A method for electrolytic synthesis of benzyl alcohol using a continuous flow microreactor

Abstract

The application provides a method for electrolytic synthesis of benzyl alcohol by using a continuous flow microreactor, and belongs to the technical field of combination of electrochemistry and flow chemistry. The application discloses benzyl alcohol as shown in formula I, wherein Ar is selected from aryl; R is selected from at least one of H or a hydrocarbon group; and provides a method for electrolytic synthesis of benzyl alcohol by using a continuous flow microreactor, wherein the method determines the optimal process conditions by investigating electrolysis electrodes, the distance between electrolysis electrodes, electrolysis flow rate, electrolysis reaction conditions and other factors; meanwhile, the inventors have investigated substrate universality, and the results prove that the method has wide substrate universality; in conclusion, the technical scheme of the application has the advantages of high originality, simple operation, low cost, environmental friendliness, good industrial amplification prospect and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of electrochemistry combined with flow chemistry, and particularly relates to a method for electrolytic synthesis of benzyl alcohol by using a continuous flow microreactor. BACKGROUND

[0002] Electrochemical reaction usually occurs on an electrode, and electrons act as an oxidizing and reducing agent, and molecules are oxidized or reduced by gaining or losing electrons. Compared with traditional organic synthesis, electrochemistry is more in line with the requirements of green chemistry, and the reaction process can be controlled by electrode potential to improve the selectivity of the main reaction.

[0003] Continuous flow chemistry technology is a technology for providing power by a pump to perform a chemical reaction in a microchannel in a continuous flow manner. The microreactor is based on the principle of repeated impact under the push of a high-pressure constant-flow pump to perform a reaction, the conversion rate of raw materials is increased by more than 20%, the impurities of side reactions are reduced by more than 30%, the reaction time is shortened to 1.3% of the kettle type, the amplification effect in the reaction process is eliminated, and full-intelligent and full-automatic production of chemical reactions is realized, which is suitable for large-scale continuous production of chemicals. Compared with the conventional kettle reaction, the microreactor has great advantages, such as high heat transfer capacity, high mass transfer capacity, continuous controllable reaction process, small volume, low consumption, and high safety.

[0004] Benzyl alcohol is widely used in industrial chemicals, and can be used to prepare floral oil and drugs, and also used as a solvent and a fixative for perfumes; used as a solvent, a plasticizer, a preservative, and used in the manufacture of perfumes, soaps, medicines, dyes, etc. In the prior art, no related literature on electrolytic synthesis of benzyl alcohol by using a continuous flow microreactor has been found.

[0005] The present application combines continuous flow microreaction technology and electrolytic synthesis and applies it to the synthesis process of benzyl alcohol to solve the problems of low conversion rate of raw materials, many by-products, excessive oxidation of products, high risk and environmental pollution in the synthesis process. SUMMARY

[0006] In view of the above-mentioned technical problems of low conversion rate of raw materials, many by-products, excessive oxidation of products and high risk in the synthesis of benzyl alcohol, the present application provides a method for electrolytic synthesis of benzyl alcohol by using a continuous flow microreactor, which has originality, few side reactions, low energy consumption, good safety, conforms to green chemical industry, and has good prospects for industrial scale-up production.

[0007] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0008] One of the technical solutions of the present application provides a benzyl alcohol shown in formula I, and the benzyl alcohol has the following structure:

[0009]

[0010] wherein Ar is selected from aryl; R is selected from at least one of H, alkyl or aryl.

[0011] In some embodiments, wherein aryl is selected from substituted or unsubstituted heterocycle, substituted or unsubstituted phenyl, substituent of phenyl is selected from C1-C4 alkyl, C1-C4 alkoxy, halogen; alkyl is selected from C1-C4 alkyl, C1-C4 alkoxy.

[0012] Preferably, aryl is selected from substituted or unsubstituted phenyl, substituent of phenyl is selected from C1-C4 alkyl, C1-C4 alkoxy, halogen; alkyl is selected from methyl, ethyl, n-propyl, iso-propyl.

[0013] Further preferably, aryl is selected from phenyl, 4-methoxyphenyl, 4-chlorophenyl; alkyl is selected from methyl.

[0014] In some embodiments, a benzyl alcohol of formula I has the following structure:

[0015]

[0016]

[0017] The present application is a second technical solution, which provides a preparation method for synthesizing the benzyl alcohol of formula I by electrolysis using a continuous flow microreactor.

[0018] The present application provides a method for synthesizing benzyl alcohol by electrolysis using a continuous flow microreactor. The reaction process is as follows:

[0019]

[0020] wherein Ar is selected from aryl; R is selected from at least one of H or alkyl; aryl and alkyl are defined as above.

[0021] In another aspect, the present application provides a preparation method for the benzyl alcohol of formula I, comprising the following steps:

[0022] 1) dissolving a substrate of formula A, trifluoroacetic acid and 2,6-dimethylpyridine in a dried reaction solvent;

[0023] 2) pushing the solution in step 1) through an electrolytic cell at a certain flow rate using a syringe pump for reaction;

[0024] 3) after the reaction is completed, collecting the effluent from the outlet of the electrolytic cell, and optionally post-treating to obtain the benzyl alcohol compound of formula I.

[0025] The solvent for the reaction in step 1 is selected from one of acetonitrile, dichloromethane, a mixture solution of dichloromethane and hexafluoroisopropanol.

[0026] The molar ratio of trifluoroacetic acid to the substrate of formula A in step 1 is 1:1 to 10:1. In some embodiments, the molar ratio of trifluoroacetic acid to the substrate of formula A in step 1 is 2:1. In some embodiments, the molar ratio of trifluoroacetic acid to the substrate of formula A in step 1 is 4:1.

[0027] The molar ratio of 2,6-dimethylpyridine to the substrate of formula A in step 1 is 1:1 to 10:1. In some embodiments, the molar ratio of 2,6-dimethylpyridine to the substrate of formula A in step 1 is 2:1. In some embodiments, the molar ratio of 2,6-dimethylpyridine to the substrate of formula A in step 1 is 1.5:1.

[0028] The reaction concentration of the substrate in step 1 ranges from 0.01 mol / L to 0.5 mol / L. In some embodiments, the reaction concentration of the substrate in step 1 is 0.045 mol / L or 0.06 mol / L or 0.25 mol / L.

[0029] The flow rate in step 2 is 0.1 mL / min to 50 mL / min. In some embodiments, the flow rate in step 2 is 0.40 mL / min to 50 mL / min. -1 .

[0030] The electrolytic cell in step 2 can be a flow electrolytic cell equipped with a graphite anode and a platinum cathode. In some embodiments, the electrolytic cell in step 2 can be a flow electrolytic cell equipped with a Pt anode and a graphite cathode.

[0031] The constant current for the reaction in the electrolytic cell in step 2 ranges from 1 mA to 1000 mA. In some embodiments, the constant current for the reaction in the electrolytic cell in step 2 ranges from 58 mA to 81 mA. In some embodiments, the constant current for the reaction in the electrolytic cell in step 2 ranges from 81 mA to 127 mA. In some embodiments, the constant current for the reaction in the electrolytic cell in step 2 is 543 mA.

[0032] The electric quantity for the reaction in the electrolytic cell in step 2 ranges from 1 F mol -1 -10 F mol -1 . In some embodiments, the electric quantity for the reaction in the electrolytic cell in step 2 ranges from 2 F mol -1 -3 F mol -1 . In some embodiments, the electric quantity for the reaction in the electrolytic cell in step 2 is 2.7 F mol -1 .

[0033] The exposed surface area of the electrode reaction in the electrolytic cell in step 2 is 1 cm 2 - 100 cm 2 The inter-electrode distance in the reaction in the electrolytic cell in step 2 is 100 μm-1000 μm. In some embodiments, the inter-electrode distance in the reaction in the electrolytic cell in step 2 is 150 μm.

[0034] The post-treatment in step 3 includes: removing the solvent in the effluent, dissolving in acetonitrile, then adding saturated NaHCO3 solution, stirring at room temperature, adding water, and extracting with ethyl acetate; the organic phase is treated with dilute H2SO4, extracted with ethyl acetate, the solvent is removed, and the product I is obtained by column chromatography.

[0035] In some embodiments, a method for preparing a benzyl alcohol of formula I includes the following steps: 1. dissolving a substrate of formula A, trifluoroacetic acid, and 2,6-dimethylpyridine in dry acetonitrile; 2. pushing the solution in step 1 through an electrolytic cell at a flow rate of 0.1 mL / min-10 mL / min using a syringe pump to react; 3. after the reaction is complete, collecting the effluent at the outlet of the electrolytic cell, and optionally post-treating to obtain a benzyl alcohol compound of formula I; wherein the electrolytic cell in step 2 is a flow electrolytic cell equipped with a graphite anode and a platinum cathode, the exposed surface area of the electrode reaction is 10 cm 2 , the inter-electrode distance is 150 μm, and the constant current range in the reaction in the electrolytic cell is 58 mA-81 mA; the post-treatment in step 3 includes: removing the solvent in the effluent, dissolving in acetonitrile, then adding saturated NaHCO3 solution, stirring at room temperature, adding water, and extracting with ethyl acetate; the organic phase is treated with dilute H2SO4, extracted with ethyl acetate, the solvent is removed, and the product I is obtained by column chromatography.

