A method for electrochemically synthesizing oxothiazolizine alkane compounds

Abstract

The application discloses a method for electrochemically synthesizing oxothiazolazine alkane compounds, which utilizes an electrochemical sulfur and oxygen oxidation method for olefins by using olefin radical cations and diprotic nucleophiles, can synthesize N / S heterocyclic compounds in a single reaction container, utilizes easily obtained thiols and styrene azide, does not need external oxidants or redox catalysts, can synthesize N / S heterocyclic compounds in a single reaction container, and can widen the way of obtaining complex molecular structures for pharmaceutical chemistry and material science.

Description

Technical Field

[0001] This invention relates to electrochemical synthesis technology, specifically a method for the electrochemical synthesis of oxothiazolinone compounds. Background Technology

[0002] In organic synthesis, regioselective functionalization of alkenes to construct nitrogen- and sulfur-containing heterocyclic compounds is a key research area, as these heterocyclic compounds are crucial in the fields of pharmaceuticals and materials science due to their unique electronic and biological properties.

[0003] The main pharmacological activities of oxothiazolinone compounds are antitumor and antibacterial. They can inhibit the proliferation of various tumor cells, induce apoptosis, and exert their effects against Gram-positive bacteria, some Gram-negative bacteria, and mycobacteria by inducing reactive oxygen species generation, causing oxidative damage, and inhibiting ribosomal protein synthesis. They also have anti-inflammatory, antioxidant, and inhibitory activities against alkaline phosphatase, α-glucosidase, and other enzymes. Some derivatives also have anti-vascular calcification, antiviral, antifungal, analgesic, and anticonvulsant pharmacological effects. These compounds have the characteristics of multiple targets and multiple activities, and have good research and application prospects in the fields of drug-resistant tumors and drug-resistant bacterial infections (Chem. Soc. Rev., 2022, 51, 7206-7237). Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of existing technologies by providing a method for the electrochemical synthesis of oxothiazolinane compounds. This method utilizes readily available thiols and styrene azides, requires no external oxidants or redox catalysts, and enables the synthesis of N / S heterocyclic compounds in a single reaction vessel, thus broadening the pathways for obtaining complex molecular structures for medicinal chemistry and materials science.

[0005] The technical solution to achieve the objective of this invention is: A method for the electrochemical synthesis of oxothiazolinane compounds, wherein the general synthetic formula for the oxothiazolinane compounds is: R = aromatic group, aliphatic group; Among them, the electrolytes are: tetrabutylammonium fluoroborate and tetrabutylammonium iodide; Solvents: N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile.

[0006] The electrochemical synthesis process of oxothiazolinone compounds is as follows: In a 10 mL three-necked round-bottom flask, 0.4 mmol, 1.0 equivalent of alkenyl azide, 1.4 mmol, 3.5 equivalent of thiol, and 1 equivalent of electrolyte were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. Then, 7 mL of solvent was added to the three-necked flask, and electrolysis was carried out at a constant current of 5-8 mA at room temperature for 1-3 hours. After the reaction was completed, the reaction mixture was washed with water and extracted with 3 × 10 mL of dichloromethane. The organic layers were combined, dried with sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product.

[0007] Under electrochemical conditions, the free radical cations derived from olefins possess both the characteristics of free radicals and electrophilic carbocations, providing an unconventional route for introducing binucleophilic reagents. This method transcends the limitations of traditional free radical-mediated functionalization reactions (where olefins act only as free radical acceptors), expands the possibilities for coupling reactions, and successfully synthesizes oxothiazolinone compounds under electrochemical conditions.

[0008] This technical solution utilizes olefin radical cations and amphiphilic reagents to electrochemically oxidize olefins, enabling the synthesis of N / S heterocyclic compounds in a single reaction vessel. This method leverages readily available thiols and styrene azides, eliminating the need for external oxidants or redox catalysts. The in-situ generation of sulfur-centered radicals facilitates efficient cyclization reactions and exhibits excellent regioselectivity and chemoselectivity.

