Method for preparing benzyl carboxylic acid through electric carboxylation reaction of benzyl carbon-hydrogen bonds and application

Abstract

The invention discloses a method for preparing benzyl carboxylic acid through an electro-carboxylation reaction of a benzyl carbon-hydrogen bond and application of the benzyl carboxylic acid. The method comprises the following steps: in a CO2 atmosphere, mixing a substrate containing a benzyl carbon-hydrogen bond, a supporting electrolyte and an optional additive in a solvent, carrying out an electro-carboxylation reaction under a power-on condition, and carrying out an esterification reaction on a benzyl carboxylic acid compound prepared after an optional electro-carboxylation reaction. By adopting an electrochemical synthesis method, ring-opening carboxylation of reaction substrates of first-stage, second-stage and third-stage C-H bonds and carbon dioxide can be realized. The electrochemical synthesis method has the characteristics of mild reaction conditions, cleanness, greenness and simplicity in reaction operation.

Description

Technical Field

[0001] The present invention relates to the technical field of organic chemistry. Further, it relates to a method for preparing benzylic carboxylic acids by electrocarboxylation of benzylic C-H bonds, the prepared benzylic carboxylic acids, and their applications. Background Art

[0002] As an ideal C1 feedstock, carbon dioxide has attracted much attention for its potential in the conversion to high-value carboxylic acids. With the revival of electrosynthesis technology, the use of traceless electrons to achieve high-efficiency carbon dioxide utilization provides broad prospects for the production of high-value-added carboxylic acids. Among them, benzylic carboxylic acids have attracted great interest from researchers due to their wide presence in various drugs and bioactive molecules. In recent years, the research on electrochemical benzylic carboxylic acid synthesis has mainly focused on the carboxylation reaction of (pseudo)halides. However, the low atom economy severely limits its further application. Direct electrochemical benzylic C-H carboxylation reaction provides a highly atom-economic, efficient, and economical synthetic route, although the challenges brought by the inherent inertness of benzylic C-H bonds and carbon dioxide still need to be urgently solved. Early studies mainly relied on deprotonation reactions promoted by strong bases, followed by nucleophilic attack of carbon dioxide to achieve carboxylation. In recent years, photocarboxylation of benzylic C-H bonds has provided more possibilities for the synthesis of benzylic carboxylic acids through a photoredox catalytic system, which can be carried out in the presence of different photocatalysts, transition metals, or hydrogen atom transfer reagents.

[0003] However, the general methods for the carboxylation of primary, secondary, and tertiary C-H bonds with carbon dioxide are still not mature enough and urgently need further exploration and development. Summary of the Invention

[0004] To solve the problems in the prior art, the present invention provides a method for preparing benzylic carboxylic acids by electrocarboxylation of benzylic C-H bonds, the prepared benzylic carboxylic acids, and their applications. The present invention adopts an electrochemical synthesis method to achieve the carboxylation reaction of reaction substrates containing primary, secondary, and tertiary C-H bonds with carbon dioxide. And this electrochemical synthesis method has the characteristics of mild reaction conditions, clean and green, and simple reaction operation.

[0005] The first aspect of the present invention is to provide a method for electrocarboxylation of benzylic C-H bonds, comprising the following steps: in a CO2 atmosphere, after mixing a substrate containing benzylic C-H bonds, a supporting electrolyte, and an optional additive in a solvent, an electrocarboxylation reaction occurs under an energized condition, and optionally, a methylation reaction is carried out on the benzylic carboxylic acid compound obtained after the electrocarboxylation reaction.

[0006] As a preferred embodiment, the substrate containing benzylic C-H bonds has the following general structural formula:

[0007]

[0008] In Formula 1, is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;

[0009] Said R 1 is selected from hydrogen, alkyl, cyano, halogen atom, alkoxy, haloalkyl, ester group, phenoxy; R 2 , R 3 are each independently selected from hydrogen, alkyl, substituted or unsubstituted aryl, alkylphenyl;

[0010] In Formula 2, is selected from polycyclic aromatic hydrocarbon group, benzocycloalkenyl.

[0011] As a preferred embodiment, in Formula 1, is When; said R 1 is selected from hydrogen, alkyl, cyano, halogen atom;

[0012] Said R 1 is selected from hydrogen, alkyl, cyano, halogen atom, alkoxy, ester group; R 2 , R 3 are each independently selected from hydrogen, C1-C10 alkyl, substituted or unsubstituted phenyl, C7-C12 alkylphenyl; and / or,

[0013] In Formula 2, is n is an integer from 1 to 5;

[0014] Preferably,

[0015] Said Formula 1 and Formula 2 are selected from at least one of the following compounds:

[0016]

[0017] As a preferred embodiment, in Formula 1, is When; said R 1 is selected from hydrogen, alkyl, alkoxy, cyano, halogen atom, ester group; R 2 , R 3 are each independently selected from C1-C10 alkyl, phenyl;

[0018] Preferably, R 2 , R 3 are each independently selected from C1-C5 alkyl, phenyl;

[0019] More preferably, said Formula 1 is selected from at least one of the following compounds:

[0020]

[0021] As a preferred embodiment, in Formula 1, is when;

[0022] said R 1 is selected from hydrogen, alkyl, phenoxy, alkoxy, haloalkyl, cyano, halogen atom, ester group; R 2 , R 3 are each independently selected from hydrogen, C1-C10 alkyl;

[0023] Preferably,

[0024] Formula 1 is selected from at least one of the following compounds:

[0025]

[0026]

[0027] As a preferred embodiment, the supporting electrolyte is selected from at least one of alkyl salts; preferably, the alkyl salt is selected from at least one of tetraalkylammonium salts; more preferably, the tetraalkylammonium salt is selected from at least one of tetrabutylammonium hexafluorophosphate, tetrabutylammonium bromide, tetrabutylammonium perchlorate, tetrabutylammonium tetrafluoroborate; and / or,

[0028] The molar ratio of the supporting electrolyte to the substrate containing a benzylic C-H bond is (0.5-2):1; and / or;

[0029] When an additive is included, the additive is selected from at least one of NaI, NaBr, CoBr2, NH4I or n Bu4NI; and / or, the molar ratio of the additive to the substrate containing a benzylic C-H bond is (0.05-1):1; and / or;

[0030] The solvent is selected from at least one of halogenated hydrocarbon solvents; and / or,

[0031] The concentration of the substrate containing a benzylic C-H bond in the solvent is 0.05-0.4 mol / L;

[0032] Preferably, the concentration of the substrate containing a benzylic C-H bond in the solvent is 0.1-0.3 mol / L; and / or,

[0033] The organic solvent is selected from at least one of dichloroethane and dichloromethane.

[0034] As a preferred embodiment, during the reaction, a constant current is passed, preferably,

[0035] The constant current is 5-80 mA; and / or,

[0036] The reaction time is 3 - 40 h; and / or,

[0037] The reaction temperature is 0 - 50 °C; and / or,

[0038] More preferably,

[0039] The constant current is 10 - 20 mA; and / or,

[0040] The reaction time is 8 - 12 h; and / or,

[0041] The reaction temperature is 18 - 25 °C; and / or,

[0042] During the reaction, among the electrodes used, the cathode material is selected from graphite felt, platinum sheet or nickel sheet; the anode material is selected from graphite felt, platinum sheet or nickel sheet; and / or,

[0043] The post-treatment includes acidification treatment. Preferably, during the acidification treatment, the concentration of the acid used is 1 - 2 mol / L; the acid used is hydrochloric acid.

[0044] The post-treatment also includes directly extracting and concentrating to obtain a crude product; steps of purifying the obtained crude product; or the post-treatment includes directly extracting and concentrating to obtain a crude product; performing a methylation reaction on the obtained crude product, preparing it into a carboxylic acid methyl ester and then performing purification and other steps.

[0045] The second aspect of the present invention is to provide a benzylic carboxylic acid compound prepared by the method described in the first aspect of the present invention; preferably,

[0046] The benzylic carboxylic acid compound has the following general structural formula:

[0047]

[0048] In Formula 3, is selected from aryl or heteroaryl; -COOX is -COOH or -COOR 4 R 4 is preferably alkyl;

[0049] The R 1 is selected from hydrogen, alkyl, cyano, halogen atom, alkoxy, haloalkyl, ester group, phenoxy; R 2 R 3 are each independently selected from hydrogen, alkyl, substituted or unsubstituted aryl, alkylphenyl;

[0050] In Formula 4, is selected from polycyclic aromatic hydrocarbon group, benzocycloalkenyl group.

