x 2 mm) were added 0.3 mmol of compound I-7 and 5 mL of compound II-1 as reaction substrates, 0.3 mmol of electrolyte n- butyl ammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid, and the reaction was carried out at room temperature by passing a current of 15 mA for 4 h. After the reaction, 70 mg (75% yield) of white solid (m.p. 100~102°C) was obtained by silica gel column chromatography, which was compound III-7.

[0068] 1 H NMR (600 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.55 (t, J = 8.8 Hz,4H), 7.47 – 7.42 (m, 4H), 6.06 (q, J = 6.6 Hz, 1H), 1.63 (d, J = 6.6 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.24, 140.40, 139.92, 139.58, 131.92,128.68, 127.14, 126.75, 121.75, 71.89, 22.03; HRMS (ESI) calcd for C 15 H 13 BrO2:[M+Na] + 326.9991, found 326.9987.

[0069] Example 8

[0070] The benzyl ester compound 1-(4'-bromo-[1,1'-biphenyl]-4-yl)pentyl formate (III-8) was prepared by a method of esterification of alkylarenes and amides by radical polarity reversal at the benzyl position, and the specific preparation method is as shown below:

[0071] 0.3 mmol of compound I-8 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 78 mg (75% yield) of white solid (mp 47~49℃) was obtained by silica gel column chromatography, which was compound III-8.

[0072] 1 H NMR (600 MHz, Chloroform-d) δ 8.13 (s, 1H), 7.57 – 7.52 (m, 4H), 7.48 – 7.40 (m, 4H), 5.89 (t, J = 6.7 Hz, 1H), 2.03 – 1.97 (m, 1H), 1.89 –1.82 (m, 1H), 1.40 – 1.33 (m, 3H), 1.31 – 1.24 (m, 1H), 0.91 (t, J = 6.4 Hz,3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.45, 139.81, 139.62, 139.59, 131.93,128.69, 127.20, 127.07, 121.73, 75.76, 35.84, 27.59, 22.39, 13.92; HRMS (ESI)calcd for C 18 H 19 BrO2: [M+Na] + 369.0461, found 369.0458.

[0073] Example 9

[0074] The benzyl ester compound 1-(4'-bromo-[1,1'-biphenyl]-4-yl)heptyl formate (III-9) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0075] 0.3 mmol of compound I-9 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 79 mg (71% yield) of white solid (mp 49~51℃) was obtained by silica gel column chromatography, which was compound III-9.

[0076] 1 H NMR (600 MHz, Chloroform-d) δ 8.13 (s, 1H), 7.56 – 7.52 (m, 4H), 7.45 – 7.41 (m, 4H), 5.89 (t, J = 6.9 Hz, 1H), 2.03 – 1.95 (m, 1H), 1.88 –1.82 (m, 1H), 1.38 – 1.28 (m, 8H), 0.88 (t, J = 6.9 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.45, 139.81, 139.62, 139.59, 131.92, 128.69, 127.19,127.07, 121.72, 75.77, 36.13, 31.65, 28.95, 25.42, 22.56, 14.04; HRMS (ESI)calcd for C 20 H 23 BrO2: [M+Na] + 397.0774, found 397.0773.

[0077] Example 10

[0078] The benzyl ester compound 1-(4'-iodo-[1,1'-biphenyl]-4-yl)butyl formate (III-10) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0079] 0.3 mmol of compound I-10 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 82 mg (72% yield) of white solid (mp 43~45℃) was obtained by silica gel column chromatography, which was compound III-10.

[0080] 1 H NMR (600 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.3 Hz,2H), 5.90 (t, J = 6.9 Hz, 1H), 2.01 – 1.94 (m, 1H), 1.84 – 1.79 (m, 1H), 1.44– 1.38 (m, 1H), 1.35 – 1.31 (m, 1H), 0.95 (t, J = 7.4 Hz, 3H); 13 C NMR (151MHz, Chloroform-d) δ 160.37, 140.20, 139.89, 139.65, 137.90, 128.92, 127.18,127.00, 93.15, 75.49, 38.19, 18.70, 13.69; HRMS (ESI) calcd for C 17 H 17 IO2: [M+Na] + 403.0165, found 403.0165.