[0009] This method utilizes readily available thiols and styrene azides, without the need for external oxidants or redox catalysts, to synthesize N / S heterocyclic compounds in a single reaction vessel, thus broadening the pathways for obtaining complex molecular structures for medicinal chemistry and materials science. Detailed Implementation

[0010] The present invention will be further described below with reference to embodiments, but this is not intended to limit the scope of the invention.

[0011] Example 1: Preparation and characterization of 3-methyl-3-phenyl-1,4,2-oxothiazolinone:

[0012] In a 10 mL three-necked round-bottom flask, styrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask. Electrolysis was performed at a constant current of 8 mA for 1.5 h at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried with sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (63 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 80% yield. 1 H NMR (500MHz, CDCl3) δ 7.57 (m, 2H), 7.36 (m, 2H), 7.28 (m, 1H), 3.58-3.49 (m, 2H), 2.56 (m, 2H), 1.94 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 141.8, 128.5, 128.0,126.1, 75.2, 61.2, 33.4, 29.5. HRMS (m / z) (ESI): calcd for C 10 H 14 NOS + [M+H] + 196.0791, found 196.0796.

[0013] Example 2: Preparation and characterization of 3-methyl-3-(p-tolyl)-1,4,2-oxothiazolinone:

[0014] In a 10 mL three-necked round-bottom flask, p-methylstyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. Acetonitrile (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 1 hour at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product, characterized as follows: The title compound (70.5 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 85% yield.1H NMR (500MHz, CDCl3) δ7.45 (m, 2H), 7.17-7.15 (m, 2H), 3.60-3.49 (m, 2H), 2.61-2.52(m, 2H), 2.34 (s, 3H), 1.92 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 139.0, 137.9,129.3, 126.1, 75.3, 61.3, 33.6, 29.6, 21.1. HRMS (m / z) (ESI): calcd forC 11 H 16 NOS + [M+H] + 210.0948, found 210.0941.

[0015] Example 3: Preparation and characterization of 3-methyl-3-(4-propylphenyl)-1,4,2-oxothiazolinone:

[0016] In a 10 mL three-necked round-bottom flask, p-propylstyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium iodide (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. The flask was then filled with dimethyl sulfoxide (7 mL), and electrolysis was performed at a constant current of 8 mA for 1 hour at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (74 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 78% yield. 1 H NMR (400MHz, CDCl3) δ 7.47-7.45(m, 2H), 7.17-7.15 (m, 2H), 3.57-3.50 (m, 2H), 2.59-2.55 (m, 4H), 1.93 (s, 3H), 1.66-1.61 (m, 2H), 0.95-0.92 (m, 3H). 13 C NMR (101MHz, CDCl3) δ 142.7, 139.2, 128.7, 126.0, 75.3, 61.3, 37.7, 33.6, 29.6, 24.5,14.0. HRMS (m / z) (ESI): calcd for C 13 H 20 NOS + [M+H] + 238.1261, found 238.1266.

[0017] Example 4: Preparation and characterization of 3-(4-(tert-butyl)phenyl)-3-methyl-1,4,2-oxothiazolinone:

[0018] In a 10 mL three-necked round-bottom flask, p-tert-butylstyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium iodide (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. Acetonitrile (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 2 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product, characterized as follows: The title compound (70.3 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 70% yield. 1H NMR (400MHz, CDCl3) δ7.49-7.46 (m, 2H), 7.37-735(m, 2H), 3.62-3.50 (m, 2H), 2.59-2.56(m, 2H), 1.93 (s, 3H), 1.31 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 151.1, 138.8,125.8, 125.5, 75.2, 61.4, 34.6, 33.6, 31.4, 29.6. HRMS (m / z) (ESI): calcd forC14H22NOS+ [M+H]+ 252.1417, found 252.1418.