[0051] As a preferred embodiment, the benzylic carboxylic acid compound is selected from at least one of the following compounds:

[0052]

[0053]

[0054] The third aspect of the present invention is to provide an application of the method as described in the first aspect of the present invention in constructing molecules containing benzylic carboxylic acids; preferably in constructing pharmaceutical molecules containing benzylic carboxylic acids.

[0055] More preferably, the pharmaceutical molecules containing benzylic carboxylic acids are selected from at least one of the following compounds:

[0056]

[0057] The reaction mechanism of the present invention is as follows:

[0058]

[0059] DCE is prone to obtaining an electron to form a chloride anion, which is then oxidized at the anode. The hydrogen atom transfer process between the chlorine radical and the substrate I containing a benzylic C-H bond generates a benzyl carbon radical II and HCl. II is oxidized to form III, which couples with the chloride anion to form benzyl chloride. The in-situ generated IV then loses a chloride ion and obtains an electron to form V. The final product is obtained after the nucleophilic attack of CO2. In addition, the iodide anion generated by the ionization of NaI can also be oxidized at the anode.

[0060] In the present invention, some carboxylic acids are not easily separated and purified, and the generated carboxylic acids are further converted into methyl esters for purification.

[0061] The present invention has the following advantages:

[0062] 1. In the present invention, by adding a substrate, an electrolyte, and a supporting electrode into a container, the supporting electrolyte enhances the conductivity of the solvent, and a constant current is passed through the two electrodes at room temperature. The carboxylation of the benzylic C-H bond is efficiently achieved, and this method has mild reaction conditions, wide substrate adaptability, can be applied to a wide range of pharmaceutical molecular structures, and has good industrial application prospects.

[0063] 2. In the present invention, by adjusting the magnitude of the current and the electrode material of the anode, the reaction substrate can be selectively electrolyzed. It can be simultaneously applied to the carboxylation of primary, secondary, and tertiary benzylic C-H bonds, and is compatible with ester groups, cyano groups, and halogens to obtain benzylic carboxylic acids in relatively high yields.

[0064] 3. The electrochemical synthesis method of the present invention can be applied to high-current conditions. At a constant current of 70 mA, it can still provide good yields and selectivities, and the reaction can be completely converted within 12 h.

[0065] 4. The method of the present invention has a high tolerance to substrate functional groups. For different substituents, whether electron-withdrawing groups or electron-donating groups, it shows good reactivity, and the target products have high yields and selectivities. Moreover, it also shows good compatibility with complex late-modified drug molecules and natural products.

[0066] In summary, the remarkable features of this strategy of the present invention include: a) direct carboxylation of the benzylic C-H bond, maximizing the atom utilization rate; b) providing a general method for synthesizing secondary, tertiary, and quaternary carbon benzylic carboxylic acids; c) without the participation of transition metals and bases, having good functional group tolerance, and being able to be compatible with substrates bearing sensitive alkenes, ketones, and halides; d) directly synthesizing drug molecules such as fenoprofen, ketoprofen, and ibuprofen. The present invention realizes the carboxylation of the benzylic carbon-hydrogen bond, featuring mild reaction conditions, clean and green, and simple reaction operation. Detailed implementation manners

[0067] The present invention will be specifically described below in conjunction with specific embodiments. It is necessary to point out here that the following embodiments are only used for further illustration of the present invention and cannot be construed as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention still fall within the protection scope of the present invention.

[0068] In addition, it should be noted that among the various specific technical features described in the following detailed implementation manners, they can be combined in any suitable manner without contradiction. To avoid unnecessary repetition, the present invention will not separately describe various possible combination methods. In addition, any combination can be made between different embodiments of the present invention as long as it does not violate the idea of the present invention. The technical solutions formed thereby belong to a part of the original public content of this specification and also fall within the protection scope of the present invention.

[0069] The raw materials used in the embodiments, if not specifically limited, are all disclosed in the prior art. For example, they can be directly purchased or prepared according to the preparation methods disclosed in the prior art.

[0070] Example 1

[0071] An electrochemical synthesis method for preparing benzylic carboxylic acids or their derivatives by benzylic carbon-hydrogen bond carboxylation reaction provided by a preferred embodiment of the present invention specifically comprises the following steps:

[0072] In a 15 mL reaction tube, fix the electrodes: a graphite felt anode (10 mm wide, 15 mm long, 3.0 mm thick), and a nickel sheet cathode (10 mm wide, 15 mm long, 0.1 mm thick) (the electrodes are fixed on both sides of the tube with rubber stoppers). Add a magnetic stirrer, substrate (0.3 mmol, 1.0 equiv) to the reaction tube in sequence, nBu4NClO4 (102.6 mg, 0.3 mmol, 1.0 equiv). The air in the reaction tube was replaced with CO2 through a double-tube gas conduction system (repeated three times, three minutes each time), and then anhydrous dichloroethane (5.0 mL) was added by syringe under a CO2 atmosphere. The CO2 balloon was connected, and the stirrer was started. After all the solids were completely dissolved, the electrode was immersed in the solution. Electrolysis was carried out at a constant current of 20.0 mA for 12 h. Then, the reaction mixture was acidified with an aqueous HCl solution (2.0 mol / L), the aqueous phase was extracted with ethyl acetate (5 × 10 mL), the combined organic phases were washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to obtain the crude product. There are two ways to post-treat the crude product. One is that the crude product is purified by column chromatography to obtain the desired benzylic carboxylic acid product. The other is that in Example 1, some of the benzylic carboxylic acid substances have relatively high polarity, and there is a large loss during direct column chromatography separation. The inventor converted the crude product into the corresponding methyl carboxylate, that is, the corresponding carboxylic acid derivative was generated and then purified. The steps are as follows: The crude product was dissolved in a mixed solvent (ether: methanol: 3 mL: 1 mL), and under an ice bath, a TMSCH2N2 solution was added dropwise, and the mixture was stirred under an ice bath for 2 h. Then, the solvent was removed, and the desired carboxylic acid derivative product was obtained by column chromatography purification.

[0073] The substrates containing benzylic C-H bonds in Example 1 are as follows:

[0074]

[0075] The results of the benzylic carboxylic acids or their derivatives in Example 1 are as follows:

[0076]

[0077] This method is applicable to substrates with different chain lengths (1 - 3) and different steric hindrances (4 and 5). This electrochemical strategy also demonstrates a high degree of site selectivity in substrates with multiple possible benzylic sites (6 and 7). Substituted ethylbiphenyl and diphenylmethane derivatives can rapidly afford the corresponding carboxylic acid products, including those bearing electrochemically sensitive cyano groups (8 - 12). Four-membered, five-membered, and six-membered rings can all afford the desired carboxylated products (14 - 16). Different cumene derivatives react well under the standard conditions, providing 18 - 27 in yields of 48% to 72%. Some electrochemically sensitive functional groups, such as esters and bromides, are well tolerated, providing potential opportunities for further applications. Although diaryl-substituted ethanes and triphenylmethanes have large steric hindrances, they are also reactive and afford 26 and 27 in acceptable yields. Substrates containing benzylic primary C-H bonds tolerate a variety of functional groups. We also endeavored to expand the scope of biphenylacetic acid derivatives and provided 44 - 53 in yields of 53% to 85%. Heterocycles and fused aromatics 2-methylthiophene and 2-methylnaphthalene can couple with carbon dioxide to afford benzylic carboxylic acids 54 and 55 in moderate yields.