[0036] In some embodiments, a method for preparing a benzyl alcohol of formula I includes the following steps: 1. dissolving a substrate of formula A, trifluoroacetic acid, and 2,6-dimethylpyridine in a mixed solution of dry dichloromethane and hexafluoroisopropanol; 2. pushing the solution in step 1 through an electrolytic cell at a flow rate of 0.1 mL / min-10 mL / min using a syringe pump to react; 3. after the reaction is complete, collecting the effluent at the outlet of the electrolytic cell, and optionally post-treating to obtain a benzyl alcohol compound of formula I; wherein the electrolytic cell in step 2 is a flow electrolytic cell equipped with a Pt anode and a graphite cathode, the exposed surface area of the electrode reaction is 10 cm 2, the distance between electrodes is 150 mu m, the constant current range of the reaction in the electrolytic cell is 81mA-127mA; the post-treatment in step 3 includes: removing the solvent in the effluent, dissolving in acetonitrile, adding saturated NaHCO3 solution, stirring at room temperature, adding water, and extracting with ethyl acetate; the organic phase is treated with dilute H2SO4, extracted with ethyl acetate, the solvent is removed, and the product I is obtained by column chromatography.

[0037] The third technical scheme of the application is the use of the benzyl alcohol shown in the above formula I in the preparation of a drug for preventing or treating diseases, or the use of the benzyl alcohol shown in the above formula I in the preparation of a floral oil, a solvent and a fixative for a perfume, as a solvent, a plasticizer, a preservative, a soap, a medicine, a dye, etc., which has a good application prospect.

[0038] In the technical scheme of the application, a continuous flow microreactor is creatively used to synthesize benzyl alcohol by an electrolytic synthesis method, the effects of electrolytic electrodes, the distance between electrolytic electrodes, electrolytic flow rate, electrolytic reaction conditions such as reaction solvent, addition of acid equivalent, addition of base equivalent, etc. on the yield and purity are investigated, the optimal process conditions are determined, and the benzyl alcohol compound I prepared by the optimized process has a high yield; meanwhile, the inventors have prepared many substrates, and applied these substrates to the synthesis of benzyl alcohol by the above method, and the results prove that the method of the application has a wide substrate universality; in summary, the technical scheme of the application has the advantages of high originality, simple operation, low cost, environmental friendliness, good industrial amplification prospect, etc.

[0039] In summary, the application has the following beneficial technical effects:

[0040] 1. The benzyl alcohol shown in the formula I provided by the application has a good application prospect in the chemical industry.

[0041] 2. The method for electrolytically synthesizing benzyl alcohol by using a continuous flow microreactor provided by the application solves the problems of low raw material conversion rate, many by-products, excessive oxidation of products, high danger and environmental pollution compared with traditional kettle reactions; at the same time, the continuous flow microreactor can meet the high requirements of environmental safety and stable process parameters due to the relatively closed reaction system and the high mass and heat exchange performance.

[0042] 3、The application provides a method for synthesizing benzyl alcohol by electrolysis of a continuous flow microreactor, and the influence of factors such as an electrolysis electrode, a distance between electrolysis electrodes, an electrolysis flow rate, electrolysis reaction conditions such as a reaction solvent, an acid equivalent, and an alkali equivalent on the yield and purity is investigated, and the optimal process conditions are determined, the benzyl alcohol compound I prepared by the optimized process has high yield, and the application is proved to have wide substrate universality by synthesizing benzyl alcohol by applying the above method to a plurality of substrates.

[0043] In the description of the present application, it should be understood that the terms "first", "second" are used only for the purpose of description, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first", "second" can be explicitly or implicitly included one or more of the features. In the description of the present application, the meaning of "a plurality of" is two or more, unless otherwise specifically limited.

[0044] In the description of the present application, the description of the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present application, the illustrative description of the above terms is not necessarily for the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any suitable manner in any one or more embodiments or examples. In addition, the skilled in the art can combine and combine the different embodiments or examples described in the present application and the features of the different embodiments or examples without contradiction.

[0045] In the present application, the expressions such as "compound A" and "compound represented by formula A" and "formula A" represent the same compound.

[0046] In the present application, "optionally" or "optionally" means that there can be or there can not be, or it can be performed or it can not be performed, such as "optionally adding a reaction solvent to the crude product obtained in step (C)" means that a reaction solvent can be added to the crude product obtained in step (C) or no reaction solvent can be added to the crude product obtained in step (C). BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1 Assembly and installation of flow reactor;

[0048] Figure 2 20 parallel reactor scale-up reaction device. DETAILED DESCRIPTION

[0049] In order for those skilled in the art to better understand the technical solutions of the present application, some non-limiting embodiments are further disclosed below to make a further detailed description of the present application.

[0050] The reagents used in the present application can be purchased from the market or can be prepared by the method described in the present application.

[0051] In the present application, min represents minute; h represents hour; g represents gram; mL represents milliliter; mg represents milligram.

[0052] In the present application, 1 HNMR represents nuclear magnetic resonance hydrogen spectrum. 13 C NMR represents nuclear magnetic resonance carbon spectrum.

[0053] Example 1

[0054]

[0055] Electrolysis was carried out using a flow electrolysis cell equipped with a graphite anode and a platinum cathode, the exposed surface area of the electrode reaction was 10 cm 2 , the distance between the electrodes was 150 μm (see Figure 1 ). A solution containing the substrate 4-ethylanisole (0.045 M), TFA (2.0 equivalents), 2,6-lutidine (2.0 equivalents) in dry acetonitrile was pushed through the electrolysis cell using a syringe pump at a flow rate of 0.40 mL min -1 , the constant current of the reaction was 61 mA, the electric quantity was 2.1 F mol -1 , the outlet flow of the electrolysis cell was collected for 20 min (8 mL in total) and the solvent was distilled under reduced pressure. After the residue was dissolved in 4 mL of acetonitrile, 2 mL of saturated NaHCO3 solution was added, and stirred at room temperature for 30 minutes. After stirring was completed, the residue was diluted with H2O, extracted with ethyl acetate, and the solvent was distilled under reduced pressure. Finally, the residue was separated by silica gel column chromatography using ethyl acetate / petroleum ether as the eluent to obtain the product (44 mg), i.e. compound I-1, with a yield of 81%.

[0056] 1 H NMR (500 MHz, CDCl3) δ 7.31-7.27 (m, 2H), 6.92-6.80 (m, 2H), 4.84 (q, J = 6.4 Hz, 1H), 3.80 (s, 3H), 1.93 (s, 1H), 1.47 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 159.1, 138.2, 126.8, 114.0, 70.1, 55.4, 25.1.

[0057] Example 2

[0058] The effect of other parameters on the reaction was investigated following the procedure of Example 1 and the results are shown in Table 1.

[0059] Table 1 Effect of electrolysis conditions on reaction yield

[0060]

[0061]

[0062]

[0063] Standard conditions as in Example 1. The yield was analyzed by H NMR. 1 H NMR.

[0064] __________________________________________________________________

[0065] Example 3

[0066]

[0067] The electrolysis was performed using a flow electrolysis cell equipped with a Pt anode and a graphite cathode, the electrode reactions exposed surface area being 10 cm 2 , the distance between the electrodes being 150 μm. A solution containing the substrate 3 (0.06 M), TFA (4.0 eq), 2,6-dimethylpyridine (1.5 eq) in dry dichloromethane / hexafluoroisopropanol (19:1) was pushed through the electrolysis cell using a syringe pump at a flow rate of 0.40 mL min -1 , the constant current of the reaction being 93 mA, the electric charge being 2.4 F mol -1 , the outlet flow of the electrolysis cell being collected for 15 min (6 mL in total). The solvent was evaporated under reduced pressure. The residue was dissolved in 4 mL of acetonitrile and 2 mL of a saturated NaHCO3solution was added, stirring at room temperature for 60 min. After stirring was complete, the residue was diluted with H2O and extracted with ethyl acetate. In order to remove the 2,6-dimethylpyridine, the organic phase was treated with 0.3 M H2SO4, extracted with ethyl acetate and the solvent was evaporated under reduced pressure. Finally the residue was separated by column chromatography on silica gel using ethyl acetate / petroleum ether as eluent, obtaining the product (45 mg), compound I-2, in a 79% yield.

[0068] 1H NMR (500 MHz, CDC13) δ 7.32 - 7.27 (m, 4H), 4.86 (q, J = 6.5 Hz, 1H), 2.06 (br s, 1H), 1.46 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 144.4, 133.2, 128.7, 126.9, 69.8, 25.4.

[0069] Example 4

[0070] According to the method in Example 3, the influence of other parameters on the reaction was investigated, and the results are shown in Table 2.

[0071] Table 2 Influence of electrolysis conditions on reaction yield

[0072]

[0073] Serial number Deviation from standard conditions Yield % 1 None 8 2 0.30 mL min -1 ]] 79 3 0.50 mL min -1 ]] 81 4 Electrode spacing (0.25 mm) 71 5 Pt (+) / Pt (-) 14 6 C (+) / Pt (-) 26 7 2,6-lutidine (0.5 eq.) 75 8 2,6-lutidine (4 eq.) 65 9 MeCOOH instead of TFA 0 10 CH3SO3H instead of TFA 8 11 Pyridine instead of 2,6-lutidine 81 12 [iPr2NEt instead of 2,6-dimethylpyridine] 83 13 DCM instead of DCM:HFIP = 19:1 70 14 HFIP instead of DCM:HFIP = 19:1 67 15 DCM:HFIP = 4:1 instead of DCM:HFIP = 19:1 83 16 MeCN instead of DCM:HFIP = 19:1 6 17 Same method as in Example 1 6

[0074] Standard conditions same as in Example 3. The yield was analyzed by H NMR. 1 H NMR.

