2-substituted benzoxazole derivatives, processes for their synthesis and use thereof

Abstract

The application discloses a 2-substituted benzoxazole derivative and a synthesis method and application thereof, and belongs to the technical field of heterocyclic compound preparation. The method comprises the following steps: taking o-aminophenol as a starting material, dissolving the o-aminophenol in a nitrile, taking the nitrile as a reaction solvent and a carbon source of a 2-position substituent at the same time, and forming a reaction system; performing constant-current electrolysis on the reaction system in an undivided electrolytic cell in the presence of an alkaline catalyst, so that the o-aminophenol and the nitrile are subjected to an electrocatalytic oxidation cyclization reaction to obtain a reaction product; extracting the obtained reaction product, then post-treating the obtained organic phase, and obtaining a crude product; and purifying the crude product to obtain the 2-substituted benzoxazole derivative. The method solves the technical problem of a complex preparation process in the prior art.

Description

Technical Field

[0001] This invention belongs to the field of heterocyclic compound preparation technology, specifically relating to a 2-substituted benzoxazole derivative, its synthesis method, and its application. Background Technology

[0002] Benzooxazoles, as an important nitrogen-containing heterocyclic skeleton, are composed of a benzene ring and an oxazole ring fused together. Their rigid planar conjugated system allows them to serve as bioisosteres of natural nucleotides, readily embedding into the aromatic pockets of biomolecules to form stable π-π stacking or hydrophobic interactions. Based on this structural feature, benzooxazoles are widely found in natural products and synthetic molecules with activities such as antitumor, antibacterial, antiviral, fluorescent probes, and organic optoelectronic materials (Faydali N, Arpaci O T. Chem. Biodivers., 2024, 21(6): e202400123). Traditional synthetic methods often rely on the condensation reaction of o-aminophenol with carboxylic acid derivatives or aldehydes (Xiao Liwei, Gao Hongjie, Kong Jie, Organic Chemistry, 2014, 34(06): 1048-1060). Although this route has become increasingly mature, it still faces many constraints in practical applications: on the one hand, harsh conditions such as high temperature, strong acid or strong base limit the tolerance of sensitive functional groups; on the other hand, the dependence on prefunctionalized raw materials and the introduction of equivalent chemical oxidants violate the development of modern chemical synthesis towards atom economy and environmental friendliness. Among numerous synthetic routes, using nitrile compounds as carbon sources to construct oxazole ring systems exhibits unique simplicity (Das A, Bhattacharya K, Das LK, et al. Dalton Trans., 2018, 47(28): 9385-9399; Hossain E, Deng SM, Gozem S, et al. J. Am. Chem. Soc., 2017, 139(32):11138-11148.). Acetonitrile not only possesses excellent electrochemical windows and solvation capabilities, but its cyano carbon atom can also directly participate in cyclization reactions as a synthon. This leads to the development of a mild, green, and efficient electrosynthetic methodology that enables the one-step direct cyclization of o-aminophenol and nitrile through constant current electrolysis. Summary of the Invention

[0003] The purpose of this invention is to provide a 2-substituted benzoxazole derivative, its synthesis method, and its application, in order to solve the technical problem of complex preparation processes in existing methods.

[0004] To achieve the above objectives, the present invention employs the following technical solution: This invention discloses a method for synthesizing 2-substituted benzoxazole derivatives, comprising the following steps: Starting with o-aminophenol, it is dissolved in a nitrile, which serves as both the reaction solvent and the carbon source for the substituent at the 2-position, to form a reaction system. The reaction system is then subjected to constant current electrolysis in an undivided electrolytic cell in the presence of an alkaline catalyst, allowing o-aminophenol and the nitrile to undergo an electrocatalytic oxidative cyclization reaction to obtain the reaction product. The obtained reaction product was extracted, and then the obtained organic phase was post-processed to obtain the crude product. The crude product was purified to obtain a 2-substituted benzoxazole derivative.

[0005] Furthermore, the alkaline catalyst is triethylamine.