[0078] Example 2

[0079] An electrochemical synthesis method for preparing benzylic carboxylic acids by benzylic C-H bond carboxylation reaction provided by a preferred embodiment of the present invention comprises the following specific steps:

[0080] In a 15 mL reaction tube, fix the electrodes: graphite felt anode (10 mm wide, 15 mm long, 3.0 mm thick), nickel sheet cathode (10 mm wide, 15 mm long, 0.1 mm thick) (the electrodes are fixed to both sides of the tube with rubber stoppers). Add a magnetic stir bar, the substrate (0.3 mmol, 1.0 equiv), nBu4NClO4 (102.6 mg, 0.3 mmol, 1.0 equiv). The air in the reaction tube was replaced with CO2 by a double-row gas-conducting system (repeated three times, three minutes each time), and then anhydrous dichloroethane (5.0 mL) was added through a syringe under a CO2 atmosphere. The CO2 balloon was connected and the stirrer was started until all the solids were completely dissolved, and then the electrode was immersed in the solution. Electrolysis was carried out at a constant current of 20.0 mA for 12 h. Then, the reaction mixture was acidified with an aqueous solution of HCl (2.0 mol / L), the aqueous phase was extracted with ethyl acetate (5×10 mL), the organic phases were combined and washed with saturated brine, dried with anhydrous MgSO4, filtered, and concentrated in vacuo to obtain a crude product. Some of the benzyl carboxylic acids in Example 2 have a large polarity, and direct column chromatography separation has a large loss. The inventor converted the crude product into the corresponding carboxylic acid methyl ester and then purified it. The steps are as follows: the crude product is dissolved in a mixed solvent (ether: methanol: 3 mL: 1 mL), TMSCH2N2 solution is added dropwise under ice bath, and stirred under ice bath for 2 hours. Then, the solvent is removed and the desired carboxylic acid derivative product is obtained by purification by column chromatography.

[0081] The substrate containing benzylic carbon-hydrogen bonds in Example 2 is as follows:

[0082]

[0083] The results of the benzylic acid or its derivatives in Example 2 are as follows:

[0084]

[0085] From the above, it can be seen that this reaction can be applied to the post-modification of complex drugs and complex natural products.

[0086] Example 3

[0087] A preferred embodiment of the present invention provides an electrochemical synthesis method for preparing benzylic acid by carboxylation of benzylic carbon-hydrogen bonds, and the specific steps are as follows:

[0088] In a 15mL reaction tube, fix the electrodes: graphite felt anode (width 10mm length 15mm thickness 3.0mm), nickel sheet cathode (width 10mm length 15mm thickness 0.1mm) (the electrodes are fixed on both sides of the tube with rubber stoppers). Add a stirrer, substrate (0.3mmol, 1.0equiv), nBu4NClO4 (102.6 mg, 0.3 mmol, 1.0 equiv). The air in the reaction tube was replaced with CO2 through a double-tube gas conduction system (repeated three times, three minutes each time), and then anhydrous dichloroethane (5.0 mL) was added via a syringe under a CO2 atmosphere. The CO2 balloon was connected, and the stirrer was started. After all the solids were completely dissolved, the electrode was immersed in the solution. Electrolysis was carried out at a constant current of 20.0 mA for 12 h. Then, the reaction mixture was acidified with an aqueous HCl solution (2.0 mol / L), the aqueous phase was extracted with ethyl acetate (5 × 10 mL), the combined organic phases were washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to obtain the crude product. The crude product was purified by column chromatography to obtain the desired benzylic carboxylic acid product.

[0089] The substrates containing benzylic C-H bonds in Example 3 are as follows:

[0090]

[0091] The results of the benzylic carboxylic acids or their derivatives in Example 3 are as follows:

[0092]

[0093] As can be seen from the above, this reaction can be applicable to the direct synthesis of drug molecules.

[0094] Examples 4 - 19

[0095] Gram-scale experiment:

[0096]

[0097] The reaction conditions were changed and the yields were compared.

[0098] Reaction conditions: reaction substrate 1a (0.3 mmol), tetrabutylammonium perchlorate (0.3 mmol), NaI (0.03 mmol), dichloroethane (5 mL), nickel sheet as the cathode, graphite felt as the anode, constant current electrolysis at room temperature (I = 20 mA).

[0099]

[0100] The changes in reaction conditions and their yields are shown in the following table:

[0101] Table 1

[0102] Serial number Change situation of reaction conditions Yield (1) % Example 4 None 82 Example 5 Power off No reaction Example 6 Do not add NaI 64 Example 7 <![CDATA[Replace NaI with NH4I]]> 68 Example 8 Replace NaI with NaBr 44 Example 9 <![CDATA[Replace NaI with CoBr2]]> 74 Example 10 <![CDATA n Replace NaI with Bu4NI]]> 57 Example 11 <![CDATA n Replace with Bu4NI n Bu4NClO4]]> Trace Example 12 <![CDATA[Replace LiClO4 with n Bu4NClO4]]> No reaction Example 13 <![CDATA n Replaced with Bu4NBF4 n Bu4NClO4]]> 32 Example 14 Use DMF as solvent No reaction Example 15 Use DCM as solvent 72 Example 16 Replace Ni with GF 38 Example 17 Replace GF with Mg No reaction Example 18 Replace 20 mA with 10 mA 66 Example 19 Replace 20 mA with 25 mA 74 Example 19 Replace 20 mA with 70 mA 67

[0103] The yields in Table 1 above are isolated yields.

[0104] As can be seen from Table 1 above, the carboxylation yield of the benzylic C-H bond under the reaction conditions of the present invention is as high as 82%. A series of control experiments show that changing the electrode material will reduce the yield. When using a sacrificial anode material, no target carboxylation product is formed. When using other supporting electrolytes or solvents, the yield decreases significantly. Lowering or raising the current results in a slight decrease in the yield. The investigation of the current shows that 20 mA is the optimal current value.

[0105] The parameters of some products synthesized in the present invention are as follows:

[0106] Product 1, property: yellow liquid; 1 H NMR (400 MHz, Chloroform-d) 11.26 (brs, 1H), 7.31–7.25 (m, 5H), 3.55 (t, J = 8.0 Hz, 1H), 2.09–2.00 (m, 1H), 1.80–1.71 (m, 1H), 1.32–1.25 (m, 2H), 0.90 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, Chloroform-d) δ 180.7, 138.6, 128.7, 128.1, 127.5, 51.4, 35.2, 20.7, 13.8.

[0107] Product 2, property: yellow liquid; 1 H NMR (400 MHz, Chloroform-d) δ 7.32–7.31 (m, 4H), 7.28–7.24 (m, 1H), 3.47–3.43 (m, 1H), 2.16–2.04 (m, 1H), 1.87–1.75 (m, 1H), 0.92–0.88 (m, 3H). 13 C NMR (100 MHz, Chloroform-d) δ 180.7, 138.4, 128.7, 128.1, 127.5, 53.4, 26.3, 12.1.

[0108]

[0109] Product 3, property: colorless liquid; 1 H NMR (400 MHz, Chloroform-d) δ 11.09 (brs, 1H), 7.25–7.22 (m, 4H), 7.21–7.16 (m, 1H), 3.66 (q, J = 7.2 Hz, 1H), 1.43 (d, J = 7.2 3H). 1313C NMR (100 MHz, Chloroform-d) δ 181.2, 139.8, 128.8, 127.7, 127.5, 45.5, 18.2.

[0110] Product 4, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.34–7.29 (m, 4H), 7.28–7.23 (m, 1H), 3.13 (d, J = 10.8 Hz, 1H), 2.37–2.28 (m, 1H), 1.07 (d, J = 6.8 Hz, 3H), 0.70 (d, J = 6.4 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 180.4, 137.7, 128.6×2 (128.62, 128.57), 127.5, 60.1, 31.6, 21.5, 20.1.

[0111] Product 5, Property: Yellow solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.30–7.27 (m, 5H), 7.22–7.16 (m, 3H), 7.10–7.07 (m, 2H), 3.84 (t, J = 8.0 Hz, 1H), 3.42–3.37 (m, 1H), 3.05–3.00 (m, 1H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.8, 138.8, 138.1, 128.9, 128.7, 128.4, 128.1, 127.6, 126.5, 53.5, 39.3.

[0112] Product 6, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.78 (brs, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 7.6 Hz, 2H), 3.76 (q, J = 7.2 Hz, 1H), 2.39 (s, 3H), 1.56 (d, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 181.2, 137.1, 136.8, 129.4, 127.5, 45.0, 21.1, 18.1.