[0075] _____________________________________________________________________

[0076] Example 5

[0077] According to the method in Example 1 or Example 2, the influence of other reaction substrates on the reaction was investigated, and the results are shown in Table 3.

[0078] Table 3 Influence of substrates on reaction yield

[0079]

[0080] Investigation of substrate universality

[0081] Example 6

[0082] According to the preparation method of Reference Compound I-2, the constant current of the reaction was 116 mA, the electric quantity was 3.0 F mol -1 , the hydrolysis time was reduced to 30 minutes, and other conditions were unchanged. The end product 42 mg was prepared, and the structure is shown below, with a yield of 65%.

[0083]

[0084] 1H NMR (500 MHz, CDC13) δ 7.39 - 7.33 (m, 2H), 7.08 - 7.01 (m, 2H), 4.86 (q, J = 6.5 Hz, 1H), 2.28 (s, 3H), 2.09 (br s, 1H), 1.46 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 169.7, 149.9, 143.5, 126.6, 121.6, 69.9, 25.2, 21.2.

[0085] Example 7

[0086] The preparation method of reference compound I-2 was used, the constant current of the reaction was 108 mA, and the electric quantity was 2.8 F mol -1 , and other conditions were unchanged. The end product 43 mg was prepared, the structure was as shown below, and the yield was 79%.

[0087]

[0088] 1 H NMR (500 MHz, CDC13) δ 7.33 - 7.28 (m, 2H), 7.23 - 7.17 (m, 2H), 4.87 (q, J = 6.4 Hz, 1H), 2.66 (q, J = 7.6 Hz, 2H), 1.97 (br s, 1H), 1.49 (d, J = 6.4 Hz, 3H), 1.25 (t, J = 7.6 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 143.6, 143.2, 128.1, 125.6, 70.4, 28.6, 25.1, 15.7.

[0089] Example 8

[0090] The preparation method of reference compound I-2 was used, the constant current of the reaction was 108 mA, and the electric quantity was 2.8 F mol -1 , and other conditions were unchanged. The end product 61 mg was prepared, the structure was as shown below, and the yield was 86%.

[0091]

[0092] 1 H NMR (500 MHz, CDC13) δ 7.64 - 7.56 (m, 4H), 7.49 - 7.41 (m, 4H), 7.40 - 7.33 (m, 1H), 4.95 (q, J = 6.5 Hz, 1H), 2.00 (br s, 1H), 1.55 (d, J = 6.4 Hz, 3H). 13C NMR (126 MHz, CDCI3) δ 144.9, 141.0, 140.5, 128.9, 127.4 (2C), 127.2, 126.0, 70.3, 25.2.

[0093] Example 9

[0094] The preparation method of reference compound I-2 was used, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and the final product 28 mg was prepared with the structure shown below under the same conditions, and the yield was 63%.

[0095]

[0096] 1 H NMR (500 MHz, CDCI3) δ 7.40 - 7.30 (m, 4H), 7.30 - 7.23 (m, 1H), 4.88 (q, J = 6.5 Hz, 1H), 1.93 (br s, 1H), 1.49 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 145.9, 128.6, 127.6, 125.5, 70.5, 25.3.

[0097] Example 10

[0098] The preparation method of reference compound I-2 was used, the constant current of the reaction was 116 mA, and the electric quantity was 3.0 F mol -1 , and the final product 45 mg was prepared with the structure shown below under the same conditions, and the yield was 70%.

[0099]

[0100] 1 H NMR (500 MHz, CDCI3) δ 8.17 - 7.83 (m, 2H), 7.54 - 7.37 (m, 2H), 4.93 (q, J = 6.5 Hz, 1H), 3.89 (s, 3H), 1.48 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 167.1, 151.1, 130.0, 129.3, 125.4, 70.1, 52.2, 25.4.

[0101] Example 11

[0102] The preparation method of reference compound I-2 was used, the constant current of the reaction was 108 mA, and the electric quantity was 2.8 F mol -1 , and the final product 34 mg was prepared with the structure shown below under the same conditions, and the yield was 57%.

[0103]

[0104] 1 H NMR (500 MHz, CDCI3) δ 7.92 - 7.89 (m, 2H), 7.47 - 7.41 (m, 2H), 4.94 (q, J = 6.5 Hz, 1H), 2.57 (s, 3H), 2.25 (brs, 1H), 1.48 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 198.2, 151.4, 136.3, 128.7, 125.6, 70.0, 26.7, 25.4.

[0105] Example 12

[0106] According to the preparation method of compound I-2, the constant current of the reaction was 108 mA, the electric quantity was 2.8 F mol -1 , and other conditions were unchanged. The end product 19 mg was prepared, the structure was as shown below, and the yield was 35%.

[0107]

[0108] 1 H NMR (500 MHz, CDCI3) δ 7.62 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 4.95 (q, J = 6.5 Hz, 1H), 1.49 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 151.3, 132.5, 126.2, 119.0, 111.2, 69.8, 25.5.

[0109] Example 13

[0110] According to the preparation method of compound I-2, the constant current of the reaction was 89 mA, the electric quantity was 2.3 F mol -1 , and other conditions were unchanged. The end product 73 mg was prepared, the structure was as shown below, and the yield was 88%.

[0111]

[0112] 1H NMR (400 MHz, CDC13) δ 7.47 - 7.43 (m, 2H), 7.22 - 7.17 (m, 2H), 4.62 (dd, J = 7.5, 5.8 Hz, 1H), 1.95 (br s, 1H), 1.81 - 1.57 (m, 2H), 1.48 - 1.21 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H). 13 CNMR (101 MHz, CDC13) δ 144.0, 131.6, 127.8, 121.3, 73.9, 41.3, 19.0, 14.0.

[0113] Example 14

[0114] The preparation method of reference compound I-2 was used, the constant current of the reaction was 108 mA, and the electric quantity was 2.8 F mol -1 , and other conditions were unchanged to prepare 32 mg of the end product, which had the following structure, and the yield was 50%.

[0115]

[0116] 1 H NMR (500 MHz, CDC13) δ 8.05 - 8.03 (m, 1H), 7.97 - 7.91 (m, 1H), 7.62 - 7.56 (m, 1H), 7.45 - 7.37 (m, 1H), 4.95 (q, J = 6.5 Hz, 1H), 3.91 (s, 3H), 1.51 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 167.2, 146.4, 130.4, 130.1, 128.7 (2C), 126.7, 70.0, 52.2, 25.4.

[0117] Example 15

[0118] The preparation method of reference compound I-2 was used, the constant current of the reaction was 116 mA, and the electric quantity was 3.0 F mol -1 , and other conditions were unchanged to prepare 66 mg of the end product, which had the following structure, and the yield was 85%.

[0119]

[0120] 1 H NMR (500 MHz, CDC13) δ 7.59 - 7.53 (m, 2H), 7.49 - 7.36 (m, 4H), 7.23 - 7.18 (m, 2H), 4.92 (q, J = 6.5 Hz, 1H), 2.16 (br s, 1H), 1.53 (d, J = 6.5 Hz, 3H). 13CNMR (126MHz, CDCl3) δ 159.9 (d, J C-F =248.0Hz), 147.6(d,J) C-F =7.2Hz), 135.7, 130.9 (d, J) C-F =4.3Hz), 129.1(d,J C-F =3.4Hz), 128.6, 128.0 (d, J) C-F =13.6Hz), 127.7, 121.4 (d, J) C-F =3.5Hz), 113.2(d,J C-F =23.6Hz), 69.7, 25.2. 19 F NMR (471MHz, CDCl3) δ-117.6.

[0121] Example 16

[0122] Following the preparation method of compound I-2, the reaction was conducted at a constant current of 100 mA, with a charge of 2.6 F mol. -1 Under the same conditions, 56 mg of final product was obtained, with the structure shown below, and the yield was 88%.

[0123]

[0124] 1 H NMR(500MHz, CDCl3)δ7.05(d,J=1.6Hz,2H),6.98–6.97(m,1H),4.86(q,J=6.5Hz,1H) ,2.65(q,J=7.6Hz,4H),1.89(brs,1H),1.51(d,J=6.5Hz,3H),1.26(t,J=7.6Hz,6H). 13 C NMR (126MHz, CDCl3) δ146.0,144.7,126.8,122.4,70.7,29.0,25.2,15.7.

[0125] Example 17

[0126] Following the preparation method of compound I-2, the reaction was carried out under a constant current of 10⁸ mA and a charge of 2.8 F mol. -1 Under the same conditions, 61 mg of the final product was obtained, with the structure shown below and a yield of 66%.

[0127]

[0128] 1H NMR (500 MHz, CDC13) δ 8.09 - 8.05 (m, 2 H), 8.00 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 1.7 Hz, 1 H), 7.52 - 7.40 (m, 4 H), 5.03 (q, J = 6.5 Hz, 1 H), 1.56 (d, J = 6.4 Hz, 3 H). 13 C NMR (126 MHz, CDC13) δ 163.4, 151.0, 144.2, 141.3, 131.6, 129.0, 127.7, 127.1, 122.4, 119.7, 107.6, 70.3, 25.7. IR (neat, cm -1 ): 3447, 2924, 1637, 706. ESI HRMS m / z (M+H) + calcd 240.1019, obsd 240.1023.

[0129] Example 18

[0130] The preparation method of reference compound I-2 was used, the constant current of the reaction was 104 mA, the electric quantity was 2.7 F mol -1 , and other conditions were unchanged to obtain 70 mg of the end product, the structure of which is shown below, with a yield of 81%.

