Method for preparing quinone compound by copper-catalyzed phenol oxidation

Abstract

Disclosed in the present invention is a copper-catalyzed method for preparing a quinone compound by direct oxidation of phenol using oxygen as an oxidant. The method comprises directly oxidizing a phenol to generate a quinone compound in an organic solvent at room temperature by using copper chloride dihydrate (CuCl2·2H2O) and a nitrogen oxide as catalysts, and oxygen as an oxidant. The present invention has many advantages, such as simple and safe operation, cheap and readily available catalysts and raw materials, mild reaction conditions, excellent yield, good compatibility with substrate functional groups, and an environmentally friendly reaction process meeting green chemistry requirements, and has industrial application prospects.

Description

A method for preparing quinone compounds by copper-catalyzed oxidation of phenols Technical Field

[0001] This invention belongs to the field of chemical synthesis technology and relates to a method for preparing quinone compounds by direct oxidation of phenols using oxygen as an oxidant and catalysis with copper. Background Technology

[0002] Quinones are widely used in pharmaceutical and dye synthesis, and are also important intermediates in organic synthesis (Rappoport, Z. The Chemistry of Phenols, John Wiley & Sons, 2003). Therefore, the synthesis of quinones is a key area of ​​research interest. The oxidation of phenol is a simple and efficient method for synthesizing quinones (Uliana, MP; Vieira, YW; Donatoni, MC;). AG; Brocksom, U.; Brocksom, TJJ Braz. Chem. Soc., 2008, 19, 1484.), but this method usually requires the addition of an equivalent amount of high-valent iodine reagent or peroxide as an oxidant to achieve this process (Dohi, T.; Tomofumi N.; Takenaga, N.; Uchiyama, T.; Fukushima, K.; Fujioka, H.; Kita, Y. Synthesis 2012, 44, 1183.; Pancrazzi, F.; Maestri, G.; Maggi, R.; Viscardi, R. Eur. J. Org. Chem. 2021, 39, 5407.; K.; G.; K.; Join, B.; Junge, K.; Beller, M. Chem. Eur. J. 2010, 16, 10300.). In comparison, oxygen, as an abundant, clean, and inexpensive oxidant, has a significant advantage in oxidation reactions (Arends, IWCE; Sheldon, Ramodern Oxidation Methods, Wiley-VCH, Weinheim, 2004, pp. 83; Mallat, T.; Baiker, A. Chem. Rev. 2004, 104, 3037; Markó, IE; Giles, PR; Tsukazaki, M.; Chellé-Regnaut, I.; Gautier, A.; Dumeunier, R.; Philippart, F.; Doda, K.; Mutonkole, J.-L.; Brown, SM; Urch, CJAdv. Inorg. Chem. 2004, 56, 211; Zhan, BZ; Thompson, A.; Tetrahedron). 2004, 60, 2917; Schultz, MJ; Sigman, MSTetrahedron 2006, 62, 8227; Matsumoto, T.; Ueno, M.; Wang, N.; Kobayashi, S. Chem. Asian J. 2008, 3, 196; Parmeggiani, C.; Cardona, F. Green Chem. 2012, 14, 547.. Copper, as an inexpensive and readily available metal, is used to catalyze various organic reactions and is also widely used in oxidation reactions (Allen, SE; Walvoord, RR; Padilla-Salinas, R.; Kozlowski, MCChem. Rev. 2013, 113, 6234; McCann, SD; Stahl, SSAcc. Chem. Res. 2015, 48, 1756.). TEMPO, as a stable nitric oxide radical, exhibits unique reactivity in catalytic oxidation reactions (Allen, SE; Walvoord, RR; Padilla-Salinas, R.; Kozlowski, MCChem. Rev. 2013, 113, 6234.; Ryland, BL; Stahl, SSAngew.).

[0003] Chem. Int. Ed. 2014, 53, 8824.; McCann, SD; Stahl, SSAcc. Chem. Res. 2015, 48, 1756.). However, the reaction of phenol oxidation to prepare quinone in Cu / TEMPO system with oxygen as oxidant has not been reported. Summary of the Invention

[0004] This invention overcomes the shortcomings of the prior art and provides a copper-catalyzed method for preparing quinone compounds by oxidizing phenols with oxygen as the oxidant. This method is low-cost, suitable for industrial production, has mild reaction conditions, and is easy to operate.

[0005] This invention overcomes the shortcomings of existing oxidation technologies, such as the use of stoichiometric or excessive amounts of oxidants that generate byproducts, harsh reaction conditions, and high costs. It utilizes oxygen, a greener, cleaner, and cheaper oxidant, to oxidize phenols and prepare quinones. The reaction uses readily available and inexpensive industrial copper chloride dihydrate and nitric oxide radicals as catalysts, with oxygen as the oxidant, successfully achieving the oxidation of phenols to quinones. This invention requires low costs, uses widely available raw materials, and involves a green and clean reaction process. It also offers advantages such as mild reaction conditions, simple operation, suitability for industrial production, and environmental friendliness.

[0006] This invention provides a copper-catalyzed method for the direct oxidation of phenol to prepare quinone compounds using oxygen as an oxidant. Under room temperature conditions and in an organic solvent, phenol is used as a raw material, with copper chloride dihydrate and nitrogen oxides as catalysts, and oxygen as the oxidant, to directly oxidize the phenol to prepare quinone compounds. The reaction process is shown in reaction formula (1):

[0007] in,

[0008] R is selected from alkyl, heteroatom substituent, aryl, and alkyl with functional groups;

[0009] The functional groups in the alkyl group are alkenyl, hydroxyl, phenyl, etc.; the heteroatom substituents are methoxy, mercaptomethyl, dimethylamino, acetamido, etc.; the aryl group is phenyl, naphthyl, indole, etc.