[0113] Product 7, Property: Yellow liquid; 11H NMR (400 MHz, Chloroform-d) δ 7.27 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 3.74 (q, J = 7.2 Hz, 1H), 2.95–2.88 (m, 1H), 1.53 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 6.8 Hz, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 180.5, 148.0, 137.1, 127.5, 126.7, 44.9, 33.7, 24.0, 18.1. HRMS (ESI) m / z [M-H] - calcd for C 12 H 15 NO2 - , 191.1077, found: 191.1078.

[0114] Product 8, property: yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.62 (d, J = 7.2 Hz, 2H), 7.55–7.52 (m, 2H), 7.50–7.39 (m, 4H), 7.35–7.32 (m, 1H), 3.83 (q, J = 7.2 Hz, 1H), 3.72 (s, 3H), 1.59 (d, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 175.0, 141.7, 141.1, 141.0, 129.1, 128.8, 127.4, 127.2, 126.4×2 (126.44, 126.37), 126.0, 52.1, 45.5, 18.7.

[0115] Product 9, property: white solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.58–7.48 (m, 3H), 7.44–7.35 (m, 5H), 7.33–7.25 (m, 1H), 3.70–3.68 (m, 3H), 3.50 (t, J = 7.6 Hz, 1H), 2.19–2.08 (m, 1H), 1.89–1.80 (m, 1H), 0.95–0.90 (m, 3H). 1313C NMR (100 MHz, Chloroform-d) δ 174.5, 140.8, 140.1, 138.1, 128.8, 128.4, 127.3×2 (127.32, 127.26), 127.1, 53.1, 52.0, 26.8, 12.2.

[0116] Product 10, property: yellow solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 3.81 (q, J = 7.2 Hz, 1H), 1.56 (d, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 180.5, 145.1, 140.4, 138.3, 132.7, 128.5, 127.7, 127.6, 118.9, 111.0, 45.1, 18.1. HRMS (ESI) m / z [M-H] - calcd for C 16 H 12 NO2 - , 252.1019, found: 252.1018.

[0117] Product 11, property: brown solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.36–7.26 (m, 10H), 5.05 (s, 1H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.7, 137.9, 128.7, 127.6, 57.0.

[0118] Product 12, property: yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.27–7.24 (m, 4H), 7.03–6.99 (m, 4H), 4.99 (s, 1H), 3.74 (s, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.8, 162.1 (d, J = 245.0 Hz), 134.2 (d, J = 3.0 Hz), 130.1 (d, J = 9.0 Hz), 115.6 (d, J = 22.0 Hz), 55.4, 52.5.19 F NMR (375 MHz, Chloroform-d) δ -115.1. HRMS (ESI) m / z [M + H] + calcd for C 15 H 13 F2O2 + , 263.0878, found: 263.0882.

[0119] Product 13, Property: White solid; 1 H NMR (400 MHz, DMSO-d6) δ 12.84 (brs, 1H), 7.89 (d, J = 7.2 Hz, 2H), 7.66 (d, J = 7.6 Hz, 2H), 7.45–7.42 (m, 2H), 7.38–7.34 (m, 2H), 4.97 (s, 1H). 13 C NMR (100 MHz, DMSO-d6) δ 172.3, 141.8, 141.3, 128.3, 127.7, 126.1, 120.6, 53.8.

[0120] Product 14, Property: Yellow liquid; 1 H NMR (400 MHz, Chloroform-d) δ 7.22–7.17 (m, 2H), 7.14–7.13 (m, 1H), 7.07–7.05 (m, 1H), 4.28–4.26 (m, 1H), 3.69 (s, 3H), 3.45–3.42 (m, 2H). 13 C NMR (100 MHz, Chloroform-d) δ 172.7, 144.3, 142.8, 128.3, 127.4, 123.0, 122.6, 52.0, 45.8, 34.1.

[0121] Product 15, Property: Brown solid; 1 H NMR (400 MHz, Chloroform-d) δ 12.21 (brs, 1H), 7.51 (d, J = 7.2 Hz, 1H), 7.34–7.27 (m, 3H), 4.15 (t, J = 7.2 Hz, 1H), 3.23–3.15 (m, 1H), 3.04–2.96 (m, 1H), 2.55–2.40 (m, 2H). 1313C NMR (100 MHz, Chloroform-d) δ 180.8, 144.2, 140.1, 127.9, 126.6, 125.0, 124.8, 50.1, 31.8, 28.7.

[0122] Product 16, Property: Brown solid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.90 (brs, 1H), 7.24–7.10 (m, 4H), 3.84 (t, J = 5.2 Hz, 1H), 2.88–2.72 (m, 2H), 2.22–2.16 (m, 1H), 2.06–1.94 (m, 2H), 1.80–1.76 (m, 1H). 13 13C NMR (100 MHz, Chloroform-d) δ 181.4, 137.3, 132.5, 129.7, 129.5, 127.1, 125.8, 44.5, 29.1, 26.5, 20.4.

[0123] Product 17, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.29 (brs, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.32–7.25 (m, 2H), 6.67 (s, 1H), 4.04 (q, J = 6.8 Hz, 1H), 1.70 (d, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.0, 155.4, 154.8, 128.2, 124.1, 122.8, 120.9, 111.2, 103.6, 39.7, 15.5.

[0124] Product 18, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.40 (d, J = 7.8 Hz, 2H), 7.35–7.31 (m, 2H), 7.27–7.23 (m, 1H), 1.60 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 183.4, 143.8, 128.5, 127.0, 125.9, 46.3, 26.2.

[0125] Product 19, Property: White solid; 11H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 1.57 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 183.5, 158.5, 135.9, 127.0, 113.8, 55.3, 45.5, 26.3.

[0126] Product 20, property: white solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.29 (d, J = 7.6 Hz, 3H), 7.15 (d, J = 7.6 Hz, 2H), 2.33 (s, 3H), 1.59 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 182.7, 136.6, 129.2, 125.7, 45.9, 26.2, 21.0. HRMS (ESI) m / z [M+H] + calcd for C 11 H 15 O2 + , 179.1067, found: 179.1068.

[0127] Product 21, property: yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.41–7.36 (m, 4H), 7.26–7.22 (m, 4H), 7.17–7.13 (m, 1H), 3.49 (s, 3H), 1.44 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.2, 143.8, 140.7, 139.6, 128.8, 127.3, 127.2, 127.1, 126.1, 52.3, 46.4, 26.6. HRMS (ESI) m / z [M+H] + calcd for C 11 H 15 O2 + , 179.1067, found: 179.1068.

[0128] Product 22, property: yellow solid; 11H NMR (400 MHz, Chloroform-d) δ 8.01 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 1.60 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 179.8, 167.0, 154.2, 129.6, 128.6, 124.5, 72.6, 52.1, 31.7.

[0129] Product 23, Appearance: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.67 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 1.65 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 182.0, 149.0, 132.3, 126.9, 118.6, 111.1, 46.8, 26.0. HRMS (ESI) m / z [M+H] + calcd for C 11 H 12 NO2 + , 190.0863, found: 190.0856.

[0130] Product 24, Appearance: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.68 (brs, 1H), 7.58 (s, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.29–7.25 (m, 1H), 1.63 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 182.6, 146.1, 130.2, 130.0, 129.2, 124.7, 122.7, 46.3, 26.2. HRMS (ESI) m / z [M-H] - calcd for C 10 H 10 BrO2 - , 240.9869, found: 240.9868.

[0131] Product 25, Appearance: White solid; 11H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 1.62 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 182.9, 142.8, 131.6, 127.8, 121.1, 46.1, 26.1.

[0132] Product 26, Appearance: White liquid; 1 1H NMR (400 MHz, DMSO-d6) δ 7.34–7.31 (m, 4H), 7.26 (d, J = 6.4 Hz, 2H), 7.22 (d, J = 7.6 Hz, 4H), 1.84 (s, 3H). 13 13C NMR (100 MHz, DMSO-d6) δ 176.5, 145.2, 128.4, 128.2, 127.0, 56.3, 27.3.

[0133] Product 27, Appearance: White solid; 1 1H NMR (400 MHz, DMSO-d6) δ 7.32–7.29 (m, 9H), 7.14 (d, J = 7.6 Hz, 6H). 13 13C NMR (100 MHz, DMSO-d6) δ 179.5, 148.5, 135.1, 132.9, 131.9, 72.1. HRMS (ESI) m / z [M+Na] + calcd for C 20 H 16 NaO2 + , 311.1043, found: 311.1041.