[0019] Example 5: Preparation and characterization of 3-([1,1'-biphenyl]-4-yl)-3-methyl-1,4,2-oxothiazolinone:

[0020] In a 10 mL three-necked round-bottom flask, p-phenylstyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask. Electrolysis was performed at a constant current of 8 mA at room temperature for 1 hour. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried with sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (83.4 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 77% yield. 1 H NMR (500MHz, CDCl3) δ 7.65-7.57 (m, 6H), 7.44 (m, 2H), 7.36 (m, 1H), 3.62-3.54 (m,2H), 2.67-2.56 (m, 2H), 1.98 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 140.9, 140.3,129.0, 127.7, 127.2, 126.7, 33.6, 29.6. HRMS (m / z) (ESI): calcd for C 16 H 18 NOS + [M+H] + 272.1104, found 272.1110.

[0021] Example 6: Preparation and characterization of 3-(4-fluorophenyl)-3-methyl-1,4,2-oxothiazolinone:

[0022] In a 10 mL three-necked round-bottom flask, p-fluorostyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. The flask was then filled with dimethyl sulfoxide (7 mL), and electrolysis was performed at a constant current of 8 mA for 2.5 h at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (68 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 80% yield. 1 H NMR (400MHz, CDCl3) δ 7.57-7.53 (m, 2H), 7.05-7.01(m, 2H), 3.59-3.54 (m, 2H), 2.57 –2.52 (m, 2H), 1.92 (s, 3H). 13 HRMS (m / z) (ESI): calcd for C 10 H 13 FNOS + [M+H] + 214.0697, found214.0671.

[0023] Example 7: Preparation and characterization of 3-(4-chlorophenyl)-3-methyl-1,4,2-oxothiazolinone:

[0024] In a 10 mL three-necked round-bottom flask, p-chlorostyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. The flask was then filled with dimethyl sulfoxide (7 mL), and electrolysis was performed at a constant current of 8 mA for 2.5 h at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (75.1 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 82% yield. 1 H NMR (500MHz, CDCl3) δ 7.52-7.50 (m, 2H), 7.33-7.26 (m, 2H), 3.59-3.53 (m, 2H), 2.57-2.50 (m, 2H), 1.90 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 140.6, 133.9, 128.7,127.7, 74.7, 61.2, 33.4, 29.6. HRMS (m / z) (ESI): calcd for C 10 H 13 ClNOS + [M+H] + 230.0401, found 230.0409.

[0025] Example 8: Preparation and characterization of 3-(4-bromophenyl)-3-methyl-1,4,2-oxothiazolinone:

[0026] In a 10 mL three-necked round-bottom flask, p-bromostyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. The flask was then filled with dimethyl sulfoxide (7 mL), and electrolysis was performed at a constant current of 8 mA for 2 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (92.8 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 85% yield. 1 H NMR (400MHz, CDCl3) δ 7.46 (mz, 4H), 3.61-3.49 (m, 2H), 2.52 (m, 7.2 Hz, 2H), 1.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 141.1, 131.6, 128.0, 122.0, 74.7, 61.1,33.3, 29.5. HRMS (m / z) (ESI): calcd for C 10 H 13 BrNOS + [M+H] + 273.9896, found273.9890.

[0027] Example 9: Preparation and characterization of 3-methyl-3-(4-(trifluoromethyl)phenyl)-1,4,2-oxothiazolinone:

[0028] In a 10 mL three-necked round-bottom flask, p-trifluoromethylstyrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylfluoroborate ammonium (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. Acetonitrile (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (85.2 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 81% yield. 1 H NMR (400MHz, CDCl3) δ 7.72-7.70 (m, 2H), 7.62-7.60 (m, 2H), 3.64-3.53 (m, 2H), 2.59-2.47 (m, 2H), 1.94 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 146.0, 130.4, 130.1,126.8, 125.6,, 74.7, 61.2, 33.4, 29.6. 19 F NMR (376 MHz, CDCl3) δ -62.63 (s,3F). HRMS (m / z) (ESI): calcd for C 11 H 13 F3NOS + [M+H] + 264.0665, found 264.0664.