[0010] Preferably, R is selected from methyl, 2,6-dimethyl, 2,3-dimethyl, 2,3,5-trimethyl, 2,3,6-trimethylethyl, n-propyl, isopropyl, isobutyl, tert-butyl, benzyl, allyl, phenyl, methoxy, methylthio, dimethylamino, acetamido, etc.

[0011] In a specific embodiment, the phenolic compound is ArOH, which is o-cresol, m-cresol, o-sec-butylphenol, 2-tert-butylphenol, 2,6-dimethylphenol, 2,3-dicresol, 3,5-dimethylphenol, 2,5-dimethylphenol, thymol, propofol, 2,6-di-tert-butylphenol, 2,3,5-trimethylphenol, 2,3,6-trimethylphenol, 1-naphthol, 4-hydroxyindole, 2-benzylphenol, o-hydroxyphenylethanol, 2-allylphenol, 2-(3-methyl-2-butenyl)phenol, o-phenylphenol, 2,6-diphenylphenol, N-(3-hydroxyphenyl)acetamide, 3-methoxyphenol, 3,5-dimethoxyphenol, 3-(methylsulfinyl)phenol, and 3-hydroxy-N,N-dimethylaniline.

[0012] In the method of the present invention, the nitrogen oxide is one or more of 2,2,6,6-tetramethylpiperidine nitride oxide (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine nitride oxide (4-OH-TEMPO), 4-acetamido-2,2,6,6-tetramethylpiperidine nitride oxide (4-AcNH-TEMPO), etc.; preferably, it is 2,2,6,6-tetramethylpiperidine nitride oxide (TEMPO).

[0013] In the method of the present invention, the organic solvent is one or more of 1,2-dichloroethane, toluene, acetonitrile, methanol, ethanol, isopropanol, tert-butanol, etc.; preferably, it is a mixture of acetonitrile and tert-butanol.

[0014] In the method of the present invention, the molar ratio of the raw materials phenol ArOH, copper chloride dihydrate, and nitrogen oxides is 100:(1-10):(1-10); preferably, the molar ratio of the raw materials phenol ArOH, copper chloride dihydrate, and nitrogen oxides is 100:10:10.

[0015] In this invention, the reaction temperature is room temperature.

[0016] In this invention, the reaction time is 12-45 hours; preferably, it is 18 hours.

[0017] In this invention, the source of oxygen is pure oxygen or air; preferably, it is pure oxygen.

[0018] The possible mechanism of this invention is as follows: First, phenol forms a phenolic oxygen radical under the combined action of copper chloride dihydrate and nitrogen oxides. This radical has a resonance structure. Then, the carbon radical of this resonance structure captures oxygen to form a peroxide radical, which is then protonated to form a peroxide compound. Finally, elimination occurs to obtain quinone compounds. The reaction mechanism is shown in the following equation (2):

[0019] The essential innovation of this invention is as follows: (1) A novel and efficient catalytic system is developed, which utilizes copper chloride dihydrate and nitrogen oxides as a new catalytic system to directly oxidize phenol to obtain quinone compounds; (2) Based on the concept of phenol oxidation to prepare quinones, this invention proposes a convenient and simple method to achieve phenol oxidation. However, most of the previously reported methods rely on the use of oxidants that generate by-products in equal or excessive amounts, such as high-valent iodine and peroxides, which greatly increases the production cost. The copper / TEMPO system is not only cheaper, but also has not been reported before.

[0020] The beneficial effects of this invention include: This invention proposes a method for directly oxidizing phenol to quinone compounds in an organic solvent at room temperature, using phenol as a raw material, copper chloride dihydrate and nitrogen oxides as catalysts, and oxygen as an oxidant. This invention utilizes oxygen as an oxidant to oxidize phenols containing multiple functional groups (such as heteroatom substituents and aryl groups) to quinone compounds. This invention has broad substrate applicability, high yield, and uses inexpensive and environmentally friendly copper chloride dihydrate and TEMPO as catalysts, and abundant and readily available oxygen as an oxidant, effectively solving the problems of harsh reaction conditions and the need for equivalent oxidant participation in current methods. This invention has many advantages, including simple operation, inexpensive and readily available catalysts and raw materials, mild reaction conditions, excellent yield, good substrate functional group compatibility, and an environmentally friendly reaction process. The method of this invention can be used for both small-scale laboratory synthesis and large-scale industrial production.

[0021] This invention utilizes oxygen or air, a green, inexpensive, and widely available clean energy source, to replace the chemical oxidants required in traditional oxidation methods. Its byproduct is water, and the entire reaction process produces virtually no environmental pollution, meeting the requirements of green chemistry. The copper chloride dihydrate and nitric oxide radicals used in this invention are commercially available reagents that are inexpensive and have high yields, effectively reducing production costs. The reaction conditions are mild, and the post-processing is simple, making the operation convenient and easy to control. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to specific embodiments. The processes, conditions, and experimental methods for implementing the present invention, except as specifically mentioned below, are all common knowledge and general knowledge in the field, and the present invention does not have any particular limitations.

