3-arylindolone derivatives, processes for their preparation and their use in food preservation

Abstract

This invention belongs to the field of organic synthesis technology, specifically relating to a 3-arylindolone derivative, its preparation method, and its application in food antibacterial applications. The preparation method includes the following steps: under light irradiation, α-aryldiazoamide is reacted in a solvent using air or oxygen as a raw material; by controlling whether or not a base catalyst is added, 3-hydro-3-arylindolone derivatives or 3-hydroxy-3-arylindolone derivatives are synthesized divergently. This invention achieves the divergent synthesis of 3-hydro-3-arylindolone and 3-hydroxy-3-arylindolone derivatives through photo-induced catalysis combined with base regulation without the addition of external metal catalysts or photocatalysts. It features mild conditions, simple operation, green and efficient operation, a wide range of applicable substrates, and high atom economy. Furthermore, the 3-hydroxyindolone derivative prepared by this invention exhibits excellent performance in food antibacterial applications and has potential application value in drug synthesis.

Description

Technical Field

[0001] This invention belongs to the field of photoinduced synthesis technology, specifically relating to a 3-arylindolone derivative, its preparation method, and its application in food antibacterial applications. Background Technology

[0002] Indolone derivatives are an important class of nitrogen-containing heterocyclic compounds, exhibiting irreplaceable value in both medicinal chemistry and materials science. Based on the different substituents at the 3-position, these compounds can be mainly divided into two important substructures: one is 3-hydro-3-arylindolone, and the other is 3-hydroxy-3-arylindolone (i.e., containing both an aryl and a hydroxyl group at the 3-position). This unique skeleton endows these compounds with rich biological activities, including anticancer, anti-inflammatory, and antibacterial properties, and has broad prospects for medical applications. For example, MaxiPost, used to treat acute ischemic stroke; Convolutamydines, which inhibits the differentiation of HL60 leukemia cells; TMC-95, a proteasome inhibitor; Arundaphine, an alkaloid with antioxidant and anticancer properties; SM-130686, an oral non-peptide hormone growth hormone; and Maremycins, which has anti-cytotoxic effects on human leukemia cells K562, all contain a 3-hydroxyindolone skeleton. In addition, 3-arylindolone derivatives are also important organic synthesis intermediates. The synergistic effect of active functional groups in their molecular structure can efficiently guide the precise synthesis of 3,3-disubstituted indolone derivatives through nucleophilic substitution reactions, coupling reactions and other pathways.

[0003]

[0004] In recent years, with the rapid development of medicinal chemistry and materials science, higher demands have been placed on the structural diversity of 3-arylindolone derivatives, and significant progress has been made in the research of their synthetic methodologies. Currently, the synthetic strategies for the two types of products mainly present a "divide and conquer" pattern: the methods for synthesizing 3-hydroxy-3-arylindolone derivatives mainly include the addition reaction of indigo with aryl borides or other nucleophiles, the oxidation reaction of indole or indolone derivatives, and the intramolecular nucleophilic addition reaction of ortho-substituted aryl α-ketoamides; while the main synthetic methods for 3-arylindolone derivatives (referring to 3-hydrogenated products) involve the reductive nucleophilic addition of indigo, the α-arylation of indolone, and the CH bond insertion reaction of electron-rich aromatic hydrocarbons with 3-diazoindolone.

[0005] However, existing synthetic strategies generally face the limitation of "one type of product relying on one type of method," making it difficult to flexibly switch synthetic directions starting from the same raw materials. Specifically, existing technologies face the following multiple challenges: First, the starting material compatibility is poor. The commercial availability of raw materials such as indigo, specifically substituted indoles, or indoleones is limited. To obtain products with different substitution modes, different starting materials are often required, which severely restricts the structural diversity of products and makes it difficult to meet the needs of rapid compound library construction in drug development. Second, the reaction conditions are harsh. Existing methods mostly rely on transition metal catalysts such as palladium, nickel, and cobalt or electrochemical assistance to proceed smoothly. This results in problems such as high catalyst costs, complex reaction systems, and easy generation of metal residues, which are not conducive to the development concept of green pharmaceuticals. Third, even if some reactions can be achieved through strong base and heating conditions, they still face the dilemma of low yield, poor substrate tolerance, and a large number of by-products, which limits the versatility and practicality of the methods.

[0006] It is noteworthy that visible light-induced catalysis, as a green and mild renewable energy-driven mode, has become a focus of attention for chemists in recent years. Photocatalysis has the advantages of mild reaction conditions, low energy consumption, environmental friendliness, and excellent selectivity, providing a powerful tool for the innovation of organic synthesis methods. However, how to use photocatalysis technology to achieve the divergent synthesis of two important skeletons, 3-hydro-3-arylindolone and 3-hydroxy-3-arylindolone, from the same simple starting materials by precisely controlling the reaction parameters remains a technical challenge that urgently needs to be solved.

