Photo-initiated synthetic aminophenol compound method and application

Abstract

The invention relates to a photo-initiated synthetic aminophenol compound method and application, and belongs to the technical field of organic synthesis. The synthesis method comprises the following steps: deprotonating a 1-hydroxybenzotriazole compound under an alkaline condition, and carrying out cracking reaction under the excitation of visible light to generate a high-activity biradical intermediate which is unstable and can be rapidly tautomerized into a more stable nitrosobenzene anion intermediate; the intermediate further reacts with cyclohexenone substances to synthesize the aminophenol derivative in one step. The method is simple and efficient, simple and convenient to operate, free of transition metal and additional oxidizing agents, simple and easily available in raw material reagent, high in product yield and capable of realizing large-scale synthesis, and a new method is provided for rapidly synthesizing the aminophenol compound. The synthesized aminophenol compound has good antibacterial activity, and especially has huge potential in the aspect of preventing and treating anthracnose of tea trees.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis methods, and more specifically, relates to a method and application of photo-initiated synthesis of aminophenol compounds. Background Technology

[0002] Aminophenol structural units are widely found in many best-selling drugs and highly bioactive natural products. For example, Tagrisso (osimertinib), a targeted drug for treating lung cancer, rifaximin, afatinib for EGFR-mutant positive non-small cell lung cancer, and deuterocelexitinib, a TYK2 inhibitor for psoriasis treatment, all contain this key scaffold. Furthermore, aminophenol compounds are also precursors and intermediates for the synthesis of important heterocyclic structures such as benzoxazine, benzimidazole, and indole. Therefore, developing efficient and universal synthetic methods to achieve the direct and rapid construction and modification of this scaffold is of great value for accelerating the discovery, structural optimization, and subsequent functionalization of new drug lead compounds.

[0003] However, existing methods for synthesizing aminophenol, such as diazotization after nitro reduction and amination / hydroxylation of aryl halides, generally suffer from lengthy synthetic steps, difficulty in controlling regioselectivity, limited functional group tolerance, the need for transition metals as catalysts which increases synthesis costs, and the frequent use of highly toxic reagents (such as nitrobenzene and diazonium salts), which limit its application in drug development and industrial production.

[0004] Based on the aforementioned research background, the purpose of this invention is to provide a novel method for preparing aminophenol that features mild reaction conditions, readily available raw materials, simple operation, and is environmentally friendly, thereby solving a long-standing technical challenge in this field. This method employs green synthesis strategies such as visible light catalysis, enabling the efficient and highly selective construction of aminophenol structures under mild conditions, and possesses promising prospects for industrial application. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a simple and efficient photo-initiated method for synthesizing aminophenol compounds. This method uses 1-hydroxybenzotriazole and cyclohexenone compounds as starting materials, and synthesizes a series of aminophenol derivatives in one step under the action of light and alkali.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The first aspect of this invention provides a photo-initiated method for synthesizing aminophenol compounds, using 1-hydroxybenzotriazole 1 and cyclohexenone compounds 2 or 3 as raw materials, reacting under alkaline conditions and light irradiation for 4-8 hours, and then post-processing to obtain aminophenol compounds with the characteristics of compound 4 or 5, the reaction formula of which is as follows:

[0007] In formula (1), Ar is selected from benzene, naphthalene, anthracene, phenanthrene, fluorene, pyridine, quinoline, isoquinoline, furan, and benzofuran.

[0008] R1, R2, R3, and R4 may be the same or different, and each is selected from hydrogen, alkyl groups with 1 to 10 carbons, cycloalkyl groups with 3 to 10 carbons, alkoxy groups, alkenyl groups, alkynyl groups, substituted or unsubstituted aryl groups, heterocyclic groups, halogen groups, mercapto groups, nitro groups, cyano groups, carboxyl groups, ester groups, aldehyde groups, acyl groups, acyloxy groups, amino groups, substituted amino groups, or amide groups.

