Method for synthesizing arylboronic acid pinacol ester
Through the synthesis method of arylboronic acid pennamol ester in situ generated organic calcium reagent under mechanochemical conditions, the problems of large amount of organic solvents and harsh reaction conditions in the prior art are solved, and high efficiency and gentle arylboronic acid penis are achieved. Preparation of alcohol esters has expanded the application of organic calcium reagents, with high yield and good applicability.
Patent Information
- Application Number
- CN202411339872.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-25
- Publication Date
- 2025-01-03
AI Technical Summary
The existing aryl borate esters synthesis methods have problems such as large amount of organic solvents, harsh reaction conditions and cumbersome steps. In particular, the preparation method of Grignard reagents based on magnesium requires complex inert gas protection and the pre-preparation of highly reactive reagents. , limits its application.
The arylborate methyl phenol ester synthesis method is adopted in situ generating organic calcium reagent under mechanochemical conditions. The aryl boric acid reagent is mixed and ground under aerobic conditions by mixing halogenated aromatic hydrocarbons, liquid-assisted grinding reagents and metal calcium under aerobic conditions, and the calcium reagent is activated by mechanical force. Achieve efficient preparation of arylborate esters, avoiding complex anhydrous and anaerobic operations and the use of large amounts of organic solvents.
Improve the reaction efficiency, simplify the experimental operation, and realize the borylation reaction of insoluble bromine aromatic hydrocarbons. The reaction conditions are mild, the yield is high and the applicability is good. The yield of arylborate olefin can be higher than 70%. , expanding the application of organic calcium reagents in organic synthesis.
Smart Images
Figure SMS_1 
Figure SMS_2 
Figure SMS_5
Abstract
Description
Technical Field
[0001] The invention relates to a method for preparing an aryl boronic acid pinacol ester, in particular to a method for synthesizing an aryl boronic acid pinacol ester with the participation of an in-situ generated organic calcium reagent under mechanochemical conditions. Background Art
[0002] As extremely important coupling reagents, aryl borate ester compounds can participate in various types of cross-coupling reactions (such as Suzuki-Miyaura coupling) and play a pivotal role in the fields of new drug development, functional material molecular design, and synthesis of natural products and bioactive molecules. Although in recent years, transition metal-catalyzed cross-coupling reactions (such as Miyaura-Ishiyama borylation), transition metal-catalyzed CH bond activation, photocatalysis and electrochemical methods have successfully opened up a variety of effective pathways for the synthesis of aryl boron reagents, the above strategies usually require the use of expensive transition metal catalysts and complex reaction equipment, and the reaction efficiency will be significantly reduced during large-scale experiments. These limitations make it difficult to apply the above strategies to actual production.
[0003] As is known to all, the most widely used method for synthesizing arylboron reagents, whether in laboratory preparation or actual production, is the Brown-Cole synthesis method (HC Brown, TECole, Organometallics 1983, 2, 1316.), which uses a pre-prepared aryl lithium reagent (Ar-Li) and an excess of trialkyl borane to undergo a transmetallation reaction, followed by acid hydrolysis to obtain the target product. Due to the high reactivity of aryl lithium reagents, the reaction temperature must be strictly controlled in this method, and it is usually carried out at -78°C and under inert gas protection. The following reaction formula is shown:
[0004]
[0005] Recently, the Singaram research group used a pre-prepared Grignard reagent (R-MgBr) as a carbon nucleophile to synthesize various types of aryl boronic acid pinacol esters through nucleophilic substitution reaction with pinacol borane HBpin. At the same time, the team explored and optimized the reaction conditions and realized the "one-pot method" of preparing aryl boronic acid pinacol esters with bromoaryl, magnesium metal, and pinacol borane. However, this method also requires the use of a large amount of organic solvents and cumbersome inert gas protection operations. As shown in the following reaction formula:
[0006]
[0007] It is particularly important to develop greener and more efficient methods for the synthesis of arylboron compounds and overcome the limitations of existing strategies. It is well known that calcium (Ca), as a cognate element of magnesium (Mg), is rarely used in heavy organic synthesis in comparison with magnesium-based Grignard reagents (R-MgX). The main reason is that there is still a lack of effective methods for the preparation of organic calcium reagents. Considering the obvious electronegativity difference between calcium and carbon, organic calcium reagents, as carbon nucleophiles, have great application potential in organic synthesis. Since the atomization enthalpy of calcium is much greater than that of magnesium (Ca: 178.2 kJ mol -1 Mg: 147.7 kJ mol -1 ), so compared with the preparation of Grignard reagents, it is very difficult to directly prepare organic calcium reagents using naturally inert metal calcium. Traditional methods for preparing organic calcium reagents usually require the use of toxic liquid ammonia or a strong reduction system of metallic lithium to pre-activate the metal calcium. Whether in laboratory preparation or industrial production, these cumbersome pre-activation processes seriously restrict the practical application of organic calcium reagents.