[0029] Example 10: Preparation and characterization of 4-(3-methyl-1,4,2-oxothiazo[3,4-b]thiazo-3-yl)benzonitrile:

[0030] In a 10 mL three-necked round-bottom flask, p-cyanostyl styrene azide (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutyl fluoroborate ammonium (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. Acetonitrile (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried with sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (46.7 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 53% yield. 1 H NMR (400MHz, CDCl3) δ 7.72-7.69 (m, 2H), 7.64 (m, 2H), 3.59-3.54 (m, 2H), 2.57-2.43(m, 2H), 1.92 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 147.3, 132.4, 127.2, 111.9,61.1, 33.2, 29.4. HRMS (m / z) (ESI): calcd for C 11 H 13 N2OS + [M+H] + 221.0744, found 221.0748.

[0031] Example 11: Preparation and characterization of methyl 4-(3-methyl-1,4,2-oxothiazo[3,4-b]thiazo-3-yl)benzoate:

[0032] In a 10 mL three-necked round-bottom flask, methyl 4-(1-azidopentenyl)benzoate (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutyl fluoroborate ammonium (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask. Electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (80 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 79% yield. 1 H NMR (400MHz, CDCl3) δ 8.02 (d, 2H), 7.65 (d, 2H), 3.92 (s, 3H), 3.60-3.48 (m, 2H), 2.56-2.50 (m, 2H), 1.94 (s, 3H)). 13 C NMR (101 MHz, CDCl3) δ 166.7, 147.0,129.9, 126.37 (s), 74.8, 61.2, 52.4, 33.5, 29.4. HRMS (m / z) (ESI): calcd forC 12 H 16 NO3S + [M+H] + 254.0846, found 254.0839.

[0033] Example 12: Preparation and characterization of 3-methyl-3-(m-tolyl)-1,4,2-oxothiazolinone:

[0034] In a 10 mL three-necked round-bottom flask, meta-methylstyrene (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask. Electrolysis was performed at a constant current of 8 mA at room temperature for 2 hours. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (66.1 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 79% yield. 1 H NMR (400MHz, CDCl3) δ 7.38-7.36 (m, 2H), 7.23 (m, 1H), 7.10-7.08(m, 1H), 3.61-3.49(m, 2H), 2.59-2.55 (m, 4.0 Hz, 2H), 2.37 (s, 3H), 1.93 (s, 3H). 13 C NMR (101MHz, CDCl3) δ 141.9, 138.3, 128.8, 128.5, 126.8, 123.3, 75.3, 61.3, 33.6,29.6, 21.7. HRMS (m / z) (ESI): calcd for C 11 H 15 NOS + [M+H] + 210.0874, found210.0883.

[0035] Example 13: Preparation and characterization of 3-(3-chlorophenyl)-3-methyl-1,4,2-oxothiazolinone:

[0036] In a 10 mL three-necked round-bottom flask, m-chlorostyrene (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylammonium fluoroborate (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. The flask was then filled with dimethyl sulfoxide (7 mL), and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (77.9 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 85% yield. 1 H NMR (400MHz, CDCl3) δ 7.53 (m, 1H), 7.43-7.40 (m, 1H), 7.26-7.19 (m, 2H), 3.58-3.47(m, 2H), 2.56-2.44 (m, 2H), 1.86 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 144.2,134.6, 129.9, 128.2, 126.6, 124.5, 74.6, 61.3, 33.5, 29.6. HRMS (m / z) (ESI):calcd for C 10 H 13 ClNOS + [M+H] + 230.0401, found 230.0403.