[0009] R5, R6, R7, and R8 may be the same or different, and each is selected from alkyl groups with 1 to 10 carbon atoms, cycloalkyl groups with 3 to 10 carbon atoms, alkoxy groups, alkenyl groups, alkynyl groups, substituted or unsubstituted aryl groups, heterocyclic groups, ester groups, aldehyde groups, acyl groups, acyloxy groups, amino groups, substituted amino groups, or amide groups.

[0010] R9, R 10 R 11 R 12 They may be the same or different, each selected from hydrogen, alkyl groups of 1 to 10 carbons, cycloalkyl groups of 3 to 10 carbons, alkoxy groups, alkenyl groups, alkynyl groups, substituted or unsubstituted aryl groups, heterocyclic groups, halogen groups, mercapto groups, nitro groups, cyano groups, ester groups, aldehyde groups, acyl groups, acyloxy groups, amino groups, substituted amino groups, or amide groups.

[0011] The above synthetic method involves the following steps: Compound 1, compound 2 or 3, a base, and a solvent are added sequentially to a clean, anhydrous reaction tube. The reaction tube is placed under light irradiation for 4–8 hours. After the reaction is complete, a saturated sodium bicarbonate solution is added to quench the reaction, and the reaction solution is extracted three times with ethyl acetate. The extracts are then washed three times with a saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, filtered, concentrated, and separated by column chromatography to obtain aminophenol compounds 4 or 5.

[0012] In some instances, the molar ratio of 1-hydroxybenzotriazole 1, cyclohexenone 2 or 3, and alkali used is 1:1.0~2.0:1.0~3.0; preferably 1:1.0~1.5:2.0~3.0.

[0013] In some instances, the base used includes lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, calcium hydride, lithium methoxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium diisopropylamino, lithium hexamethyldisilamino, sodium hexamethyldisilamino, potassium hexamethyldisilamino, phenyl lithium, or n-butyllithium. Lithium hydroxide, lithium methoxide, lithium tert-butoxide, and phenyl lithium are preferred.

[0014] In some instances, the light source for the blue light irradiation is an LED lamp, preferably with a power of 25 to 40 watts, and more preferably 35 watts.

[0015] In some instances, the wavelength of the illumination is a single wavelength; the wavelength of the single wavelength is 405 nm, 430 nm, 455 nm, or 525 nm, preferably 430 nm.

[0016] In some instances, the reaction solvent used is selected from... N,N -Dimethylformamide, N,N -Any of dimethylacetamide and dimethyl sulfoxide. Preferably: N,N -Dimethylacetamide.

[0017] The second aspect of the present invention provides an aminophenol compound obtained by the method of the first aspect.

[0018] The third aspect of this invention provides the application of aminophenol compounds prepared by the method of the first aspect in the prevention and control of anthracnose in tea trees, wherein the pathogen of anthracnose in tea trees is *Colletotrichum gloeosporioides* (…). Colletotrichum gloeosporioides ).

[0019] Beneficial effects: This invention addresses the problems of existing methods for synthesizing aminophenol compounds, which require transition metals, demanding reaction conditions, and expensive and difficult-to-prepare starting materials. Using readily available and inexpensive 1-hydroxybenzotriazole derivatives and cyclohexenone derivatives as raw materials, aminophenol compounds are efficiently synthesized in a single reaction under visible light, exhibiting high yield and chemoselectivity. Furthermore, the synthesized aminophenol compounds demonstrate good inhibitory effects against *Colletotrichum gloeosporioides* in antibacterial experiments, showing broad application prospects in the control of anthracnose in tea trees. Attached Figure Description