[0007] Therefore, developing a universal, green, simple-to-operate preparation method with divergent synthesis capabilities, capable of selectively constructing two types of indole ketone derivatives from the same starting materials under relatively mild conditions, is of great practical significance for enriching the structural diversity of these compounds and promoting their application in drug development and materials science. Summary of the Invention

[0008] To overcome the shortcomings of the prior art, this invention provides a 3-arylindolone derivative, its preparation method, and its application in food antibacterial applications. The aim is to overcome the defects of existing technologies, such as "one type of product depends on one type of method," poor raw material adaptability, dependence on metal catalysts, and harsh reaction conditions. This invention provides a universal, green, and simple method for preparing 3-arylindolone derivatives, enabling the divergent synthesis of two important skeletons—3-hydro-3-arylindolone and 3-hydroxy-3-arylindolone—by controlling the presence or absence of a base catalyst, starting from the same raw materials.

[0009] The objective of this invention is achieved through the following technical solution:

[0010] A method for preparing a 3-arylindolone derivative includes the following steps:

[0011] Under light conditions, in an air or oxygen atmosphere, α-aryldiazoamide of Formula I is reacted in a solvent as a raw material; by controlling whether or not a base catalyst is added, 3-arylindolone derivatives of Formula II are synthesized by divergent synthesis.

[0012]

[0013] When the reaction is carried out in the presence of a base-free catalyst, a 3-hydro-3-arylindolone derivative of formula II with R4 being H is obtained.

[0014] When the reaction is carried out in the presence of a base catalyst, a 3-hydroxy-3-arylindolone derivative of formula II, in which R4 is OH, is obtained;

[0015] R1 and R3 represent substituents at any position on the benzene ring, and each is independently selected from H, halogen atom, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, trifluoromethoxy, and cyano; R2 is selected from C1-C6 alkyl, phenyl, and benzyl.

[0016] This invention provides a divergent synthesis method using α-aryldiazoamide as a starting material: without external metal catalysts or photocatalysts, using air or oxygen as an oxidant, and through photoinduced carbene C−H bond insertion reaction, the divergent synthesis of two derivatives, 3-hydro-3-arylindolone and 3-hydroxy-3-arylindolone, can be achieved solely through base regulation. The application of these derivatives in the field of food antibacterial agents is also explored. This method combines the advantages of being green and economical, simple to operate, and offering diverse synthesis capabilities. It also possesses a broad substrate range, gram-scale synthesis capability, and the products can undergo various drug modifications through multiple reactions, demonstrating significant potential for drug modification. This method solves the problems of harsh conditions, high reagent costs, and heavy metal residues encountered in the preparation of such products using traditional methods.

[0017] Further, the illumination condition is visible light irradiation; the alkaline catalyst is at least one selected from triethylamine, dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium pentanoate, potassium acetate, sodium oxalate, cesium fluoride, potassium phosphate, sodium carbonate, cesium carbonate, sodium methoxide, and sodium hydroxide.

[0018] Furthermore, the wavelength of the visible light is 400–490 nm, and the power is 5–50 W.

[0019] Furthermore, the amount of the base catalyst used is 0.5 to 2.5 times that of α-aryldiazoamide, based on the molar amount of α-aryldiazoamide.

[0020] Furthermore, the reaction temperature is 10–40 °C, and the time is 0.5–12 h.

[0021] Furthermore, the reaction temperature is 25 °C; when the reaction is carried out in the absence of an alkaline catalyst, the reaction time is preferably 2 h; when the reaction is carried out in the presence of an alkaline catalyst, the reaction time is preferably 12 h.

[0022] Further, the solvent is at least one selected from methanol, ethanol, tert-butanol, hexafluoroisopropanol, n-hexane, 1,4-dioxane, dichloromethane, 1,2-dichloroethane, toluene, water, N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, and tetrahydrofuran; the ratio of α-aryldiazoamide to solvent is 1 mmol:(5-50) mL; preferably 1 mmol:(5-20) mL.

[0023] Furthermore, the α-aryldiazoamide shown in Formula I is prepared by reacting the amide compound shown in Formula III and the sulfonyl azide compound in acetonitrile in the presence of an organic base.

[0024]

[0025] R1 and R3 represent substituents at any position on the benzene ring, and each is independently selected from H, halogen atom, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, trifluoromethoxy, and cyano; R2 is selected from C1-C6 alkyl, phenyl, and benzyl.

[0026] Further, the sulfonyl azide compound is p-acetaminobenzenesulfonyl azide; the organic base is 1,8-diazabicyclo[5.4.0]undec-7-ene; the molar ratio of the amide compound, the sulfonyl azide compound and the organic base is 1:(1.5-3):(1.5-3); and the reaction time is 4-12 h.