[0131]

[0132] 1 H NMR (500 MHz, CDC13) δ 8.09 - 8.05 (m, 2 H), 8.00 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 1.7 Hz, 1 H), 7.52 - 7.40 (m, 4 H), 5.03 (q, J = 6.5 Hz, 1 H), 1.56 (d, J = 6.4 Hz, 3 H). 13 C NMR (126 MHz, CDC13) δ 163.4, 151.0, 144.2, 141.3, 131.6, 129.0, 127.7, 127.1, 122.4, 119.7, 107.6, 70.3, 25.7. IR (neat, cm -1 ): 3447, 2924, 1637, 706. ESI HRMS m / z (M+H) + calcd 240.1019, obsd 240.1023.

[0133] Example 19

[0134] Referring to the preparation method of compound I-1, the constant current of the reaction was 78 mA, and the electric quantity was 2.7 F mol -1 , the hydrolysis time was prolonged to 60 minutes, and the final product was prepared with 44 mg of the structure shown below, and the yield was 58%.

[0135]

[0136] 1 H NMR (500 MHz, CDCl3) δ 8.01-7.73 (m, 2H), 7.64-7.51 (m, 2H), 7.50-7.39 (m, 1H), 7.38-7.30 (m, 2H), 5.05 (q, J = 6.5 Hz, 1H), 2.13 (brs, 1H), 1.57 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 156.6 (2C), 145.9, 127.1, 124.2, 123.6, 122.8, 120.7, 120.3, 111.8, 108.6, 70.7, 25.7. IR (neat, cm -1 ): 3293, 2924, 1425, 1073, 823, 744, 726. ESI HRMS m / z (M-H) - calcd 211.0765, obsd 211.0765.

[0137] Example 20

[0138] Referring to the preparation method of compound I-1, the constant current of the reaction was 81 mA, and the electric quantity was 2.8 F mol -1 , and the final product was prepared with 51 mg of the structure shown below, and the yield was 54%.

[0139]

[0140] 1 H NMR (500 MHz, CDCl3) δ 6.89 (d, J = 3.8 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 4.81 (t, J = 6.7 Hz, 1H), 2.04 (brs, 1H), 1.88-1.66 (m, 2H), 1.50-1.19 (m, 6H), 0.93-0.85 (m, 3H). 13 CNMR (126 MHz, CDCl3) δ 150.8, 129.4, 124.1, 111.4, 70.7, 39.2, 31.7, 25.4, 22.7, 14.1.

[0141] Example 21

[0142] Referring to the preparation method of compound I-1, the constant current of the reaction was 78 mA, and the electric quantity was 2.7 F mol -1 , other conditions unchanged, the end product 48 mg was prepared, the structure was as shown below, and the yield was 59%.

[0143]

[0144] 1 H NMR (500 MHz, CDCl3) δ 7.43 (d, J = 2.4 Hz, 1H), 7.27 (dd, J = 8.8, 2.5 Hz, 1H), 6.72 (d, J = 8.8 Hz, 1H), 4.73 (t, J = 4.3 Hz, 1H), 4.29 - 4.19 (m, 2H), 2.14 - 2.04 (m, 1H), 2.03 - 1.95 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 153.8, 132.6, 132.2, 126.4, 119.1, 112.5, 63.1, 62.3, 30.8.

[0145] Example 22

[0146] Referring to the preparation method of compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , the hydrolysis time was shortened to 30 minutes, other conditions unchanged, the end product 32 mg was prepared, the structure was as shown below, and the yield was 60%.

[0147]

[0148] 1 H NMR (500 MHz, CDCl3) δ 7.47 - 7.40 (m, 1H), 7.25 - 7.17 (m, 2H), 7.14 - 7.08 (m, 1H), 4.84 - 4.74 (m, 1H), 2.88 - 2.68 (m, 2H), 2.09 - 1.85 (m, 4H), 1.85 - 1.73 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 138.9, 137.2, 129.1, 128.7, 127.6, 126.3, 68.2, 32.4, 29.4, 18.9.

[0149] Example 23

[0150] Referring to the preparation method of compound I-1, the constant current of the reaction was 72 mA, and the electric quantity was 2.5 F mol -1Without post-treatment with dilute sulfuric acid, other conditions unchanged, the final product 47 mg was prepared, the structure is shown below, the yield was 68%.

[0151]

[0152] 1 H NMR (500 MHz, CDCl3) δ 7.51-7.40 (m, 2H), 7.10 (dd, J = 8.5, 2.8 Hz, 1H), 4.89 (dd, J = 7.4, 3.9 Hz, 1H), 3.81 (s, 3H), 2.97-2.84 (m, 1H), 2.60-2.49 (m, 1H), 2.37-2.27 (m, 1H), 2.20-2.04 (m, 1H). 13 C NMR (126 MHz, CDCl3) δ 197.8, 159.6, 138.2, 132.3, 128.9, 121.9, 109.5, 67.4, 55.6, 34.9, 32.1.

[0153] Example 24

[0154] Referring to the preparation method of compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , the hydrolysis time was shortened to 30 minutes, and other conditions were unchanged. The final product 25 mg was prepared, the structure is shown below, the yield was 51%.

[0155]

[0156] 1 H NMR (500 MHz, CDCl3) δ 7.43-7.37 (m, 1H), 7.30-7.19 (m, 3H), 5.23 (dd, J = 6.8, 5.3 Hz, 1H), 3.25-2.95 (m, 1H), 2.93-2.67 (m, 1H), 2.55-2.37 (m, 1H), 2.09-1.81 (m, 2H). 13 CNMR (126 MHz, CDCl3) δ 145.1, 143.4, 128.4, 126.8, 125.0, 124.3, 76.6, 36.0, 29.9.

[0157] Example 25

[0158] Referring to the preparation method of compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , other conditions unchanged, the final product 75 mg was prepared, the structure is shown below, the yield was 80%.

[0159]

[0160] 1 H NMR (500 MHz, CDC13) δ 7.77 (d, J = 1.8 Hz, 1H), 7.43 (d, J = 1.7 Hz, 1H), 5.37 (dd, J = 7.6, 3.9 Hz, 1H), 2.67 (s, 3H), 2.29, 2.04 (AB of ABX, J AB = 13.6 Hz, J AX = 7.6 Hz, J BX = 3.9 Hz, 2H), 1.40 (s, 3H), 1.37 (s, 9H), 1.26 (s, 3H). 13 C NMR (126 MHz, CDC13) δ 202.8, 154.5, 152.4, 142.3, 133.8, 126.3, 124.8, 73.3, 48.9, 42.9, 35.0, 31.5, 31.1, 30.0, 28.1.

[0161] Example 26

[0162] Referring to the preparation method of compound I-1, the constant current of the reaction was 72 mA, and the electric quantity was 2.5 F mol -1 , without post-treatment with dilute sulfuric acid, and other conditions were unchanged, to obtain 60 mg of the final product, with a structure as shown below, and a yield of 80%.

[0163]

[0164] 1 H NMR (500 MHz, CDC13) δ 7.08 (d, J = 2.1 Hz, 2H), 5.30 (dd, J = 6.6, 2.5 Hz, 1H), 3.95 (s, 3H), 3.87 (s, 3H), 3.04, 2.53 (AB of ABX, J AB = 18.7 Hz, J AX = 6.6 Hz, J BX = 2.5 Hz, 2H). 13 CNMR (126 MHz, CDC13) δ 202.1, 156.0, 151.0, 150.6, 129.5, 106.8, 103.6, 68.4, 56.4, 56.3, 47.4.

[0165] Example 27

[0166] Referring to the preparation method of compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1, the hydrolysis time was shortened to 15 minutes, and the other conditions were unchanged, to obtain 83 mg of the final product, with a structure as shown below, at a yield of 85%.

[0167]

[0168] 1 H NMR (500 MHz, CDCl3) δ 7.84-7.76 (m, 2H), 7.20-7.13 (m, 2H), 6.79-6.73 (m, 4H), 5.77 (s, 1H), 4.52 (brs, 1H), 3.72 (s, 3H), 3.65 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 197.4, 164.1, 159.7, 131.9, 131.6, 129.1, 126.4, 114.6, 114.0, 75.3, 55.5, 55.3.

[0169] Example 28

[0170] According to the preparation method of Reference Compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , and no hydrolysis post-treatment was performed, and the other conditions were unchanged, to obtain 58 mg of the final product, with a structure as shown below, at a yield of 98%.

[0171]

[0172] 1 H NMR (500 MHz, CDCl3) δ 7.46-7.36 (m, 2H), 6.96-6.88 (m, 2H), 5.43 (s, 1H), 3.81 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 160.7, 128.4, 127.6, 119.2, 114.6, 63.2, 55.5.

[0173] Example 29

[0174] According to the preparation method of Reference Compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and the other conditions were unchanged, to obtain 52 mg of the final product, with a structure as shown below, at a yield of 60%.

[0175]

[0176] 1H NMR (500 MHz, CDCI3) δ 7.65 - 7.57 (m, 4H), 7.55 - 7.49 (m, 2H), 7.48 - 7.44 (m, 2H), 7.41 - 7.34 (m, 1 H), 5.26 (s, 1 H), 3.80 (s, 3H), 3.57 (s, 1 H). 13 C NMR (126 MHz, CDCI3) δ 174.2, 141.6, 140.7, 137.4, 129.0, 127.6, 127.5, 127.3, 127.2, 72.9, 53.2.

[0177] Example 30

[0178] According to the preparation method of reference compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged, and the end product 65 mg was prepared, and the structure was as shown below, and the yield was 84%.