[0008] Among them, the liquid ammonia pre-activation system developed by Westerhausen's research group is the most widely used (M. H. M.Westerhausen, Synthesis 2007, 725–730), firstly, metallic calcium is dissolved in liquid ammonia under nitrogen protection atmosphere at -60°C to obtain a black opaque liquid, which is a complex formed by metallic calcium and NH3 after ionization; then, the liquid ammonia is removed under vacuum conditions to obtain a golden solid, and further vacuumization is performed to obtain a gray solid compound, which is the activated metallic calcium. Finally, the corresponding halogenated hydrocarbon and ether solvent are added to obtain an organic calcium reagent (R-CaX). It can be found that this method requires extremely cumbersome experimental operation processes, as shown below:
[0009] Summary of the invention
[0010] Purpose of the invention: The purpose of the present invention is to provide a method for synthesizing aryl boric acid pinacol esters, which solves the problems of large amount of organic solvent used, harsh reaction conditions and complicated steps in the existing preparation methods.
[0011] Technical solution: The method for synthesizing aryl boric acid pinacol ester described in the present invention uses halogenated aromatic hydrocarbons, liquid auxiliary grinding reagents, metal calcium and pinacol borane as starting materials, and mixes and grinds them under aerobic conditions to obtain aryl boric acid pinacol ester.
[0012] The present invention utilizes the continuous mechanical force provided by mechanical grinding vibration, and only needs one hour to complete the preparation of aryl boric acid pinacol ester, which greatly improves the reaction efficiency. The traditional synthesis method needs to prepare aryl lithium (Ar-Li) or Grignard reagent (Ar-MgX) with high reaction activity and difficult to preserve in advance under harsh conditions. The key of this method is to utilize the aryl calcium reagent (Ar-CaX) generated in situ under ball milling conditions as a nucleophilic reagent, without the need to pre-activate metallic calcium, and realize the application of heavy Grignard reagent based on calcium in CB bond construction for the first time. At the same time, the synthesis method developed by the present invention does not require complicated anhydrous and oxygen-free operation and the use of a large amount of organic solvents. More importantly, the mechanochemical method can realize the borylation reaction of insoluble bromoaryl hydrocarbons, and it is difficult to realize the conversion of such molecules using the established traditional synthesis method based on solution conditions.
[0013] In some embodiments, the reaction formula of the preparation method of aryl sulfide salt is as follows:
[0014]
[0015] Wherein, Ph represents phenyl, HBpin represents pinacol borane, jar represents stainless steel ball mill, ball represents stainless steel grinding ball, THF represents tetrahydrofuran, and stainless steel represents stainless steel material.
[0016] Preferably, the halogenated aromatic hydrocarbon is selected from any one of the following compounds:
[0017]
[0018] Preferably, the arylboronic acid pinacol ester comprises any one of the following compounds:
[0019]
[0020] in,
[0021] Preferably, the molar ratio of the halogenated aromatic hydrocarbon to the pinacol borane is 1:1.5-3.
[0022] Preferably, the molar ratio of the halogenated aromatic hydrocarbon to metallic calcium is 1:1-2.
[0023] Preferably, the molar ratio of the halogenated aromatic hydrocarbon to tetrahydrofuran is 1:3-5.