[0027] A second aspect of the present invention provides a 3-arylindolone derivative, prepared by the method described in the first aspect above, wherein the 3-arylindolone derivative is any one of the following compounds:

[0028]

[0029]

[0030] A third aspect of the present invention provides the application of the 3-arylindolone derivative described in the second aspect above in food antibacterial applications.

[0031] Furthermore, it is used to inhibit Gram-negative bacteria.

[0032] The present invention has the following advantages over the prior art:

[0033] 1. This invention is the first to realize the divergent synthesis of two derivatives, 3-hydro-3-arylindolone and 3-hydroxy-3-arylindolone, from the same starting materials by simply adjusting the presence or absence of an alkaline catalyst, avoiding the cumbersome operation of changing raw materials required by traditional methods.

[0034] 2. This invention employs visible light-induced catalysis, resulting in mild reaction conditions and low energy consumption. It avoids the use of precious metal catalysts such as palladium and nickel, as well as photocatalysts, eliminating metal residue issues and aligning with the development concept of green chemistry. The reaction steps are simple, requiring no strict anhydrous or oxygen-free operation, and post-processing is convenient, making it suitable for large-scale preparation. Furthermore, it possesses advantages such as a broad substrate range, gram-scale synthesis capability, and the product can be used for diverse drug modifications through various reactions, demonstrating significant potential for drug modification.

[0035] 3. The 3-arylindolone derivatives prepared by this invention have inhibitory effects on Gram-negative Escherichia coli and have broad application prospects in the field of food preservation. Attached Figure Description

[0036] Figure 1 This is a schematic diagram of the specific structure of the raw material aryl α-diazoamide 1a-1o of the present invention;

[0037] Figure 2 The antibacterial results of the 3-arylindolone derivatives 3a and 3b of this invention are shown.

[0038] Figure 3 The antibacterial results of the 3-arylindolone derivatives 3c and 3d of this invention are shown.

[0039] Figure 4 The antibacterial results of the 3-arylindolone derivatives 3e and 3f of this invention;

[0040] Figure 5 The antibacterial results of 3g and 3h of the 3-arylindolone derivative of the present invention;

[0041] Figure 6 The antibacterial results of the 3-arylindolone derivatives 3i, 3j+3j′ of this invention are shown.

[0042] Figure 7 The antibacterial results of the 3-arylindolone derivatives 3K and 3L of this invention;

[0043] Figure 8 The antibacterial results of the 3-arylindolone derivatives 3m and 3n of this invention are shown.

[0044] Figure 9The antibacterial results of the 3-arylindolone derivative of the present invention at 3°C ​​and 2h are shown.

[0045] Figure 10 The antibacterial results of the 3-arylindolone derivative 2i of the present invention are shown. Detailed Implementation

[0046] The technical solution of the present invention will be further described below with reference to specific embodiments. However, those skilled in the art should understand that the following embodiments are only for illustrating the present invention and should not be regarded as limiting the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the reagents or instruments used are all conventional products obtained through commercial channels.

[0047] Preparation Example

[0048] The specific structure of the raw material aryl α-diazoamide 1a-1o in the embodiments of the present invention is shown in the figure. Figure 1 It is prepared by the following process:

[0049]

[0050] In an air atmosphere, starting amide S3 (5 mmol) and p-acetaminobenzenesulfonyl azide (p-ABSA, 1.8 g, 7.5 mmol) were dissolved in acetonitrile (20 mL) at 0 °C. 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.5 mL, 10 mmol) was added, and the reaction was carried out for 4 h. The solvent was removed by rotary evaporation, and then the mixture was purified by thin-layer chromatography (petroleum ether / ethyl acetate = 10:1, v / v) to obtain a red, oily aryl α-diazo compound 1a-1o. Compounds 1a-1i, 1m, and 1o are known compounds, while compounds 1j-1l and 1n are novel compounds.

[0051] The structure of aryl α-diazoamide 1a-1o is characterized as follows:

[0052] The yield of compound 1a was 63%. 1 H NMR (400 MHz, Chloroform-d) δ 7.52 (d, J = 8.3Hz, 2H), 7.39 – 7.33 (m, 4H), 7.27 – 7.22 (m, 1H), 7.19 – 7.15 (m, 2H), 3.42(s, 3H).

[0053] The yield of compound 1b was 84%. 1H NMR (400 MHz, Chloroform-d) δ 7.56 (d, J = 8.6Hz, 2H), 7.37 (dd, J = 8.3, 3.3 Hz, 4H), 7.28 (d, J = 7.4 Hz, 1H), 7.21 –7.14 (m, 2H), 3.42 (s, 3H).