[0081] Example 11

[0082] The benzyl ester compound 1-(4'-cyano-[1,1'-biphenyl]-4-yl)butyl formate (III-11) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0083] 0.3 mmol of compound I-11 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 18 h at room temperature. After the reaction was completed, 50 mg (60% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-11.

[0084] 1 H NMR (600 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 7.9 Hz, 2H), 7.46 (d, J = 7.9 Hz,2H), 5.91 (t, J = 6.9 Hz, 1H), 2.01 – 1.95 (m, 1H), 1.85 – 1.79 (m, 1H), 1.46– 1.38 (m, 1H), 1.34 – 1.30 (m, 1H), 0.95 (t, J = 7.4 Hz, 3H); 13 C NMR (151MHz, Chloroform-d) δ 160.39, 145.11, 140.76, 138.94, 132.63, 127.69, 127.39,127.34, 118.85, 111.11, 75.35, 38.21, 18.70, 13.72; HRMS (ESI) calcd forC 18 H 17 NO2: [M+Na] + 302.1151 was found to be 302.1154.

[0085] Example 12

[0086] The benzyl ester compound 1-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)ethyl formate (III-12) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0087] 0.3 mmol of compound I-12 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 12 h at room temperature. After the reaction was completed, 46 mg (53% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-12.

[0088] 1 H NMR (600 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.71 – 7.66 (m, 4H), 7.60 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 6.07 (q, J = 6.6 Hz, 1H),1.64 (d, J = 6.6 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.22, 144.17,141.01, 139.65, 129.59 (q, J = 32.5 Hz), 127.49, 127.38, 126.80, 125.74 (q, J= 3.7 Hz), 71.83, 22.05; 19 F NMR (565 MHz, Chloroform-d) δ -62.46; HRMS (ESI)calcd for C 16 H 13 F3O2: [M+Na] + 317.0760, found 317.0760.

[0089] Example 13

[0090] The benzyl ester compound 1-(4'-formyl-[1,1'-biphenyl]-4-yl)ethyl formate (III-13) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0091] 0.3 mmol of compound I-13 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 24 mg (32% yield) of white solid (mp 56~58℃) was obtained by silica gel column chromatography, which was compound III-13.

[0092] 1 H NMR (600 MHz, Chloroform-d) δ 10.06 (s, 1H), 8.12 (s, 1H), 7.96 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 7.49(d, J = 8.2 Hz, 2H), 6.07 (q, J = 6.5 Hz, 1H), 1.63 (d, J = 6.6 Hz, 3H); 13 CNMR (151 MHz, Chloroform-d) δ 191.72, 160.22, 146.59, 141.30, 139.62, 135.42,130.26, 127.65, 127.60, 126.82, 71.81, 22.07; HRMS (ESI) calcd for C 16 H 14 O3: [M+Na] + 277.0835, found 277.0840.

[0093] Example 14

[0094] The benzyl ester compound 1-(4'-acetyl-[1,1'-biphenyl]-4-yl)propyl formate (III-14) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0095] 0.3 mmol of compound I-14 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 7 h at room temperature. After the reaction was completed, 60 mg (75% yield) of white solid (mp 72~75℃) was obtained by silica gel column chromatography, which was compound III-14.

[0096] 1 H NMR (600 MHz, Chloroform-d) δ 8.14 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 8.2 Hz,2H), 5.84 (t, J = 6.9 Hz, 1H), 2.63 (s, 3H), 2.05 – 1.97 (m, 1H), 1.94 – 1.87(m, 1H), 0.95 (t, J = 7.4 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 197.56,160.38, 145.18, 139.94, 139.69, 136.07, 128.92, 127.38, 127.23, 127.17,76.90, 29.16, 26.57, 9.80; HRMS (ESI) calcd for C 18 H 18 O3: [M+Na] + 305.1148, found 305.1146.