[0023] Note: In the reaction formulas of the following examples, mol represents moles; CuCl2·2H2O represents copper(II) chloride dihydrate; TEMPO represents 2,2,6,6-tetramethylpiperidine oxide; MeCN represents acetonitrile; tBuOH represents tert-butanol; DCE represents 1,2-dichloroethane; MeOH represents methanol; Toluene represents toluene; EtOH represents ethanol. i PrOH represents isopropanol; rt represents room temperature; O2 [1.0 MPa] in autoclave indicates that the reaction is carried out in a reactor under a 1 MPa oxygen atmosphere; h represents hours; the boiling range of petroleum ether is 60-90℃; the NMR yield is determined by... 1 Identification was performed by 1H NMR, with dibromomethane as the internal standard. The silica gel used for short column chromatography was 100-200 mesh, and for column chromatography it was 300-400 mesh.

[0024] Example 1

[0025] Step I: Add CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1a (108.6 mg, 1.0 mmol), and MeCN (2 mL) sequentially to a 25 mL reaction vessel. t BuOH (2 mL). Oxygen was introduced at 1.0 MPa, and the reaction was stirred at room temperature for 18 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation. The product was then purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1) to give a yellow solid 2a (91.6 mg, 75%).

[0026] mp68.0-69.0℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.81-6.69 (m, 2H, = CH), 6.68-6.59 (m, 1H, = CH), 2.07 (d, J = 1.6Hz, CH3); 13 C NMR (100MHz, CDCl3): δ = 187.6, 187.5, 145.7, 136.5, 136.4, 133.2, 15.7. IR (neat): v (cm -1 )=3056,2925,1653,15981489,1347,1298,1156,1092; MS(EI,70eV):m / z(%)=122([M] + ,100).

[0027] Example 2

[0028] The procedure is the same as step I in Example 1 of this invention, with 1b (108.6 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeCN (2 mL). t The reaction was carried out with BuOH (2 mL) for 18 hours to give a yellow solid 2a (92.8 mg, 76%) (eluent: petroleum ether / dichloromethane = 20 / 1).

[0029] 1 H NMR (400MHz, CDCl3) δ = 6.81-6.70 (m, 2H, = CH), 6.69-6.60 (m, 1H, = CH), 2.07 (d, J = 1.6Hz, 3H, CH3); 13 C NMR (100MHz, CDCl3) δ = 187.7, 187.5, 145.8, 136.5, 136.4, 133.3, 15.8;

[0030] Example 3

[0031] The procedure is the same as step I in Example 1 of this invention, with 1c (151.0 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow liquid 2c (114.9 mg, 70%) (eluent: petroleum ether / ethyl acetate = 30 / 1).

[0032] 1 H NMR (400MHz, CDCl3): δ=6.82-6.68(m,2H,=CH),6.58-6.49(m,1H,=CH)2.94-2.79(Sext,J=6.8Hz,1H,CH),1.64-1.52(m,1H,one proton of CH2),1.51-1.39(m,1H,one proton of CH2),1.12(d,J=6.8Hz,3H,CH3),0.89(t,J=7.6Hz,3H,CH3); 13 C NMR (100MHz, CDCl3): δ = 187.9, 187.1, 153.9, 136.9, 135.8, 131.0, 33.1, 28.4, 18.7, 11.5. IR (neat): v (cm -1)=2965,2876,1651,1598,1460,1382,1295,1218,1122,1049; MS (EI, 70eV): m / z (%)=164 ([M] + ,1.38),137(100).

[0033] Example 4

[0034] The procedure is the same as step I in Example 1 of this invention, 1 day (151.0 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid 2d (144.5 mg, 88%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0035] mp55.9-57.8℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.71 (s, 2H, = CH), 6.61 (s, 1H, = CH), 1.30 (s, 9H, CH3 × 3); 13 C NMR (100MHz, CDCl3): δ = 187.9, 187.1, 155.5, 138.3, 134.6, 131.2, 34.9, 28.8. IR (neat): v (cm -1 )=2960,2873,1650,1588,1461,1338,1287,1107,1010; MS(EI,70eV):m / z(%)=164([M] + ,44.0),121(100).

[0036] Example 5

[0037] The procedure is the same as step I in Example 1 of this invention, with 1e (122.3 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), and MeOH (2 mL). t The reaction was carried out with BuOH (2 mL) for 18 hours to give a yellow solid 2e (106.2 mg, 78%) (eluent: petroleum ether / ethyl acetate = 30 / 1).

[0038] mp70.0-70.7℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.56 (s, 2H, = CH), 2.06 (s, 6H, CH3 × 2); 13 C NMR (100MHz, CDCl3): δ = 188.1, 187.6, 145.7, 133.2, 15.9; IR (neat): v (cm -1 )=3042,2968,1649,1612,1439,1376,1289,1180,1023; MS (EI, 70eV): m / z (%)=136 ([M] + ,63.3),68(100).

[0039] Example 6

[0040] The procedure is the same as step I in Example 1 of this invention, with 1f (122.3 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), and MeOH (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid 2e (108.9 mg, 80%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0041] 1 H NMR (400MHz, CDCl3): δ = 6.56 (s, 2H, = CH), 2.06 (s, 6H, CH3 × 2); 13 C NMR (100MHz, CDCl3): δ = 187.5, 186.9, 145.1, 132.6, 15.3.

