Preparation method of arylboronic acid ester derivative

Abstract

The invention provides a preparation method of an arylboronic acid ester derivative as shown in a formula III, which comprises the following steps: S1, carrying out electrolytic reaction on a compound as shown in a formula I and a compound as shown in a formula II in a current mode to obtain the compound as shown in the formula III; wherein R1 and R2 are respectively and independently selected from hydrogen, hydroxyl, amido, cyano, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, halogen, halogenated C1-6 alkyl, C1-6 acyloxy, C1-6 alkoxy carbonyl, C1-6 alkylsulfonyl, C6-10 aryl, 5-10-membered heteroaryl and 3-6-membered heterocyclic radical, or C3-6 cycloalkyl, C3-6 cyclic aryl or 5-10-membered heteroaryl formed by R1, R2 and carbon connected with R1 and R2. The preparation method does not need to use a metal catalyst, alkali and an external oxidant, and is mild in reaction condition and environment-friendly; the method is of great significance in promoting the progress of green chemistry and meeting the sustainable development requirement of the pharmaceutical industry.

Description

Technical Field

[0001] The present invention belongs to the technical field of electrochemical preparation of compounds, and particularly relates to a method for preparing an aryl borate derivative. Background Art

[0002] Aryl borate esters are important intermediates for constructing carbon-carbon bonds and carbon-heteroatom bonds. They are widely used in drug synthesis, material preparation, and environmental monitoring. They have the advantages of high stability, low toxicity, and easy operation.

[0003] Currently, the synthesis of aryl boronates primarily relies on cross-coupling reactions: for example, through the reaction of borate esters with Grignard reagents or lithium reagents, through the reaction of aryl halides with borate esters, or through decarboxylative borylation reactions. However, for compounds containing functional groups such as cyano, nitro, and carbonyl groups, aryl borate esters cannot be directly prepared using organometallic reagents. Furthermore, while transition-metal-catalyzed borylation of aryl halides or halide-like compounds is a direct method for constructing carbon-boron bonds, the use of halides limits the versatility and green nature of the reaction.

[0004] Among the many cross-coupling methods, decarboxylation borylation has attracted widespread attention from chemists due to its representativeness. So far, there are different types of aromatic sources for decarbonylation borylation reactions, such as amides, esters, carboxylic acids, and aromatic anhydrides. Among them, carboxylic acids, as a naturally occurring, non-toxic, and stable compound under laboratory conditions, are ideal aromatic sources. However, the traditional decarboxylation process of carboxylic acids and their derivatives usually requires the addition of chemical oxidants, transition metal catalysts (such as nickel, palladium, and rhodium), and a large amount of base, and the scope of application of raw materials is narrow; this not only increases costs, but may also have an impact on the environment. For example, in pharmaceutical applications, metal contamination is also a problem. In addition, the high temperature (>100°C) required for the decarboxylation reaction can also lead to reduced selectivity, especially when dealing with sensitive heteroaromatic substrates.

[0005] Therefore, it is urgent to provide a method for synthesizing aryl borate derivatives with mild reaction conditions (no metal catalyst, no base and no external oxidant) and environmental friendliness. Summary of the Invention

[0006] In order to solve the above-mentioned problems existing in the prior art, a method for preparing aryl borate derivatives is provided. The preparation method does not require the use of metal catalysts, bases and external oxidants, has mild reaction conditions and is environmentally friendly. It is of great significance for promoting the progress of green chemistry and meeting the sustainable development needs of the pharmaceutical industry.

[0007] The present invention provides a method for preparing an aryl borate derivative represented by formula III, comprising the following steps:

[0008]

[0009] S1: electrolyzing a compound of formula I and a compound of formula II in a current mode to obtain a compound of formula III;

[0010] Wherein, R1 and R2 are each independently selected from hydrogen, hydroxyl, amino, cyano, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, halogen, halogenated C 1-6 Alkyl, C 1-6 Acyloxy, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic group, or R1 and R2 and the carbon to which they are attached form C 3-6 Cycloalkyl, C 6-10 Aryl or 5-10 membered heteroaryl;

[0011] The heteroatoms in the 5-10 membered heteroaryl and 3-6 membered heterocyclic group are independently selected from 1, 2, 3 or 4 of N, O and S;

[0012] The heteroatoms in the 5-10 membered heteroaryl group are independently selected from 1, 2, 3 or 4 of N, O and S.