[0037] Example 14: Preparation and characterization of 3-(3,5-difluorophenyl)-3-methyl-1,4,2-oxothiazolinone:

[0038] In a 10 mL three-necked round-bottom flask, 0.4 mmol of 3,5-difluorostyrene, 1.0 equivalent, 1.4 mmol of thiol, and 1 equivalent of tetrabutylammonium iodide were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum cathode were configured. Acetonitrile (7 mL) was then added to the flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (80 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 86% yield. 1 H NMR (400MHz, CDCl3) δ 7.13 (m, 2H), 6.73 (m, 1H), 3.66-3.55 (m, 2H), 2.63-2.49 (m,2H), 1.89 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 164.3, 161.8, 146.4, 109.89-109.42 (m), 103.5, 74.2, 61.2, 33.4, 29.5. 19 F NMR (376 MHz, CDCl3) δ -109.44(s, 2F). HRMS (m / z) (ESI): calcd for C 10 H 12 F2NOS + [M+H] + 232.0603, found232.0601.

[0039] Example 15: Preparation and characterization of 3-(3,4-dichlorophenyl)-3-methyl-1,4,2-oxothiazolinone:

[0040] In a 10 mL three-necked round-bottom flask, 0.4 mmol of 3,4-dichlorostyrene, 1.0 equivalent, 1.4 mmol of thiol, and 1 equivalent of tetrabutylammonium iodide were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum cathode were configured. Acetonitrile (7 mL) was then added to the flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (78.9 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 75% yield. 1 H NMR (400MHz, CDCl3) δ 7.69-7.64 (m, 1H), 7.41 (m, 2H), 3.60-3.56 (m, 2H), 2.57-2.48(m, 2H), 1.88 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 142.4, 132.7), 132.1, 130.5,128.4, 125.8, 74.1, 61.2, 33.3, 29.6. HRMS (m / z) (ESI): calcd for C 10 H 12 Cl2NOS + [M+H] + 264.0012, found 264.0021.

[0041] Example 16: Preparation and characterization of 2-methyl-1-phenyl-4-(3-methyl-1,4,2-oxothiazo[3,4-b]thiazo-3-yl)benzoate:

[0042] In a 10 mL three-necked round-bottom flask, 0.4 mmol of adamatan-1-ylmethyl-4-(1-aminovinyl)benzoate (1.0 equivalence), 1.4 mmol of thiol (1.4 mmol of 3.5 equivalence), and 1 equivalence of tetrabutylfluoroborate were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask. Electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel. The product was characterized as follows: The title compound (116.1 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 75% yield. 1 H NMR (400MHz, CDCl3) δ 8.04-8.02 (m, 2H), 7.67-7.65 (m, 2H), 3.92 (s, 2H), 3.59-3.53(m, 2H), 2.60-2.48 (m, 2H), 2.04-2.02 (m, 3H), 1.94 (s, 3H), 1.77-1.67 (m, 7H), 1.66-1.62 (m, 5H). 13 C NMR (101 MHz, CDCl3) δ 166.2, 146.8, 130.3, 129.9,126.4, 74.9, 74.8, 61.3, 39.6, 37.1, 33.7, 33.5, 29.5, 28.2. HRMS (m / z)(ESI): calcd for C 22 H 30 NO3S + [M+H] + 388.1491, found 388.1496.

[0043] Example 17: Preparation and characterization of cyclododecylmethyl 4-(2-methyl-1,4,2-oxothiazolo[3,4-b]thiazolyl-3-yl)benzoate:

[0044] In a 10 mL three-necked round-bottom flask, cyclododecylmethyl 4-(1-azidopentenyl)benzoate (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylfluoroborate ammonium (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (117.3 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 70% yield. 1 H NMR (400MHz, CDCl3) δ 8.02-8.00 (m, 2H), 7.65-7.63(m, 2H), 3.62-3.49 (m, 2H), 2.60-2.47 (m, 2H), 1.94 (s, 3H), 1.81 (m, 1H), 1.66 (m, 1H), 1.51-1.31 (m, 20H). 13 C NMR (101 MHz, CDC l3 ) δ 165.8, 146.7, 130.7, 129.8, 126.3, 74.9, 73.3,61.2, 33.5, 29.5, 29.3, 24.3, 24.1, 23.5, 24.3, 21.0. HRMS (m / z) (ESI): calcdfor C 24 H 28 NO3S + [M+H] + 420.2567, found 420.2572.