[0042] Example 7

[0043] The procedure is the same as step I in Example 1 of this invention, using 1g (122.3mg, 1.0mmol), CuCl2·2H2O (17.0mg, 0.1mmol), TEMPO (15.6mg, 0.1mmol), and MeOH (2mL). t The reaction of BuOH (2 mL) for 18 hours yielded 2 g (91.2 mg, 67%) of a yellow solid (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0044] mp53.8.-55.0℃,petroleum ether / dichloromethane;1 H NMR (400MHz, CDCl3): δ = 6.72 (s, 2H, = CH), 2.04 (s, 6H, CH3 × 2); 13 C NMR (100MHz, CDCl3): δ = 186.3, 139.9, 135.2, 11.1; IR (neat): v (cm -1 )=3056,2957,1651,1600,1441,1382,1307,1136,1065; MS(EI,70eV):m / z(%):136([M] + ,100).

[0045] Example 8

[0046] The procedure is the same as step I in Example 1 of this invention: 1 hour (122.5 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), MeOH (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid (104.8 mg, 77%) for 2 hours (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0047] mp121.2-121.9℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.65-6.56 (m, 2H, = CH), 2.04 (d, J = 1.6Hz, 6H, CH3 × 2); 13 C NMR (100MHz, CDCl3): δ = 187.8, 145.6, 133.2, 15.3; IR (neat): v (cm -1 )=3045,2961,2926,1659,1639,1610,1437,1374,1349,1250,1152,1003; MS(EI,70eV):m / z(%):136([M] + ,100).

[0048] Example 9

[0049] The procedure is the same as step I in Example 1 of this invention, using 1i (150.1 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeOH (2 mL). tThe reaction was carried out with BuOH (2 mL) for 18 hours to give a yellow solid 2i (114.9 mg, 70%) (eluent: petroleum ether / ethyl acetate = 40 / 1).

[0050] mp46.6-47.3℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.59 (s, 1H, = CH), 6.52 (s, 1H, = CH), 3.03 (hept, J = 6.8Hz, 1H, CH), 2.04 (s, 3H, CH3), 1.13 (d, J = 6.8Hz, 3H, CH3 × 2); 13 C NMR (100MHz, CDCl3): δ = 188.6, 187.4, 154.9, 145.1, 133.8, 130.3, 26.5, 21.3, 15.3; IR (neat): v (cm -1 )=3048,2967,1642,1611,1463,1358,1245,1132,1023; MS(EI,70eV):m / z(%):164([M] + ,100).

[0051] Example 10

[0052] The procedure is the same as step I in Example 1 of this invention, with 1j (178.2 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow liquid 2j (151.9 mg, 79%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0053] 1 H NMR (400MHz, CDCl3): δ = 6.48 (s, 2H, = CH), 3.07 (hept, J = 6.8Hz, 2H, CH), 1.13 (d, J = 6.8Hz, 12H, CH3 × 4); 13 C NMR (100MHz, CDCl3): δ = 188.7, 186.8, 155.4, 129.7, 26.9, 21.4; IR (neat): v (cm -1 )=2965,2874,1654,1610,1466,1385,1288,1198,1066; MS(EI,70eV):m / z(%)=192([M] +,36.81),149(100).

[0054] Example 11

[0055] The procedure is the same as step I in Example 1 of this invention, with 1kJ (206.4 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid 2k (187.3 mg, 85%) (eluent: petroleum ether / ethyl acetate = 40 / 1).

[0056] mp63.5-64.5℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.51 (s, 2H, = CH), 1.28 (s, 18H, CH3 × 6); 13 C NMR (100MHz, CDCl3): δ = 189.1, 187.8, 157.9, 130.1, 35.5, 29.4. IR (neat): v (cm -1 )=2964,2869,1654,1598,1458,1362,1316,1244,1154,1073; MS (EI, 70eV): m / z (%)=220 ([M] + ,49.1),177(100).

[0057] Example 12

[0058] The procedure is the same as step I in Example 1 of this invention, using 11 (136.3 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeOH (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded 2 L of yellow liquid (77.6 mg, 56%) (eluent: petroleum ether / ethyl acetate = 30 / 1).

[0059] 1 H NMR (400MHz, CDCl3): δ = 6.64-6.50 (m, 1H, = CH), 2.07-1.99 (m, 9H, CH3 × 3); 13C NMR (100MHz, CDCl3): δ = 187.8, 187.4, 145.2, 140.8, 140.6, 133.0, 15.8, 12.2, 11.9. IR (neat): v (cm -1 )=2960,2924,2858,1643,1617,1437,1375,1315,1261,1188,1102; MS (EI, 70eV): m / z (%)=150 ([M] + ,100).

[0060] Example 13

[0061] The procedure is the same as step I in Example 1 of this invention, using 1 mg (136.3 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded 2 L of yellow liquid (127.7 mg, 85%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0062] 1 H NMR (400MHz, CDCl3): δ = 6.60-6.52 (m, 1H, = CH), 2.06-2.00 (m, 9H, CH3 × 3); 13 C NMR (100MHz, CDCl3): δ=187.7,187.3,145.2,140.8,140.6,132.9,.15.7,12.2,11.9.

[0063] Example 14

[0064] The procedure is the same as step I in Example 1 of this invention, with 1n (184.5 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid 2n (134.8 mg, 68%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0065] mp43.0-44.1℃,petroleum ether / ethyl acetate; 1H NMR (400MHz, CDCl3): δ=7.36-7.28(m,2H,ArH),7.28-7.22(m,1H,ArH),7.22-7. 16(m,2H,ArH),6.80-6.65(m,2H,=CH),6.41-6.30(m,1H,=CH),3.73(s,2H,CH2); 13 C NMR (100MHz, CDCl3): δ = 187.6, 187.1, 148.5, 136.5, 136.3, 136.2, 133.2, 129.3, 128.7, 126.9, 35.1. IR (neat): v (cm -1 )=3058,2917,1656,1596,1453,1353,1281,1070; MS (EI, 70eV): m / z (%)=198 ([M] + ,100).