[0054] The yield of compound 1c was 84%. 1 H NMR (400 MHz, Chloroform-d) δ 7.42 (d, J = 2.0Hz, 1H), 7.40 (d, J = 2.1 Hz, 1H), 7.39 – 7.33 (m, 2H), 7.27 – 7.22 (m, 2H),7.17 (d, J = 1.5 Hz, 1H), 7.15 (s, 2H), 7.13 (d, J = 2.0 Hz, 1H), 3.41 (s, 3H).

[0055] The yield of compound 1d was 70%. 1 H NMR (400 MHz, Chloroform-d) δ 7.38 – 7.32 (m,2H), 7.28 (t, J = 2.0 Hz, 1H), 7.23 – 7.20 (m, 1H), 7.20 – 7.13 (m, 3H), 7.12– 7.04 (m, 2H), 3.41 (s, 3H).

[0056] The yield of compound 1e was 79%. 1 H NMR (400 MHz, Chloroform-d) δ 7.35 (t, J = 7.7Hz, 2H), 7.29 (t, J = 8.1 Hz, 1H), 7.22 (d, J = 7.6 Hz, 2H), 7.18 – 7.14 (m,2H), 7.12 – 7.08 (m, 1H), 6.95 (dt, J = 8.2, 1.1 Hz, 1H), 3.41 (s, 3H).

[0057] The yield of compound 1f was 86%. 1H NMR (400 MHz, Chloroform-d) δ 7.53 (d, J = 8.3Hz, 1H), 7.38 (d, J = 9.0 Hz, 1H), 7.31 – 7.22 (m, 2H), 6.82 – 6.71 (m, 3H), 6.68 (t, J = 2.2 Hz, 2H), 3.76 (s, 3H), 3.40 (s, 3H).

[0058] The yield of compound 1g was 83%. 1 H NMR (400 MHz, Chloroform-d) δ 7.54 (d, J = 8.4Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.18 – 7.11 (m, 2H), 7.09 – 7.02 (m, 2H), 3.38 (s, 3H).

[0059] The yield of the compound was 74% after 1 hour. 1 H NMR (400 MHz, Chloroform-d) δ 7.60 (d, J = 8.2Hz, 2H), 7.53 (d, J = 8.1 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.7Hz, 2H), 3.44 (s, 3H).

[0060] The yield of compound 1i was 84%. 1 H NMR (400 MHz, Chloroform-d) δ 7.56 (d, J = 8.3Hz, 2H), 7.54 – 7.46 (m, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.06 (dd, J = 8.7,1.6 Hz, 2H), 3.40 (s, 3H).

[0061] The yield of compound 1j was 41%. 1 H NMR (400 MHz, Chloroform-d) δ 7.53 (d, J = 8.4Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.27 – 7.21 (m, 2H), 7.06 (d, J = 7.6 Hz,1H), 6.96 (d, J = 6.2 Hz, 2H), 3.40 (s, 3H), 2.32 (s, 3H).13 C NMR (101 MHz, Chloroform-d) δ 164.2, 143.7, 140.2, 132.1, 129.9, 128.1, 127.3 (q, 2 J C-F =32.8 Hz), 126.3, 125.7 (q, 3 J C-F = 3.9 Hz), 124.3 (q, 1 J C-F = 273.0 Hz), 124.2,122.7, 63.9, 38.7, 21.3. 19 F NMR (376 MHz, Chloroform-d) δ -62.28.

[0062] The yield of compound 1k was 68%. 1 H NMR (400 MHz, Chloroform-d) δ 7.52 (d, J = 9.1Hz, 2H), 7.36 (d, J = 9.1 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2H), 7.09 – 7.04 (m,2H), 3.40 (s, 3H), 2.62 (q, J = 7.6 Hz, 2H), 1.21 (td, J = 7.5, 1.8 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 164.3, 148.2, 141.3, 132.2, 128.5, 128.0,127.3 (q, 2 J C-F = 32.3 Hz), 125.7, 125.6 (q, 3 J C-F = 3.7 Hz), 124.4, 124.2 (q, 1 J C-F = 273.0 Hz), 122.8, 63.9, 62.1, 38.7, 38.0, 33.8, 23.9. 19 F NMR (376 MHz, Chloroform-d) δ -62.31.

[0063] The yield of compound 1L was 72%. 1H NMR (400 MHz, Chloroform-d) δ 7.51 (d, J = 8.4Hz, 2H), 7.35 (d, J = 8.3 Hz, 2H), 7.18 (d, J = 6.5 Hz, 2H), 7.06 (d, J = 8.4Hz, 2H), 3.40 (s, 3H), 2.87 (p, J = 6.9 Hz, 1H), 1.21 (s, 3H), 1.20 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 164.3, 148.2, 141.3, 132.2, 128.0, 127.3 (q, 2 J C-F = 32.6 Hz), 125.7, 125.6 (q, 3 J C-F = 4.0 Hz), 124.4, 124.2 (q, 1 J C-F =273.0 Hz), 38.7, 33.8, 23.9. 19 F NMR (376 MHz, Chloroform-d) δ -62.29.