[0097] Example 15

[0098] The benzyl ester compound 4'-(1-(formyloxy)butyl)-[1,1'-biphenyl]-4-carboxylic acid (III-15) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0099] 0.3 mmol of compound I-15 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 5 h at room temperature. After the reaction was completed, 50 mg (56% yield) of white solid (mp 145~150℃) was obtained by silica gel column chromatography, which was compound III-15.

[0100] 1 H NMR (600 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 8.14 (s,1H), 7.69 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.2 Hz,2H), 5.93 (t, J = 6.9 Hz, 1H), 2.03 – 1.97 (m, 1H), 1.86 – 1.80 (m, 1H), 1.46 – 1.40 (m, 1H), 1.38 – 1.32 (m, 1H), 0.96 (t, J = 7.4 Hz, 3H); 13 C NMR (151MHz, Chloroform-d) δ 171.40, 160.39, 145.95, 140.30, 139.71, 130.77, 128.20,127.45, 127.21, 127.11, 75.46, 38.21, 18.68, 13.67; HRMS (ESI) calcd forC 18 H 18 O4: [M+Na] + 321.1097, found 327.1106.

[0101] Example 16

[0102] The benzyl ester compound ethyl 4'-(1-(formyloxy)ethyl)-[1,1'-biphenyl]-4-carboxylate (III-16) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0103] 0.3 mmol of compound I-16 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 10 h at room temperature. After the reaction was completed, 55 mg (62% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-16.

[0104] 1 H NMR (600 MHz, Chloroform-d) δ 8.12 (s, 2H), 8.10 (s, 1H), 7.64 (d,J = 8.1 Hz, 2H), 7.62 (d, J = 7.9 Hz, 2H), 7.47 (d, J = 7.7 Hz, 2H), 6.06 (q,J = 6.4 Hz, 1H), 4.40 (q, J = 7.0 Hz, 2H), 1.63 (d, J = 6.5 Hz, 3H), 1.41 (t,J = 6.9 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 166.44, 160.26, 144.92,140.87, 139.98, 130.09, 129.50, 127.50, 126.96, 126.74, 71.87, 60.97, 22.07,14.34; HRMS (ESI) calcd for C 18 H 18 O4: [M+Na] + 321.1097, found 327.1103.

[0105] Example 17

[0106] The benzyl ester compound 1-(4''-cyano-[1,1':4',1''-terphenyl]-4-yl)pentyl formate (III-17) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0107] 0.3 mmol of compound I-17 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 40 mg (36% yield) of white solid (mp 105~110℃) was obtained by silica gel column chromatography, which was compound III-17.

[0108] 1 H NMR (600 MHz, Chloroform-d) δ 8.14 (s, 1H), 7.77 – 7.60 (m, 10H), 7.45 (d, J = 8.1 Hz, 2H), 5.91 (t, J = 7.0 Hz, 1H), 2.04 – 1.97 (m, 1H), 1.91– 1.84 (m, 1H), 1.40 – 1.25 (m, 4H), 0.91 (t, J = 7.1 Hz, 3H); 13 C NMR (151MHz, Chloroform-d) δ 160.41, 145.11, 141.04, 140.02, 139.70, 138.12, 132.64,127.76, 127.62, 127.57, 127.20, 127.19, 118.85, 111.06, 75.78, 35.83, 27.58,22.36, 13.86; HRMS (ESI) calcd for C 25 H 23 NO2: [M+Na] + 369.1729, found 369.1729.

[0109] Example 18

[0110] The benzyl ester compound 1-(2,3'',4'',5''-tetrafluoro-[1,1':4',1''-terphenyl]-4-yl)propyl formate (III-18) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0111] 0.3 mmol of compound I-18 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 5 h at room temperature. After the reaction was completed, 85 mg (73% yield) of white solid (mp 85~90℃) was obtained by silica gel column chromatography, which was compound III-18.

