An electro-synthesis method of 2,5-disubstituted oxazoles

Abstract

The application discloses an electro-synthesis method of 2,5-disubstituted oxazole compounds, which comprises the following steps: dispersing a ketone compound, a benzylamine, an iodide and potassium bicarbonate in an organic solvent to prepare an electrolyte, and then performing electrolysis by electrifying, so as to obtain the 2,5-disubstituted oxazole compounds. The electro-synthesis method of the 2,5-disubstituted oxazole compounds has the advantages of simple process, green environmental protection, cheap and easily obtained raw materials, low cost, high yield, easy separation and purification of products and the like, and is suitable for large-scale popularization and application.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and specifically to an electrosynthesis method for 2,5-disubstituted oxazole compounds. Background Technology

[0002] Oxazoles are five-membered heterocyclic organic compounds widely used in organic synthesis, often as synthetic intermediates or drug skeletons. Oxazole compounds possess a variety of biological activities (e.g., antibacterial, anticancer, and anti-inflammatory), playing an important role in the pharmaceutical field. Furthermore, oxazole compounds can also be used in pesticides and dyes.

[0003] Currently, the main methods for synthesizing oxazole compounds include the following:

[0004] 1) Togo et al. obtained 2,5-disubstituted oxazoles and 2,4,5-trisubstituted oxazoles by first mixing acetonitrile, iodoaromatics, potassium persulfate, and trifluoromethanesulfonic acid in a single pot and reacting at 0°C for 2 hours, then adding aromatic ketone compounds and refluxing for 4 hours. This method involves many reaction steps and has low production efficiency. [Reaction formula:] Y.Ishiwata, H.Togo, Tetrahedron.65(2009)10720-10724.];

[0005] 2) Jiang et al. obtained polysubstituted oxazole compounds by reacting olefin compounds with amine compounds in dimethyl sulfoxide at 100°C for 12 h under the action of elemental iodine. The advantage of this method is that it uses readily available amines and olefins as raw materials, but it requires a large amount of strong oxidizing agents such as tert-butanol hydrogen peroxide (TBHP) and elemental iodine [reaction formula:] HFJiang,H.Huang,H.Cao,C.Qi,Org.Lett.12(2010)5561-5563.];

[0006] 3) Wang et al. reacted 2-amino-1-acetophenone hydrochloride and benzaldehyde as substrates in N,N-dimethylformamide (DMF) under the action of Lewis acid and tert-butyl hydroperoxide to obtain 2,5-disubstituted oxazole compounds. This method also requires a large amount of strong oxidizing agent tert-butanol hydroperoxide (TBHP) and elemental iodine [reaction formula:] C.Wan,L.Gao,Q.Wang,J.Zhang,Z.Wang,Org.Lett.12(2010)3902-3905.];

[0007] 4) Liu et al. obtained 2,5-disubstituted oxazoles by using chalcone (enone) and benzylamine as starting materials, adding pyridine, copper bromide and potassium iodide, and heating to 110°C for 11 h in an oxygen atmosphere and toluene. The substrate enone used in this method is not readily available [reaction formula:] D.Liu,J.Yu,J.Cheng,Tetrahedron.70(2014)1149-1153.];

[0008] 5) Hu et al. synthesized various oxazole-2-amine derivatives in a single step via the electrochemical desulfurization cyclization reaction of isothiocyanate and α-aminoketone under conditions without metal catalysts or added oxidants. Specifically, they used phenyl isothiocyanate and 2-aminoacetophenone hydrochloride as starting materials, tetrabutylammonium iodide as the conductive salt, triethylamine as the base, acetonitrile / methanol as the solvent, and platinum-platinum electrodes. Electrolysis was carried out at a current intensity of 15 mA and 0 °C for 2 h. This method also suffers from the problem of difficult substrate availability [reaction formula: ] JHHu,HLHong,YWQin,YFHu,SYPu,G.Liang,YBHuang,Org.Lett.23(2021)1016-1020.];

[0009] 6) Wu et al. used aromatic ketones and benzylamine as starting materials and elemental iodine as a promoter to react in dimethyl sulfoxide at 100°C for 5 hours to obtain 2,5-disubstituted oxazoles. The advantage of this method is that it uses readily available aromatic ketones and benzylamine as starting materials, but it requires an excess of elemental iodine (2 equivalents), which generates a large amount of HI, making the waste liquid difficult to treat. Furthermore, the reaction temperature is high, resulting in significant energy consumption. [The reaction formula is:] QHGao,Z.Fei,YPZhu,M.Lian,FCJia,MCLiu,NFShe,AXWu,Tetrahedron.69(2013)22-28.].