[0006] Furthermore, in the undivided electrolytic cell, the anode is a glassy carbon electrode and the cathode is a foamed copper electrode; the undivided electrolytic cell also contains an electrolyte, which is tetra-n-butyltetrafluoroborate ammonium, and the concentration of the electrolyte in the reaction system is 0.05~0.2 M.

[0007] Furthermore, the constant current electrolysis is performed at a temperature of 25~70 ℃, with a current of 10~30 mA, and for a time of 6~10 h. The ratio of o-aminophenol, nitrile, and alkaline catalyst is 0.5~1.5 mmol: 6~10 mL: 5~20 μL.

[0008] Furthermore, the nitrile is acetonitrile or benzonitrile; the constant current electrolysis is carried out under stirring conditions; and the alkaline catalyst is triethylamine.

[0009] Furthermore, the extraction is performed using dichloromethane; the post-treatment includes sequential washing, drying, and rotary evaporation; the drying is performed using anhydrous sodium sulfate; and the rotary evaporation is performed under reduced pressure for 30-45 minutes using a rotary evaporator.

[0010] Furthermore, the purification method is column chromatography purification; the column used in the column chromatography purification method consists of 1-2 cm of quartz sand and 10-25 cm of silica gel from bottom to top, and the eluent used is petroleum ether and dichloromethane, wherein the volume ratio of petroleum ether to dichloromethane is 4:1 to 8:1.

[0011] The present invention also discloses a 2-substituted benzoxazole derivative, which is prepared by the above preparation method.

[0012] Furthermore, the structural formula of the 2-substituted benzoxazole derivative is as follows: ; Wherein: R1 is hydrogen, methyl, or halogen; R2 is methyl.

[0013] This invention also discloses the applications of the above-mentioned 2-substituted benzoxazole derivatives in medicinal chemistry, organic optoelectronic materials, ligands and catalysts.

[0014] Compared with the prior art, the present invention has the following beneficial effects: This invention discloses a method for synthesizing 2-substituted benzoxazole derivatives. The method uses o-aminophenol as the starting material, dissolves it in a nitrile, and utilizes the nitrile as both the reaction solvent and the carbon source for the 2-substituent. In the presence of an alkaline catalyst, an electrocatalytic oxidation cyclization reaction is carried out in an undivided electrolytic cell using constant current electrolysis, thereby constructing 2-substituted benzoxazole derivatives in one step. This method replaces both organic solvents and carboxylic acid / aldehyde condensing reagents in traditional synthesis methods with nitriles. The reaction system requires no metal catalysts or chemical oxidants, using only electrons as a clean redox reagent. The only byproduct is hydrogen gas, eliminating heavy metal pollution and chemical waste at the source, aligning with the principles of green chemistry. Furthermore, this method can be carried out efficiently under mild conditions of 25–70°C, avoiding the harsh conditions of strong acids, strong bases, or high temperatures and pressures required in traditional methods. It exhibits good tolerance to functional groups, reducing safety risks during operation. Moreover, this method starts with inexpensive and readily available o-aminophenol and nitriles, obtaining the target product through a one-step electrocatalytic oxidative cyclization, eliminating the need for multi-step synthesis or pre-functionalization. The use of an undivided electrolytic cell simplifies the electrolysis equipment, and the constant current mode facilitates scale-up production. Additionally, the dual role of nitriles as both solvent and synthon reduces the types of reaction components and post-processing steps, significantly improving synthesis efficiency. The synthetic strategy established in this invention, which uses nitriles as solvents and synthons—alkaline electrocatalysis—to construct benzoxazole rings in one step, overcomes the shortcomings of traditional methods, such as reliance on strong acids / bases, the need for metal catalysts and chemical oxidants, and complex post-processing. It provides a novel electrochemical synthetic route for the green, efficient, and mild preparation of 2-substituted benzoxazole derivatives.

[0015] Furthermore, the method of the present invention has good universality of substrates, and the substrates are inexpensive and the target product is easy to separate, which has potential application value in the fields of medicine and materials. Detailed Implementation

[0016] To enable those skilled in the art to understand the features and effects of the present invention, the terms and expressions used in the specification and claims are explained and defined in general below. Unless otherwise specified, all technical and scientific terms used herein have the ordinary meaning understood by those skilled in the art regarding the present invention, and in case of conflict, the definitions in this specification shall prevail.