[0112] 1 H NMR (600 MHz, Chloroform-d) δ 8.15 (s, 1H), 7.60 (d, J = 8.2 Hz,2H), 7.47 – 7.44 (m, 4H), 7.41 – 7.37 (m, 1H), 7.25 – 7.21 (m, 2H), 5.85 (t,J = 6.9 Hz, 1H), 2.07 – 1.98 (m, 1H), 1.97 – 1.87 (m, 1H), 0.96 (t, J = 7.4Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) 160.63, 160.35, 158.98, 152.08,152.05, 152.02, 151.99, 150.43, 150.40, 150.36, 150.33, 143.07, 143.02,140.00, 138.83, 138.82, 130.45, 130.43, 127.30, 127.08, 123.17, 123.15,114.91, 114.75, 113.16, 113.14, 113.11, 113.05, 113.02, 112.99, 76.87, 29.15, 9.78; 19 F NMR (565 MHz, Chloroform-d) δ -117.32, -134.38 (d, J = 20.7 Hz), -161.43 (t, J = 21.4 Hz); HRMS (ESI) calcd for C 22 H 16 F4O2: [M+Na] + 411.0979, found 411.0977.

[0113] Example 19

[0114] The benzyl ester compound [1,1'-biphenyl]-4-ylmethyl formate (III-19) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0115] 0.3 mmol of compound I-19 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 49 mg (77% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-19.

[0116] 1 H NMR (600 MHz, Chloroform-d) δ 8.17 (s, 1H), 7.63 – 7.56 (m, 4H), 7.48 – 7.43 (m, 4H), 7.37 (t, J = 7.4 Hz, 1H), 5.26 (s, 2H); 13 C NMR (151 MHz, Chloroform-d) δ 160.74, 141.56, 140.60, 134.23, 128.84, 128.83, 127.53,127.41, 127.15, 65.44.

[0117] Example 20

[0118] The benzyl ester compound 4-phenoxybenzyl formate (III-20) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0119] 0.3 mmol of compound I-20 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 1.5 h at room temperature. After the reaction was completed, 44 mg (65% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-20.

[0120] 1 H NMR (600 MHz, Chloroform-d) δ 8.14 (s, 1H), 7.37 – 7.33 (m, 4H), 7.13 (t, J = 7.4 Hz, 1H), 7.04 – 6.99 (m, 4H), 5.18 (s, 2H); 13 C NMR (151 MHz,Chloroform-d) δ 160.71, 157.73, 156.84, 130.20, 129.92, 129.81, 123.60,119.19, 118.71, 65.26; HRMS (ESI) calcd for C 14 H 12 O3: [M+Na] + 251.0679, found251.0680.

[0121] Example 21

[0122] The benzyl ester compound 4-methoxybenzyl formate (III-21) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0123] 0.3 mmol of compound I-21 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 1.5 h at room temperature. After the reaction was completed, 28 mg (56% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-21.

[0124] 1 H NMR (600 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.31 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 5.14 (s, 2H), 3.81 (s, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.90, 159.93, 130.28, 127.45, 114.11, 65.58, 55.35.

[0125] Example 22

[0126] 2-methoxybenzyl formate (compound III-22) was prepared by esterification of alkyl aromatics and amides via benzylic radical polarity reversal. The specific preparation method is shown below:

[0127] 0.3 mmol of compound I-22 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 1.5 h at room temperature. After the reaction was completed, 32 mg (65% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-22.

[0128] 1 H NMR (600 MHz, Chloroform-d) δ 8.15 (s, 1H), 7.37 – 7.29 (m, 2H), 6.96 (t, J = 7.2 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 5.27 (s, 2H), 3.86 (s,3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.94, 157.69, 130.08, 129.97, 123.56, 120.51, 110.58, 61.34, 55.46.

[0129] Example 23

[0130] The benzyl ester compound 3,4,5-trimethoxybenzyl formate (III-23) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. Its structural formula is as follows: The specific preparation method is shown below:

[0131] 0.3 mmol of compound I-23 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 32 mg (47% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-23.

[0132] 1 H NMR (600 MHz, Chloroform-d) δ 8.15 (s, 1H), 6.60 (s, 2H), 5.13 (s, 2H), 3.87 (s, 6H), 3.85 (s, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 160.66,153.45, 138.39, 130.70, 105.74, 65.89, 60.82, 56.20; HRMS (ESI) calcd forC 11 H 14 O5: [M+Na] + 249.0733, found 249.0734.