[0134] Product 28, Appearance: Colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.44 (brs, 1H), 7.41–7.33 (m, 5H), 3.70 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.4, 133.3, 129.4, 128.7, 127.4, 41.2.

[0135] Product 29, Appearance: Colorless liquid; 11H NMR (400 MHz, Chloroform-d) δ 7.26–7.22 (m, 1H), 6.87–6.82 (m, 3H), 3.79 (s, 3H), 3.61 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.6, 159.7, 134.7, 129.7, 121.7, 115.1, 112.9, 55.2, 41.2.

[0136] Product 30, Appearance: Colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.25 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 3.85 (s, 3H), 3.64 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.4, 158.9, 130.4, 125.3, 114.1, 55.3, 40.2.

[0137] Product 31, Appearance: Colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.35 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 3.69 (s, 3H), 3.60 (s, 2H), 1.31 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.3, 150.0, 130.9, 128.9, 125.6, 52.0, 40.7, 34.5, 31.3.

[0138] Product 32, Appearance: Colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.22–7.17 (m, 4H), 3.64 (s, 2H), 2.37 (s, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.4, 137.1, 130.2, 129.4, 129.3, 40.7, 21.1.

[0139] Product 33, Appearance: Colorless liquid; 11H NMR (400 MHz, DMSO-d6) δ 7.38 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 7.6 Hz, 2H), 4.69 (s, 2H), 3.57 (s, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ 173.0, 136.8, 135.7, 130.2, 129.7, 40.8, 34.9. HRMS (ESI) m / z [M-H] - calcd for C9H8ClO2 - , 183.0218, found: 183.0215.

[0140] Product 34, property: yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 10.94 (brs, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 3.71 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 173.0, 137.1 (q, J = 1.0 Hz), 129.8×2 (129.83, 129.81 (q, J = 32.0 Hz)), 125.6 (q, J = 4.0 Hz), 124.1 (q, J = 270.0 Hz), 40.8. 19 19F NMR (375 MHz, Chloroform-d) δ -62.6.

[0141] Product 35, property: yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 8.03 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 3.94 (s, 3H), 3.74 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 176.5, 166.8, 138.3, 129.9, 129.5, 129.3, 52.2, 40.9.

[0142] Product 36, property: yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.46 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 3.55 (s, 2H). 1313C NMR (100 MHz, Chloroform-d) δ 176.1, 138.4, 132.4, 130.3, 118.6, 111.5, 40.9.

[0143] Product 37, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.30–7.24 (m, 2H), 7.13–7.04 (m, 2H), 3.71 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.0, 161.1 (d, J = 245.0 Hz), 131.5 (d, J = 4.0 Hz), 129.4 (d, J = 8.0 Hz), 124.2 (d, J = 4.0 Hz), 120.7 (d, J = 16.0 Hz), 115.5 (d, J = 12.0 Hz), 34.3. 19 19F NMR (375 MHz, Chloroform-d) δ -117.0.

[0144] Product 38, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.16 (brs, 1H), 7.31–7.24 (m, 1H), 7.06–6.96 (m, 3H), 3.64 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.7, 162.8 (d, J = 244.0 Hz), 135.4 (d, J = 8.0 Hz), 130.1 (d, J = 8.0 Hz), 125.1 (d, J = 3.0 Hz), 116.5 (d, J = 21.0 Hz), 114.4 (d, J = 21.0 Hz), 40.7. 19 19F NMR (375 MHz, Chloroform-d) δ -112.9.

[0145] Product 39, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 10.96 (s, 1H), 7.25–7.22 (m, 2H), 7.04–6.98 (m, 2H), 3.62 (s, 2H). 1313C NMR (100 MHz, Chloroform-d) δ 178.0, 162.1 (d, J = 245.0 Hz), 131.0 (d, J = 9.0 Hz), 128.9 (d, J = 3.0 Hz), 115.6 (d, J = 22.0 Hz), 40.2. 19 19F NMR (375 MHz, Chloroform-d) δ -112.9.

[0146] Product 40, property: white solid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.30 (brs, 1H), 7.14–7.07 (m, 2H), 7.00–6.97 (m, 1H), 3.61 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.6, 151.3 (dd, J = 40.0, 12.0 Hz), 148.8 (dd, J = 39.0, 12.0 Hz), 129.9 (dd, J = 6.0, 4.0 Hz), 125.5 (dd, J = 6.0, 4.0 Hz), 118.5 (d, J = 18.0 Hz), 117.4 (d, J = 17.0 Hz) 40.1. 19 19F NMR (375 MHz, Chloroform-d) δ -137.4 (d, J = 18.8 Hz), -139.6 (d, J = 18.8 Hz).

[0147] Product 41, property: colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 10.55 (brs, 1H), 7.39–7.37 (m, 1H), 7.29–7.26 (m, 1H), 7.24–7.21 (m, 2H), 3.81 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.2, 134.7, 131.7, 131.6, 129.6, 129.0, 127.0, 38.9.

[0148] Product 42, property: colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.16 (brs, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 3.61 (s, 2H). 1313C NMR (100 MHz, Chloroform-d) δ 177.7, 133.4, 131.6, 130.8, 128.8, 40.4.

[0149] Product 43, Property: Colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.04 (brs, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 3.39 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 177.7, 132.1, 131.8, 131.1, 121.5, 40.4.

[0150] Product 44, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.47–7.32 (m, 9H), 3.66 (s, 5H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.4, 142.5, 141.1, 131.8, 130.3, 130.2, 129.3, 128.2, 127.6, 127.2, 52.0, 38.8.

[0151] Product 45, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.61–7.58 (m, 4H). 7.43–7.40 (m, 4H), 7.20–7.12 (m, 5H), 3.77 (s, 3H), 3.73 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.1, 157.2, 156.9, 139.5, 135.8, 132.8, 129.9, 129.8, 128.4, 127.1, 123.5, 119.1, 119.1, 52.2, 40.8. HRMS (ESI) m / z [M+H] + calcd for C 21 H 19 O3 + , 319.1329, found: 319.1322.

[0152] Product 46, Property: White solid; 11H NMR (400 MHz, Chloroform-d) δ 7.51 (d, J = 8.4 Hz, 4H), 7.33 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 3.71 (s, 3H), 3.66 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.1, 159.2, 139.7, 133.3, 132.4, 129.6, 128.1, 126.9, 114.2, 55.4, 52.1, 40.8.

[0153] Product 47, Property: Yellow solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.42 (d, J = 8.4 Hz, 2H), 7.35–7.27 (m, 4H), 7.24 (d, J = 8.0 Hz, 2H), 3.63 (s, 2H), 3.62 (s, 3H), 1.36 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.5, 150.0, 142.4, 138.1, 131.7, 130.4, 130.3, 128.9, 127.4, 127.2, 125.1, 52.0, 38.8, 34.6, 31.4. HRMS (ESI) m / z [M+Na] + calcd for C 15 H 22 O2Na + , 305.1512, found: 305.1517.

[0154] Product 48, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.54–7.50 (m, 3H), 7.48–7.45 (m, 3H), 7.40–7.36 (m, 1H), 7.24 (d, J = 7.6 Hz, 1H), 3.70 (s, 3H), 3.68 (s, 2H), 1.36 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.0, 150.4, 141.5, 138.0, 134.4, 129.0, 128.1, 127.9, 126.9, 125.9, 125.7, 52.1, 41.3, 34.6, 31.4. HRMS (ESI) m / z [M+Na] +Calculated for C 19 H 22 O2Na + , 305.1512, found: 305.1521.

[0155] Product 49, Appearance: White solid 1 1H NMR (400 MHz, Chloroform-d) δ 7.45–7.40 (m, 4H), 7.34 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 3.58 (s, 3H), 3.54 (s, 2H), 1.25 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.1, 150.3, 140.0, 138.0, 132.8, 129.7, 127.3, 126.8, 125.8, 52.1, 40.9, 34.6, 31.5. HRMS (ESI) m / z [M+H] + Calculated for C 19 H 23 O2 + , 283.1693, found: 283.1700.