[0017] The theories or mechanisms described and disclosed herein, whether right or wrong, should not in any way limit the scope of the invention, that is, the contents of the invention can be implemented without being limited by any particular theory or mechanism.

[0018] In this document, all features defined by numerical ranges or percentage ranges, such as numerical values, quantities, contents, and concentrations, are for the sake of brevity and convenience only. Accordingly, descriptions of numerical ranges or percentage ranges should be considered as covering and specifically disclosing all possible sub-ranges and individual numerical values ​​(including integers and fractions) within those ranges.

[0019] In this article, unless otherwise specified, “contains,” “includes,” “containing,” “has,” or similar terms cover the meanings of “composed of” and “mainly composed of,” for example, “A contains a” covers the meanings of “A contains a and others” and “A contains only a.”

[0020] For the sake of brevity, not all possible combinations of the technical features in each implementation scheme or embodiment are described herein. Therefore, as long as there is no contradiction in the combination of these technical features, the technical features in each implementation scheme or embodiment can be combined arbitrarily, and all possible combinations should be considered within the scope of this specification.

[0021] This invention provides a method for the electrochemical synthesis of 2-substituted benzoxazole derivatives, using o-aminophenol as the reactant, triethylamine as the catalyst, and tetra-n-butyltetrafluoroborate as the electrolyte. The reaction is carried out in an undivided electrolytic cell at 60 °C, followed by separation and purification to obtain 2-substituted benzoxazole and its derivatives. The main steps include: Step 1: Add o-aminophenol and acetonitrile to the undivided electrolytic cell, carry out electrocatalysis at 25-70 °C with simultaneous stirring, then extract, and wash, dry and rotary evaporate the obtained organic phase to obtain crude product. Step 2: The crude product is purified to obtain 2-substituted benzoxazole and its derivatives.

[0022] Preferably, in the undivided electrolytic cell, the anode is a glassy carbon electrode with a size of 10 mm × 20 mm × 3 mm, the cathode is a foamed copper electrode with a size of 10 mm × 20 mm × 1 mm, the electrolyte concentration is 0.05-0.2 M, and the nitrile content is 4-10 mL.

[0023] Preferably, the temperature environment is 25-70 ℃.

[0024] Preferably, the electrocatalytic intensity is 10-30 mA DC, and the stirring time is 6-10 h.

[0025] Preferably, dichloromethane is used for extraction, and the organic phases are combined after extraction.

[0026] Preferably, anhydrous sodium sulfate is used for drying.

[0027] Preferably, rotary evaporation is performed using a rotary evaporator under reduced pressure for 30-45 minutes.

[0028] Preferably, the purification method is column chromatography, in which the column consists of 1-2 cm of quartz sand and 10-25 cm of silica gel from bottom to top, and the eluent is petroleum ether: dichloromethane = 4:1-8:1.

[0029] Preferably, the reaction formula for the 2-substituted benzoxazole is: .

[0030] Wherein, R1 is hydrogen, methyl, or halogen; R2 is methyl or phenyl.

[0031] The structural formula of the 2-substituted benzoxazole obtained by the above method is: ; Wherein, R1 is hydrogen, methyl, or halogen; R2 is methyl or phenyl.

[0032] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0033] The following examples use instruments and equipment conventional in the art. Experimental methods in the following examples, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. All raw materials used in the following examples are conventional commercially available products with specifications conventional in the art. In this specification and the following examples, unless otherwise specified, "%" refers to weight percentage, "parts" refers to parts by weight, and "ratio" refers to weight proportion.