[0133] Example 24

[0134] 1-([1,1'-biphenyl]-4-yl)ethyl acetate (III-24), a benzyl ester compound, was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. Its structural formula is as follows: The specific preparation method is shown below:

[0135] 0.3 mmol of compound I-1 and 5 mL of compound II-2 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 28 h at room temperature. After the reaction was completed, 17 mg (21% yield) of white solid (mp 35 – 36 °C) was obtained by silica gel column chromatography, which was compound III-24.

[0136] In addition, 0.3 mmol of compound I-1 and 5 mL of compound II-4 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet), along with 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid. The reaction was carried out at 15 mA for 5 h at room temperature. After the reaction was completed, compound III-24 was separated by silica gel column chromatography in a yield of 5%.

[0137] 1 H NMR (600 MHz, Chloroform-d) δ 7.58 (d, J = 7.7 Hz, 4H), 7.46 –7.41 (m, 4H), 7.35 (t, J = 7.2 Hz, 1H), 5.94 (q, J = 6.4 Hz, 1H), 2.10 (s,3H), 1.58 (d, J = 6.5 Hz, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 170.35,140.90, 140.79, 140.68, 128.77, 127.35, 127.28, 127.13, 126.58, 72.10, 22.14,21.37.

[0138] Example 25

[0139] 4-methoxybenzyl acetate (III-25), a benzyl ester compound, was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. Its structural formula is as follows: The specific preparation method is shown below:

[0140] 0.3 mmol of compound I-21 and 5 mL of compound II-2 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 2 h at room temperature. After the reaction was completed, 6 mg (10% yield) of colorless oil was obtained by silica gel column chromatography, which was compound III-25.

[0141] 1 H NMR (600 MHz, Chloroform-d) δ 7.29 (d, J = 8.6 Hz, 2H), 6.89 (d, J= 8.7 Hz, 2H), 5.04 (s, 2H), 3.81 (s, 3H), 2.07 (s, 3H); 13 C NMR (151 MHz, Chloroform-d) δ 170.87, 159.71, 130.05, 128.18, 114.00, 66.08, 55.28, 20.99.

[0142] Example 26

[0143] The benzyl ester compound [1,1'-biphenyl]-4,4'-diylbis(ethane-1,1-diyl) diformate (III-26) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0144] 0.3 mmol of compound I-24 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 3 h at room temperature. After the reaction was completed, 53 mg (59% yield) of white solid (mp 125~130℃) was obtained by silica gel column chromatography, which was compound III-26.

[0145] 1H NMR (400 MHz, Chloroform-d) δ 8.11 (s, 2H), 7.57 (d, J = 8.2 Hz, 4H), 7.44 (d, J = 8.2 Hz, 4H), 6.05 (q, J = 6.6 Hz, 2H), 1.62 (d, J = 6.6 Hz,6H); 13 C NMR (101 MHz, Chloroform-d) δ 160.34, 140.58, 140.10, 127.33, 126.68,71.96, 22.06; HRMS (ESI) calcd for C 18 H 18 O4: [M+Na] + 321.1097, found 321.1091.

[0146] Example 27

[0147] The benzyl ester compound 1-(4'-ethyl-[1,1'-biphenyl]-4-yl)ethyl formate (III-27) was prepared by esterification of alkyl aromatics and amides via benzyl radical polarity reversal. The specific preparation method is shown below:

[0148] 0.3 mmol of compound I-24 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical apparatus (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet). 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added. The reaction was carried out at 15 mA for 1.5 h at room temperature. After the reaction was completed, 48 mg (60% yield) of white solid (mp 40~42℃) was obtained by silica gel column chromatography, which was compound III-27.