[0020] Figure 1 It is compound 3a in the embodiments of the present invention. 1 H NMR spectrum; Figure 2 It is compound 3a in the embodiments of the present invention. 13 C NMR spectrum; Figure 3 It is compound 3b in the embodiments of the present invention. 1 H NMR spectrum; Figure 4 It is compound 3b in the embodiments of the present invention. 13 C NMR spectrum; Figure 5 It is compound 3c in the embodiments of the present invention. 1 H NMR spectrum; Figure 6It is compound 3c in the embodiments of the present invention. 13 C NMR spectrum; Figure 7 It is compound 3d in the embodiments of the present invention. 1 H NMR spectrum; Figure 8 It is compound 3d in the embodiments of the present invention. 13 C NMR spectrum; Figure 9 It is compound 3e in the embodiments of the present invention. 1 H NMR spectrum; Figure 10 It is compound 3e in the embodiments of the present invention. 13 C NMR spectrum; Figure 11 It is compound 3f in the embodiments of the present invention. 1 H NMR spectrum; Figure 12 It is compound 3f in the embodiments of the present invention. 13 C NMR spectrum; Figure 13 It is 3g of the compound in the embodiments of the present invention. 1 H NMR spectrum; Figure 14 It is 3g of the compound in the embodiments of the present invention. 13 C NMR spectrum; Figure 15 It is compound 3h in the embodiments of the present invention. 1 H NMR spectrum; Figure 16 It is compound 3h in the embodiments of the present invention. 13 C NMR spectrum; Figure 17 It is compound 3j in the embodiments of the present invention. 1 H NMR spectrum; Figure 18 It is compound 3j in the embodiments of the present invention. 13 C NMR spectrum; Figure 19 It is compound 3k in the embodiments of the present invention. 1 H NMR spectrum; Figure 20 It is compound 3k in the embodiments of the present invention. 13 C10 NMR spectrum. Detailed Implementation

[0021] The present invention will be described in detail below with reference to the embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0022] Example 1: Preparation of aminophenol compound 3a Add cyclohexenone compound 1a (0.1 mmol, 1.0 equiv) and 1-hydroxybenzotriazole 2a (0.15 mmol, 1.5 equiv) sequentially to a dry 10 mL reaction tube, then add 1 mL of [the solution is missing here]. N,N -Dimethylacetamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, and the mixture was then magnetically stirred at room temperature for 4 hours under blue light (wavelength 405 nm, light intensity 25 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to obtain 21.0 mg of aminophenol compound 3a as a brown solid, in 88% yield.

[0023] The equation for the above reaction is as follows:

[0024] The relevant data for aminophenol compound 3a are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.22-7.18 (m, 2H), 7.08 (s, 1H), 6.89-6.87(m, 2H), 6.82 (t, J = 7.3 Hz, 1H), 6.63 (s, 1H), 5.43 (s, 1H), 5.18 (t, J =1.8 Hz, 1H), 4.97 (dd, J = 2.1, 1.1 Hz, 1H), 4.64 (s, 1H), 2.21 (s, 3H), 1.98(t, J = 1.2 Hz, 3H). 13 C NMR (150 MHz, CDCl3) δ 167.8, 157.5, 145.8, 140.7, 131.6, 129.7,127.0, 122.6, 120.2, 114.2, 112.0, 51.8, 15.7. HRMS (ESI) calcd for C 16 H 18 NO2 [M + H] +Found: 240.1383, Found: 240.1386. Example 2: Preparation of aminophenol compound 3b Add cyclohexenone compound 1b (0.1 mmol, 1.0 equiv) and 1-hydroxybenzotriazole 2b (0.1 mmol, 1.0 equiv) sequentially to a dry 10 mL reaction tube, then add 1 mL of [the solution is missing here]. N,N -Dimethylformamide was used to obtain a mixture. Lithium tert-butoxide (0.2 mmol, 2.0 equiv) was added to the resulting mixture, and then the mixture was magnetically stirred at room temperature for 4 hours under blue light (wavelength 430 nm, light intensity 30 W). After the reaction was completed, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction solution was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to obtain 18.3 mg of aminophenol compound 3b as a brown solid, in 80% yield.