[0024] Preferably, the aerobic condition is an air atmosphere, and the grinding time is 0.5-2h.
[0025] Preferably, the grinding method is ball milling.
[0026] In some embodiments, ball milling can be performed using an MM 400 ball mill; the continuous mechanical energy generated by the vibration of the ball mill provides sufficient energy for the activation of inert metallic calcium, promoting the direct insertion of calcium into the carbon-halogen bond of halogenated aromatic hydrocarbons. The ball milling jar replaces the glass container, does not require the use of a large amount of organic solvent, greatly simplifies the experimental operation, has mild reaction conditions, and has unique substrate applicability compared to the traditional solution method.
[0027] Preferably, the vibration frequency of the ball mill is 20-40 Hz, and the diameter of the grinding balls used in the ball mill does not exceed 20 mm. The grinding balls can be made of stainless steel, and the material of the grinding jar can be stainless steel.
[0028] Preferably, the liquid auxiliary grinding agent includes at least one of tetrahydrofuran, dichloromethane, chloroform, formamide, dioxane, carbon tetrachloride, acetone, ethyl acetate, n-butanol, and diethyl ether.
[0029] In some embodiments, after the grinding reaction is completed, the crude product is extracted and dried. The specific method of extraction and drying includes: neutralizing with a saturated sodium chloride aqueous solution, extracting with dichloromethane, combining the organic phases and adding anhydrous magnesium sulfate to dry, removing the solvent by rotary evaporation on a rotary evaporator, using ethyl acetate / petroleum ether as the mobile phase for the crude product, loading a column with silica gel powder, and separating and purifying by column chromatography to obtain the target product.
[0030] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:
[0031] The present invention uses an aryl calcium reagent produced in situ by a mechanochemical method as a carbon nucleophilic reagent to prepare the corresponding aryl boric acid pinacol ester compounds through a nucleophilic substitution reaction with pinacol borane HBpin. This method not only provides a new idea for the preparation of aryl boron compounds, but also expands the application reaction of organic calcium reagents in organic synthesis. More importantly, the mechanochemical method can avoid the use of a large amount of organic solvents and has the great potential to be compatible with insoluble halogenated hydrocarbons, which reflects the synthetic advantages of mechanochemistry.
[0032] The invention does not need to use a large amount of organic solvent, has a short reaction time, mild reaction conditions, good substrate universality, and a high reaction yield, and the yield of arylboronic acid pinacol ester can be higher than 70%. DETAILED DESCRIPTION
[0033] The technical solution of the present invention is further described below.
[0034] Example 1: A method for preparing arylboronic acid pinacol ester is as follows:
[0035]
[0036] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 1 (116.5 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product (114.9 mg, yield 81%) was obtained. The product was a white solid, namely compound 3.
[0037] The product structure characterization data are as follows:
[0038] 1 H NMR (400MHz, CDCl3) δ7.88(d,J=7.9Hz,2H),7.61(dd,J=8.2,2.9Hz,4H),7.44(t,J=7.7Hz,2H),7.35(t,J=7.3Hz,1H),1.36(s,12H).
[0039] 13 C NMR (101MHz, CDCl3) δ135.3,128.8,127.6,127.2,126.5,83.8,24.9.
[0040] Example 2: A method for preparing arylboronic acid pinacol ester is as follows:
[0041]
[0042] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 4 (87.0 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product 5 (79.0 mg, yield 71%) was obtained. The product was a colorless liquid, namely compound 5.
[0043] 1 H NMR (400MHz, CDCl3) δ7.56(d,J=7.3Hz,1H),7.47(d,J=9.2Hz,1H),7.33(q,J=7.0,6.6Hz,1H),7.13(t,J=9.8Hz,1H),1.34(s,12H)
[0044] 13 C NMR (101MHz, CDCl3) δ162.5 (d, J = 246.6Hz), 130.3 (d, J = 2.9Hz), 129.4 (d, J = 7.2Hz), 120.9 (d, J = 19.2Hz), 118.1 (d, J = 21.1Hz), 84.1, 24.8.