[0149] 1H NMR (400 MHz, Chloroform-d) δ 8.12 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.2 Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz,2H), 6.06 (q, J = 6.6 Hz, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.63 (d, J = 6.6 Hz,3H), 1.28 (t, J = 7.6 Hz, 3H); 13 C NMR (101 MHz, Chloroform-d) δ 160.36,143.60, 141.16, 139.53, 138.03, 128.31, 127.18, 127.04, 126.61, 72.05, 28.51,22.02, 15.50; HRMS (ESI) calcd for C 17 H 18 O2: [M+Na] + 277.1199, found 277.1190.

[0150] Example 28

[0151] The effects of different reaction conditions on the esterification of alkyl aromatics and amides via benzylic radical polarity reversal are investigated as follows:

[0152] The preparation method in Example 1 was used as the basic reaction: 0.3 mmol of compound I-1 and 5 mL of compound II-1 were added as reaction substrates to an electrochemical device (anode: 52 mm × 8 mm × 0.2 mm graphite sheet, cathode: 52 mm × 8 mm × 2 mm graphite sheet), 0.3 mmol of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) and 0.5 mmol of trifluoroacetic acid were added, and the reaction was carried out at 15 mA for 4 h at room temperature. After the reaction was completed, 55 mg (81% yield) of white solid (mp 114~117℃) was obtained by silica gel column chromatography, which was compound III-1.

[0153] 1. Effect of different electrolytes on the yield of benzyl ester compounds:

[0154] The electrolytes in the above basic reaction were replaced with tetrabutylammonium tetrafluoroborate (nBu4NBF4) and tetrabutylammonium chloride (nBu4NCl), tetrabutylammonium bromide (nBu4NBr), potassium iodide, sodium bromide, tetrabutylammonium hexafluorophosphate (nBu4NPF6), and tetrabutylammonium perchlorate (nBu4NClO4), respectively, while keeping other conditions unchanged. The yields of compound III-1 under different electrolyte reactions were obtained, and the results are shown in Table 1.

[0155] Table 1. Effect of different electrolytes on the yield of compound III-1

[0156]

[0157] Therefore, in the method of esterification of alkyl aromatics and amides by reversing the polarity of benzylic radicals in this invention, any one of tetrabutylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, or tetrabutylammonium perchlorate can be used as the electrolyte to prepare the target product.

[0158] 2. Effect of different amounts of electrolyte added on the yield of benzyl ester compounds:

[0159] The amount of electrolyte tetrabutylammonium tetrafluoroborate (nBu4NBF4) added in the above basic reaction was adjusted from 0.5 mmol to 0.03 mmol, 0.15 mmol, 0.45 mmol, 0.6 mmol, 0.9 mmol and 1.2 mmol, respectively, while keeping other conditions unchanged. The yields of compound III-1 under different additive reactions were obtained, and the results are shown in Table 2.

[0160] Table 2 Yields of III-1 with different amounts of electrolyte added

[0161]

[0162] Therefore, in the method of esterification of alkyl aromatics and amides by polarity reversal of benzyl radicals in this invention, the amount of electrolyte added has a weak effect on the reaction. The target product can be prepared in the range of 0.1 to 4 times the molar amount of compound I, and the yield of benzyl ester compounds is above 22%.

[0163] 3. Effect of different additives on the yield of benzyl ester compounds:

[0164] The additive trifluoroacetic acid added in the above basic reaction was replaced with 4-cyanopyridine, 2,6-dimethylpyridine, hexafluoroisopropanol, copper acetate, copper bromide, nickel diacetylacetonate, silver carbonate, copper sulfate, copper trifluoromethanesulfonate, or copper tetraacetonitrile tetrafluoroborate, respectively, while keeping other conditions unchanged. The yields of compound III-1 under different additives were obtained, and the results are shown in Table 3.

[0165] Table 3. Yields of benzyl ester compound III-1 under different additive reactions

[0166]

[0167] Therefore, in the method of esterification of alkyl aromatics and amides by reversing the polarity of benzyl radicals in this invention, any one of copper acetate, nickel diacetylacetonate, silver carbonate, copper sulfate, copper trifluoromethanesulfonate, copper tetraacetonitrile tetrafluoroborate, and trifluoroacetic acid can be used as an additive to prepare benzyl ester compounds.