[0025] The equation for the above reaction is as follows:

[0026] The relevant data for aminophenol compound 3b are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.22-7.18 (m, 2H), 7.08 (s, 1H), 6.89-6.87(m, 2H), 6.82 (t, J = 7.3 Hz, 1H), 6.63 (s, 1H), 5.43 (s, 1H), 5.18 (t, J =1.8 Hz, 1H), 4.97 (dd, J = 2.1, 1.1 Hz, 1H), 4.64 (s, 1H), 2.21 (s, 3H), 1.98(t, J = 1.2 Hz, 3H). 13 C NMR (150 MHz, CDCl3) δ 167.8, 157.5, 145.8, 140.7, 131.6, 129.7,127.0, 122.6, 120.2, 114.2, 112.0, 51.8, 15.7. HRMS (ESI) calcd for C 14 H 16NO2 [M + H] + Found: 230.1176, Found: 230.1181. Example 3: Preparation of aminophenol compound 3c In a dry 10 mL reaction tube, add cyclohexenone compound 1c (0.1 mmol, 1.0 equiv) and 1-hydroxybenzotriazole 2a (0.2 mmol, 2.0 equiv) sequentially, and then add 1 mL of [amount missing] [unit missing] [concentration missing]. N,N -Dimethylformamide was used to obtain a mixture. Lithium methoxide (0.3 mmol, 3.0 equiv) was added to the resulting mixture, followed by magnetic stirring under blue light (wavelength 455 nm, light intensity 35 W) at room temperature for 6 hours. After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether:ethyl acetate = 2.5:1) to obtain 19.9 mg of aminophenol compound 3c as a brown solid, with a yield of 73%.

[0027] The equation for the above reaction is as follows:

[0028] The relevant data for the 3c content of aminophenol compounds are as follows: 1 H NMR (400 MHz, CDCl3) δ 12.01 (s, 1H), 7.20 (t, J = 7.8 Hz, 2H), 6.87 (t, J = 7.0 Hz, 1H), 6.68 (d, J = 8.2 Hz, 2H), 6.58 (s, 1H), 6.46 (s,1H), 5.06 (s, 1H), 3.92 (s, 3H), 2.54 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 172.3, 160.9, 158.1, 146.3, 141.7, 129.4,120.4, 114.7, 113.9, 109.8, 105.5, 52.0, 24.4. HRMS (ESI) calcd for C 15 H 16 NO4 [M + H] +Found: 274.1074, Found: 274.1079. Example 4: Preparation of aminophenol compound 3d Cyclohexenone compound 1d (0.1 mmol, 1.0 equiv) and 1-hydroxybenzotriazole 2a (0.15 mmol, 1.5 equiv) were added sequentially to a dry 10 mL reaction tube. 1 mL of dimethyl sulfoxide was then added to obtain a mixture. Phenyllithium (0.25 mmol, 2.5 equiv) was added to the resulting mixture, and the mixture was then magnetically stirred at room temperature for 6 hours under blue light (wavelength 525 nm, light intensity 40 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracted solutions were combined and washed three times with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to obtain 24.7 mg of aminophenol compound 3d as a brown solid, with a yield of 85%.

[0029] The equation for the above reaction is as follows:

[0030] The relevant data for aminophenol compound 3d are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.61 (d, J = 7.2 Hz, 2H), 7.44 (t, J = 7.7Hz, 2H), 7.36 (t, J = 7.4 Hz, 1H), 7.21 (t, J = 7.9 Hz, 2H), 6.93 (d, J = 1.6Hz, 1H), 6.86 (t, J = 7.3 Hz, 1H), 6.73-6.71 (m, 3H), 6.04 (s, 1H), 5.17 (s, 1H), 3.80 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 155.8, 153.9, 146.3, 141.0, 140.8, 129.4,128.8, 127.6, 127.1, 120.1, 116.2, 114.8, 106.7, 102.3, 55.9. HRMS (ESI) calcd for C19 H 18 NO2 [M + H] + Found: 292.1332, Found: 292.1334. Example 5: Preparation of aminophenol compound 3e Add cyclohexenone compound 1e (0.1 mmol, 1.0 equiv) and 1-hydroxybenzotriazole 2a (0.15 mmol, 1.5 equiv) sequentially to a dry 10 mL reaction tube, then add 3 mL of [the solution is missing here]. N,N -Dimethylformamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, followed by magnetic stirring under blue light (wavelength 430 nm, light intensity 35 W) at room temperature for 6 hours. After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain 26.1 mg of aminophenol compound 3e as a brown solid, with a yield of 91%.