[0064] The yield of compound 1m was 62%. 1 H NMR (400 MHz, Chloroform-d) δ 7.52 (d, J = 8.6Hz, 2H), 7.37 (dt, J = 8.0, 3.6 Hz, 4H), 7.29 – 7.24 (m, 2H), 7.20 – 7.06 (m,2H), 3.88 (q, J = 7.1 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H).

[0065] The yield of compound 1n was 65%. 1 H NMR (400 MHz, Chloroform-d) δ 7.57 (d, J = 8.3Hz, 2H), 7.47 (d, J = 8.2 Hz, 2H), 7.40 – 7.34 (m, 4H), 7.28 – 7.23 (m, 2H),7.22 – 7.15 (m, 4H). 13C NMR (101 MHz, Chloroform-d) δ 165.3, 143.1, 129.7,127.7 (q, J = 32.9 Hz), 126.8, 126.5, 125.8 (q, J = 3.8 Hz), 124.2 (q, J =274.0 Hz), 124.3. 19 F NMR (376 MHz, Chloroform-d) δ -62.33.

[0066] The yield of compound 1o was 65%. 1 H NMR (400 MHz, Chloroform-d) δ 7.55 (d, J = 8.1Hz, 2H), 7.42 (d, J = 7.9 Hz, 2H), 7.34 – 7.30 (m, 3H), 7.29 (d, J = 2.7 Hz,3H), 7.28 (d, J = 2.9 Hz, 1H), 7.26 – 7.21 (m, 1H), 7.08 (dd, J = 7.6, 2.1Hz, 2H), 5.05 (s, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 164.2, 142.3, 137.2,132.0, 130.0, 128.7, 128.6, 127.7, 127.5, 127.5 (q, J = 32.7 Hz), 126.6,125.7 (q, J = 3.7 Hz), 124.4, 124.2 (q, J = 273.0 Hz), 64.0, 54.4. 19 F NMR (376 MHz, Chloroform-d) δ -62.27.

[0067] Example 1

[0068] Example 1 provides a 3-hydro-3-arylindolone derivative, named 2a, whose synthesis process includes the following steps:

[0069]

[0070] Under air atmosphere, 0.1 mmol of α-aryldiazoamide 1a was weighed and placed in a reaction tube, and 1 mL of anhydrous acetonitrile was added. The mixture was thoroughly mixed to obtain a mixed solution. The mixed solution was irradiated with a 15 W, 460 nm blue LED lamp for 2 h, and the solvent was removed by rotary evaporation. Then, thin-layer chromatography (petroleum ether / ethyl acetate = 10:1, v / v) was used to separate and purify the solution to obtain 3-hydro-3-arylindolone derivative 2a with a yield of 94%. 1 H NMR (400 MHz, Chloroform-d) δ 7.59 (d, J = 8.6 Hz,2H), 7.40 – 7.32 (m, 3H), 7.16 (dt, J = 7.4, 1.4 Hz, 1H), 7.10 (td, J = 7.5,1.0 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 4.68 (s, 1H), 3.26 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 175.3, 144.6, 140.7, 129.9 (q, 2 J C-F = 32.6 Hz),129.0, 127.9, 125.9 (q, 3 J C-F = 3.8 Hz), 125.2, 124.2 (q, 1 J C-F = 272.7 Hz),123.1, 108.6, 51.8, 26.7. 19 F NMR (376 MHz, Chloroform-d) δ -62.45. HRMS(ESI): m / z [M+H] + calcd for [C 16 H 13 F3NO] + requires 292.0944, found 292.0944.

[0071] Example 2

[0072] Example 2 provides a 3-hydro-3-arylindolone derivative, named 2b, with the following structural formula:

[0073] ;

[0074] The preparation method of compound 2b is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1b.

[0075] In this embodiment, the yield of compound 2b was 97%. 1 H NMR (400 MHz, Chloroform-d) δ 7.66 –7.58 (m, 2H), 7.39 (d, J = 7.7 Hz, 1H), 7.34 (d, J = 8.3 Hz, 2H), 7.15 (d, J= 7.4 Hz, 1H), 7.10 (td, J = 7.4, 1.0 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 4.67(s, 1H), 3.25 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 174.7, 144.6, 142.0,132.7, 129.4, 129.2, 127.3, 125.1, 123.2, 118.7, 111.6, 108.7, 51.9, 26.7.HRMS (ESI): m / z [M+Na] + calcd for [C 16 H 12 NO2Na] + requires 271.0842, found271.0839.

[0076] Example 3

[0077] Example 3 provides a 3-hydro-3-arylindolone derivative, named 2c, with the following structural formula:

[0078] ;

[0079] The preparation method of compound 2c is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1c.