[0179]

[0180] 1 H NMR (500 MHz, CDCI3) δ 7.32 - 7.27 (m, 4H), 5.09 (dd, J = 8.7, 4.1 Hz, 1 H), 3.70 (s, 3H), 2.75 - 2.64 (m, 2H). 13 C NMR (126 MHz, CDCI3) δ 172.7, 141.1, 133.6, 128.8, 127.2, 69.7, 52.0, 43.2.

[0181] Example 31

[0182] According to the preparation method of reference compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , and other conditions were unchanged, and the end product 105 mg was prepared, and the structure was as shown below, and the yield was 76%.

[0183]

[0184] 1H NMR (500 MHz, CDC13) δ 7.30 - 7.23 (m, 2H), 6.87 (d, J = 8.6 Hz, 2H), 5.05 (d, J = 9.0 Hz, 1H), 4.74 (dd, J = 8.3, 5.1 Hz, 1H), 4.40 - 4.26 (m, 1H), 4.26 - 4.08 (m, 2H), 3.79 (s, 3H), 2.42 (br s, 1H), 2.17 - 2.05 (m, 2H), 2.05 - 1.95 (m, 1H), 1.44 (s, 9H), 0.96 (d, J = 6.8 Hz, 3H), 0.91 - 0.86 (m, 3H). 13 C NMR (126 MHz, CDC13) δ 172.7 (2C), 159.3, 155.8, 136.2 (2C), 127.1, 114.1, 79.9, 70.8, 70.7, 62.4, 58.8, 55.4, 38.0, 37.9, 31.3, 28.4, 19.1, 17.8, 17.7. IR (neat, cm -1 ): 3440, 2963, 1717, 1514, 1248, 1174, 832. ESI HRMS m / z (M + Na) + calcd 404.2044, obsd 404.2048.

[0185] Example 32

[0186] The preparation method of reference compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4F mol -1 , and other conditions were unchanged to prepare 59 mg of the end product, and the structure was as shown below, and the yield was 76%.

[0187]

[0188] 1 H NMR (500 MHz, CDC13) δ 7.41 - 7.33 (m, 4H), 7.35 - 7.26 (m, 1H), 4.94 - 4.87 (m, 1H), 3.62 - 3.52 (m, 1H), 3.46 - 3.34 (m, 1H), 2.37 - 2.26 (m, 1H), 2.26 - 1.91 (m, 2H). 13 C NMR (126 MHz, CDC13) δ 143.7, 128.8, 128.1, 125.9, 72.4, 41.7, 30.3.

[0189] Example 33

[0190] Following the preparation method of compound I-2, the reaction was carried out at a constant current of 93 mA and a charge of 2.4 F mol. -1 Under the same conditions, 48 ​​mg of final product was obtained, with the structure shown below and a yield of 46%.

[0191]

[0192] 1 H NMR(500MHz, CDCl3)δ7.95–7.85(m,2H),7.69–7.61(m,1H),7.58–7.50(m,2H),7.34–7.29(m,2H),7.28–7.24 (m,3H),4.79(dd,J=7.5,5.8Hz,1H),4.40–4.26(m,1H),4.14–4.01(m,1H),2.11(brs,1H),2.09–2.00(m,2H). 13 C NMR (126MHz, CDCl3) δ143.6,136.2,133.9,129.4,128.8,128.0,125.8,70.4,68.0,38.2.IR(neat,cm -1 ):3403,2924,1449,1360,1187,754.ESI HRMS m / z(M+Na) + calcd 315.0662,obsd 315.0668.

[0193] Example 34

[0194] Following the preparation method of compound I-2, the reaction was carried out at a constant current of 93 mA and a charge of 2.4 F mol. -1 Under the same conditions, 48 ​​mg of the final product was obtained, with the structure shown below, and the yield was 72%.

[0195]

[0196] 1 H NMR (500MHz, CDCl3) δ7.42–7.33(m,8H),7.31–7.26(m,2H),5.84(s,1H). 13 CNMR (126MHz, CDCl3) δ143.9,128.6,127.7,126.7,76.4.

[0197] Example 35

[0198] Following the preparation method of compound I-1, the reaction was carried out under a constant current of 64 mA and a charge of 2.2 F mol. -1, the hydrolysis time was extended to 60 minutes, no dilute sulfuric acid was used for post-treatment, and other conditions were unchanged. The final product was prepared in an amount of 41 mg, and the structure was as shown below, with a yield of 83%.

[0199]

[0200] 1 H NMR (500 MHz, CDCl3) δ 7.28-7.23 (m, 2H), 6.91-6.83 (m, 2H), 4.57 (s, 2H), 3.79 (s, 3H), 2.08 (brs, 1H). 13 C NMR (126 MHz, CDCl3) δ 159.3, 133.3, 128.7, 114.0, 65.0, 55.4.

[0201] Example 36

[0202] Referring to the preparation method of compound I-2, the constant current of the reaction was 100 mA, and the electric quantity was 2.6 F mol -1 , and other conditions were unchanged. The final product was prepared in an amount of 36 mg, and the structure was as shown below, with a yield of 61%.

[0203]

[0204] 1 H NMR (500 MHz, CDCl3) δ 7.43-7.38 (m, 2H), 7.33-7.29 (m, 2H), 4.65 (s, 2H), 1.34 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ 150.8, 138.1, 127.0, 125.6, 65.2, 34.7, 31.5.

[0205] Example 37

[0206] Referring to the preparation method of compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged. The final product was prepared in an amount of 43 mg, and the structure was as shown below, with a yield of 73%.

[0207]

[0208] 1H NMR (500 MHz, CDCI3) δ 7.37 - 7.29 (m, 4H), 7.30 - 7.22 (m, 1H), 4.73 (dd, J = 8.1, 5.4 Hz, 1H), 1.89 (brs, 1H), 1.76 - 1.65 (m, 2H), 1.55 - 1.46 (m, 1H), 0.97 - 0.90 (m, 6H). 13 C NMR (126 MHz, CDCI3) δ 145.3, 128.6, 127.6, 126.0, 73.0, 48.5, 24.9, 23.2, 22.4.

[0209] Example 38

[0210] According to the preparation method of reference compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged, and the end product 33 mg was prepared, and the structure was as shown below, and the yield was 51%.

[0211]

[0212] 1 H NMR (500 MHz, CDCI3) δ 7.39 - 7.31 (m, 4H), 7.33 - 7.25 (m, 1H), 4.83 (dd, J = 8.1, 5.1 Hz, 1H), 2.40 - 2.18 (m, 3H), 2.06 - 1.94 (m, 2H), 1.95 - 1.84 (m, 1H). 13 C NMR (126 MHz, CDCI3) δ 144.1, 128.7, 127.9, 126.0, 84.0, 73.3, 69.1, 37.6, 15.3.

[0213] Example 39

[0214] According to the preparation method of reference compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , and other conditions were unchanged, and the end product 52 mg was prepared, and the structure was as shown below, and the yield was 81%.

[0215]

[0216] 1H NMR (500 MHz, CDCI3) δ 7.29 - 7.25 (m, 2H), 6.94 - 6.74 (m, 2H), 5.87 - 5.66 (m, 1H), 5.24 - 4.99 (m, 2H), 4.67 (t, J = 6.5 Hz, 1H), 3.79 (s, 3H), 2.60 - 2.37 (m, 2H), 2.07 (br s, 1H). 13 C NMR (126 MHz, CDCI3) δ 159.2, 136.2, 134.7, 127.2, 118.3, 113.9, 73.1, 55.4, 43.8.

[0217] Example 40

[0218] According to the preparation method of reference compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , and other conditions were unchanged, and the end product 41 mg was prepared, and the structure was as shown below, and the yield was 63%.

[0219]

[0220] 1 H NMR (500 MHz, CDCI3) δ 7.30 - 7.24 (m, 2H), 6.89 - 6.85 (m, 2H), 4.86 (dd, J = 8.9, 3.8 Hz, 1H), 3.84 - 3.75 (m, 5H), 2.05 - 1.93 (m, 1H), 1.92 - 1.79 (m, 1H). 13 C NMR (126 MHz, CDCI3) δ 159.1, 136.7, 127.0, 114.0, 73.8, 61.4, 55.4, 40.6.

[0221] Example 41

[0222] According to the preparation method of reference compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged, and the end product 96 mg was prepared, and the structure was as shown below, and the yield was 68%.

[0223]

[0224] 1H NMR (500 MHz, CDC13) δ 7.70 - 7.61 (m, 2H), 7.42 - 7.30 (m, 2H), 7.26 - 7.20 (m, 2H), 6.82 - 6.76 (m, 3H), 4.82 (dd, J = 8.1, 3.4 Hz, 1H), 3.83 - 3.72 (m, 4H), 3.48 - 3.33 (m, 1H), 1.58 (s, 6H). 13 C NMR (126 MHz, CDC13) δ 174.9, 167.6, 155.2, 138.1, 135.6, 132.6, 129.0, 128.6, 127.0, 119.4, 79.4, 73.1, 52.7, 47.9, 25.5 (2C). IR (neat, cm -1 ): 3294, 2920, 1733, 1636, 1289, 1144, 760. ESI HRMS m / z (M + Na) + calcd 414.1079, obsd 414.1084.

[0225] Example 42

[0226] The preparation method of reference compound I-2 was used, the constant current of the reaction was 100 mA, and the electric quantity was 2.6 F mol -1 , and other conditions were unchanged to prepare 82 mg of the end product, with a structure as shown below, and a yield of 80%.