[0031] The equation for the above reaction is as follows:

[0032] The relevant data for aminophenol compound 3e are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.55 (dd, J = 7.9, 1.3 Hz, 1H), 7.31-7.27(m, 3H), 7.18 (td, J = 7.4, 1.2 Hz, 1H), 7.14-7.07 (m, 2H), 6.95-6.89 (m,2H), 6.75 (d, J = 7.7 Hz, 2H), 5.72 (s, 1H), 5.26 (s, 1H), 2.74 (s, 4H). 13 C NMR (100 MHz, CDCl3) δ 152.0, 145.4, 139.8, 132.8, 132.0, 131.7,130.0, 128.2, 127.5, 126.6, 126.4, 123.9, 120.2, 114.3, 113.9, 30.2, 29.9. HRMS (ESI) calcd for C 20 H 18 NO [M + H] + Found: 288.1383, Found: 288.1381. Example 6: Preparation of aminophenol compound 3f Add cyclohexenone compound 1f (0.1 mmol, 1.0 equiv) and 1-hydroxybenzotriazole 2a (0.15 mmol, 1.5 equiv) sequentially to a dry 10 mL reaction tube, then add 1 mL of [the solution is missing here]. N,N -Dimethylacetamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, followed by magnetic stirring at room temperature for 6 hours under blue light (wavelength 430 nm, light intensity 35 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to obtain 25.3 mg of aminophenol compound 3f as a brown solid, in 70% yield.

[0033] The equation for the above reaction is as follows:

[0034] The relevant data for aminophenol compound 3f are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.20 (t, J = 7.7 Hz, 3H), 6.90 (d, J = 8.5Hz, 1H), 6.84 (t, J = 7.3 Hz, 1H), 6.62 (d, J = 8.2 Hz, 2H), 6.19 (s, 1H), 4.85 (s, 1H), 2.76 (dd, J = 17.5, 5.8 Hz, 1H), 2.59-2.40 (m, 3H), 2.27-2.24(m, 1H), 2.12 (dt, J = 18.8, 8.7 Hz, 1H), 2.04-1.92 (m, 3H), 1.62-1.44 (m,5H), 1.37-1.26 (m, 1H), 0.90 (s, 3H). 13 C NMR (100 MHz, CDCl3)) δ 221.0, 152.0, 146.1, 135.4, 132.5, 129.6,125.2, 119.7, 114.1, 112.1, 50.3, 48.0, 44.1, 37.7, 35.9, 31.6, 26.1, 26.0,25.4, 21.5, 13.9. HRMS (ESI) calcd for C 24 H 28 NO2 [M + H] + Found: 362.2115, Found: 362.2118. Example 7: Preparation of 3g of aminophenol compound In a dry 10 mL reaction tube, add 1 g (0.1 mmol, 1.0 equiv) of a cyclohexenone compound and 0.15 mmol (1.5 equiv) of 1-hydroxybenzotriazole 2a, followed by 3 mL of [amount missing] solution. N,N -Dimethylacetamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, followed by magnetic stirring at room temperature for 6 hours under blue light (wavelength 430 nm, light intensity 35 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to obtain 32.5 mg of aminophenol compound as a brown solid, with a yield of 65%.