[0156] Product 50, Appearance: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.34–7.30 (m, 3H), 7.29–7.22 (m, 3H), 7.11–7.06 (m, 2H), 3.62 (s, 3H), 3.57 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.2, 162.2 (d, J = 245.0 Hz), 141.5, 137.0 (d, J = 4.0 Hz), 131.9, 130.8 (d, J = 8.0 Hz), 130.4, 130.3, 127.8, 127.3, 115.1 (d, J = 2.0 Hz), 52.0, 38.7. 19 19F NMR (375 MHz, Chloroform-d) δ -115.4.

[0157] Product 51, Appearance: Yellow liquid; 11H NMR (400 MHz, Chloroform-d) δ 7.55–7.52 (m, 2H), 7.45–7.37 (m, 3H), 7.26 (d, J = 7.6 Hz, 1H), 7.14–7.09 (m, 2H), 3.71 (s, 3H), 3.69 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.0, 162.5 (d, J = 245.0 Hz), 140.6, 137.0 (d, J = 3.0 Hz), 134.6, 129.1, 128.8 (d, J = 8.0 Hz), 128.2, 128.0, 125.9, 115.6 (d, J = 21.0 Hz), 52.2, 41.2. 19 19F NMR (375 MHz, Chloroform-d) δ -115.7. HRMS (ESI) m / z [M+H] + calcd for C 15 H 14 FO2 + , 245.0973, found: 245.0972.

[0158] Product 52, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 8.17 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.56–7.53 (m, 3H), 7.46–7.42 (m, 1H), 7.32 (d, J = 7.6 Hz, 1H), 3.72 (s, 5H), 2.67 (s, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 198.1, 171.9, 141.4, 140.6, 137.6, 134.7, 131.8, 129.2, 129.1, 128.8, 128.2, 127.3, 127.0, 126.1, 52.2, 41.2, 26.8. HRMS (ESI) m / z [M+H] + calcd for C 17 H 17 O3 + , 269.1172, found: 269.1180.

[0159] Product 53, Property: Yellow liquid; 11H NMR (400 MHz, DMSO-d6) δ 12.36 (brs, 1H), 7.54 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 7.6 Hz, 2H), 7.23 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 6.06 (s, 2H), 3.60 (s, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ 173.2, 148.4, 147.2, 138.7, 134.7, 134.3, 130.3, 126.8, 120.5, 109.1, 107.5, 101.6, 40.7. HRMS (ESI) m / z [M+H] + calcd for C 15 H 13 O4 + , 257.0809, found: 257.0804.

[0160] Product 54, property: colorless liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 11.51 (brs, 1H), 7.24–7.22 (m, 1H), 6.98–6.96 (m, 3H), 3.88 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 176.9, 134.0, 127.3, 127.0, 125.4, 35.1.

[0161] Product 55, property: white solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.81–7.77 (m, 3H), 7.71 (s, 1H), 7.46–7.41 (m, 2H), 7.39 (d, J = 8.4 Hz, 1H), 3.79 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 178.0, 133.4, 132.6, 130.7, 128.4, 128.2, 127.7(127.72, 127.70), 127.3, 126.3, 126.0, 41.3.

[0162] Product 56, property: white solid; 11H NMR (400 MHz, Chloroform-d) δ 7.78 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.00–6.94 (m, 4H), 3.68 (s, 3H), 3.61 (s, 2H), 1.82 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 194.0, 172.3, 171.5, 159.5, 149.5, 138.3, 136.3, 132.2, 132.1, 131.2, 130.7, 130.5, 128.6, 121.2, 117.3, 79.5, 52.1, 40.4, 25.4. HRMS (ESI) m / z [M+Na] + calcd for C 26 H 23 ClO6Na + , 489.1075, found: 489.1075.

[0163] Product 57, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.67–7.65 (m, 2H), 7.57–7.54 (m, 2H), 7.33–7.26 (m, 5H), 7.23–7.20 (m, 3H), 7.04 (d, J = 8.4 Hz, 2H), 3.58 (s, 3H), 3.52 (s, 2H), 3.20 (t, J = 7.2 Hz, 2H), 3.07 (t, J = 7.2 Hz, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.7, 170.7, 161.7, 149.8, 145.6, 135.2, 132.5, 131.7, 130.4, 129.0, 128.8, 128.7, 128.6, 128.2, 127.9, 126.6, 121.7, 52.0, 40.4, 31.2, 23.5. HRMS (ESI) m / z [M+Na] + calcd for C 27 H 23 NO5Na + , 464.1468, found: 464.1465.

[0164] Product 58, Property: White solid; 11H NMR (400 MHz, Chloroform-d) δ 9.37 (d, J = 1.6 Hz, 1H), 8.82 (dd, J = 4.8, 1.6 Hz, 1H), 8.42–8.39 (m, 1H), 7.44–7.41 (m, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 3.68 (s, 3H), 3.65 (s, 2H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.6, 163.7, 154.0, 151.2, 149.5, 137.5, 132.0, 130.4, 125.4, 123.5, 121.6, 52.0, 40.4. HRMS (ESI) m / z [M+H] + calcd for C 15 H 14 NO4 + , 272.0918, found: 272.0922.

[0165] Product 59, property: white solid; 1 1H NMR (400 MHz, Chloroform-d) δ 8.84 (s, 1H), 8.26 (d, J = 8.8 Hz, 1H), 8.10 (s, 1H), 8.06–7.99 (m, 2H), 7.88 (d, J = 8.4 Hz, 1H), 7.71 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.8 Hz, 1H), 3.94 (s, 3H), 3.78 (s, 3H), 3.72 (s, 2H), 2.29 (s, 6H), 2.20 (s, 3H), 1.90 (s, 6H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.9, 165.4, 159.1, 150.3, 141.8, 139.1, 136.3, 132.4, 131.8, 131.7, 131.3, 130.5, 129.9, 128.5, 126.7, 126.2, 126.0, 125.9 124.8, 122.0, 112.2, 55.2, 52.2, 40.7, 40.7, 37.3, 37.2, 29.2. HRMS (ESI) m / z [M+Na] + calcd for C 37 H 36 O5Na +,583.2455,found:583.2458.

[0166] Product 60, property: yellow liquid; 1 H NMR(400MHz,Chloroform-d)δ7.31(d,J=8.4Hz,2H),7.06(d,J=8.4Hz,2H),3.70(s,3H),3.63(s,2H),2.57(t,J=7.6Hz,2H),1.81–1.74(m,2H),1.46–1.31(m,16H),0.94–0.90(m,3H). 13 C NMR(100MHz,Chloroform-d)δ172.2,171.7,149.9,131.4,130.3,121.7,52.0,40.5,34.4,31.9,29.6,29.5,29.4,29.3,29.1,25.0,22.7,14.1.HRMS(ESI)m / z[M+Na] + calcdfor C 21 H 32 O4Na + ,371.2193,found:371.2194.

[0167] Product 61, property: white solid; 1 H NMR(400MHz,Chloroform-d)δ8.24(d,J=8.0Hz,1H),7.67–7.63(m,1H),7.42–7.36(m,3H),7.20–7.16(m,3H),3.72(s,3H),3.66(s,2H),2.33(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.8,169.8,163.0,151.2,149.6,134.7,132.2,131.9,130.5,126.2,124.1,122.5,121.8,52.1,40.6,21.1.HRMS(ESI)m / z[M+Na] + calcd for C 18 H 16 O6Na + ,351.0839,found:351.0841.

[0168] Product 62, property: white solid; 11H NMR (400 MHz, Chloroform-d) δ 8.03 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 4.68–4.63 (m, 2H), 4.46 (s, 1H), 4.32 (d, J = 11.6 Hz, 1H), 4.26 (d, J = 7.6 Hz, 1H), 3.95 (d, J = 12.8 Hz, 1H), 3.79 (d, J = 12.9 Hz, 1H), 3.69 (s, 5H), 1.54 (s, 3H), 1.46 (s, 3H), 1.37 (s, 3H), 1.34 (s, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.2, 165.6, 139.3, 130.0, 129.4, 128.8, 109.1, 108.8, 101.6, 70.8, 70.5, 70.1, 65.3, 61.3, 52.2, 41.1, 26.5, 25.9, 25.6, 24.0. HRMS (ESI) m / z [M+Na] + calcd for C 22 H 28 O9Na + , 459.1625, found: 459.1623.