[0010] In summary, existing methods for synthesizing oxazole compounds all have obvious defects and shortcomings (e.g., substrates are not readily available, dangerous strong oxidants and excessive amounts of elemental iodine are required, a lot of waste is generated, which is not environmentally friendly, and energy consumption is high), making it difficult to fully meet the requirements of practical applications.

[0011] Therefore, it is of great significance to develop a method for synthesizing oxazole compounds that is simple, environmentally friendly, uses inexpensive and readily available raw materials, has low cost, high yield, and allows for easy separation and purification of the products. Summary of the Invention

[0012] The purpose of this invention is to provide an electrosynthesis method for 2,5-disubstituted oxazole compounds.

[0013] The technical solution adopted in this invention is:

[0014] An electrosynthetic method for 2,5-disubstituted oxazole compounds includes the following steps: dispersing a ketone compound, benzylamine, iodide, and potassium bicarbonate in an organic solvent to prepare an electrolyte; the ketone compound being one of acetophenone, p-methylacetophenone, p-methoxyacetophenone, p-fluoroacetophenone, p-chloroacetophenone, p-bromoacetophenone, 4-trifluoromethylacetophenone, 2-methylacetophenone, 2-chloroacetophenone, 3-chloroacetophenone, 3,4-dichloroacetophenone, 2-acetylfuran, 2-acetylthiophene, and 4-biphenylacetophenone; and then electrolyzing the solution to obtain the 2,5-disubstituted oxazole compound.

[0015] Preferably, the molar ratio of the ketone compound to benzylamine is 1:1 to 2.

[0016] Preferably, the molar ratio of the ketone compound, iodide, and potassium bicarbonate is 1:2 to 4:0.5 to 1.5.

[0017] Preferably, the iodide is at least one of ammonium iodide, sodium iodide, and potassium iodide.

[0018] More preferably, the iodide is ammonium iodide.

[0019] Preferably, the organic solvent is at least one selected from dimethyl sulfoxide, N,N-dimethylformamide, acetonitrile, and methanol.

[0020] More preferably, the organic solvent is dimethyl sulfoxide.

[0021] Preferably, the concentration of iodide in the electrolyte is 0.5 mol / L to 1.0 mol / L.

[0022] Preferably, the electrolysis method is constant current electrolysis, with a current of 0.03A to 0.05A.

[0023] Preferably, the electrolysis is carried out at room temperature (15℃~35℃) for 6h~10h.

[0024] Preferably, the electrolysis is performed using a single-chamber electrolytic cell, with the anode being a platinum electrode or a graphite electrode, and the cathode comprising at least one of nickel, copper, platinum, tin, and titanium.

[0025] Preferably, the anode is a graphite electrode and the cathode is a nickel electrode.

[0026] Preferably, after electrolysis, extraction, vacuum distillation, and column chromatography separation are performed.

[0027] Preferably, the solvent used for extraction is either ethyl acetate or dichloromethane.

[0028] Preferably, the eluent used in the column chromatography separation consists of ethyl acetate and petroleum ether.

[0029] The electrosynthesis method of the 2,5-disubstituted oxazole compounds of the present invention involves the following reaction formulas:

[0030]

[0031] The principle of this invention: This invention uses iodides as both a supporting electrolyte and an electrochemical promoter. By utilizing the synergistic effect of active species such as elemental iodine and iodine free radicals generated in situ by electrochemical reactions, ketone compounds are efficiently converted into iodoketones in situ, which further generate 2,5-disubstituted oxazole compounds.

[0032] The beneficial effects of this invention are: the electrosynthesis method of 2,5-disubstituted oxazole compounds of this invention has the advantages of simple process, green and environmentally friendly, cheap and readily available raw materials, low cost, high yield, and easy separation and purification of products, and is suitable for large-scale promotion and application.

[0033] Specifically:

[0034] 1) This invention uses inexpensive and readily available ketone compounds and benzylamine as starting materials, which can reduce production costs;

[0035] 2) This invention does not require the use of dangerous strong oxidants and elemental iodine, which greatly reduces the generation of waste and waste liquid, making it more environmentally friendly;

[0036] 3) Compared with existing methods, this invention is more environmentally friendly, and the synthesis at room temperature does not require heating, resulting in lower energy consumption, readily available raw materials, lower production costs, and greater practical application value. Attached Figure Description

[0037] Figure 1 The image shows the 1H NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 1.