[0066] Example 15

[0067] The procedure is the same as step I in Example 1 of this invention, using 10 (140.0 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 45 hours yielded a yellow liquid 2O (98.9 mg, 65%) (eluent: petroleum ether / ethyl acetate = 2 / 1).

[0068] 1 H NMR (400MHz, Acetone-d) 6 ): δ=6.77-6.52(m,3H,=CH),3.83(t,J=5.6Hz,1H,OH),3.60(q,J=6.0Hz,2H,CH2),2.49(td,J1=6.4Hz,J2=1.2Hz,2H,CH2); 13 C NMR (100MHz, CDCl3): δ = 187.6, 187.4, 146.5, 136.8, 136.2, 133.7, 59.6, 32.3; IR (neat): v (cm -1 )=3385,2973,2927,2888,1693,1653,1600,1455,1353,1294,1255,1043; MS (EI, 70eV): m / z (%)=152 ([M] + ,3.03),123(100).

[0069] Example 16

[0070] The procedure is the same as step I in Example 1 of this invention, with 1p (134.5 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow liquid 2p (100.7 mg, 68%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0071] 1 H NMR (400MHz, CDCl3): δ = 6.84-6.68 (m, 2H, = CH), 6.59 (s, 1H, = CH), 5.92-5.72 (m, 1H, = CH), 5.27-5.11 (m, 2H, = CH), 3.19 (d, J = 6.8Hz, 2H, CH2); 13 C NMR (100MHz, CDCl3): δ = 187.6, 187.0, 147.6, 136.6, 136.3, 132.8, 132.6, 119.0, 32.9; IR (neat): v (cm -1 )=3080,2980,1653,1598,1426,1351,1293,1063; MS (EI, 70eV): m / z (%)=148 ([M] + ,88),147(100).

[0072] Example 17

[0073] The procedure is the same as step I in Example 1 of this invention, with 1q (162.7 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow liquid 2q (96.9 mg, 55%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0074] 1 H NMR (400MHz, CDCl3): δ=6.83-6.67(m,2H,=CH), 6.61-6.47(m,1H,=CH), 5.15(t,J =7.2Hz,1H,=CH),3.12(d,J=7.2Hz,2H,CH2),1.77(s,3H,CH3),1.64(s,3H,CH3);13 C NMR (100MHz, CDCl3): δ = 187.9, 187.6, 148.5, 136.7, 136.5, 136.3, 132.3, 117.8, 27.4, 25.7, 17.7; IR (neat): v (cm -1 )=2971,2916,2857,,1654,1599,1448,1379,1345,1297,1106,1074; MS(EI,70eV):m / z(%)=176([M] + ,34.73),161(100).

[0075] Example 18

[0076] The procedure is the same as step I in Example 1 of this invention, using 1r (170.4 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeOH (2 mL). t The reaction of BuOH (2 mL) for 45 hours yielded a yellow solid 2r (55.3 mg, 30%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0077] mp107.5-108.4℃,petroleum ether / dichloromethane; 1 H NMR (400MHz, CDCl3): δ = 7.52-7.42 (m, 5H, ArH), 6.95-6.73 (m, 3H, = CH); 13 C NMR (100MHz, CDCl3): δ = 187.5, 186.5, 145.8, 137.0, 136.1, 132.6, 130.0, 129.2, 128.5. IR (neat): v (cm -1 )=3056,2924,1645,1591,1443,1296,1203,1091; MS (EI, 70eV): m / z (%)=184 ([M] + ,49.3),186(100).

[0078] Example 19

[0079] The procedure is the same as step I in Example 1 of this invention: 1s (246.5mg, 1.0mmol), CuCl2·2H2O (17.0mg, 0.1mmol), TEMPO (15.7mg, 0.1mmol), MeCN (2mL).t The reaction of BuOH (2 mL) for 45 hours yielded a yellow solid 2s (72.9 mg, 28%) (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0080] mp134.7-135.7℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 7.53-7.48 (m, 4H, ArH), δ = 7.48-7.42 (m, 6H, ArH), 6.91 (s, 2H, = CH); 13 C NMR (100MHz, CDCl3): δ = 187.5, 186.1, 146.4, 133.1, 132.6, 130.0, 129.4, 128.4; IR (neat): v (cm -1 )=3036,2927,1642,1590,1445,1292,1113; MS (EI, 70eV): m / z (%)=260 ([M] + ,20.53),262(100).

[0081] Example 20

[0082] The procedure is the same as step I in Example 1 of this invention, using 1 t (144.3 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded 2 t (118.6 mg, 75%) of a yellow solid (eluent: petroleum ether / ethyl acetate = 20 / 1).

[0083] mp123.3-124.0℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ=8.14-8.02(m,2H,ArH),7.82-7.72(m,2H,ArH),6.99(s,2H,=CH); 13 C NMR (100MHz, CDCl3): δ = 184.9, 138.6, 133.8, 131.8, 126.3. IR (neat): v (cm -1 )=3059,3029,2968,1657,1587,1300,1146,1115,1055,1019; MS (EI, 70eV): m / z (%)=158 ([M]+ ,100).