[0013] Preferably, R1 and R2 are each independently selected from hydrogen, hydroxyl, amino, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, tert-butoxy, fluorine, chlorine, bromine, iodine, difluoromethyl, trifluoromethyl, formyloxy, acetoxy, propionyloxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, phenyl, or R1 and R2 and the carbon atoms to which they are attached form a C 5-6 Cycloalkyl, C 6-8 Aryl or 5-8 membered heteroaryl;

[0014] The heteroatoms in the 5-8 membered heteroaryl group are independently selected from 1 or 2 of N, O and S.

[0015] Preferably, the anode electrode of the electrolysis reaction is selected from one of a carbon anode and a graphite anode, and the cathode electrode is one of a carbon cathode, a graphite cathode and a platinum cathode.

[0016] Preferably, the anode electrode is a carbon anode, and the cathode electrode is one of a carbon cathode and a platinum cathode.

[0017] Preferably, the molar ratio of the compound of formula I to the compound of formula II is 1:(1-3).

[0018] Preferably, the electrolyte of the electrolysis reaction is selected from one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium bromide, tetrabutylammonium iodide, tetra-n-butylammonium hexafluorophosphate, sodium tetrafluoroborate and tetraethylammonium p-toluenesulfonate; preferably one or more of tetrabutylammonium bromide and tetrabutylammonium iodide.

[0019] Preferably, the molar ratio of the electrolyte to the compound of formula I is 1:(1-3).

[0020] Preferably, the reaction temperature of the electrolysis reaction is 20-30° C., and the reaction time is 4-10 h.

[0021] Preferably, the current of the electrolysis reaction is a constant current of 5 to 10 mA.

[0022] Preferably, the solvent for the electrolysis reaction is selected from one or more of acetonitrile, dimethyl sulfoxide, dichloromethane, N,N-dimethylformamide, methanol, tetrahydrofuran and water.

[0023] Preferably, the solvent for the electrolysis reaction is a mixed solvent of acetonitrile and water, and the volume ratio of acetonitrile to water is (5-15):1; preferably (8-12):1; more preferably 10:1.

[0024] Preferably, the method further comprises the step of separating and purifying after the electrolysis reaction is completed to obtain the compound of formula III.

[0025] Preferably, the separation and purification is to remove the solvent from the reaction solution under reduced pressure, add saturated sodium chloride aqueous solution, extract with an organic solvent, dry with anhydrous sodium sulfate, concentrate under vacuum, and separate and purify by column chromatography to obtain the compound of formula III.

[0026] Preferably, the organic solvent is selected from one or more of dichloromethane, ethyl acetate, acetone, methanol, ethanol and n-hexane.

[0027] Preferably, the separation and purification uses a mixed solvent of petroleum ether and ethyl acetate as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is (5-10):1.

[0028] Compared with the prior art, the beneficial effects of the present invention are: the present invention does not require the use of metal catalysts, bases and external oxidants, the reaction conditions are mild, the operation is simple, the safety is high, the raw materials are cheap and readily available, and it is environmentally friendly; it is of great significance for promoting the progress of green chemistry and meeting the sustainable development needs of the pharmaceutical industry. The present invention demonstrates a wide range of applicability of raw material substrates, can adapt to a variety of raw materials with different structures and properties, has good versatility and flexibility, and a yield of up to 62%; at the same time, it maintains excellent atom economy and step economy. The preparation method of the present invention has completed scale-up experiments in the laboratory, with excellent results, is suitable for large-scale industrial production, and has high application value and market prospects. DETAILED DESCRIPTION

[0029] To make the technical solutions and beneficial effects of the present disclosure more clearly understood, the following is a detailed description by listing specific embodiments. Unless otherwise defined, the technical and scientific terms used herein have the same meanings as those in the technical field to which this application belongs.