[0227]

[0228] C1 and C2 were separated by chromatography. C1: 1 H NMR (500 MHz, CDC13) δ 7.24 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 6.16 (s, 1H), 4.78 (dd, J = 8.0, 3.6 Hz, 1H), 3.74 - 3.59 (m, 1H), 3.37 - 3.28 (m, 1H), 2.88 - 2.60 (m, 7H), 1.22 (t, J = 7.6 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 173.4, 144.4, 138.8, 128.2, 125.9, 118.8 (dd, J C-F = 285.9, 268.5 Hz), 73.3, 47.4, 39.3 - 38.4 (m), 28.6, 28.1 (dd, J C-F = 14.7, 3.8 Hz), 15.6. 19F NMR (471 MHz, CDCb) δ -82.0 (d, J = 192.5 Hz), -98.5 (d, J = 192.3 Hz). IR (neat, cm -1 ): 3305, 2925, 1645, 1556, 1298, 1167, 904. ESI HRMS m / z (M + Na) + calcd 306.1276, obsd 306.1280. C2: 1 H NMR (500 MHz, CDCb) δ 7.31 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 5.60 (s, 1H), 4.87 (q, J = 6.5 Hz, 1H), 3.56 - 3.43 (m, 2H), 2.90 - 2.75 (m, 4H), 2.72 - 2.58 (m, 3H), 1.48 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDCb) δ 172.22, 144.37, 137.90, 128.98, 125.94, 118.88 (dd, J C-F = 286.1, 268.5 Hz), 70.22, 40.95, 38.79 (t, J C-F = 24.1 Hz), 35.35, 28.27 (dd, J C-F = 14.9, 3.8 Hz), 25.33. 19 F NMR (471 MHz, CDCb) δ -82.0 (d, J = 192.5 Hz), -98.7 (d, J = 192.5 Hz). IR (neat, cm -1 ): 3305, 2925, 1644, 1546, 1298, 1165, 897. ESI HRMS m / z (M + Na) + calcd 306.1276, obsd 306.1274.

[0229] Example 43

[0230] Referring to the preparation method of compound I-2, the constant current of the reaction was 108 mA, the electric quantity was 2.8 F mol -1 , and other conditions were unchanged, and the end product 46 mg was prepared, the structure was as shown below, and the yield was 63%.

[0231]

[0232] 1H NMR (500 MHz, CDC13) δ 7.33 - 7.28 (m, 2H), 7.22 - 7.18 (m, 2H), 4.87 (q, J = 6.5 Hz, 1H), 2.56 - 2.46 (m, 1H), 1.94 - 1.80 (m, 5H), 1.80 - 1.72 (m, 1H), 1.50 (d, J = 6.5 Hz, 3H), 1.48 - 1.35 (m, 4H), 1.31 - 1.22 (m, 1H). 13 C NMR (126 MHz, CDC13) δ 147.6, 143.3, 127.1, 125.5, 70.4, 44.4, 34.6, 27.0, 26.3, 25.0.

[0233] Example 44

[0234] The preparation method of reference compound I-2 was used, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged to prepare 34 mg of the end product, the structure of which was shown below, with a yield of 55%.

[0235]

[0236] 1 H NMR (500 MHz, CDC13) δ 7.39 - 7.32 (m, 4H), 4.88 (q, J = 6.5 Hz, 1H), 4.57 (s, 2H), 2.05 (br s, 1H), 1.47 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 146.2, 136.8, 128.9, 125.9, 70.1, 46.1, 25.3.

[0237] Example 45

[0238] The preparation method of reference compound I-2 was used, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged to prepare 48 mg of the end product, the structure of which was shown below, with a yield of 52%.

[0239]

[0240] 1 H NMR (500 MHz, CDC13) δ 8.10 - 7.97 (m, 2H), 7.61 - 7.50 (m, 1H), 7.47 - 7.37 (m, 6H), 5.34 (s, 2H), 4.91 (q, J = 6.4 Hz, 1H), 2.08 (br s, 1H), 1.49 (d, J = 6.5 Hz, 3H). 13C NMR (126 MHz, CDC13) δ 166.6, 146.1, 135.3, 133.2, 130.2, 129.8, 128.5 (2C), 125.8, 70.2, 66.6, 25.3. IR (neat, cm -1 ): 3428, 2925, 1720, 1272, 1110, 711. ESI HRMS m / z (M + Na) + calcd 279.0992, obsd 279.0998.

[0241] Example 46

[0242] The preparation method of reference compound I-1 was used, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 The reaction solution was directly introduced into 4 mL of saturated NaHC03with stirring. 8 mL of the reaction solution was collected, and stirring was continued at room temperature for 30 min. Without post-treatment with dilute sulfuric acid, the final product was prepared under the same conditions, and the structure was as shown below, and the yield was 72%.

[0243]

[0244] 1 H NMR (500 MHz, CDC13) δ 7.33 (d, J = 8.4 Hz, 1H), 6.76 (dd, J = 8.4, 2.7 Hz, 1H), 6.62 (d, J = 2.6 Hz, 1H), 4.74 (t, J = 4.3 Hz, 1H), 3.78 (s, 3H), 2.85 - 2.75 (m, 1H), 2.75 - 2.62 (m, 1H), 2.01 - 1.84 (m, 3H), 1.82 - 1.69 (m, 2H). 13 C NMR (126 MHz, CDC13) δ 159.0, 138.7, 131.4, 130.2, 113.5, 112.6, 67.8, 55.3, 32.5, 29.7, 18.7.

[0245] Example 47

[0246] The preparation method of reference compound I-1 was used, the constant current of the reaction was 85 mA, and the electric quantity was 2.2 F mol -1 The final product was prepared under the same conditions, and the structure was as shown below, and the yield was 50%.

[0247]

[0248] 1H NMR (500 MHz, CDCI3) δ 7.83 - 7.71 (m, 2H), 7.62 - 7.52 (m, 2H), 7.42 - 7.36 (m, 2H), 7.34 - 7.28 (m, 1H), 4.98 (q, J = 6.4 Hz, 1H), 3.89 (s, 2H), 1.97 (brs, 1H), 1.56 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 144.7, 143.7, 143.5, 141.6, 141.3, 126.9, 126.8, 125.2, 124.3, 122.2, 120.0, 119.9, 70.8, 37.0, 25.4.

[0249] Example 48

[0250] The preparation method of reference compound I-1 was used, the constant current of the reaction was 58 mA, and the electric quantity was 2.0 F mol -1 . The hydrolysis time was shortened to 5 minutes, no dilute sulfuric acid was used for post-treatment, and the other conditions were unchanged. Finally, 121 mg of the end product was prepared, and the yield was 89%, and the structure was as follows.

[0251]

[0252] 1 H NMR (500 MHz, CDCI3) δ 7.83 - 7.71 (m, 2H), 7.62 - 7.52 (m, 2H), 7.42 - 7.36 (m, 2H), 7.34 - 7.28 (m, 1H), 4.98 (q, J = 6.4 Hz, 1H), 3.89 (s, 2H), 1.97 (brs, 1H), 1.56 (d, J = 6.4 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 162.5 (d, J C-F = 247.5 Hz), 145.7, 143.9, 143.0, 134.0, 132.3, 131.0, 130.5 (d, J C-F = 3.3 Hz), 128.7, 127.5 (d, J C-F = 8.0 Hz), 126.7, 122.7, 120.2, 115.9 (d, J C-F = 21.8 Hz), 68.9, 18.8. 19 F NMR (471 MHz, CDCI3) δ -114.3. IR (neat, cm -1 ): 3385, 2925, 1509, 1233, 810. ESI HRMS m / z (M-H) -Calcd 374.9860, obsd 374.9852.

[0253] Example 49

[0254] Referring to the preparation method of compound I-2, the constant current of the reaction was 127 mA, and the electric quantity was 3.3 F mol -1 , other conditions unchanged, the end product 39 mg was prepared, the structure was as shown below, and the yield was 45%.

[0255]

[0256] 1 H NMR (500 MHz, CDCl3) δ 7.86 (d, J = 8.0 Hz, 2H), 7.37-7.19 (m, 7H), 4.92 (dd, J = 7.7, 5.6 Hz, 1H), 3.14-3.02 (m, 2H), 2.56 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 198.0, 144.0, 143.7, 135.7, 129.9, 128.6 (2C), 128.0, 126.0, 75.2, 45.9, 26.7.

[0257] Example 50

[0258] Referring to the preparation method of compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , without post-treatment with dilute sulfuric acid, other conditions unchanged, the end product 71 mg was prepared, the structure was as shown below, and the yield was 86%.

[0259]

[0260] 1 H NMR (500 MHz, CDCl3) δ 7.47-7.43 (m, 2H), 7.43-7.38 (m, 2H), 7.37-7.32 (m, 1H), 7.32-7.28 (m, 2H), 6.99-6.95 (m, 2H), 5.07 (s, 2H), 4.85 (q, J = 6.4 Hz, 1H), 1.49 (d, J = 6.5 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 158.3, 138.4, 137.1, 128.7, 128.0, 127.5, 126.8, 114.9, 70.1, 70.0, 25.1.

[0261] Example 51

[0262] Referring to the preparation method of compound I-2, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 Without post-treatment with dilute sulfuric acid, other conditions were unchanged, and the final product 38 mg was prepared, the structure of which is shown below, with a yield of 49%.

[0263]

[0264] 1 H NMR (500 MHz, CDC13) δ 8.55 - 8.41 (m, 1H), 7.63 - 7.57 (m, 1H), 7.41 - 7.36 (m, 2H), 7.35 - 7.30 (m, 2H), 7.26 - 7.21 (m, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.14 - 7.10 (m, 1H), 4.81 (dd, J = 7.8, 4.5 Hz, 1H), 2.99 - 2.95 (m, 2H), 2.22 - 2.13 (m, 2H). 13 C NMR (126 MHz, CDC13) δ 161.5, 148.7, 145.3, 137.0, 128.4, 127.2, 125.9, 123.4, 121.3, 73.7, 38.2, 34.5.