[0084] Example 21

[0085] The procedure is the same as step I in Example 1 of this invention: 1u (133.5mg, 1.0mmol), CuCl2·2H2O (17.0mg, 0.1mmol), TEMPO (15.6mg, 0.1mmol), MeOH (2mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid of 2 u (47.1 mg, 32%) (eluent: petroleum ether / ethyl acetate = 2 / 1).

[0086] mp174.3-176.4℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, Acetone-d) 6 ): δ=11.74(brs,1H,NH),7.27(d,J=2.8Hz,1H,ArH),6.61(s,2H,=CH),6.58(d,J=2.8Hz,1H,ArH); 13 C NMR (100MHz, Acetone-d) 6 ): δ = 183.1, 177.0, 137.6, 136.2, 131.0, 125.8, 125.5, 107.1; IR (neat): v (cm -1 )=3400-3000,3094,2930,1632,1580,1494,1383,1078,1046; MS (EI, 70eV): m / z (%)=147 ([M] + ,100).

[0087] Example 22

[0088] The procedure is the same as step I in Example 1 of this invention, with 1v (151.6mg, 1.0mmol), CuCl2·2H2O (17.1mg, 0.1mmol), TEMPO (15.8mg, 0.1mmol), and MeCN (2mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid, 2 v (125.5 mg, 76%) (eluent: petroleum ether / ethyl acetate = 2 / 1).

[0089] mp142.7-144.6℃,petroleum ether / ethyl acetate; 1H NMR (400MHz, CDCl3): δ = 8.17 (s, 1H, NH), 7.58 (d, J = 2.4Hz, = CH), 6.85-6.70 (m, 2H, = CH), 2.27 (s, 3H, CH3); 13 C NMR (100MHz, CDCl3): δ = 187.9, 182.6, 169.4, 138.2, 138.0, 133.1, 114.6, 24.8; IR (neat): v (cm -1 )=3400-3200,3000,2924,1693,1594,1503,1425,1368,1322,1232,1094,1007; MS(EI,70eV):m / z(%)=165([M] + ,85.23),125(100).

[0090] Example 23

[0091] The procedure is the same as step I in Example 1 of this invention, with 1w (124.3mg, 1.0mmol), CuCl2·2H2O (17.0mg, 0.1mmol), TEMPO (15.5mg, 0.1mmol), and MeCN (2mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid, 2 w (121.5 mg, 88%) (eluent: petroleum ether / ethyl acetate = 2 / 1).

[0092] mp133.6-134.3℃,petroleum ether / dichloromethane; 1 H NMR (400MHz, CDCl3): δ = 6.73 (s, 2H, = CH), 5.96 (s, 1H, = CH), 3.85 (s, 3H, CH3); 13 C NMR (100MHz, CDCl3): δ = 187.4, 181.6, 158.6, 137.2, 134.4, 107.6, 56.2. IR (neat): v (cm -1 )=3067,2949,1643,1588,1461,1358,1314,1235,1109; MS(EI,70eV):m / z(%)=138([M] + ,1.87),140(100).

[0093] Example 24

[0094] The procedure is the same as step I in Example 1 of this invention, using 1x (154.2 mg, 1.0 mmol), CuCl2·2H2O (17.1 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), and MeCN (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded a yellow solid 2x (141.2 mg, 84%) (eluent: petroleum ether / ethyl acetate = 2 / 1).

[0095] mp250.1-251.1℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 5.86 (s, 2H, = CH), 3.83 (s, 6H, CH3 × 2); 13 C NMR (100MHz, CDCl3): δ = 186.9, 176.7, 157.3, 107.4, 56.5. IR (neat): v (cm -1 )=3061,2952,1641,1589,1440,1379,1321,1215,1103,1003; MS (EI, 70eV): m / z (%)=168 ([M] + ,27.95),69(100).

[0096] Example 25

[0097] The procedure is the same as step I in Example 1 of this invention, using 1y (140.3 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeOH (2 mL). t The reaction of BuOH (2 mL) for 18 hours yielded an orange solid 2y (100.2 mg, 65%) (eluent: petroleum ether / ethyl acetate = 10 / 1).

[0098] mp144.3-146.3℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 6.86-6.70 (m, 2H, = CH), 6.36 (d, J = 2.4Hz, 1H, = CH), 2.34 (s, 3H, CH3); 13 CNMR (100MHz, CDCl3): δ = 183.8, 183.7, 153.9, 137.5, 136.0, 124.6, 13.5; IR (neat): v (cm -1)=3047,2919,1658,1637,1544,1419,1318,1279,1110,1008; MS (EI, 70eV): m / z (%)=156 ([M] + ,100).

[0099] Example 26

[0100] The procedure is the same as step I in Example 1 of this invention, using 1z (137.3 mg, 1.0 mmol), CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and MeCN (2 mL). t The reaction was carried out with BuOH (2 mL) for 18 hours to give 2z (45.3 mg, 30%), a purple solid (eluent: petroleum ether / ethyl acetate = 2 / 1).

[0101] mp108.7-109.4℃,petroleum ether / ethyl acetate; 1 H NMR (400MHz, CDCl3): δ = 7.37-7.24 (m, 2H, Ar-H), 7.23-7.10 (m, 3H, Ar-H), 3.67 (s, 3H, OCH3), 2.95 (t, J = 8.0Hz, 2H, CH2), 2.63 (t, J = 7.8Hz, 2H, CH2); 13 C NMR (100MHz, CDCl3): δ = 173.3, 140.5, 128.5, 128.2, 126.2, 51.5, 35.7, 30.9; IR (neat): v (cm -1 )=3042,2928,1673,1633,1555,1441,1384,1294,1229,1088,1067; MS (EI, 70eV): m / z (%)=151 ([M] + ,100).