[0030] The present invention provides a method for preparing an aryl borate derivative represented by formula III, comprising the following steps:

[0031]

[0032] S1: electrolyzing a compound of formula I and a compound of formula II in a current mode to obtain a compound of formula III;

[0033] Wherein, R1 and R2 are each independently selected from hydrogen, hydroxyl, amino, cyano, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, halogen, halogenated C 1-6 Alkyl, C 1-6 Acyloxy, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic group, or R1 and R2 and the carbon to which they are attached form C 3-6 Cycloalkyl, C 6-10 Aryl or 5-10 membered heteroaryl;

[0034] The heteroatoms in the 5-10 membered heteroaryl and 3-6 membered heterocyclic group are independently selected from 1, 2, 3 or 4 of N, O and S;

[0035] The heteroatoms in the 5-10 membered heteroaryl group are independently selected from 1, 2, 3 or 4 of N, O and S.

[0036] In certain embodiments, R1 and R2 are each independently selected from hydrogen, hydroxyl, amino, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, tert-butoxy, fluorine, chlorine, bromine, iodine, difluoromethyl, trifluoromethyl, formyloxy, acetoxy, propionyloxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, phenyl, or R1 and R2 and the carbon to which they are attached form a C 5-6 Cycloalkyl, C 6-8 Aryl or 5-8 membered heteroaryl;

[0037] The heteroatoms in the 5-8 membered heteroaryl group are independently selected from 1 or 2 of N, O and S.

[0038] In certain embodiments, the anode electrode of the electrolysis reaction is selected from one of a carbon anode and a graphite anode, and the cathode electrode is one of a carbon cathode, a graphite cathode and a platinum cathode.

[0039] In certain embodiments, the anode electrode is a carbon anode, and the cathode electrode is one of a carbon cathode and a platinum cathode.

[0040] In certain embodiments, the anode electrode is a carbon anode and the cathode electrode is a carbon cathode.

[0041] In certain embodiments, the anode electrode is a carbon anode and the cathode electrode is a platinum cathode.

[0042] In certain embodiments, the molar ratio of the compound of formula I to the compound of formula II is 1:(1-3), for example, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, etc.

[0043] In certain embodiments, the electrolyte of the electrolysis reaction is selected from one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium bromide, tetrabutylammonium iodide, tetra-n-butylammonium hexafluorophosphate, sodium tetrafluoroborate, and tetraethylammonium p-toluenesulfonate.

[0044] In certain embodiments, the electrolyte of the electrolysis reaction is selected from one or more of tetrabutylammonium bromide and tetrabutylammonium iodide.

[0045] In certain embodiments, the molar ratio of the electrolyte to the compound of formula I is 1:(1-3), for example, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, etc.

[0046] In certain embodiments, the reaction temperature of the electrolysis reaction is 20-30°C, for example, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, etc.; the reaction time is 4-10h, for example, 4h, 5h, 6h, 7h, 8h, 9h, 10h, etc.

[0047] In certain embodiments, the current of the electrolysis reaction is a constant current of 5 to 10 mA.

[0048] In certain embodiments, the solvent for the electrolysis reaction is selected from one or more of acetonitrile, dimethyl sulfoxide, dichloromethane, N,N-dimethylformamide, methanol, tetrahydrofuran, and water.

[0049] In some embodiments, the solvent for the electrolysis reaction is a mixed solvent of acetonitrile and water, and the volume ratio of acetonitrile to water is (5-15):1, for example, 5:1, 5.1:1, 5.2:1, 5.3:1, 5.4:1, 5.5:1, 5.6:1, 5.7:1, 5.8:1, 5.9:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, etc.

[0050] In certain embodiments, the solvent for the electrolysis reaction is a mixed solvent of acetonitrile and water, and the volume ratio of acetonitrile to water is (8-12):1.

[0051] In certain embodiments, the solvent for the electrolysis reaction is a mixed solvent of acetonitrile and water, and the volume ratio of acetonitrile to water is 10:1.

[0052] In certain embodiments, the step of separating and purifying after the electrolysis reaction is completed to obtain the compound of formula III is further included.

[0053] In certain embodiments, the separation and purification is to remove the solvent from the reaction solution under reduced pressure, add saturated sodium chloride aqueous solution, extract with an organic solvent, dry with anhydrous sodium sulfate, concentrate under vacuum, and separate and purify by column chromatography to obtain the compound of formula III.