[0265] Example 52

[0266] Referring to the preparation method of compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 Without post-treatment with dilute sulfuric acid, other conditions were unchanged, and the final product 72 mg was prepared, the structure of which is shown below, with a yield of 64%.

[0267]

[0268] 1 H NMR (500 MHz, CDC13) δ 7.34 - 7.26 (m, 4H), 7.24 - 7.14 (m, 3H), 6.92 - 6.85 (m, 2H), 5.09 (dd, J = 9.1, 3.8 Hz, 1H), 4.14 (t, J = 6.5 Hz, 2H), 3.79 (s, 3H), 3.17 (brs, 1H), 2.84 - 2.56 (m, 4H), 2.01 - 1.92 (m, 2H). 13 C NMR (126 MHz, CDC13) δ 172.4, 159.4, 141.2, 134.9, 128.6, 128.5, 127.1, 126.2, 114.1, 70.1, 64.3, 55.4, 43.4, 32.2, 30.2. IR (neat, cm -1): 3489, 2925, 1732, 1514, 1248, 1031, 833, 700. ESI HRMS m / z (M+Na) + Calcd 337.1410, obsd 337.1417.

[0269] Example 53

[0270] The procedure of Reference Compound I-2 was followed, with a constant current of 93 mA and a charge of 2.4 F mol -1 The final product was obtained as 72 mg with a yield of 78% under the same conditions, and the structure was shown as follows.

[0271]

[0272] 1 H NMR (500 MHz, CDC13) δ 7.40 - 7.35 (m, 2 H), 7.32 - 7.27 (m, 4 H), 7.24 - 7.19 (m, 3 H), 4.85 (dd, J = 8.9, 4.5 Hz, 1 H), 3.08 - 2.93 (m, 2 H), 1.96 (br s, 1 H), 1.32 (s, 9 H). 13 C NMR (126 MHz, CDC13) δ 150.7, 141.0, 138.5, 129.6, 128.6, 126.7, 125.7, 125.4, 75.2, 46.1, 34.7, 31.5.

[0273] Example 54

[0274] The procedure of Reference Compound I-2 was followed, with a constant current of 93 mA and a charge of 2.4 F mol -1 The final product was obtained as 39 mg with a yield of 45% under the same conditions, and the structure was shown as follows.

[0275]

[0276] 1 H NMR (500 MHz, CDC13) δ 7.26 - 7.20 (m, 4 H), 7.19 - 7.12 (m, 5 H), 4.80 (dd, J = 8.8, 4.6 Hz, 1 H), 3.05 - 2.79 (m, 3 H), 1.84 (br s, 1 H), 1.18 (d, J = 6.9 Hz, 6 H). 13 C NMR (126 MHz, CDC13) δ 148.5, 141.4, 138.5, 129.6, 128.6, 126.7, 126.6, 126.0, 75.3, 46.1, 34.0, 24.1. IR (neat, cm-1 ): 3422, 2959, 1454, 1078, 830, 699. ESI HRMS m / z (M+Na) + calcd 263.1406, obsd 263.1406.

[0277] Example 55

[0278] Referring to the preparation method of compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , the hydrolysis time was extended to 60 minutes, no dilute sulfuric acid was used for post-treatment, and other conditions were unchanged, and the final product was prepared 89 mg, and the structure was as shown below, the yield was 74%.

[0279]

[0280] 1 H NMR (500 MHz, CDC13) δ 7.33 - 7.18 (m, 3H), 7.04 - 6.96 (m, 4H), 5.31 (s, 2H), 4.68 (s, 2H), 2.82 - 2.71 (m, 1H), 2.66 (s, 3H), 2.28 (brs, 1H), 1.88 - 1.76 (m, 6H), 1.73 - 1.67 (m, 1H), 1.39 - 1.22 (m, 3H). 13 C NMR (126 MHz, CDC13) δ 159.1, 141.9, 136.6, 135.4, 135.1, 129.5, 129.1, 127.9, 126.1, 122.1, 105.8, 65.9, 46.9, 36.9, 31.9, 26.5, 25.7, 17.0. IR (neat, cm -1 ): 3311, 2926, 1453, 1029, 838, 731. ESI HRMS m / z (M+H) + calcd 335.2118, obsd 335.2119.

[0281] Example 56

[0282] Referring to the preparation method of compound I-1, the constant current of the reaction was 69 mA, and the electric quantity was 2.4 F mol -1 , the hydrolysis time was extended to 60 minutes, and other conditions were unchanged, and the final product was prepared 57 mg, and the structure was as shown below, the yield was 59%.

[0283]

[0284] 1H NMR (400 MHz, CDC13) δ 8.08 - 7.95 (m, 2H), 7.58 (s, 1H), 7.51 - 7.39 (m, 3H), 4.75 (s, 2H), 2.50 (s, 3H), 2.48 (s, 3H). 13 C NMR (126 MHz, CDC13) δ 168.3, 153.0, 136.5, 134.4, 133.7, 133.6, 131.0, 130.7, 129.1, 127.5, 122.2, 59.0, 20.2, 19.2. IR (neat, cm -1 ): 3365, 2923, 1478, 764. ESI HRMS m / z (M+H) + calcd 270.0947, obsd 270.0952.

[0285] Example 57

[0286] The final product was prepared according to the procedure for the preparation of Reference Compound I-2, constant current of 81 mA, charge of 2.1 F mol -1 , with other conditions unchanged, to give the final product 52 mg, yield 60%.

[0287]

[0288] 1 H NMR (400 MHz, DMSO-d6) δ 8.24 - 8.06 (m, 2H), 7.72 (s, 1H), 7.66 - 7.51 (m, 4H), 5.31 (s, 1H), 4.61 (s, 2H), 2.34 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 161.9, 148.9, 140.0, 138.9, 131.9, 131.6, 129.2, 127.1, 126.7, 120.0, 108.1, 61.0, 18.3. IR (neat, cm -1 ): 3344, 2919, 1445, 1272, 1095, 1022, 702. ESI HRMS m / z (M+H) + calcd 240.1019, obsd 240.1022.

[0289] Example 58

[0290] The final product was prepared according to the procedure for the preparation of Reference Compound I-1, constant current of 58 mA, charge of 2.0 F mol -1, the hydrolysis time was extended to 60 minutes, no dilute sulfuric acid was used for post-processing, and other conditions were unchanged. The final product 60 mg was prepared, the structure was as shown below, and the yield was 58%.

[0291]

[0292] 1 H NMR (500 MHz, CDCl3) δ 7.11 (s, 1H), 7.03 (s, 1H), 4.62 (s, 2H), 3.50 (s, 3H), 2.90-2.76 (m, 1H), 2.67-2.53 (m, 4H), 2.22 (brs, 1H), 1.37 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 179.5, 140.1, 135.5, 132.1, 131.2, 125.3 (q, J C-F = 278.4 Hz), 120.4, 120.1, 64.9, 43.9, 40.9 (q, J C-F = 28.1 Hz), 29.9, 25.6, 19.1. 19 F NMR (471 MHz, CDCl3) δ -61.9. IR (neat, cm -1 ): 3462, 2924, 1686, 1604, 1457, 1363, 1184, 1073, 753. ESI HRMS m / z (M+Na) + calcd 310.1025, obsd 310.1030.

[0293] Example 59

[0294] Referring to the preparation method of reference compound I-1, the constant current of the reaction was 67 mA, and the electric quantity was 2.3 F mol -1 , the hydrolysis time was extended to 60 minutes, no dilute sulfuric acid was used for post-processing, and other conditions were unchanged. The final product 60 mg was prepared, the structure was as shown below, and the yield was 58%.

[0295]

[0296] 1 H NMR (500 MHz, CDCl3) δ 7.20-7.19 (m, 1H), 7.00 (d, J = 1.9 Hz, 1H), 4.62 (s, 2H), 3.80 (s, 6H), 3.25 (s, 3H), 3.14 (s, 2H), 2.35 (s, 3H), 2.11 (brs, 1H). 13C NMR (126 MHz, CDC13) δ 169.7, 169.6, 140.0, 137.4, 131.6, 128.8, 127.8, 122.9, 64.5, 57.9, 53.6, 39.6, 36.1, 20.9. IR (neat, cm -1 ): 3444, 1644, 1084. ESI HRMS m / z (M+Na) + calcd 344.1105, obsd 344.1115.

[0297] Example 60

[0298] The preparation method of reference compound I-2 was used, the constant current of the reaction was 93 mA, and the electric quantity was 2.4 F mol -1 , and other conditions were unchanged to prepare 62 mg of the end product, which had the following structure, and the yield was 73%.

[0299]

[0300] 1 H NMR (500 MHz, CDC13) δ 7.28 - 7.23 (m, 4H), 4.32 (d, J = 6.9 Hz, 1H), 3.71 (q, J = 7.2 Hz, 1H), 3.64 (s, 3H), 1.98 - 1.89 (m, 2H), 1.48 (d, J = 7.2 Hz, 3H), 0.98 (d, J = 6.7 Hz, 3H), 0.79 (d, J = 6.8 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 175.2, 142.7, 139.7, 127.4, 127.0, 79.8, 52.1, 45.2, 35.3, 19.1, 18.7, 18.3.