[0035] The equation for the above reaction is as follows:

[0036] The relevant data for 3g of aminophenol compound are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.22-7.17 (m, 3H), 6.89 (d, J = 8.5 Hz, 1H), 6.83 (t, J = 7.3 Hz, 1H), 6.61 (d, J= 7.7 Hz, 2H), 6.15 (s, 1H), 4.83 (s,1H), 2.80-2.69 (m, 2H), 2.61 (s, 1H), 2.54-2.48 (m, 1H), 2.41-2.37 (m, 1H), 2.30 (t, J = 7.5 Hz, 2H), 2.27-2.23 (m, 1H), 2.03 (td, J = 14.3, 13.2, 3.9Hz, 2H), 1.86-1.77 (m, 3H), 1.72-1.67 (m, 1H), 1.65-1.61 (m, 2H), 1.53-1.46(m, 1H), 1.38-1.25 (m, 9H), 0.90-0.87 (m, 6H). 13 C NMR (150 MHz, CDCl3) δ 172.4, 151.9, 146.1, 135.5, 132.9, 129.6,125.2, 125.2, 119.7, 114.1, 111.9, 84.2, 83.5, 74.8, 47.9, 47.7, 43.6, 38.5,37.4, 34.7, 33.2, 31.5, 28.7, 26.9, 26.5, 25.5, 24.9, 23.3, 22.5, 14.1, 13.5. HRMS (ESI) calcd for C 24 H 28 NO2 [M + H] + Found: 500.3159, Found: 500.3160. Example 8: Preparation of aminophenol compound 3h In a dry 10 mL reaction tube, cyclohexenone compound 1h (0.1 mmol, 1.0 equiv), 7-chloro-1-hydroxybenzotriazole 2b (0.15 mmol, 1.5 equiv), and then 1 mL of [amount missing] solution were added sequentially. N,N-Dimethylacetamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, followed by magnetic stirring at room temperature for 6 hours under blue light (wavelength 430 nm, light intensity 35 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to obtain 28.1 mg of aminophenol compound as a brown solid for 3 hours, with a yield of 92%.

[0037] The equation for the above reaction is as follows:

[0038] The relevant data for aminophenol compound over 3 hours are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.33 (dd, J = 8.0, 1.4 Hz, 1H), 7.05-7.01(m, 1H), 6.79-6.75 (m, 2H), 6.32-6.29 (m, 2H), 5.47 (s, 1H), 3.88 (s, 3H),2.32 (s, 3H), 2.05 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 170.0, 154.9, 142.0, 136.6, 135.1, 129. 5,128.2, 127.1, 123.1, 120.3, 120.1, 114.4, 113.8, 52.0, 20.1, 15.2. HRMS (ESI) calcd for C 16 H 17 ClNO3 [M + H]+: 306.0891, Found: 306.0896. Example 9: Preparation of aminophenol compound 3j In a dry 10 mL reaction tube, cyclohexenone compound 1h (0.1 mmol, 1.0 equiv), 5-methoxy-1-hydroxybenzotriazole 2c (0.15 mmol, 1.5 equiv), and then 1 mL of [amount missing] solution were added sequentially. N,N-Dimethylacetamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, followed by magnetic stirring at room temperature for 6 hours under blue light (wavelength 430 nm, light intensity 35 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether:ethyl acetate = 3:1) to obtain 23.2 mg of aminophenol compound 3j as a brown solid, with a yield of 77%.