[0054] In certain embodiments, the organic solvent is selected from one or more of dichloromethane, ethyl acetate, acetone, methanol, ethanol and n-hexane.

[0055] In certain embodiments, the organic solvent is selected from dichloromethane.

[0056] In certain embodiments, the separation and purification uses a mixed solvent of petroleum ether and ethyl acetate as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is (5-10):1, for example, 5:1, 5.1:1, 5.2:1, 5.3:1, 5.4:1, 5.5:1, 5.6:1, 5.7:1, 5.8:1, 5.9:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc.

[0057] In certain embodiments, the separation and purification uses a mixed solvent of petroleum ether and ethyl acetate as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is 10:1.

[0058] The method of the present invention is described below by means of specific examples. It should be understood that these examples are used to illustrate the basic principles, main features and advantages of the present invention, and the present invention is not limited to the scope of the following examples. The implementation conditions adopted in the examples can be further adjusted according to specific requirements. The implementation conditions not specified are generally the conditions in routine experiments.

[0059] In the following examples, unless otherwise indicated, all temperatures are in degrees Celsius. Unless otherwise indicated, various starting materials and reagents were commercially available or synthesized according to known methods, and commercially available materials and reagents were used directly without further purification.

[0060] Unless otherwise specified in the examples, the solution in the reaction refers to an aqueous solution.

[0061] Unless otherwise specified in the examples, the reaction temperature is room temperature, 20°C to 30°C.

[0062] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0063] Main instruments

[0064] Cell: A single-compartment electrolytic cell equipped with a carbon anode (8 mm x 2 mm) and a carbon cathode (8 mm x 2 mm).

[0065] Example 1: Preparation of Compound B1

[0066]

[0067] A1 (0.3 mmol), bis(pinacolato)diboron (0.45 mmol, 114.27 mg), water (0.4 mL), acetonitrile solvent (4.0 mL), and tetrabutylammonium iodide electrolyte (0.15 mmol) were added to the cell and stirred to form a mixture. The mixture was placed at room temperature and electrolyzed at a constant current (I = 5 mA) with magnetic stirring. The reaction progress was monitored by thin-layer chromatography (TLC). The complete disappearance of A1 indicated completion of the electrolysis, which lasted for 6 h. After completion, the solvent was removed under reduced pressure, and the residue was poured into a saturated sodium chloride aqueous solution and extracted with dichloromethane (3 × 20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. Finally, the residue was purified by silica gel column chromatography using a mixed eluent of petroleum ether / ethyl acetate (v:v = 10:1) to obtain the target product B1 (white powder, 39.91 mg) in a yield of 61%.

[0068] Example 2: Preparation of Compound B2

[0069]

[0070] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A2 was used instead of raw material A1. The yield of the obtained target product B2 was 58%.

[0071] 1 H NMR (500MHz, CDCl3) δ7.81 (d, J=6.9Hz, 2H), 7.44 (t, J=7.4Hz, 1H), 7.36 (t, J=7.5Hz, 2H), 1.33 (s, 12H).

[0072] 13 C NMR (126MHz, CDCl3) δ134.74(s), 131.17(s), 127.65(s), 83.71(s), 24.86(s).

[0073] Example 3: Preparation of Compound B3

[0074]

[0075] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A3 was used instead of raw material A1. The yield of the obtained target product B3 was 50%.

[0076] 1H NMR (500MHz, CDCl3) δ7.41 (d, J=7.2Hz, 1H), 7.33 (d, J=2.5Hz, 1H), 7.28 (t, J=7.7Hz, 1H), 6.99 (dd, J=8.2, 2.7Hz, 1H), 3.80 (s, 3H), 1.33 (s, 12H).

[0077] 13 C NMR (126MHz, CDCl3) δ159.06(s), 128.81(s), 127.13(s), 118.89(s), 117.70(s), 83.69(s), 55.09(s), 24.78(s).

[0078] Example 4: Preparation of Compound B4

[0079]

[0080] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A4 was used instead of raw material A1. The yield of the obtained target product B4 was 51%.