[0168] 4. Effect of different amounts of additives on the yield of benzyl ester compounds:

[0169] The amount of trifluoroacetic acid added in the above basic reaction was replaced with 0.1 mmol, 0.3 mmol and 1.0 mmol respectively, while keeping other conditions unchanged. The yields of compound III-1 with different amounts of trifluoroacetic acid were obtained, and the results are shown in Table 4.

[0170] Table 4. Yields of benzyl ester compound III-1 at different amounts of trifluoroacetic acid.

[0171]

[0172] Therefore, in the method of esterification of alkyl aromatics and amides by polarity reversal of benzyl radicals in this invention, the amount of additive has a weak effect on the reaction yield. When the molar ratio of compound I-1 to additive is in the range of 0.3:0.1~1.2, the yield of benzyl ester compounds can exceed 50%.

[0173] 5. The effect of the magnitude of the current applied during the reaction on the yield of benzyl ester compounds:

[0174] By replacing the current of 15 mA in the above basic reaction with 0 mA, 1 mA, 2 mA, 4 mA, 8 mA, 12 mA and 16 mA respectively, the yield of compound III-1 under different currents was obtained, and the results are shown in Table 5.

[0175] Table 5 Effect of different currents on the yield of compound III-1

[0176]

[0177] Therefore, it can be seen that in the method of esterification of alkyl aromatics and amides by reversing the polarity of benzylic radicals in the present invention, the target product can be prepared by reacting within the above-mentioned current range (1~16mA).

[0178] 6. The effect of different electrode materials on the yield of benzyl esters in the electrochemical device:

[0179] When the electrode material (a graphite sheet with dimensions of 52 mm x 8 mm x 2 mm) in the electrochemical device of the above basic reaction was replaced with an electrode material of other materials of the same dimensions, while keeping other conditions unchanged, the yields of compound III-1 under different currents were obtained, and the results are shown in Table 6.

[0180] Table 6. Effect of different electrode materials on the yield of III-1 in the electrochemical device

[0181]

[0182] Therefore, in the method of esterification of alkyl aromatics and amides by reversing the polarity of benzylic free radicals in the present invention, the anode material in the electrochemical device can be any one of graphite sheet, platinum sheet (Pt), carbon felt or glassy carbon electrode, and the cathode material can be any one of carbon graphite sheet, platinum sheet, stainless steel sheet or nickel foam.

[0183] 7. Effect of different reactant addition amounts on the yield of benzyl ester compounds:

[0184] When the ratio of I-1 and II-1 in the above basic reaction was changed while other conditions remained unchanged, the yields of compound III-1 with different amounts of reactants were obtained, and the results are shown in Table 7.

[0185] Table 7 Effect of different reactant addition amounts on the yield of III-1

[0186]

[0187] Therefore, in the method of esterification of alkyl aromatics and amides by reversing the polarity of benzyl radicals in this invention, as long as the amount of compound II-1 added is sufficient to dissolve compound I-1, additives and electrolytes in the reaction, benzyl ester compounds can be obtained.

[0188] Example 28

[0189] The general reaction formula of the present invention is as follows:

[0190] .

[0191] To investigate the reaction mechanism of the method for esterification of alkyl aromatics and amides via benzylic radical polarity reversal in this invention, the following studies were conducted:

[0192] 1. Free Radical Scavenging Experiment: To further investigate the reaction mechanism, under standard conditions, twice the equivalent of the free radical scavengers 2,2,6,6-tetramethylpiperidine oxide (TEMPO) and 2,6-di-tert-butyl-4-methylphenol (BHT) were added to the reaction process of Examples 1 and 21, respectively. After the reaction proceeded for a period of time, a small amount of the reaction solution was taken for high-resolution mass spectrometry detection. The addition of the two additives completely inhibited the formation of the target product, as detailed below. Figure 1 As shown.