[0038] Figure 2 The image shows the carbon NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 1.

[0039] Figure 3 The image shows the 1H NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 2.

[0040] Figure 4 The image shows the carbon NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 2.

[0041] Figure 5 The image shows the 1H NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 4.

[0042] Figure 6 The image shows the carbon NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 4.

[0043] Figure 7 The image shows the 1H NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 9.

[0044] Figure 8 The image shows the carbon NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 9.

[0045] Figure 9 The image shows the 1H NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 10.

[0046] Figure 10 The image shows the carbon NMR spectrum of the 2,5-disubstituted oxazole compound synthesized in Example 10. Detailed Implementation

[0047] The present invention will be further explained and described below with reference to specific embodiments.

[0048] Example 1:

[0049] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0050] 1.0 mmol of acetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 84%).

[0051] The structure of the 2,5-disubstituted oxazole compound synthesized in this embodiment was determined by its proton nuclear magnetic resonance (NMR) spectrum (e.g., Figure 1 As shown), carbon nuclear magnetic resonance spectrum (such as...) Figure 2 (As shown) and confirm with GC-MS.

[0052] The spectral data are as follows:

[0053] 1H NMR (500MHz, CDCl3): δ (ppm) 8.12 (dd, J = 7.7, 1.9 Hz, 2H), 7.73 (dd, J = 8.4, 1.3 Hz, 2H), 7.53-7.41 (m, 6H), 7.35 (d, J = 7.5 Hz, 1H).

[0054] 13 C NMR (125MHz, CDCl3): δ (ppm) 161.2, 151.3, 130.4, 129.0, 128.9, 128.5, 128.0, 127.4, 126.3, 124.2, 123.4.

[0055] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2,5-diphenyloxazole.

[0056] Example 2:

[0057] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0058] 1.0 mmol of p-methylacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 76%).

[0059] The structure of the 2,5-disubstituted oxazole compound synthesized in this embodiment was determined by its proton nuclear magnetic resonance (NMR) spectrum (e.g., Figure 3 As shown), carbon nuclear magnetic resonance spectrum (such as...) Figure 4 (As shown) and confirm with GC-MS.

[0060] The spectral data are as follows:

[0061] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.16-8.11 (m, 2H), 7.66-7.61 (m, 2H), 7.53-7.46 (m, 3H), 7.42 (s, 1H), 7.28 (s, 2H), 2.41 (s, 3H).

[0062] 13C NMR (125MHz, CDCl3): δ (ppm) 160.8, 151.5, 138.5, 130.2, 129.6, 128.8, 127.5, 126.3, 125.3, 124.2, 122.8, 21.4.

[0063] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(4-methylphenyl)oxazole.

[0064] Example 3:

[0065] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0066] 1.0 mmol of p-methoxyacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 75%).

[0067] The structures of the 2,5-disubstituted oxazole compounds synthesized in this embodiment were confirmed by proton NMR, carbon NMR, and GC-MS.

[0068] The spectral data are as follows:

[0069] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.16-8.04 (m, 2H), 7.66 (d, J = 8.7Hz, 2H), 7.53-7.42 (m, 3H), 7.33 (s, 1H), 6.98 (d, J = 8.8Hz, 2H), 3.86 (s, 3H).

[0070] 13 C NMR (125MHz, CDCl3): δ (ppm) 160.6, 159.9, 151.4, 130.1, 128.8, 127.6, 126.2, 125.8, 121.9, 120.9, 114.4, 55.4.

[0071] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(4-methoxyphenyl)oxazole.

[0072] Example 4:

[0073] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0074] 1.0 mmol of p-fluoroacetophenone, 1.5 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 85%).

[0075] The structure of the 2,5-disubstituted oxazole compound synthesized in this embodiment was determined by its proton nuclear magnetic resonance (NMR) spectrum (e.g., Figure 5 As shown), carbon nuclear magnetic resonance spectrum (such as...) Figure 6 (As shown) and confirm with GC-MS.

[0076] The spectral data are as follows:

[0077] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.10 (dd, J = 7.7, 1.9Hz, 2H), 7.72-7.66 (m, 2H), 7.52-7.43 (m, 3H), 7.39 (s, 1H), 7.14 (t, J = 8.7Hz, 2H).