[0045] Example 18: Preparation and characterization of adamatan-1-yl-4-(3-methyl-1,4,2-thiazazo-3-yl)benzoate:

[0046] In a 10 mL three-necked round-bottom flask, adamatan-1-yl-4-(1-iminovinyl)benzoate (0.4 mmol, 1.0 equivalence), thiol (1.4 mmol, 3.5 equivalence), and tetrabutylfluoroborate ammonium (1 equivalence) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (116.2 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 78% yield. 1 H NMR (400MHz, CDCl3) δ 7.97-7.94 (m, 2H), 7.63-7.60 (m, 2H), 3.59-3.48 (m, 2H), 2.59-2.46 (m, 2H), 2.24-2.22 (m, 9H), 1.93 (s, 3H), 1.74-1.67 (m, 6H). 13 C NMR (101MHz, CDCl3) δ 165.0, 146.3, 131.8, 129.7, 126.1, 81.5, 74.9, 61.2, 41.5,36.3, 33.5, 31.0, 29.5. HRMS (m / z) (ESI): calcd for C 21 H 28 NO3S + [M+H] + 374.1785, found 374.1779.

[0047] Example 19: Preparation and characterization of 2-isopropyl-5-methylcyclohexyl 4-(3-methyl-142-oxothiazo[3,4-b]thiazo-3-yl)benzoate:

[0048] In a 10 mL three-necked round-bottom flask, 0.4 mmol of 2-isopropyl-5-methylcyclohexyl-4-(1-azidovinyl)benzoate (1.0 equivalence), 1.4 mmol of thiol (1.4 equivalence), and 1 equivalence of tetrabutylfluoroborate were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (108 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 72% yield. 1 H NMR (400MHz, CDCl3) δ 8.01 (m, 2H), 7.64 (m, 2H), 4.93 (m, 1H), 3.65-3.50 (m, 2H), 2.61-2.45 (m, 2H), 1.93 (s, 3H), 1.73 (m, 2H), 1.60-1.51 (m, 2H), 1.25 m,1H), 0.92 (m, 8H), 0.79 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.7, 146.7,130.5, 129.9, 126.3, 75.2, 61.3, 47.4, 41.1, 34.4, 33.5, 31.5, 29.5, 26.6,23.7, 22.16, 20.9, 16.6. HRMS (m / z) (ESI): calcd for C 21 H 32 NO3S + [M+H] + 378.2098, found 378.2091.

[0049] Example 20: Preparation and characterization of 3,7-dimethyl-hept-6-en-1-yl-4-(3-methyl-1,4,2-oxothiazo[3,4-b]thiazo-3-yl)benzoate:

[0050] In a 10 mL three-necked round-bottom flask, 3,7-dimethyl-hept-6-en-1-yl-4-(1-azidovinyl)benzoate (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylfluoroborate ammonium (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried over sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (107.1 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in71% yield. 1 H NMR (500MHz, CDCl3) δ 8.00 (m, 2H), 7.65 (m, 2H), 5.38-5.34 (m, 1H), 4.35-4.28 (m,2H), 3.54 (m, 2H), 2.61-2.48 (m, 2H), 2.42 (m, 2H), 2.39-2.36 (m, 1H), 2.24(m, 2H), 2.13-2.07 (m, 2H), 1.94 (s, 3H), 1.84-1.68 (m, 1H), 1.27 (s, 3H),1.25 (m, 1H), 1.17 (m, 1H), 0.83 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 166.1,146.8, 144.3, 130.1, 129.9, 126.3, 119.1, 74.9, 63.2, 61.2, 45.9, 40.8, 38.2,36.2, 33.5, 31.8, 31.5), 29.4, 26.4, 21.3 . HRMS (m / z) (ESI): calcd forC 21 H 32 NO3S + [M+H] + 378.2098, found 378.2096.