[0102] Example 27

[0103] CuCl2·2H2O (17.4 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), DCE (3 mL) and [other active ingredients] were added sequentially to a 25 mL reaction vessel. tBuOH (1 mL). Oxygen was bubbled through at 0.5 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to give 2a. The crude NMR spectrum showed a yield of 38%.

[0104] Example 28

[0105] CuCl₂·2H₂O (17.4 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1a (108.9 mg, 1.0 mmol), DCE (3 mL), and MeOH (1 mL) were added sequentially to a 25 mL reaction vessel. Oxygen was bubbled through at 1.5 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. The crude NMR spectrum showed a yield of 10%.

[0106] Example 29

[0107] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (16.0 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), and MeCN (3 mL) were added sequentially to a 25 mL reaction vessel. t BuOH (1 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. A coarse NMR spectrum showed a yield of 69%.

[0108] Example 30

[0109] CuCl₂·2H₂O (17.4 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1a (108.2 mg, 1.0 mmol), Toluene (3 mL) and [other active ingredients] were added sequentially to a 25 mL reaction vessel. t BuOH (1 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. A coarse NMR spectrum showed a yield of 13%.

[0110] Example 31

[0111] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.7 mg, 0.1 mmol), 1a (108.9 mg, 1.0 mmol), and MeCN (4 mL) were added sequentially to a 25 mL reaction vessel. Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. The crude NMR spectrum showed a yield of 52%.

[0112] Example 32

[0113] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1a (108.5 mg, 1.0 mmol), and MeCN (1 mL) were added sequentially to a 25 mL reaction vessel. t BuOH (3 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. A coarse NMR spectrum showed a yield of 64%.

[0114] Example 33

[0115] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), and 1a (108.1 mg, 1.0 mmol) were added sequentially to a 25 mL reaction vessel. t BuOH (4 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. A coarse NMR spectrum showed a yield of 43%.

[0116] Example 34

[0117] CuCl₂·2H₂O (8.5 mg, 0.05 mmol), TEMPO (7.8 mg, 0.05 mmol), 1a (108.5 mg, 1.0 mmol), and MeCN (2 mL) were added sequentially to a 25 mL reaction vessel. t BuOH (2 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2a. A coarse NMR spectrum showed a yield of 38%.

[0118] Example 35

[0119] CuCl₂·2H₂O (17.0 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1a (108.4 mg, 1.0 mmol), and MeCN (2 mL) were added sequentially to a 25 mL reaction vessel. t BuOH (2 mL). Air was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 18 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to give 2a. The crude NMR spectrum showed a yield of 50%.

[0120] Example 36

[0121] CuCl2·2H2O (17.4 mg, 0.1 mmol), 1a (108.7 mg, 1.0 mmol), MeCN (2 mL) and [other components] were added sequentially to a 25 mL reaction vessel. t BuOH (2 mL). Air was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 18 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to give 2a. The crude NMR spectrum showed a yield of 44%.

[0122] Example 37

[0123] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1r (170.3 mg, 1.0 mmol), and MeCN (2 mL) were added sequentially to a 25 mL reaction vessel. t BuOH (2 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 18 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2r. A coarse NMR spectrum showed a yield of 18%.

[0124] Example 38

[0125] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1O (138.5 mg, 1.0 mmol), and MeCN (2 mL) were added sequentially to a 25 mL reaction vessel. tBuOH (2 mL). Oxygen was bubbled through at 1.0 MPa, and the reaction was stirred at room temperature for 18 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2O. A coarse NMR spectrum showed a yield of 54%.

[0126] Example 39

[0127] CuCl₂·2H₂O (8.9 mg, 0.05 mmol), TEMPO (7.5 mg, 0.05 mmol), 1 L (137.0 mg, 1.0 mmol), DCE (3 mL), and MeOH (1 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 13%.

[0128] Example 40

[0129] CuCl₂·2H₂O (17.0 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1 L (136.3 mg, 1.0 mmol), DCE (3 mL), and MeOH (1 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 23%.

[0130] Example 41

[0131] CuCl₂·2H₂O (17.8 mg, 0.1 mmol), 4-OH-TEMPO (17.5 mg, 0.1 mmol), 1 L (136.5 mg, 1.0 mmol), DCE (3 mL), and MeOH (1 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 12%.

[0132] Example 42

[0133] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), 1 L (136.3 mg, 1.0 mmol), MeCN (3 mL), and MeOH (1 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 26%.

[0134] Example 43

[0135] CuCl₂·2H₂O (17.8 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1 L (136.3 mg, 1.0 mmol), DCE (3 mL), and EtOH (1 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 24%.

[0136] Example 44

[0137] Add CuCl2·2H2O (17.0 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1 L (136.4 mg, 1.0 mmol), DCE (3 mL) and... sequentially to a 25 mL reaction tube. i PrOH (1 mL). An oxygen bulb was inserted, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 13%.

[0138] Example 45

[0139] Add CuCl2·2H2O (17.4 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), 1 L (136.3 mg, 1.0 mmol), DCE (3 mL) and... sequentially to a 25 mL reaction tube. t BuOH (1 mL). An oxygen bulb was inserted, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 24%.

[0140] Example 46

[0141] CuCl₂·2H₂O (17.0 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1 L (136.2 mg, 1.0 mmol), and MeCN (4 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 36%.

[0142] Example 47

[0143] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), 1 L (136.5 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.6 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 44%.