[0301] Example 61

[0302] The preparation method of reference compound I-2 was used, the constant current of the reaction was 96 mA, and the electric quantity was 2.5 F mol -1 , and other conditions were unchanged to prepare 61 mg of the end product, which had the following structure, and the yield was 51%.

[0303]

[0304] 1H NMR (500 MHz, CDC13) δ 7.38 (d, J = 1.9 Hz, 0.23H), 7.24 - 7.07 (m, 2.77H), 4.86 (t, J = 8.7 Hz, 0.23H), 4.74 (dd, J = 4.5, 1.6 Hz, 0.77H), 3.69 (s, 2.31H), 3.67 (s, 0.69H), 2.88 (hept, J = 6.9 Hz, 1H), 2.58 - 2.40 (m, 0.77H), 2.35 - 2.22 (m, 1.23H), 2.18 - 1.63 (m, 6H), 1.62 - 1.54 (m, 0.77H), 1.55 - 1.40 (m, 1.23H), 1.30 - 1.28 (m, 3.77H), 1.24 (d, J = 6.9 Hz, 6H), 1.17 (s, 2.23H). 13 C NMR (126 MHz, CDC13) δ 178.9, 178.8, 146.8, 146.7 (2C), 146.6, 137.7, 136.3, 128.3, 126.6, 125.9, 125.4, 124.3, 124.2, 70.8, 68.2, 52.2, 52.1, 47.4 (2C), 43.6, 40.0, 38.1, 37.9, 37.7, 37.6, 36.6 (2C), 33.8, 33.7, 32.9, 31.3, 29.8, 25.6, 24.2 (2C), 24.1, 24.0 (2C), 18.7, 18.5, 16.6. IR (neat, cm -1 ): 3445, 2926, 1727, 1459, 1249, 824. ESI HRMS m / z (M + Na) + calcd 353.2087, obsd 353.2088.

[0305] Example 62

[0306] The preparation method of reference compound I-1 was used, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 , the hydrolysis time was shortened to 15 minutes, and the final product was prepared with a yield of 47 mg at a yield of 44% under the other unchanged conditions.

[0307]

[0308] 1H NMR (500 MHz, CDC13) δ 8.28 (d, J = 2.4 Hz, 1H), 7.89 (dd, J = 7.6, 1.3 Hz, 1H), 7.61 - 7.51 (m, 2H), 7.50 - 7.44 (m, 1H), 7.36 (dd, J = 7.5, 1.2 Hz, 1H), 7.06 (d, J = 8.5 Hz, 1H), 5.21 (d, J = 5.4 Hz, 1H), 5.19 (s, 2H), 3.77 (s, 3H), 3.51 (d, J = 5.3 Hz, 1H). 13 C NMR (126 MHz, CDC13) δ 190.8, 174.0, 161.5, 140.6, 135.5, 133.4, 133.0, 132.3, 130.6, 129.6, 129.5, 128.0, 125.3, 121.4, 73.8, 72.3, 53.3. IR (neat, cm -1 ): 3463, 2925, 1740, 1648, 1488, 1301, 761. ESI HRMS m / z (M + Na) + calcd 321.0733, obsd 321.0742.

[0309] Example 63

[0310] The preparation method of reference compound I-1 was used, the constant current of the reaction was 61 mA, the electric quantity was 2.1 F mol -1 , and other conditions were unchanged, and the end product 189 mg was prepared, the structure was shown below, and the yield was 89%.

[0311]

[0312] 1H NMR (500 MHz, CDC13) δ 7.66 (d, J = 2.1 Hz, 0.52H), 7.59 (d, J = 2.1 Hz, 0.48H), 7.36 - 7.17 (m, 4H), 6.88 - 6.77 (m, 2H), 6.12 (s, 0.48H), 6.07 (s, 0.52H), 5.37 - 5.27 (m, 1H), 5.26 - 5.17 (m, 1H), 5.16 - 5.03 (m, 1H), 4.45 - 4.35 (m, 1H), 4.31 - 4.21 (m, 1H), 4.21 - 4.12 (m, 1H), 4.05 - 3.94 (m, 2H), 3.88 - 3.77 (m, 1H), 2.38 (br s, 1H), 2.09 - 2.03 (m, 6H), 2.02 - 1.97 (m, 3H), 1.86 (s, 1.56H), 1.65 (s, 1.44H), 1.45 - 1.33 (m, 3H). 13 C NMR (126 MHz, CDC13) δ 170.9 (2C), 170.5, 170.4, 169.6, 169.1, 169.0, 158.6 (2C), 141.4 (2C), 135.5, 135.3, 134.4, 134.3, 132.7 (2C), 129.9, 129.8, 128.6, 128.1, 127.1, 126.9 (2C), 126.7, 114.5 (2C), 79.6, 79.5, 76.2 (2C), 74.2, 72.7, 72.6, 72.2, 71.9, 68.6, 63.5, 62.4, 20.8, 20.7, 20.5, 20.3, 14.9 (2C). IR (neat, cm -1 ): 3490, 2926, 1755, 1510, 1376, 1231, 1033, 737. ESI HRMS m / z (M + Na) + calcd 615.1604, obsd 615.1612.

[0313] Example 64

[0314] The preparation method of reference compound I-1, the constant current of the reaction was 61 mA, and the electric quantity was 2.1 F mol -1 The reaction solution was directly introduced into 4 mL of saturated NaHC03with stirring. 8 mL of the reaction solution was collected and stirring was continued at room temperature for 60 min. Without post-treatment with dilute sulfuric acid, the final product was prepared under the same conditions as above, and the yield was 38 mg, and the structure was as shown below, and the yield was 64%.

[0315]

[0316] 1 H NMR (500 MHz, CDCI3) δ 7.46 - 7.38 (m, 2H), 6.93 - 6.84 (m, 2H), 3.80 (s, 3H), 1.90 (br s, 1 H), 1.57 (s, 6H). 13 C NMR (126 MHz, CDCI3) δ 158.4, 141.5, 125.7, 113.6, 72.3, 55.4, 31.9.

[0317] Example 65

[0318] The preparation method of reference compound I-2, the constant current of the reaction was 96 mA, and the electric quantity was 2.5 F mol -1 The reaction solution was directly introduced into a mixed solution of 2 mL of saturated NaHC03and 2 mL of acetonitrile while stirring. 6 mL of the reaction solution was collected, distilled under reduced pressure, and the residue was added with 4 mL of acetonitrile and 1 mL of saturated NaHC03, and stirred at room temperature for 90 min. Without post-treatment with dilute sulfuric acid, the final product was prepared under the same conditions, and the yield was 49 mg, and the structure was as shown below, and the yield was 64%.

[0319]

[0320] 1 H NMR (500 MHz, CDCI3) δ 7.48 - 7.41 (m, 2H), 7.40 - 7.29 (m, 2H), 1.87 (br s, 1 H), 1.55 (s, 6H). 13 C NMR (126 MHz, CDCI3) δ 148.3, 131.4, 126.5, 120.7, 72.5, 31.9.

[0321] The method of the present application has been described by preferred embodiments, and the related personnel can obviously modify or appropriately change and combine the method and application described herein to realize and apply the present application technology within the content, spirit and scope of the present application. Those skilled in the art can refer to the content herein to appropriately improve the process parameters. It is particularly pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they are considered to be included in the present application.

Claims

1. A process for the preparation of benzyl alcohol, characterized in that, The reaction process is as follows: ； The benzyl alcohol compound of Formula I is selected from ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; The preparation method comprises the following steps: 1) dissolving the substrate shown in formula A, trifluoroacetic acid and 2,6-dimethylpyridine in a dry reaction solvent; the reaction solvent is selected from one of anhydrous dry acetonitrile, dichloromethane, a mixed solution of dichloromethane and hexafluoroisopropanol; 2) pushing the solution in step 1 through an electrolytic cell at a certain flow rate for reaction by using a syringe pump; 3) after the reaction is completed, collecting the effluent at the outlet of the electrolytic cell, and optionally post-treating to obtain the benzyl alcohol compound shown in formula I.

2. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The molar ratio of trifluoroacetic acid to the substrate shown in formula A in step 1 is 1:1 to 10:

1.

3. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The molar ratio of 2,6-dimethylpyridine to the substrate shown in formula A in step 1 is 1:1 to 10:

1.

4. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The reaction concentration of the substrate in step 1 ranges from 0.01 mol / L to 0.5 mol / L.

5. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The certain flow rate in step 2 is 0.1 mL / min to 50 mL / min.

6. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The electrolytic cell in step 2 can be a flow electrolytic cell equipped with a graphite anode and a platinum cathode or can be a flow electrolytic cell equipped with a Pt anode and a graphite cathode.

7. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The electrolytic cell in step 2 The constant current of the reaction ranges from 1 mA to 1000 mA.

8. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The electrolytic cell in step 2 The electric quantity of the reaction ranges from 1 F / mol to 10 F / mol -1 -10 F / mol -1 The electrode reaction of the electrolytic cell in step 2) is The surface area of the dew is 1 cm 2 - 100 cm 2 The distance between the electrodes is 100 μm - 1000 μm.

9. The process for the preparation of benzyl alcohol according to claim 1, characterized in that, The post-treatment in step 3 comprises: removing the solvent in the effluent, dissolving in acetonitrile, adding saturated NaHCO3 solution, stirring at room temperature, adding water, and extracting with ethyl acetate; treating the organic phase with dilute H2SO4, extracting with ethyl acetate, removing the solvent, and separating the product I by column chromatography.

10. A benzyl alcohol characterized in that, Prepared by any of the preparation methods of claims 1-9, selected from one of the following compounds: ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； 。

Images