[0045] Example 3: A method for preparing arylboronic acid pinacol ester is as follows:
[0046]
[0047] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 6 (131.6 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product 7 (146.2 mg, yield 94%) was obtained. The product was a yellow solid, namely compound 7.
[0048] The product structure characterization data are as follows:
[0049] 1 H NMR (400MHz, CDCl3) δ8.27(d,J=7.8Hz,1H),8.20–8.13(m,1H),7.95(d,J=7.1Hz,1H),7.91–7.83(m,1H),7.53–7.39(m,3H),1.44(s,12H)
[0050] 13 C NMR (101MHz, CDCl3) δ135.2,134.2,126.5,124.3,124.0,123.7,122.5,121.3,84.4,25.0.
[0051] Example 4: A method for preparing arylboronic acid pinacol ester is as follows:
[0052]
[0053] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 8 (103.5 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product 9 (93.1 mg, yield 74%) was obtained. The product was a white solid, namely compound 9.
[0054] The product structure characterization data are as follows:
[0055] 1 H NMR (400MHz, CDCl3) δ8.89–8.80(m,1H),8.16(d,J=6.8Hz,1H),7.99(d,J=8.2Hz,1 H),7.89(d,J=8.1Hz,1H),7.64–7.57(m,1H),7.53(t,J=7.5Hz,2H),1.47(s,12H).
[0056] 13 C NMR (101MHz, CDCl3) δ135.7,133.3,131.7,128.5,128.4,126.4,125.5,125.0,83.8,25.0
[0057] Example 5: A method for preparing arylboronic acid pinacol ester is as follows:
[0058]
[0059] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 10 (99.0 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product 11 (107.4 mg, yield 82%) was obtained. The product was a white solid, namely compound 11.
[0060] The product structure characterization data are as follows:
[0061] 1 H NMR(400MHz, CDCl3)6.78(s,2H),2.37(s,6H),2.25(s,3H),1.38(s,12H)
[0062] 13 C NMR (101MHz, CDCl3)142.1,138.9,127.4,83.4,24.9,22.2,1.2.
[0063] Example 6: A method for preparing arylboronic acid pinacol ester is as follows:
[0064]
[0065] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 12 (95.7 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product 13 (86.2 mg, yield 82%) was obtained. The product was a white solid, namely compound 13.
[0066] The product structure characterization data are as follows:
[0067] 1 H NMR (400MHz, CDCl3) δ7.73(d,J=8.3Hz,2H),7.34(d,J=8.3Hz,2H),1.34(s,12H)
[0068] 13 C NMR (101MHz, CDCl3)137.5,136.1,128.0,84.0,24.8.
[0069] Example 7: A method for preparing arylboronic acid pinacol ester is as follows:
[0070]
[0071] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 14 (100.0 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded on the column, and the target product 15 (88.0 mg, yield 71%) was obtained. The product was a white solid, namely compound 15.
[0072] The product structure characterization data are as follows:
[0073] 1 H NMR (400MHz, CDCl3) δ7.70(d,J=7.8Hz,2H),6.70(d,J=7.9Hz,2H),2.99(s,6H),1.33(s,12H)
[0074] 13 C NMR (101MHz, CDCl3)136.1,111.2,83.1,40.1,24.8
[0075] Example 8: A method for preparing arylboronic acid pinacol ester is as follows:
[0076]
[0077] A 5 mL stainless steel reaction tank equipped with a 10 mm grinding ball was selected, and compound 16 (128.6 mg, 0.5 mmol), compound 2 (128.1 mg, 1.0 mmol), and calcium (30.0 mg, 0.75 mmol) were added in turn under air conditions, and a ball mill (Retsch MM 400) was used to vibrate at 30 Hz for one hour. After the reaction was completed, saturated sodium chloride aqueous solution was used for quenching, and dichloromethane was used for extraction. The organic phase was combined and dried by adding anhydrous magnesium sulfate. After the solvent was removed by rotary evaporation on a rotary evaporator, the crude product was separated and purified by column chromatography using ethyl acetate / petroleum ether as the mobile phase, silica gel powder was loaded into a column, and the target product 17 (273.8 mg, yield 90%) was obtained. The product was a white solid, namely compound 17.