[0080] In this embodiment, the yield of compound 2c was 75%. 1H NMR (400 MHz, Chloroform-d) δ 7.45 (d,J = 8.4 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 7.09 (t,J = 8.2 Hz, 3H), 6.91 (d, J = 7.8 Hz, 1H), 4.57 (s, 1H), 3.25 (s, 3H). 13 C NMR(101 MHz, Chloroform-d) δ 175.5, 144.5, 135.6, 132.0, 130.2, 128.8, 128.2,125.1, 123.0, 121.7, 108.4, 51.5 26.6. HRMS (ESI): m / z [M+H] + calcd for[C 15 H 13 BrNO] + requires 302.0175, found 302.0174.

[0081] Example 4

[0082] Example 4 provides a 3-hydro-3-arylindolone derivative, named 2d, with the following structural formula:

[0083] ;

[0084] The preparation method of compound 2d is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1d.

[0085] In this embodiment, the yield of compound 2d was 80%. 1 H NMR (400 MHz, Chloroform-d) δ 7.34 (t,J = 7.7 Hz, 1H), 7.26 (m, 2H), 7.14 (m, 3H), 7.08 (t, J = 7.5 Hz, 1H), 6.90(d, J = 7.8 Hz, 1H), 4.57 (s, 1H), 3.25 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 175.4, 144.5, 138.6, 134.7, 130.2, 128.8, 128.5, 128.1, 127.9, 127.0,125.1, 123.0, 108.4, 51.6, 26.6. HRMS (ESI): m / z [M+H] + calcd for [C 15 H 13 ClNO] + requires 258.0680, found 258.0680.

[0086] Example 5

[0087] Example 5 provides a 3-hydro-3-arylindolone derivative, named 2e, with the following structural formula:

[0088] ;

[0089] The preparation method of compound 2e is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1e.

[0090] In this embodiment, the yield of compound 2e was 78%. 1 H NMR (400 MHz, Chloroform-d) δ 7.39 –7.34 (m, 2H), 7.20 – 7.13 (m, 3H), 7.12 – 7.05 (m, 2H), 6.92 (d, J = 7.8 Hz,1H), 4.63 (s, 1H), 3.26 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 175.2,149.6, 144.5, 138.8, 130.3, 128.9, 127.8, 127.0, 125.1, 123.0, 121.2, 120.5(q, J = 257.3 Hz), 120.0, 108.5, 51.5, 26.6. 19 F NMR (376 MHz, Chloroform-d) δ-57.58. HRMS (ESI): m / z [M+H] + calcd for [C 16 H 13 F3NO2] +requires 308.0893, found 308.0900.

[0091] Example 6

[0092] Example 6 provides a 3-hydro-3-arylindolone derivative, named 2f, with the following structural formula:

[0093] ;

[0094] The preparation method of compound 2f is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1f.

[0095] In this embodiment, the yield of compound 2f was 63%. 1 H NMR (400 MHz, Chloroform-d) δ 7.33 (t,J = 7.7 Hz, 1H), 7.25 (t, J = 7.9 Hz, 1H), 7.18 (d, J = 7.4 Hz, 1H), 7.06 (t,J = 7.5 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.85 – 6.77 (m, 2H), 6.75 (d, J =2.1 Hz, 1H), 4.58 (s, 1H), 3.78 (s, 3H), 3.25 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 175.9, 160.0, 144.5, 138.1, 129.9, 128.8, 128.5, 125.1,122.8, 120.9, 114.5, 112.9, 108.2, 55.3, 52.0, 26.5. HRMS (ESI): m / z [M+H] + calcd for [C 16 H 16 NO2] + requires 254.1176, found 254.1176.

[0096] Example 7

[0097] Example 7 provides a 3-hydro-3-arylindolone derivative, named 2g, with the following structural formula:

[0098] ;

[0099] The preparation method of compound 2g is basically the same as that in Example 1, except that compound 1a in Example 1 is replaced with compound 1g.

[0100] In this embodiment, the yield of compound 2f was 94%. 1 H NMR (400 MHz, Chloroform-d) δ 7.61 (d,J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.11 – 7.03 (m, 1H), 6.92 (ddd, J= 7.8, 2.6, 1.2 Hz, 1H), 6.85 (dd, J = 8.5, 4.1 Hz, 1H), 4.67 (s, 1H), 3.25(s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 174.8, 159.5 (d, 1 J C-F = 241.3 Hz), 140.5 (d, 4 J C-F = 2.0 Hz), 130.2 (q, 2 J C-F = 32.5 Hz), 129.4 (d, 3 J C-F = 8.4 Hz), 128.9, 126.0 (q, 3 J C-F = 3.8 Hz), 124.1 (q, 1 J C-F = 273.7 Hz), 115.3 (d, 2 J C-F =23.2 Hz), 113.3 (d, 2 J C-F = 24.6 Hz), 109.0 (d, 3 J C-F = 8.2 Hz), 77.3, 52.0, 26.8. 19 F NMR (376 MHz, Chloroform-d) δ -62.55, -119.76. HRMS (ESI): m / z [M+H] + calcd for [C 16 H 12 F4NO] +requires 310.0850, found 310.0844.