[0051] Example 21: Preparation and characterization of benzo[d][1,3]dioxacyclopentan-5-ylmethyl-4-(3-methyl-1,4,2-oxadiazon-3-yl)benzoate:

[0052] In a 10 mL three-necked round-bottom flask, benzo[d][1,3]dioxane-5-ylmethyl-4-(1-azidovinyl)benzoate (0.4 mmol, 1.0 equivalent), thiol (1.4 mmol, 3.5 equivalent), and tetrabutylfluoroborate ammonium (1 equivalent) were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. N,N-dimethylformamide (7 mL) was then added to the three-necked flask, and electrolysis was performed at a constant current of 8 mA for 3 hours at room temperature. After the reaction was complete, the reaction mixture was washed with water and extracted with dichloromethane (3 × 10 mL). The organic layers were combined, dried with sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product. The product was characterized as follows: The title compound (118 mg) was isolated by flash chromatography(petroleum ether : ethyl acetate = 10 : 1 to 5 : 1) in 79% yield. 1 H NMR (400MHz, CDCl3) δ 8.05-8.00 (m, 2H), 7.66-7.61 (m, 2H), 6.95-6.90 (m, 2H), 6.81(d, J = 7.8 Hz, 1H), 5.97 (s, 2H), 5.25 (s, 2H), 3.59 – 3.46 (m, 2H), 2.58 –2.44 (m, 2H), 1.93 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.9, 147.8, 147.0,129.9, 129.7, 126.29 (s), 122.4, 109.1, 108.3, 101.3, 74.7, 66.9, 61.1, 33.2,29.3. HRMS (m / z) (ESI): calcd for C 19 H 20 NO5S + [M+H]+ 374.1057, found 374.1061.

[0053] in conclusion: This example demonstrates a simple and efficient synthetic method that constructs saturated N / S heterocycles through the reaction of olefin radical cations with amphiphilic reagents. It allows for precise control of regioselectivity and chemoselectivity under mild conditions. This method exhibits a broad substrate applicability and the ability to efficiently obtain complex natural product derivatives, highlighting its potential for industrial applications. It provides a valuable platform for the synthesis of heterocyclic compounds from olefins, offering promising prospects for medicinal chemistry and materials science.

Claims

1. A method for the electrochemical synthesis of oxothiazolinone compounds, characterized in that, The general formula for synthesizing the oxothiazolinone compounds is: R = aromatic group, aliphatic group Among them, the electrolytes are: tetrabutylammonium fluoroborate and tetrabutylammonium iodide; Solvents: N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile.

2. The method for electrochemical synthesis of oxothiazolinone compounds according to claim 1, characterized in that, The electrochemical synthesis process of oxothiazolinone compounds is as follows: In a 10 mL three-necked round-bottom flask, 0.4 mmol, 1.0 equivalent of alkenyl azide, 1.4 mmol, 3.5 equivalent of thiol, and 1 equivalent of electrolyte were added sequentially. A 6 mm diameter graphite carbon anode and a 1 cm × 1 cm platinum plate cathode were configured. Then, 7 mL of solvent was added to the three-necked flask, and electrolysis was carried out at a constant current of 5-8 mA at room temperature for 1-3 hours. After the reaction was completed, the reaction mixture was washed with water and extracted with 3 × 10 mL of dichloromethane. The organic layers were combined, dried with sodium sulfate, concentrated, and purified by rapid column chromatography on silica gel to obtain the pure product.

Images