[0078] 13 C NMR (125MHz, CDCl3): δ (ppm) 163.7and 161.7 (d, J (C, F) = 245.4Hz), 161.1, 150.5, 130.4, 128.8, 127.3, 126.3, 126.1and 126.0(d,J(C,F)=8.25Hz), 124.4and 124.3(d,J(C,F)=3.25Hz), 123.1, 116.2and 116.0(d,J(C,F)=21.7Hz).

[0079] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(4-fluorophenyl)oxazole.

[0080] Example 5:

[0081] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0082] 1.0 mmol of p-chloroacetophenone, 2.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 87%).

[0083] The structures of the 2,5-disubstituted oxazole compounds synthesized in this embodiment were confirmed by proton NMR, carbon NMR, and GC-MS.

[0084] The spectral data are as follows:

[0085] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.09 (dd, J=7.0, 2.5Hz, 2H), 7.64 (d, J=8.3Hz, 2H), 7.52-7.46 (m, 3H), 7.45-7.40 (m, 3H).

[0086] 13 C NMR (125MHz, CDCl3): δ (ppm) 161.4, 150.3, 134.2, 130.5, 129.2, 128.9, 127.2, 126.5, 126.4, 125.4, 123.8.

[0087] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(4-chlorophenyl)oxazole.

[0088] Example 6:

[0089] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0090] 1.0 mmol of p-bromoacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 84%).

[0091] The structures of the 2,5-disubstituted oxazole compounds synthesized in this embodiment were confirmed by proton NMR, carbon NMR, and GC-MS.

[0092] The spectral data are as follows:

[0093] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.10 (dd, J = 7.7, 2.0Hz, 2H), 7.61-7.55 (m, 4H), 7.51-7.47 (m, 3H), 7.45 (s, 1H).

[0094] 13 C NMR (125MHz, CDCl3): δ (ppm) 161.5, 150.3, 132.2, 130.5, 128.9, 127.3, 127.0, 126.4, 125.7, 124.0, 122.3.

[0095] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(4-bromophenyl)oxazole.

[0096] Example 7:

[0097] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0098] 1.0 mmol of 4-trifluoromethylacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 78%).

[0099] The structures of the 2,5-disubstituted oxazole compounds synthesized in this embodiment were confirmed by proton NMR, carbon NMR, and GC-MS.

[0100] The spectral data are as follows:

[0101] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.13 (dd, J = 6.7, 2.9Hz, 2H), 7.83 (d, J = 8.1Hz, 2H), 7.70 (d, J = 8.1Hz, 2H), 7.55 (s, 1H), 7.50 (dd, J = 5.3, 1.9Hz, 3H).

[0102] 13 C NMR (125MHz, CDCl3): δ (ppm) 162.0, 149.9, 131.3, 130.8, 130.2and 130.0 (d, J (C, F) = 32Hz), 128.9, 127.1, 126.5, 126.1, 126.0 (2), 125.9 (9) and 125.9(8)(q,J(C,F)=3.75Hz),125.2,124.2,122.9.

[0103] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(4-trifluoromethylphenyl)oxazole.

[0104] Example 8:

[0105] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0106] 1.0 mmol of 2-methylacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 75%).

[0107] The structures of the 2,5-disubstituted oxazole compounds synthesized in this embodiment were confirmed by proton NMR, carbon NMR, and GC-MS.

[0108] The spectral data are as follows:

[0109] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.12 (dd, J = 7.9, 1.8Hz, 2H), 7.79 (d, J = 7.5Hz, 1H), 7.52-7.45 (m, 3H), 7.36 (s, 1H), 7.33-7.27 (m, 3H), 2.55 (s, 3H).

[0110] 13 C NMR (125MHz, CDCl3): δ (ppm) 160.9, 150.8, 135.0, 131.3, 130.4, 128.9, 128.4, 127.5, 127.3, 126.9, 126.3(2), 126.3(0), 126.2, 21.9.

[0111] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(2-methylphenyl)oxazole.

[0112] Example 9:

[0113] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0114] 1.0 mmol of 2-chloroacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 54%).

[0115] The structure of the 2,5-disubstituted oxazole compound synthesized in this embodiment was determined by its proton nuclear magnetic resonance (NMR) spectrum (e.g., Figure 7 As shown), carbon nuclear magnetic resonance spectrum (such as...) Figure 8 (As shown) and confirm with GC-MS.