[0034] Example 1 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of o-aminophenol and 0.1 M (concentration in 8 mL acetonitrile) of tetra-n-butyltetrafluoroborate ammonium were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrocatalysis was performed at 60 °C with a constant current density of 20 mA and stirring for 8 h. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 1 mL of dichloromethane and 40 mL of sodium chloride solution were added. After processing mg of biphenyl, gas chromatography was performed using a GC-MID instrument. The GC internal standard yield was 64%, and the structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.53 (m, J = 7.3 Hz, 1H), 7.30 (m, J = 8.0 Hz, 1H), 7.18-7.07 (m, 2H), 2.46 (s, 3H). 13 C NMR: (101 MHz, CDCl3) δ 163.9, 151.0, 141.1, 124.5, 124.2, 119.0, 110.3, 14.6. GC-MS m / z(%):132.59(96)[M] +· , 104.09(100), 92.07(45), 78.10(74). Example 2 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of o-aminophenol and 0.1 M of tetra-n-butyltetrafluoroboric acid (concentration in 8 mL of acetonitrile) ammonium were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of benzonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrocatalysis was performed at 60 °C with a constant current density of 20 mA and stirring for 8 h. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 1 mL of dichloromethane and 40 mL of sodium chloride solution were added. After processing mg of biphenyl, gas chromatography was performed using a GC-MID instrument. The GC internal standard yield was 55%, and the structural formula of the obtained product is as follows: ; Product characterization: White soild. 1 H NMR (400 MHz, CDCl3) δ 8.27 (dd, J = 6.7, 3.2Hz, 2H), 7.83-7.73 (m, 1H), 7.62-7.55 (m, 1H), 7.55-7.47 (m, 3H), 7.40-7.30(m, 2H). 13 C NMR (101 MHz, CDCl3) δ 163.1, 150.9, 142.2, 131.6, 129.0, 127.7,127.3, 125.2, 124.6, 120.1, 110.7. GC-MS m / z (%): 192.12(100)[M] +· , 167.12(27), 77.07(16), 63.05(29). Example 3 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 2-methyl-6-aminophenol and 0.1 M of tetra-n-butyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrodes and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 18%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.9 Hz, 1H), 7.18 (t, J = 7.7 Hz, 1H), 7.07 (d, J = 7.4 Hz, 1H), 2.63 (s, 3H), 2.50 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 163.6, 150.3, 141.2, 125.6, 124.1, 120.9, 116.8, 15.2,14.7. GC-MS m / z (%): 147.11(100)[M] +· , 106.11(50), 78.09(48). Example 4 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 2-fluoro-6-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 20 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 5%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.9 Hz, 1H), 7.23 (d, J = 4.6 Hz, 1H), 7.05 (t, J = 9.1 Hz, 1H), 2.67 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 164.5, 148.2, 145.7, 144.9, 124.7 (d, J = 6.2 Hz), 115.3 (d, J =4.1 Hz), 111.5 (d, J = 16.6 Hz), 14.56. GC-MS m / z (%): 151.09(100)[M] +· , 129.10(31), 122.09(16), 101.10(45), 82.11(16). 19 F NMR (470 MHz, CDCl3) δ -134.78.HRMS (ESI) m / z: [M+H] +Calcd for C 8 h7 NOF:152.0512, found: 152.0509. Example 5 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 2-chloro-6-aminophenol and 0.1 M of tetrabutyltetrafluoroborate ammonium (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 20 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, 1H NMR spectroscopy was performed at 400 MHz. The yield of the NMR internal standard was 10%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.7 Hz,1H), 7.29-7.24 (m, 1H), 7.21 (t, J = 7.9 Hz, 1H), 2.66 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.4, 147.6, 142.8, 125.0, 125.0, 118.1, 115.6, 14.6. GC-MS m / z(%): 167.06(100)[M] +· , 169.06(33)[M+2] +·, 104.09(31), 98.06(15), 63.05(33).HRMS (ESI) m / z: [M+H] + Calcd for C 8 h7 NOCl:168.0216, found: 168.0219. Example 6 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 2-bromo-6-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 20 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 7%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow solid. 1 H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.9 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.16 (t, J = 7.9 Hz, 1H), 2.66 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.2, 149.2, 142.2, 127.7, 125.4, 118.6, 102.2, 14.7. GC-MS m / z (%): 211.00(96)[M] +· , 213.03(100)[M+2]+· , 132.08(21), 104.09(42), 63.06(48). Example 7 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 3-methyl-2-aminophenol and 0.1 M of tetrabutylammonium tetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for anode and 1 cm for cathode). Electrolysis was carried out continuously at a constant current density of 10 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 48%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.0 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 7.08 (d, J = 7.5 Hz, 1H), 2.63 (s, 3H), 2.59 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 163.1, 150.8, 140.7, 129.8, 124.8, 124.2, 107.6, 16.6,14.6. GC-MS m / z (%): 147.10(100)[M] +· , 118.08(15), 106.10(24), 78.09(57). Example 8 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 3-fluoro-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 31%. The structural formula of the obtained product is as follows: ; Product characterization: White solid. 