[0081] 1 H NMR (500MHz, CDCl3) δ7.45 (s, 2H), 7.11 (s, 1H), 2.33 (s, 6H), 1.36 (s, 12H).

[0082] 13 C NMR (126MHz, CDCl3) δ137.10(s), 132.94(s), 132.41(s), 83.64(s), 24.85(s), 21.09(s).

[0083] Example 5: Preparation of Compound B5

[0084]

[0085] The compound B5 was prepared according to the preparation method of compound B1 in Example 1, except that raw material A5 was used instead of raw material A1. The yield of the obtained target product B5 was 62%.

[0086] Example 6: Preparation of Compound B6

[0087]

[0088] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A6 was used instead of raw material A1. The yield of the obtained target product B6 was 57%.

[0089] Example 7: Preparation of Compound B7

[0090]

[0091] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A7 was used instead of raw material A1. The yield of the obtained target product B7 was 59%.

[0092] Example 8: Preparation of Compound B8

[0093]

[0094] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A8 was used instead of raw material A1. The yield of the obtained target product B8 was 62%.

[0095] Example 9: Preparation of Compound B9

[0096]

[0097] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A9 was used instead of raw material A1. The yield of the obtained target product B9 was 62%.

[0098] Example 10: Preparation of Compound B10

[0099]

[0100] The compound B1 was prepared according to the method for preparing compound B1 in Example 1, except that raw material A10 was used instead of raw material A1. The yield of the obtained target product B10 was 48%.

[0101] Example 11: Preparation of Compound B11

[0102]

[0103] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A11 was used instead of raw material A1. The yield of the obtained target product B11 was 48%.

[0104] Example 12: Preparation of Compound B12

[0105]

[0106] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A12 was used instead of raw material A1. The yield of the obtained target product B12 was 53%.

[0107] Example 13: Preparation of Compound B13

[0108]

[0109] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A13 was used instead of raw material A1. The yield of the obtained target product B13 was 50%.

[0110] Example 14: Preparation of Compound B14

[0111]

[0112] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A14 was used instead of raw material A1. The yield of the obtained target product B14 was 42%.

[0113] Example 15: Preparation of Compound B15

[0114]

[0115] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A15 was used instead of raw material A1. The yield of the obtained target product B15 was 58%.

[0116] Example 16: Preparation of Compound B16

[0117]

[0118] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A16 was used instead of raw material A1. The yield of the obtained target product B16 was 52%.

[0119] Example 17: Preparation of Compound B17

[0120]

[0121] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A17 was used instead of raw material A1. The yield of the obtained target product B17 was 54%.

[0122] Example 18: Preparation of Compound B18

[0123]

[0124] The compound B1 was prepared according to the preparation method of Example 1, except that raw material A18 was used instead of raw material A1. The yield of the obtained target product B18 was 43%.

[0125] Example 19: Amplification Experiment

[0126]

[0127] The compound was prepared according to the preparation method of compound B1 in Example 1, except that the amount of raw material A1 was 10 mmol.

[0128] A1 (10 mmol), bis(pinacolato)diboron (15 mmol, 3.8 g), water (13.5 mL), acetonitrile solvent (135 mL), and tetrabutylammonium iodide electrolyte (5 mmol) were added to a cell and stirred to form a mixture. The mixture was placed at room temperature and electrolyzed at a constant current (I = 5 mA) with magnetic stirring. The reaction progress was monitored by thin-layer chromatography (TLC). The complete disappearance of A1 indicated completion of the electrolysis, which lasted for 6 h. After completion, the solvent was removed under reduced pressure, and the residue was poured into a saturated sodium chloride solution and extracted with dichloromethane (3 × 20 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. Finally, the residue was purified by silica gel column chromatography using a mixed eluent of petroleum ether / ethyl acetate (v:v = 10:1) to obtain the target product B1 (white powder, 1.35 g) in a yield of 62%.

[0129] It should be understood that the above embodiments are exemplary and are not intended to encompass all possible implementations of the claims. Various modifications and variations may be made to the above embodiments without departing from the scope of this disclosure. Similarly, the various technical features of the above embodiments may be arbitrarily combined to form additional embodiments of the present invention that may not be explicitly described. Therefore, the above embodiments merely illustrate several implementations of the present invention and do not limit the scope of protection of the patent of this invention.