[0039] The equation for the above reaction is as follows:

[0040] The relevant data for aminophenol compound 3j are as follows: 1 H NMR (600 MHz, CDCl3) δ 6.77-6.74 (m, 3H), 6.56-6.53 (m, 3H), 4.69 (s, 1H), 3.87 (s, 3H), 3.74 (s, 3H), 2.31 (s, 3H), 2.09 (s, 3H). 13 C NMR (150 MHz, CDCl3) δ 170.1, 154.9, 153.7, 139.6, 135.9, 134.8,126.8, 124.7, 115.3, 115.0, 114.0, 55.7, 51.9, 20.1, 15.3. HRMS (ESI) calcd for C 17 H 20 NO4 [M + H] + Found: 302.1387, Found: 302.1378. Example 10: Preparation of aminophenol compound 3k In a dry 10 mL reaction tube, cyclohexenone compounds were added sequentially for 1 h (0.1 mmol, 1.0 equiv), followed by 5-methyl-1-hydroxybenzotriazole for 2 d (0.15 mmol, 1.5 equiv), and then 1 mL of [amount missing] was added. N,N-Dimethylacetamide was used to obtain a mixture. Lithium methoxide (0.25 mmol, 2.5 equiv) was added to the resulting mixture, followed by magnetic stirring at room temperature for 6 hours under blue light (wavelength 430 nm, light intensity 35 W). After the reaction was complete, a saturated sodium bicarbonate solution was added to quench the reaction, and the reaction mixture was extracted three times with ethyl acetate. The extracts were combined and washed three times with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, concentrated, and then subjected to column chromatography (eluent: petroleum ether:ethyl acetate = 4:1) to obtain 24.5 mg of aminophenol compound 3K as a brown solid, with a yield of 86%.

[0041] The equation for the above reaction is as follows:

[0042] The relevant data for aminophenol compound 3k are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.00-6.98 (m, 2H), 6.75 (s, 1H), 6.51-6.48(m, 3H), 4.77 (s, 1H), 3.87 (s, 3H), 2.31 (s, 3H), 2.25 (s, 3H), 2.09 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 170.2, 154.9, 143.5, 136.0, 135.0, 130.1,129.3, 126.8, 124.2, 114.2, 114.1, 51.9, 20.5, 20.1, 15.3. HRMS (ESI) calcd for C 17 H 20 NO3 [M + H] + Found: 286.1438, Found: 286.1434. Example 11: Application of various synthesized aminophenol compounds in the prevention and control of anthracnose in tea trees To evaluate the control efficacy of aminophenol compounds against anthracnose in tea plants, the method was adapted from the literature (Pestic Biochem Physiol. 2020, 162, 78-85). Specifically, the test compound and the control were dissolved in dimethyl sulfoxide (DMSO) to prepare a stock solution of 10000 µg / mL, which was then diluted with sterile water to a working concentration of 100 µg / mL. The test leaves were taken from healthy, disease-free one-year-old tea plants, washed with water and 75% ethanol, and then air-dried. A blank control group (CK, using sterile water containing DMSO at the same final concentration as the treatment group, with a final DMSO concentration of 100 µg / mL) and a positive control group (using azoxystrobin as the control agent) were set up. *Colletotrichum gloeosporioides* with a diameter of 5 mm was first inoculated onto the leaf surface. Colletotrichum gloeosporioides After culturing the fungal cake for 24 hours, the prepared solution was sprayed evenly. Disease development was then continuously observed, and the area of ​​lesion expansion on leaves for each treatment was measured. All experiments were independently repeated three times. Among the tested compounds, six compounds showed inhibition rates exceeding 66%, with three exceeding 77%. This demonstrates that this type of compound possesses highly efficient antibacterial activity and broad-spectrum inhibitory potential against *Anthracnose causal agent* of tea anthracnose. Compound 3a exhibited the best antibacterial activity, with an inhibition rate of 87.4%, significantly higher than the positive control pyraclostrobin (71.1%). This result fully demonstrates that through reasonable modification and optimization of the structure of this type of compound, lead molecules with higher activity than existing commercial fungicides can be obtained, possessing significant development value. The results are shown in the table below.

[0043] ; The above description is merely a preferred embodiment of the present invention. It should be understood that the present invention is not limited to the forms disclosed herein and should not be construed as excluding other embodiments. It can be used in various other combinations, modifications, and environments, and can be altered within the scope of the concept described herein through the above teachings or related technologies or knowledge. Modifications and variations made by those skilled in the art that do not depart from the spirit and scope of the present invention should be within the protection scope of the appended claims.