1 H NMR (400 MHz, CDCl3) δ 7.29-7.19 (m, 2H), 7.04-6.98 (m, 1H), 2.64 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.2, 154.4, 153.3(d, J = 7.5 Hz), 151.8, 124.9 (d, J = 7.2 Hz), 110.5 (d, J = 17.7 Hz), 106.5 (d, J =4.5 Hz), 14.6. GC-MS m / z (%): 151.10(100)[M] +· , 122.08(24), 96.07(22), 82.07(25). 19F NMR (470 MHz, CDCl3) δ -125.06. HRMS (ESI) m / z: [M+H] + Calcd for C8 h7 NOF:152.0512, found: 152.0516. Example 9 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 3-chloro-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 10 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 42%. The structural formula of the obtained product is as follows: ; Product characterization: White solid. 1 H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 8.0 Hz, 1H), 2.67 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.8, 151.7, 139.4, 125.1, 124.5, 124.1, 109.0, 14.7. GC-MS m / z(%): 167.07(100)[M]+· , 169.09(33)[M+2] +· , 104.09(27), 63.06(28). Example 10 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 3-bromo-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate ammonium (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 10 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, 1H NMR spectroscopy was performed at 400 MHz. The yield of the NMR internal standard was 36%. The structural formula of the obtained product is as follows: ; Product characterization: White solid. 1 H NMR (400 MHz, CDCl3) δ 7.43 (dd, J = 18.1, 8.1Hz, 2H), 7.17 (t, J = 8.1 Hz, 1H), 2.66 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ164.7, 151.1, 141.0, 127.4, 125.6, 112.0, 109.6, 14.7. GC-MS m / z (%): 211.01(100)[M] +· , 213.03(92)[M+2] +· , 132.10(44), 106.07(22), 104.08(20), 63.06(42). Example 11 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 5-methyl-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate ammonium (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, 1H NMR spectroscopy was performed at 400 MHz. The yield of the NMR internal standard was 71%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 1.8 Hz, 1H), 7.10 (d, J = 8.9 Hz, 1H), 2.61 (s, 3H), 2.46 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 163.4, 151.4, 139.4, 134.9, 125.4, 118.9, 110.5, 21.8,14.6. GC-MS m / z (%): 147.09(100)[M] +· , 118.07(15), 106.07(30), 78.08(62). Example 12 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 5-fluoro-2-aminophenol and 0.1 M of tetra-n-butyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 20 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 41%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 9.8, 4.9 Hz, 1H), 7.19 (d, J = 9.3 Hz, 1H), 7.04 (t, J = 8.5 Hz, 1H), 2.62 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 164.5, 159.2, 151.1, 137.9, 119.8 (d, J = 10.1 Hz), 112.0 (d, J =24.5 Hz), 98.6 (d, J = 28.1 Hz), 14.6. 19 F NMR (470 MHz, CDCl3) δ -116.42. GC-MSm / z (%): 151.07(100)[M] +·, 122.04(29), 96.05(31), 82.04(26), 81.02(18). Example 13 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 5-chloro-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 24%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.4 Hz, 1H), 7.48 (d, J = 2.2 Hz, 1H), 7.29 (d, J = 2.8 Hz, 1H), 2.63 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.7, 151.2, 140.4, 130.3, 124.9, 120.0, 111.0, 14.7. GC-MS m / z(%): 167.03(100)[M] +· , 169.02(32)[M+2] +· , 104.04(57), 63.02(37). Example 14 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 5-bromo-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 20%. The structural formula of the obtained product is as follows: ; Product characteristics: Yellow oil. 1 H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.56-7.34 (m, 2H), 2.62 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.6, 151.5, 140.8, 127.6,120.5, 117.5, 113.9, 14.6. GC-MS m / z (%): 210.99(96)[M] +· , 212.97(100)[M+2] +· ,104.06(82), 77.07(17), 63.03(53). Example 15 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 5-methyl-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate ammonium (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 20 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, 1H NMR spectroscopy was performed at 400 MHz. The yield of the NMR internal standard was 66%. The structural formula of the obtained product is as follows: ; Product Characterization: Colourless oil. 1 H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 