Claims

1. A method for preparing an aryl borate derivative represented by formula III, characterized in that: The following steps are involved: S1: electrolyzing a compound of formula I and a compound of formula II in a current mode to obtain a compound of formula III; Wherein, R1 and R2 are each independently selected from hydrogen, hydroxyl, amino, cyano, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Alkoxy, halogen, halogenated C 1-6 Alkyl, C 1-6 Acyloxy, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 6-10 Aryl, 5-10 membered heteroaryl, 3-6 membered heterocyclic group, or R1 and R2 and the carbon to which they are attached form C 3-6 Cycloalkyl, C 6-10 Aryl or 5-10 membered heteroaryl; The heteroatoms in the 5-10 membered heteroaryl and 3-6 membered heterocyclic group are independently selected from 1, 2, 3 or 4 of N, O and S; The heteroatoms in the 5-10 membered heteroaryl group are independently selected from 1, 2, 3 or 4 of N, O and S.

2. The preparation method according to claim 1, wherein: Said R1 and R2 are each independently selected from hydrogen, hydroxyl, amino, cyano, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, tert-butoxy, fluorine, chlorine, bromine, iodine, difluoromethyl, trifluoromethyl, formyloxy, acetoxy, propionyloxy, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, phenyl, or R1 and R2 and the carbon to which they are attached form a C 5-6 Cycloalkyl, C 6-8 Aryl or 5-8 membered heteroaryl; The heteroatoms in the 5-8 membered heteroaryl group are independently selected from 1 or 2 of N, O and S.

3. The preparation method according to claim 1, wherein: The anode electrode of the electrolysis reaction is selected from one of a carbon anode and a graphite anode, and the cathode electrode is one of a carbon cathode, a graphite cathode and a platinum cathode; Preferably, the anode electrode is a carbon anode, and the cathode electrode is one of a carbon cathode and a platinum cathode.

4. The preparation method according to claim 1, wherein: The molar ratio of the compound of formula I to the compound of formula II is 1:(1-3).

5. The preparation method according to claim 1, wherein: The electrolyte of the electrolysis reaction is selected from one or more of tetrabutylammonium tetrafluoroborate, tetrabutylammonium bromide, tetrabutylammonium iodide, tetra-n-butylammonium hexafluorophosphate, sodium tetrafluoroborate and tetraethylammonium p-toluenesulfonate; preferably one or more of tetrabutylammonium bromide and tetrabutylammonium iodide; Preferably, the molar ratio of the electrolyte to the compound of formula I is 1:(1-3).

6. The preparation method according to claim 1, wherein: The reaction temperature of the electrolysis reaction is 20-30° C., and the reaction time is 4-10 hours.

7. The preparation method according to claim 1, wherein: The current of the electrolysis reaction is a constant current of 5 to 10 mA.

8. The preparation method according to claim 1, wherein: The solvent of the electrolysis reaction is selected from one or more of acetonitrile, dimethyl sulfoxide, dichloromethane, N,N-dimethylformamide, methanol, tetrahydrofuran and water; Preferably, the solvent for the electrolysis reaction is a mixed solvent of acetonitrile and water, and the volume ratio of acetonitrile to water is (5-15):1; preferably (8-12):1; more preferably 10:

1.

9. The preparation method according to claim 1, characterized in that The method further comprises the steps of: separating and purifying after the electrolysis reaction to obtain a compound of formula III; Preferably, the separation and purification is to remove the solvent from the reaction solution under reduced pressure, add a saturated sodium chloride aqueous solution, extract with an organic solvent, dry with anhydrous sodium sulfate, concentrate under vacuum, and separate and purify by column chromatography to obtain the compound of formula III; Preferably, the organic solvent is selected from one or more of dichloromethane, ethyl acetate, acetone, methanol, ethanol and n-hexane.

10. The preparation method according to claim 9, characterized in that: The separation and purification uses a mixed solvent of petroleum ether and ethyl acetate as an eluent, and the volume ratio of the petroleum ether to the ethyl acetate is (5-10):1.

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