[0101] Example 8

[0102] Example 8 provides a 3-hydro-3-arylindolone derivative, named 2h, with the following structural formula:

[0103] ;

[0104] The preparation method of compound 2h is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1h.

[0105] In this example, the yield of compound 2h was 80%. 1 H NMR (400 MHz, Chloroform-d) δ 7.61 (d,J = 8.1 Hz, 2H), 7.36 – 7.30 (m, 2H), 7.13 (dd, J = 2.2, 1.2 Hz, 1H), 6.85(d, J = 8.3 Hz, 1H), 4.66 (s, 1H), 3.25 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 174.7, 143.1, 139.9, 130.2 (q, 2 J C-F = 33.3 Hz), 129.5, 128.9, 128.9,128.4, 126.1 (q, 3 J C-F = 3.7 Hz), 125.5, 124.1 (q, 1 J C-F = 273.7 Hz), 109.5, 51.7, 26.8. 19 F NMR (376 MHz, Chloroform-d) δ -62.55. HRMS (ESI): m / z [M+H] + calcd for [C 16 H 12 ClF3NO] + requires 326.0554, found 326.0549.

[0106] Example 9

[0107] Example 9 provides a 3-hydro-3-arylindolone derivative, named 2i, with the following structural formula:

[0108] ;

[0109] The preparation method of compound 2i is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1i.

[0110] The yield of compound 2i in this embodiment was 78%. 1 H NMR (400 MHz, Chloroform-d) δ 7.61 (d,J = 8.0 Hz, 2H), 7.49 (ddd, J = 8.3, 2.0, 0.9 Hz, 1H), 7.32 (d, J = 8.1 Hz,2H), 7.28 – 7.26 (m, 1H), 6.81 (d, J = 8.3 Hz, 1H), 4.67 (s, 1H), 3.25 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 174.6, 143.6, 139.8, 131.8, 130.2 (q, 2 J C-F = 33.3 Hz), 129.9, 128.9, 128.3, 126.1 (q, 1 J C-F = 273.7 Hz), 124.1 (q, 3 J C-F = 3.8 Hz), 115.7, 110.1, 51.7, 26.8. 19 F NMR (376 MHz, Chloroform-d) δ -62.51. HRMS (ESI): m / z [M+K] + calcd for [C 16 H 11 BrF3NOK] + requires 407.9608, found 407.9612.

[0111] Example 10

[0112] Example 10 provides a 3-hydro-3-arylindolone derivative, named 2j, with the following structural formula:

[0113]

[0114] The preparation method of compound 2j is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1j.

[0115] In this embodiment, the yield of compound 2j was 89%. 1 H NMR (400 MHz, Chloroform-d) δ 7.59 (d,J = 3.1 Hz, 1H), 7.57 (d, J = 3.1 Hz, 1H), 7.34 (s, 0.5H), 7.32 (s, 0.5H),7.32 – 7.26 (m, 1.5H), 7.03 (d, J = 7.5 Hz, 0.5H), 6.91 (d, J = 7.8 Hz, 1H), 6.78 (d, J = 7.8 Hz, 0.5H), 6.75 (s, 0.5H), 4.63 (s, 0.5H), 4.59 (s, 0.5H), 3.24 (s, 1.5H), 3.23 (s, 1.5H), 2.43 (s, 1.5H), 1.98 (s, 1.5H). 13 C NMR (101MHz, Chloroform-d) δ 175.6, 175.2, 144.8, 144.6, 140.9, 140.0, 139.2, 135.3,129.9 (q, 2 J C-F = 32.3 Hz), 129.8 (q, 2 J C-F = 32.3 Hz), 129.0, 128.9, 128.7,125.9 (q, 3 J C-F = 4.0 Hz), 125.8 (q, 3 J C-F = 4.0 Hz), 124.9, 124.8, 124.8, 124.2(q, 1 J C-F = 273.7 Hz), 124.1 (q, 1 J C-F = 273.7 Hz), 123.6, 109.45, 106.1, 51.6,51.47, 26.7, 26.6, 21.9, 18.7. 19F NMR (376 MHz, Chloroform-d) δ -62.46, -62.47. HRMS (ESI): m / z [M+H] + calcd for [C 17 H 15 F3NO] + requires 306.1100, found 306.1099.