[0169] Product 63, Property: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 4.64–4.59 (m, 1H), 4.41 (s, 1H), 4.22–4.19 (m, 2H), 3.96 (s, 1H), 3.57 (s, 3H), 3.56 (s, 2H), 2.76–2.71 (m, 1H), 2.13–2.06 (m, 1H), 1.77–1.74 (m, 1H), 1.51–1.33 (m, 8H), 1.05 (d, J = 6.0 Hz, 3H), 0.75 (t, J = 7.6 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.2, 166.2, 139.1, 129.8, 129.3, 129.2, 72.9, 62.6, 52.1, 48.0, 41.0, 38.9, 29.0, 28.9, 28.6, 25.5, 19.7, 19.0, 9.7. HRMS (ESI) m / z [M+Na] + calcd for C 22 H 31NO6Na + ,428.2043,found:428.2042.

[0170] Product 64, property: white solid; 1 H NMR(400MHz,Chloroform-d)δ7.97(d,J=8.4Hz,2H),7.35(d,J=8.0Hz,2H),4.91(dd,J=7.2,4.4Hz,1H),3.70(s,3H),3.68(s,2H),1.92–1.88(m,1H),1.81–1.72(m,2H),1.64–1.58(m,1H),1.27–1.21(m,2H),1.17–1.14(m,1H),1.12(s,3H),0.92(s,3H),0.89(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.3,165.8,138.9,129.8×2(129.84,129.79),129.4,81.6,52.2,49.0,47.0,45.1,41.1,38.9,33.8,27.1,20.1×2(20.14,20.08),11.6.HRMS(ESI)m / z[M+Na] + calcd for C 20 H 26 O4Na + ,353.1723,found:353.1717.

[0171] Product 65, property: white solid; 1 H NMR(400MHz,Chloroform-d)δ7.89(d,J=8.4Hz,2H),7.23(d,J=8.4Hz,2H),5.71(s,1H),4.61–4.59(m,4H),3.57(s,3H),3.56(s,2H),2.08–2.03(m,4H),1.90–1.83(m,1H),1.77–1.72(m,1H),1.62(s,2H),1.45–1.34(m,1H). 1313C NMR (100 MHz, Chloroform-d) δ 171.2, 166.2, 149.5, 139.1, 132.7, 129.9, 129.4, 129.3, 125.6, 108.8, 68.8, 52.2, 41.1, 40.9, 30.5, 27.3, 26.4, 20.8. HRMS (ESI) m / z [M+Na] + calcd for C 20 H 24 O4Na + , 351.1569, found: 351.1575.

[0172] Product 66, Appearance: Yellow liquid; 1 1H NMR (400 MHz, Chloroform-d) δ 8.00 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 7.6 Hz, 2H), 5.10 (t, J = 6.8 Hz, 1H), 4.37–4.33 (m, 2H), 3.68 (s, 3H), 3.68 (s, 2H), 2.05–1.97 (m, 2H), 1.83–1.79 (m, 1H), 1.67 (s, 3H), 1.60 (s, 3H), 1.43–1.38 (m, 1H), 1.25–1.21 (m, 1H), 0.97 (d, J = 6.4 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.2, 166.3, 139.0, 131.3, 129.8, 129.4, 129.3, 124.6, 63.4, 52.1, 41.1, 37.0, 35.5, 29.5, 25.7, 25.4, 19.5, 17.6. HRMS (ESI) m / z [M+Na] + calcd for C 20 H 28 O4Na + , 355.1880, found: 355.1876.

[0173] Product 67, Appearance: Yellow liquid; 11H NMR (400 MHz, Chloroform-d) δ 7.90 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 5.36 (t, J = 6.8 Hz, 1H), 4.73 (d, J = 7.2 Hz, 2H), 3.57 (s, 3H), 3.56 (s, 2H), 1.93 (t, J = 8.0 Hz, 2H), 1.65 (s, 3H), 1.44–1.28 (m, 5H), 1.20–1.11 (m, 8H), 1.06–0.96 (m, 6H), 0.78–0.74 (m, 12H). 13 13C NMR (100 MHz, Chloroform-d) δ 171.1, 166.2, 142.7, 138.9, 129.9, 129.5, 129.3, 118.2, 61.8, 52.1, 41.0, 39.9, 39.4, 37.4×2 (37.43, 37.36), 37.3, 36.6, 32.8, 32.7, 29.7, 28.0, 25.0, 24.8, 24.5, 22.7, 22.6, 19.8, 16.4. HRMS (ESI) m / z + calcd for C 30 H 48 O4Na + , 495.3445, found: 495.3449.

[0174] Product 68, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.89 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 5.31–5.30 (m, 1H), 4.78–4.70 (m, 1H), 3.58 (s, 3H), 3.56 (s, 2H), 2.35 (d, J = 7.6 Hz, 2H), 1.94–1.79 (m, 5H), 1.64–1.36 (m, 8H), 1.26–1.01 (m, 11H), 0.96 (s, 3H), 0.93–0.89 (m, 2H), 0.83 (d, J = 6.4 Hz, 3H), 0.77 (d, J = 6.4 Hz, 6H), 0.59 (s, 3H). 1313C NMR (100 MHz, Chloroform-d) δ 171.2, 165.6, 139.6, 138.9, 129.8×2 (129.83, 129.78), 129.3, 122.8, 74.5, 56.7, 56.2, 52.1, 50.1, 42.3, 41.1, 39.8, 39.6, 38.2, 37.1, 36.7, 36.2, 35.8, 32.0, 31.9, 28.3, 28.0, 27.9, 24.3, 23.9, 22.9, 22.6, 21.1, 19.4, 18.8, 11.9. HRMS (ESI) m / z [M+Na] + calcd for C 37 H 54 O4Na + , 585.3914, found: 585.3922.

[0175] Product 69, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.57–7.47 (m, 3H), 7.34–7.31 (m, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.24–7.22 (m, 3H), 7.12–7.09 (m, 1H), 3.93 (q, J = 7.2 Hz, 1H), 1.72 (d, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 180.4, 157.5, 157.0, 141.7, 129.9, 129.8, 123.4, 122.4, 119.0, 118.3, 117.5, 45.2, 18.1.

[0176] Product 70, Property: White solid; 1 1H NMR (400 MHz, Chloroform-d) δ 7.80 (d, J = 7.6 Hz, 3H), 7.69 (d, J = 7.6 Hz, 1H), 7.61–7.56 (m, 2H), 7.49–7.43 (m, 3H), 3.83 (q, J = 7.2 Hz, 1H), 1.56 (d, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, Chloroform-d) δ 196.5, 179.8, 140.1, 138.0, 137.4, 132.6, 131.7, 130.1, 129.4, 129.3, 128.6, 128.3, 45.2, 18.1.

[0177] Product 71, Property: White solid; 1 H NMR(400MHz, DMSO-d6) δ 12.44(brs, 1H), 7.66(d, J = 7.6Hz, 2H), 7.62(d, J = 8.0Hz, 2H), 7.48–7.45(m, 2H), 7.38(d, J = 7.6Hz, 3H), 3.65(s, 2H). 13 C NMR(100MHz, DMSO-d6) δ 173.2, 140.5, 139.0, 134.8, 130.5, 129.4, 127.8, 127.1, 40.8.

[0178] Product 72, Property: White solid; 1 H NMR(400MHz, Chloroform-d) 7.62–7.59(m, 4H), 7.49–7.36(m, 4H), 7.40–7.37(m, 1H), 3.84(q, J = 7.2Hz, 1H), 1.60(d, J = 7.2Hz, 3H). 13 C NMR(100MHz, Chloroform-d) δ 180.9, 140.7, 140.5, 138.8, 128.8, 128.1, 127.5, 127.4, 127.1, 45.1, 18.1.

[0179] Product 73, Property: White solid; 1 H NMR(400MHz, Chloroform-d) 7.52(d, J = 7.6Hz, 2H), 7.44–7.33(m, 4H), 7.18–7.13(m, 2H), 3.77(q, J = 7.2Hz, 1H), 1.55(d, J = 7.2Hz, 3H). 13 C NMR(100MHz, Chloroform-d) δ 180.6, 159.7(d, J = 247.0Hz), 140.9(d, J = 8.0Hz), 135.4, 130.9(d, J = 4.0Hz), 129.0(d, J = 3.0Hz), 128.5, 128.2(d, J = 14.0Hz), 127.8, 123.7(d, J = 4.0Hz), 115.4(d, J = 14.0Hz), 44.9, 18.0. 19 F NMR(375MHz, Chloroform-d) δ -117.3.