[0193] 2. Isotope Labeling Experiment: To further determine the origin of each element in the ester moiety of the reaction product, an isotope labeling experiment was conducted. Each component in Example 1 was replaced with an isotope reagent. After the reaction was complete, the target product III-1 was obtained. High-resolution mass spectrometry detected that the hydrogen at the end of the ester moiety originated from the hydrogen in the acyl moiety of compound II-1, and the carbonyl oxygen in the ester moiety originated from water. Deuterated water and deuterated trifluoroacetic acid had no effect on the product composition, thus ruling out their influence. Specifically, as follows... Figure 2 As shown.

[0194] 3. Mechanism Analysis: Taking the reaction described in Example 1 as an example, based on the above mechanism exploration experiments, the following reaction mechanism is proposed: First, substrate I-1 undergoes single-electron oxidation at the anode to generate a free radical cation, which then loses a proton to generate a benzylic free radical intermediate M-1. This intermediate is then further oxidized to a carbocation M-2, which is subsequently nucleophilically attacked by compound II-1 to generate an imine intermediate M-3. Following hydrolysis through intermediates M-4 and M-5, the target product, a benzylic ester compound III-1, is finally generated. Figure 3 As shown.

[0195] In summary, this invention discloses a method for esterifying alkyl aromatics and amides via benzylic radical polarity reversal, belonging to the field of compound preparation technology. This invention leverages the advantages of electrochemical anodic oxidation to anolylate the benzylic C(sp) group. 3The amide attacks the carbocation to form an imine intermediate, which is then hydrolyzed to break the C–N bond, thus achieving the synthesis of benzyl esters. This invention avoids the use of transition metals, high temperatures, high pressures, and stoichiometric amounts of hazardous oxidizing and reducing agents. It exhibits good functional group tolerance, expands the range of substrates, and provides a supplementary approach for the synthesis of benzyl esters under mild conditions. Compared with existing methods, the synthetic method of this invention is more economical and direct.

[0196] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A process for esterification of an alkylarene and an amide by benzyl radical polarity inversion, characterized in that, The reaction formula of the method is as follows: ， wherein R 1 is any one of hydrogen, fluorine, chlorine, bromine, iodine, cyano, trifluoromethyl, formyl, acetyl, carboxyl or ester, R 2 is any one of hydrogen, methyl, ethyl, n-propyl, n-butyl or n-hexyl, R 3 is any one of hydrogen or methyl, R 4 is any one of methyl or ethyl; The electrolyte is any one of n-tetrabutylammonium tetrafluoroborate, n-tetrabutylammonium hexafluorophosphate or n-tetrabutylammonium perchlorate; The additive is any one of trifluoroacetic acid, copper acetate, nickel diacetylacetone, silver carbonate, copper sulfate, copper triflate or copper tetraacetonitrile tetrafluoroborate.

2. The method of claim 1, wherein, The compound I is any one of I-1~I-15, I-17, I-19, and the corresponding chemical structural formula is as follows: 。 3. The method of claim 1, wherein, The compound II includes any one of II-1~II-4, and the corresponding chemical structural formula is as follows: 。 4. The method of claim 1, wherein, The compound III includes any one of III-1~III-15, III-17, III-19 and III-24, and the corresponding chemical structural formula is as follows: 。 5. The method of claim 1, wherein, The anode material in the electrochemical device includes any one of graphite sheet, platinum sheet, carbon felt or glassy carbon electrode; The cathode material in the electrochemical device includes any one of graphite sheet, platinum sheet, stainless steel sheet or nickel foam.

6. The method of claim 1, wherein, The current during the power-on process of the electrochemical device is 1~16 mA.

7. The method according to any one of claims 1 to 6, characterized in that, The method specifically includes the following steps: Compound I and compound II are added to the electrochemical device as reaction substrates, an additive and an electrolyte are added, stirring is performed to dissolve them, power-on is performed to react, and after the reaction is completed, the target product compound III is separated, so that the benzyl position of compound I is esterified.

8. The method of claim 7, wherein, The volume of the added compound II is greater than or equal to the volume of the compound II capable of dissolving the added compound I, additive and electrolyte.

9. The method of claim 7, wherein, The molar ratio of the compound I to the additive is 3:1~12; The molar ratio of the compound I to the electrolyte is 1:0.1~4.

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