7.32(d, J = 8.3 Hz, 1H), 7.08 (d, J = 10.0 Hz, 1H), 2.61 (s, 3H), 2.45 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 164.0, 149.3, 141.9, 134.0, 125.6, 119.5, 109.6, 21.5,14.7. GC-MS m / z (%): 147.13(100)[M] +· , 106.08(32), 78.09(63). Example 16 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 4-fluoro-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon and copper foam electrodes were inserted, and the electrode submersion height was adjusted (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 20 mA for 8 h at 60 °C with stirring. After the reaction was complete, the reactants were brought to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The combined organic phases were washed sequentially with 15 mL of deionized water and 15 mL of saturated sodium chloride solution (twice) to remove residual electrolytes and water-soluble impurities. The resulting organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 μL of triethylamine was added directly to the crude product. mmol of 1,1,2,2-tetrachloroethane was added and stirred until homogeneous. Then, 1 mL of CHCl3 and 0.6 mL of CDCl3 were added, and the NMR spectrum was measured at 400 MHz. The yield of the NMR internal standard was 43%. The structural formula of the obtained product is as follows: ; Product characterization: White soild. 1 H NMR (400 MHz, CDCl3) δ 7.44-7.22 (m, 2H), 7.01(t, J = 9.1 Hz, 1H), 2.63 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.8, 158.8,147.4, 142.4 (d, J = 13.0 Hz), 112.0, 110.5 (d, J = 10.1 Hz), 106.3 (d, J = 25.6Hz), 14.8. 19 F NMR (470 MHz, CDCl3) δ -118.59.GC-MS m / z (%): 151.09(100)[M] +· ,122.06(24), 96.06(25), 82.06(46), 81.07(16). Example 17 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 4-chloro-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate ammonium (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, 1H NMR spectroscopy was performed at 400 MHz. The yield of the NMR internal standard was 53%. The structural formula of the obtained product is as follows: ; Product characterization: White solid. 1 H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 2.5 Hz, 1H), 7.31 (d, J = 8.7 Hz, 1H), 7.21-7.15 (m, 1H), 2.56 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.4, 149.6, 142.8, 129.7, 124.8, 119.5, 111.0, 14.7. GC-MS m / z(%): 167.02(100)[M] +· , 169.05(29)[M+2] +· , 104.06(36), 98.02(21), 63.05(35). Example 18 A method for synthesizing a 2-substituted benzoxazole derivative (2-Methylbenzoxazole) includes the following steps: 1 mmol of 4-bromo-2-aminophenol and 0.1 M of tetrabutyltetrafluoroborate ammonium (concentration in 8 mL of acetonitrile) were dissolved in a specially designed Schlenk tube (equipped with a magnetic stir bar) containing 8 mL of acetonitrile. Then, 0.1 equiv of triethylamine (14 μL) was added. Glassy carbon electrode and foamed copper electrode were inserted, and the electrode plates were adjusted to the appropriate submersion height (0.5 cm for the anode and 1 cm for the cathode). Electrolysis was carried out continuously at a constant current density of 15 mA for 8 h at 60 °C with stirring. After the reaction was completed, the reactants were brought back to room temperature. After the reaction was terminated, the two-phase mixture was subjected to multi-stage extraction with dichloromethane (3 × 15 mL). The organic phases were combined and washed in reverse phase twice with 15 mL of deionized water and 15 mL of saturated sodium chloride solution to remove residual electrolytes and water-soluble impurities. The obtained organic layer was dried with anhydrous sodium sulfate for 20 min, and volatile components were removed by rotary evaporation. 0.3 mmol of 1,1,2,2-tetrachloroethane was added directly to the crude product and stirred until homogeneous. After adding 1 mL of CHCl3 and 0.6 mL of CDCl3, 1H NMR spectroscopy was performed at 400 MHz. The yield of the NMR internal standard was 51%. The structural formula of the obtained product is as follows: ; Product characterization: White solid. 1 H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.2 Hz,1H), 7.34-7.21 (m, 2H), 2.56 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.2, 150.0,143.2, 127.6, 122.6, 116.9, 111.5, 14.7. GC-MS m / z (%): 211.00(100)[M] +· ,213.03(93)[M+2] +· , 104.10(45), 91.12(16), 63.04(63). This invention pioneers a green, efficient, and mild electrochemical synthesis process. Without the need for metal catalysts or external chemical oxidants, it utilizes nitriles as solvents and synthons, employing constant-current electrolytic redox reactions to achieve a one-step construction of 2-substituted benzoxazoles. The method of this invention features broad substrate versatility, inexpensive substrates, and easily separable target products, demonstrating potential applications in the pharmaceutical and materials fields.