[0116] The spectral data are as follows:

[0117] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.02 (d, J = 6.6 Hz, 2H), 7.83-7.77 (m, 2H), 7.38 (d, J = 2.6 Hz, 4H), 7.19-7.13 (m, 2H).

[0118] 13 C NMR (125MHz, CDCl3): δ (ppm) 161.0, 147.8, 130.8, 130.6 (3), 130.5 (8), 128.9 (2), 128.8 (6), 128.5, 127.7, 127.2, 127.1, 126.8, 126.5.

[0119] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(2-chlorophenyl)oxazole.

[0120] Example 10:

[0121] An electrosynthetic method for 2,5-disubstituted oxazole compounds, comprising the following steps:

[0122] 1.0 mmol of 3-chloroacetophenone, 1.0 mmol of benzylamine, 3.0 mmol of ammonium iodide, 1.0 mmol of potassium bicarbonate, and 4 mL of dimethyl sulfoxide were added to a 15 mL single-chamber electrolytic cell (single-necked glass bottle). The mixture was then magnetically stirred, and electrolyzed at room temperature for 8 h with a graphite rod as the anode and a nickel sheet as the cathode under a constant current of 0.04 A. 10 mL of saturated sodium thiosulfate solution was added for decolorization (until the electrolyte no longer faded). The electrolyte was then extracted three times with ethyl acetate. The extract was distilled under reduced pressure, and the crude product was separated by column chromatography using ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain 2,5-disubstituted oxazole compounds (yield: 78%).

[0123] The structure of the 2,5-disubstituted oxazole compound synthesized in this embodiment was determined by its proton nuclear magnetic resonance (NMR) spectrum (e.g., Figure 9 As shown), carbon nuclear magnetic resonance spectrum (such as...) Figure 10 (As shown) and confirm with GC-MS.

[0124] The spectral data are as follows:

[0125] 1 H NMR (500MHz, CDCl3): δ (ppm) 8.11 (dd, J = 7.0, 2.5Hz, 2H), 7.73-7.70 (m, 1H), 7.59 (d, J=7.7Hz,1H),7.53-7.46(m,4H),7.38(t,J=7.9Hz,1H),7.31(dd,J=8.1,2.0Hz,1H).

[0126] 13 C NMR (125MHz, CDCl3): δ (ppm) 161.6, 149.9, 135.0, 130.6, 130.3, 129.7, 128.9, 128.4, 127.2, 126.4, 124.4, 124.1, 122.2.

[0127] In summary, the 2,5-disubstituted oxazole compound synthesized in this embodiment is 2-phenyl-5-(3-chlorophenyl)oxazole.

[0128] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for the electrosynthesis of 2,5-disubstituted oxazole compounds, characterized in that, Includes the following steps: An electrolyte is prepared by dispersing ketones, benzylamine, iodides, and potassium bicarbonate in an organic solvent. The ketone is selected from one of the following: acetophenone, p-methylacetophenone, p-methoxyacetophenone, p-fluoroacetophenone, p-chloroacetophenone, p-bromoacetophenone, 4-trifluoromethylacetophenone, 2-methylacetophenone, 2-chloroacetophenone, 3-chloroacetophenone, 3,4-dichloroacetophenone, 2-acetylfuran, 2-acetylthiophene, and 4-biphenylacetophenone. Electrolysis is then performed to obtain 2,5-disubstituted oxazone. The mixture comprises azole compounds; the molar ratio of the ketone compound and benzylamine is 1:1 to 2; the molar ratio of the ketone compound, iodide, and potassium bicarbonate is 1:2 to 4:0.5 to 1.5; the iodide is ammonium iodide; the organic solvent is dimethyl sulfoxide; the electrolysis is performed by constant current electrolysis with a current of 0.03A to 0.05A; the electrolysis is carried out at room temperature for 6 to 10 hours; the electrolysis is performed in a single-chamber electrolytic cell with a graphite rod as the anode and a nickel sheet as the cathode.

2. The electrosynthesis method according to claim 1, characterized in that: The concentration of iodide in the electrolyte is 0.5 mol / L to 1.0 mol / L.

3. The electrosynthesis method according to claim 1 or 2, characterized in that: After electrolysis, extraction, vacuum distillation, and column chromatography separation were performed.

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