[0144] Example 48

[0145] CuCl₂·2H₂O (17.4 mg, 0.1 mmol), TEMPO (16.1 mg, 0.1 mmol), 1 L (136.3 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.4 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 15%.

[0146] Example 49

[0147] CuCl₂·2H₂O (17.3 mg, 0.1 mmol), TEMPO (16.0 mg, 0.1 mmol), 1 L (136.6 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 55%.

[0148] Example 50

[0149] CuCl₂·2H₂O (17.0 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), 1 L (137.0 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 15%.

[0150] Example 51

[0151] CuCl₂·2H₂O (17.2 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1 L (136.5 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.6 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 L. A coarse NMR spectrum showed a yield of 13%.

[0152] Example 52

[0153] CuCl₂·2H₂O (17.4 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1i (150.3 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2i. A coarse NMR spectrum showed a yield of 21%.

[0154] Example 53

[0155] CuCl₂·2H₂O (17.2 mg, 0.1 mmol), TEMPO (15.7 mg, 0.1 mmol), 1kJ (206.5 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2kJ. A coarse NMR spectrum showed a yield of 49%.

[0156] Example 54

[0157] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.6 mg, 0.1 mmol), 1 M (136.5 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 M. A coarse NMR spectrum showed a yield of 37%.

[0158] Example 55

[0159] CuCl₂·2H₂O (17.0 mg, 0.1 mmol), TEMPO (15.5 mg, 0.1 mmol), 1 t (144.3 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 t. A coarse NMR spectrum showed a yield of 58%.

[0160] Example 56

[0161] CuCl₂·2H₂O (5.3 mg, 0.03 mmol), TEMPO (4.7 mg, 0.03 mmol), 1 t (144.3 mg, 1.0 mmol), DCE (3 mL), and MeOH (1 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction was stirred at room temperature for 22 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 t. A coarse NMR spectrum showed a yield of 75%.

[0162] Example 57

[0163] CuCl₂·2H₂O (17.0 mg, 0.1 mmol), TEMPO (15.8 mg, 0.1 mmol), 1 u (133.6 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2 u. A coarse NMR spectrum showed a yield of 29%.

[0164] Example 58

[0165] CuCl₂·2H₂O (17.1 mg, 0.1 mmol), TEMPO (15.7 mg, 0.1 mmol), 1x (154.2 mg, 1.0 mmol), MeCN (3 mL), and MeOH (0.2 mL) were added sequentially to a 25 mL reaction tube. An oxygen bulb was inserted, and the reaction mixture was stirred at room temperature for 24 hours. The reaction solution was filtered through a short silica gel column (2 cm), eluted with dichloromethane (30 mL), and the solvent was removed by rotary evaporation to obtain 2x. A coarse NMR spectrum showed a yield of 69%.

[0166] The scope of protection of this invention is not limited to the above embodiments. Any variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of this invention are included in this invention and are protected by the appended claims.

Claims

1. A method for preparing quinone compounds by direct oxidation of phenols catalyzed by copper, characterized in that, The method involves reacting phenol as a raw material in an organic solvent at room temperature, using copper chloride dihydrate and nitrogen oxides as catalysts, and oxygen as an oxidant, to directly oxidize the phenol to prepare quinone compounds. The reaction process is shown in reaction formula (1): in, R is selected from alkyl, alkyl with functional groups, heteroatom substituents, and aryl; The functional groups in the alkyl group are alkenyl, phenyl, or hydroxyl; The heteroatom substituents are methoxy, mercaptomethyl, dimethylamino, and acetamido. The aryl group is phenyl, naphthyl, or indole.

2. The method as described in claim 1, characterized in that, The phenols mentioned are o-cresol, m-cresol, o-sec-butylphenol, 2-tert-butylphenol, 2,6-dimethylphenol, 2,3-dicresol, 3,5-dimethylphenol, 2,5-dimethylphenol, thymol, propofol, 2,6-di-tert-butylphenol, 2,3,5-trimethylphenol, 2,3,6-trimethylphenol, 1-naphthol, 4-hydroxyindole, 2-benzylphenol, o-hydroxyphenylethanol, 2-allylphenol, 2-(3-methyl-2-butenyl)phenol, o-phenylphenol, 2,6-diphenylphenol, N-(3-hydroxyphenyl)acetamide, 3-methoxyphenol, 3,5-dimethoxyphenol, 3-(methylsulfinyl)phenol, and 3-hydroxy-N,N-dimethylaniline.

3. The method as described in claim 1, characterized in that, The nitrogen oxide is one or more of 2,2,6,6-tetramethylpiperidine nitride oxide TEMPO, 4-methoxy-2,2,6,6-tetramethylpiperidine nitride oxide 4-OMe-TEMPO, and 4-acetamido-2,2,6,6-tetramethylpiperidine nitride oxide 4-AcNH-TEMPO.

4. The method as described in claim 1, characterized in that, The organic solvent is one or a mixture of 1,2-dichloroethane, toluene, acetonitrile, methanol, ethanol, isopropanol, and tert-butanol.

5. The method as described in claim 1, characterized in that, The molar ratio of phenol, copper chloride dihydrate, and nitrogen oxides is 100:(1-10):(1-10).

6. The method as described in claim 1, characterized in that, The reaction time is 12-45 hours.

7. The method as described in claim 1, characterized in that, The oxygen source for the reaction is pure oxygen or air.

8. The method as described in claim 1, characterized in that, The reaction was carried out at room temperature.

9. Quinone compounds prepared by any one of claims 1-8.

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