[0035] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A method for synthesizing a 2-substituted benzoxazole derivative, characterized in that, Includes the following steps: Starting with o-aminophenol, it is dissolved in a nitrile, which serves as both the reaction solvent and the carbon source for the substituent at the 2-position, to form a reaction system. The reaction system is then subjected to constant current electrolysis in an undivided electrolytic cell in the presence of an alkaline catalyst, allowing o-aminophenol and the nitrile to undergo an electrocatalytic oxidative cyclization reaction to obtain the reaction product. The obtained reaction product was extracted, and then the obtained organic phase was post-processed to obtain the crude product. The crude product was purified to obtain a 2-substituted benzoxazole derivative.

2. The method for synthesizing a 2-substituted benzoxazole derivative according to claim 1, characterized in that, The alkaline catalyst is triethylamine.

3. The method for synthesizing a 2-substituted benzoxazole derivative according to claim 1, characterized in that, In the undivided electrolytic cell, the anode is a glassy carbon electrode and the cathode is a foamed copper electrode; the undivided electrolytic cell also contains an electrolyte, which is tetra-n-butyltetrafluoroborate ammonium, and the concentration of the electrolyte in the reaction system is 0.05~0.2M.

4. The method for synthesizing a 2-substituted benzoxazole derivative according to claim 1, characterized in that, The constant current electrolysis is performed at a temperature of 25~70 ℃, with a current of 10~30 mA, for a time of 6~10 h. The ratio of o-aminophenol, nitrile, and alkaline catalyst is 0.5~1.5 mmol: 6~10 mL: 5~20 μL.

5. The method for synthesizing a 2-substituted benzoxazole derivative according to claim 1, characterized in that, The nitrile is acetonitrile or benzonitrile; the constant current electrolysis is carried out under stirring conditions; the alkaline catalyst is triethylamine.

6. A method for synthesizing a 2-substituted benzoxazole derivative according to claim 1, characterized in that, The extraction was performed using dichloromethane; the post-treatment included washing, drying, and rotary evaporation performed sequentially; the drying was performed using anhydrous sodium sulfate; and the rotary evaporation was performed under reduced pressure for 30-45 minutes using a rotary evaporator.

7. A method for synthesizing a 2-substituted benzoxazole derivative according to claim 1, characterized in that, The purification method is column chromatography purification; the column used in the column chromatography purification method consists of 1-2 cm of quartz sand and 10-25 cm of silica gel from bottom to top, and the eluent is petroleum ether and dichloromethane, with a volume ratio of petroleum ether to dichloromethane of 4:1 to 8:

1.

8. A 2-substituted benzoxazole derivative, characterized in that, It is prepared by the preparation method described in any one of claims 1 to 7.

9. A 2-substituted benzoxazole derivative according to claim 8, characterized in that, The structural formula of the 2-substituted benzoxazole derivative is: ； Wherein: R1 is hydrogen, methyl, or halogen; R2 is methyl.

10. The application of a 2-substituted benzoxazole derivative as described in claim 8 or 9 in medicinal chemistry, organic optoelectronic materials, ligands and catalysts.

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