[0180] Product 74, property: white solid; 1 H NMR (400 MHz, Chloroform-d) 11.93 (brs, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.69 (q, J = 7.2 Hz, 1H), 2.44 (d, J = 7.2 Hz, 2H), 1.89–1.79 (m, 1H), 1.48 (d, J = 6.8 Hz, 3H), 0.89 (d, J = 6.4 Hz, 6H). 13 C NMR (100 MHz, Chloroform-d) δ 181.4, 140.9, 137.0, 129.4, 127.3, 45.1×2 (45.09, 45.07), 30.2, 22.5, 18.1.

[0181] Product 75, property: white solid; 1 H NMR (400 MHz, Chloroform-d) 7.70 (s, 1H), 7.67 (s, 2H), 7.41–7.39 (m, 1H), 7.14–7.11 (m, 1H), 7.09 (d, J = 2.4 Hz, 1H), 3.90 (s, 3H), 3.86 (q, J = 7.2 Hz, 1H), 1.58 (d, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, Chloroform-d) δ 180.7, 157.7, 134.9, 133.8, 129.3, 128.9, 127.3, 126.2×2 (126.21, 126.17), 119.1, 105.6, 55.3, 45.3, 18.2. 19 F NMR (375 MHz, Chloroform-d) δ -117.3.

[0182] Product 76, property: white solid; 1 H NMR (400 MHz, Chloroform-d) 11.16 (brs, 1H), 7.74 (d, J = 8.0 Hz, 1H), 6.89–6.87 (m, 2H), 4.34 (q, J = 7.2 Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H), 3.64 (s, 2H), 1.44 (t, J = 6.8 Hz, 3H), 1.36 (t, J = 6.8 Hz, 3H). 1313C NMR (100 MHz, Chloroform-d) δ 176.8, 166.4, 158.7, 138.8, 131.8, 119.8, 121.1, 114.4, 64.7, 60.8, 41.2, 14.7, 14.3. 19 19F NMR (375 MHz, Chloroform-d) δ -117.3.

[0183] Product 77, property: white solid; 1 1H NMR (400 MHz, DMSO-d6) 12.63 (brs, 1H), 7.53–7.45 (m, 2H), 3.64 (s, 2H). 13 13C NMR (100 MHz, DMSO-d6) δ 171.1, 157.1–154.6, 149.5–149.3, 146.9–146.8, 144.5–144.4, 119.7–119.5, 105.7–105.2, 33.4. 19 19F NMR (375 MHz, DMSO-d6) δ -118.1– -181.2, -136.4– -136.6, -144.1– -144.2.

[0184] The present invention has been described in detail above in combination with specific embodiments and exemplary examples, but these descriptions should not be construed as limiting the present invention. Those skilled in the art understand that without departing from the spirit and scope of the present invention, various equivalent substitutions, modifications or improvements can be made to the technical solutions and their implementation manners of the present invention, and these all fall within the scope of the present invention. The protection scope of the present invention shall be subject to the appended claims.

Claims

1. A method for electrocarboxylation of benzylic carbon-hydrogen bonds, characterized in that: The following steps are involved: In a CO2 atmosphere, a substrate containing a benzylic carbon-hydrogen bond, a supporting electrolyte and an optional additive are mixed in a solvent, and an electrocarboxylation reaction is carried out under power conditions, and the benzylic carboxylic acid compound obtained after the electrocarboxylation reaction is optionally subjected to a methylation reaction.

2. The method according to claim 1, characterized in that: The substrate containing a benzylic carbon-hydrogen bond has the following general structural formula: In formula 1, is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; The R 1 is selected from hydrogen, alkyl, cyano, halogen, alkoxy, haloalkyl, ester, phenoxy; R 2 , R 3 Each is independently selected from hydrogen, alkyl, substituted or unsubstituted aryl, alkylphenyl; In formula 2, Selected from polycyclic aromatic hydrocarbons and benzocycloalkenyls.

3. The method according to claim 2, characterized in that: In formula 1, for When; the R 1 is selected from hydrogen, alkyl, cyano and halogen atoms; The R 1 is selected from hydrogen, alkyl, cyano, halogen, alkoxy, and ester groups; R 2 , R 3 Each is independently selected from hydrogen, C1-C10 alkyl, substituted or unsubstituted phenyl, C7-C12 alkylphenyl; and / or, In formula 2, for n is an integer from 1 to 5; Preferably, The formula 1 and formula 2 are selected from at least one of the following compounds:

4. The method according to claim 2, characterized in that: In formula 1, for When; the R 1 is selected from hydrogen, alkyl, alkoxy, cyano, halogen, and ester groups; R 2 , R 3 Each independently selected from C1-C10 alkyl, phenyl; Preferably, R 2 , R 3 Each independently selected from C1-C5 alkyl, phenyl Further preferably, the formula 1 is selected from at least one of the following compounds:

5. The method according to claim 2, characterized in that: In formula 1, for hour; The R 1 is selected from hydrogen, alkyl, phenoxy, alkoxy, haloalkyl, cyano, halogen atom, ester group; R 2 , R 3 Each is independently selected from hydrogen, C1-C10 alkyl; Preferably, The formula 1 is selected from at least one of the following compounds:

6. The method according to claim 1, characterized in that: The supporting electrolyte is selected from at least one of alkyl salts; preferably, the alkyl salt is selected from at least one of tetraalkylammonium salts; more preferably, the tetraalkylammonium salt is selected from at least one of tetrabutylammonium hexafluorophosphate, tetrabutylammonium bromide, tetrabutylammonium perchlorate, and tetrabutylammonium tetrafluoroborate; and / or, The molar ratio of the supporting electrolyte to the substrate containing benzyl carbon-hydrogen bonds is (0.5-2):1; and / or; When an additive is included, the additive is selected from NaI, NaBr, CoBr2, NH4I or n At least one of Bu4NI; and / or The molar ratio of the additive to the substrate containing a benzylic carbon-hydrogen bond is (0.05-1):1; and / or; The solvent is selected from at least one of halogenated hydrocarbon solvents; and / or, The concentration of the substrate containing benzylic carbon-hydrogen bonds in the solvent is 0.05-0.4 mol / L; Preferably, the concentration of the substrate containing benzylic carbon-hydrogen bonds in the solvent is 0.1-0.3 mol / L; and / or, The organic solvent is selected from at least one of dichloroethane and dichloromethane.

7. The method according to claim 1, characterized in that: During the reaction, a constant current is passed, preferably, The constant current is 5-80 mA; and / or, The reaction time is 3-40h; and / or, The reaction temperature is 0-50°C; and / or, More preferably, The constant current is 10-20 mA; and / or, The reaction time is 8-12 hours; and / or, The reaction temperature is 18-25°C; and / or, During the reaction, in the electrodes used, the cathode material is selected from graphite felt, platinum sheet or nickel sheet; the anode material is selected from graphite felt, platinum sheet or nickel sheet; and / or, The post-treatment includes acidification. Preferably, during the acidification, the concentration of the acid used is 1-2 mol / L; the acid used is hydrochloric acid.

8. A benzylic acid compound prepared according to any one of claims 1 to 7; preferably, The benzylic carboxylic acid compound has the following general structural formula: In formula 3, is selected from aryl or heteroaryl; -COOX is -COOH or -COOR 4 , R 4 Preferably, it is an alkyl group; The R 1 is selected from hydrogen, alkyl, cyano, halogen, alkoxy, haloalkyl, ester, phenoxy; R 2 , R 3 Each is independently selected from hydrogen, alkyl, substituted or unsubstituted aryl, alkylphenyl; In formula 4, Selected from polycyclic aromatic hydrocarbons and benzocycloalkenyls.

9. The benzylic carboxylic acid compound according to claim 8, characterized in that The benzyl carboxylic acid compound is selected from at least one of the following compounds:

10. Use of the method according to any one of claims 1 to 7 in constructing molecules containing benzylic carboxylic acids; preferably in constructing drug molecules containing benzylic carboxylic acids.

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