[0078] The product structure characterization data are as follows:
[0079] 1 H NMR(400MHz, CDCl3)δ7.79(d,J=7.5Hz,2H),7.54(d,J=7.5Hz,4H),7.39–7.31(m,3H),1.36(s,12H)
[0080] 13 C NMR (101MHz, CDCl3) 134.6, 131.6, 130.7, 128.3, 83.9, 24.9.
[0081] The present invention realizes the application of heavy Grignard reagent in the construction of CB bond for the first time. Its key technical core is to use mechanical force to activate inert metal calcium and generate corresponding aryl calcium species in situ as carbon nucleophilic reagent. Under traditional solution conditions, the corresponding calcium-based heavy Grignard reagent (Ar-CaBr) is prepared by reacting pre-activated calcium element with bromoaryl hydrocarbon (Ar-Br). Then, pinacol borane (HBpin) is added under the protection of inert gas, and the corresponding aryl boride with medium yield is successfully prepared (Ar-Bpin). These experimental results not only support the generation of heavy Grignard reagent under mechanochemical conditions, but also verify the advantages of mechanochemical methods, which are mainly reflected in high reaction yield and simple experimental operation. The specific verification experimental steps are as follows:
[0082] Method 1: Preparation of calcium-based heavy Grignard reagent (Ph-CaBr) using metallic calcium activated by liquid ammonia
[0083] According to the literature, calcium and three magnetic stirring bars (the stirring bars are coated with glass and have a diameter of 6 mm) are added to a flask with a condenser, and the above device is cooled to -60°C using cryogenic cold hydrazine under nitrogen. Then, ammonia gas is passed into the flask to cool and form liquid ammonia (about 10 ml). It can be observed that metallic calcium is gradually dissolved by liquid ammonia. After stirring for 5 minutes, all calcium metal is dissolved. The ammonia gas is then removed by decompression at room temperature. In this process, as the dark blue liquid is gradually removed, a golden solid is generated and attached to the wall of the container. Further drying forms a gray active calcium powder. This active calcium is dried in a vacuum for 5 hours and can be used in the following synthesis experiment.
[0084] The flask containing active calcium was cooled to 0°C. THF (5.0 mL) and bromobenzene (0.5 mmol) were added to the flask under nitrogen protection. The mixture was stirred at 0°C for 3 hours. Then, pinacol borane (1.0 mmol) was added at 0°C under nitrogen. The resulting mixture was gradually heated to 60°C and stirred for 10 hours. 45% of the boronated product was separated by column chromatography. As shown below:
[0085]
Claims
1. A method for synthesizing arylboronic acid pinacol esters, characterized in that: Aryl boronic acid pinacol esters are prepared by mixing and grinding aryl boronic acid pinacol esters with halogenated aromatic hydrocarbons, liquid-assisted grinding agents, metal calcium and pinacol borane as starting materials under aerobic conditions.
2. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The halogenated aromatic hydrocarbon is selected from any one of the following compounds:
3. The method for synthesizing aryl boric acid pinacol ester according to claim 1, characterized in that: The arylboronic acid pinacol ester includes any of the following compounds: in, .
4. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The molar ratio of the halogenated aromatic hydrocarbon to the pinacol borane is 1:1.5-3.
5. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The molar ratio of the halogenated aromatic hydrocarbon to metallic calcium is 1:1-2.
6. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The molar ratio of the halogenated aromatic hydrocarbon to tetrahydrofuran is 1:3-5.
7. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The aerobic condition is an air atmosphere, and the grinding time is 0.5-2h.
8. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The grinding method is ball milling.
9. The method for synthesizing arylboronic acid pinacol ester according to claim 8, characterized in that: The vibration frequency of the ball mill is 20-40 Hz, and the diameter of the grinding balls used in the ball mill does not exceed 20 mm.
10. The method for synthesizing arylboronic acid pinacol ester according to claim 1, characterized in that: The liquid auxiliary grinding agent includes at least one of tetrahydrofuran, dichloromethane, chloroform, formamide, dioxane, carbon tetrachloride, acetone, ethyl acetate, n-butanol, and ether.