Claims

1. A method for photo-initiated synthesis of aminophenol compounds, characterized in that, Using 1-hydroxybenzotriazole 1 and cyclohexenone compounds 2 or 3 as raw materials, a base is added to a reaction vessel, followed by the injection of solvent. The reaction is carried out under light for 4-8 hours, and after post-treatment, aminophenol compounds 4 or 5 are obtained. ； In formula (1), Ar is selected from benzene, naphthalene, anthracene, phenanthrene, fluorene, pyridine, quinoline, isoquinoline, furan, and benzofuran; R1, R2, R3, and R4 may be the same or different, and each of them is selected from hydrogen, alkyl groups with 1 to 10 carbons, cycloalkyl groups with 3 to 10 carbons, alkoxy groups, alkenyl groups, alkynyl groups, substituted or unsubstituted aryl groups, heterocyclic groups, halogen groups, mercapto groups, nitro groups, cyano groups, carboxyl groups, ester groups, aldehyde groups, acyl groups, acyloxy groups, amino groups, substituted amino groups, or amide groups. R5, R6, R7, and R8 may be the same or different, and each is selected from alkyl groups with 1 to 10 carbons, cycloalkyl groups with 3 to 10 carbons, alkoxy groups, alkenyl groups, alkynyl groups, substituted or unsubstituted aryl groups, heterocyclic groups, ester groups, aldehyde groups, acyl groups, acyloxy groups, amino groups, substituted amino groups, or amide groups. R9, R 10 R 11 R 12 They may be the same or different, each selected from hydrogen, alkyl groups of 1 to 10 carbons, cycloalkyl groups of 3 to 10 carbons, alkoxy groups, alkenyl groups, alkynyl groups, substituted or unsubstituted aryl groups, heterocyclic groups, halogen groups, mercapto groups, nitro groups, cyano groups, ester groups, aldehyde groups, acyl groups, acyloxy groups, amino groups, substituted amino groups, or amide groups.

2. The method for photo-initiated synthesis of aminophenol compounds according to claim 1, characterized in that, The molar ratio of 1-hydroxybenzotriazole 1, cyclohexenone 2 or 3, and alkali is 1:1.0~2.0:1.0~3.

0.

3. The method for photo-initiated synthesis of aminophenol compounds according to claim 1, characterized in that, The molar ratio of 1-hydroxybenzotriazole 1, cyclohexenone 2 or 3, and alkali is 1:1.0~1.5:2.0~3.

0.

4. The method for photo-initiated synthesis of aminophenol compounds according to claim 1, characterized in that, The alkali is one or more of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, calcium hydride, lithium methoxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium diisopropylamino, lithium hexamethyldisilamino, sodium hexamethyldisilamino, potassium hexamethyldisilamino, phenyl lithium, or n-butyllithium.

5. The method for photoinitiated synthesis of aminophenol compounds according to claim 1, characterized in that, The illumination is blue light, and the light source is an LED lamp with a power of 25-40 watts.

6. The method for photo-initiated synthesis of aminophenol compounds according to claim 1, characterized in that, The wavelength of the illumination is a single wavelength; the wavelength of the single wavelength is 405 nm to 525 nm.

7. The method for photo-initiated synthesis of aminophenol compounds according to claim 1, characterized in that, The reaction solvent used is selected from N,N -Dimethylformamide, N,N - any one or more of dimethylacetamide and dimethyl sulfoxide.

8. An aminophenol compound prepared by any one of claims 1-7.

9. The application of aminophenol compounds prepared by any one of claims 1-7 in the control of anthracnose in tea trees, wherein the pathogen of anthracnose in tea trees is *Colletotrichum gloeosporioides* (…). Colletotrichum gloeosporioides ).

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