[0116] Example 11

[0117] Example 11 provides a 3-hydro-3-arylindolone derivative, named 2j′, with the following structural formula:

[0118]

[0119] The preparation method of compound 2j′ is exactly the same as that of Example 10. It is a regioisomer of compound 2j, and the regioisomer ratio rr = 1:1.

[0120] Example 12

[0121] Example 12 provides a 3-hydro-3-arylindolone derivative, named 2k, with the following structural formula:

[0122]

[0123] The preparation method of compound 2k is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1k.

[0124] The yield of compound 2k in this embodiment was 67%. 1 H NMR (400 MHz, Chloroform-d) δ 7.59 (d,J = 8.1 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 1H), 7.00 (s,1H), 6.84 (d, J = 7.9 Hz, 1H), 4.65 (s, 1H), 3.24 (s, 3H), 2.62 (q, J = 7.5Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 175.3,142.4, 140.9, 139.4, 129.9 (q, 2 J C-F= 32.5 Hz), 129.0, 128.0, 128.0, 125.9(q, 3 J C-F = 3.8 Hz), 124.8, 124.2 (q, 1 J C-F = 272.1 Hz), 108.3, 53.5, 51.9,28.6, 26.7, 16.1. 19 F NMR (376 MHz, Chloroform-d) δ -62.47. HRMS (ESI): m / z [M+H] + calcd for [C 18 H 17 F3NO] + requires 320.1257, found 320.1259.

[0125] Example 13

[0126] Example 13 provides a 3-hydro-3-arylindolone derivative, named 2l, with the following structural formula:

[0127]

[0128] The preparation method of compound 2l is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1l.

[0129] In this embodiment, the yield of compound 2l was 92%. 1 H NMR (400 MHz, Chloroform-d) δ 7.60 (d,J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 7.25 – 7.19 (m, 1H), 7.03 (s, 1H),6.85 (d, J = 8.0 Hz, 1H), 4.65 (s, 1H), 3.24 (s, 3H), 2.88 (p, J = 6.9 Hz, 1H), 1.22 (dd, J = 6.9, 4.7 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 175.3,144.1, 142.5, 140.9, 129.9 (q, 2 J C-F = 32.3 Hz), 129.0, 127.9, 126.6, 125.9(q,3 J C-F = 3.8 Hz), 124.2 (q, 1 J C-F = 272.1 Hz), 123.4, 108.29, 53.5, 52.01,34.0, 26.7, 24.5, 24.2. 19 F NMR NMR (376 MHz, Chloroform-d) δ -62.46. HRMS(ESI): m / z [M+H] + calcd for [C 19 H 19 F3NO] + requires 334.1413, found 334.1426.

[0130] Example 14

[0131] Example 14 provides a 3-hydro-3-arylindolone derivative, named 2m, with the following structural formula:

[0132]

[0133] The preparation method of compound 2m is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1m.

[0134] The yield of compound 2m in this embodiment is 95%. 1 H NMR (400 MHz, Chloroform-d) δ 7.59 (d,J = 8.3 Hz, 2H), 7.37 (dt, J = 7.7, 1.1 Hz, 1H), 7.33 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 7.3 Hz, 1H), 7.08 (td, J = 7.5, 1.0 Hz, 1H), 6.95 (d, J = 7.8Hz, 1H), 4.66 (s, 1H), 3.81 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H). 13 CNMR (101 MHz, Chloroform-d) δ 174.9, 143.7, 140.8, 129.9 (q, 2 J C-F = 32.3 Hz),128.9, 128.9, 128.2, 125.9 (q, 3J C-F = 3.8 Hz), 125.7 (q, 1 J C-F = 273.5 Hz),125.3, 122.8, 108.7, 51.8, 35.1, 12.8. 19 F NMR (376 MHz, Chloroform-d) δ -62.44. HRMS (ESI): m / z [M+H] + calcd for [C 17 H 15 F3NO] + requires 306.1100, found306.1100.

[0135] Example 15

[0136] Example 15 provides a 3-hydro-3-arylindolone derivative, named 2n, with the following structural formula:

[0137]

[0138] The preparation method of compound 2n is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1n.

[0139] In this embodiment, the yield of compound 2n was 76%. 1 H NMR (400 MHz, ) δ 7.39 (s, 1H), 7.34(t, J = 8.1 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 7.09 (q, J = 7.7 Hz, 1H), 6.92(t, J = 7.4 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 4.00 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 174.61, 144.57, 140.77, 134.38, 130.08 (q, 2 J C-F = 32.4 Hz),129.81, 129.06, 128.86, 128.40, 127.76, 126.69, 126.01 (q, 3 J C-F = 3.7 Hz), 125.49, 124.2 (q, 1 J C-F= 273.7 Hz), 123.54, 109.92, 51.97. 19 F NMR (376 MHz,Chloroform-d) δ -63.26. HRMS (ESI): m / z [M+H] + calcd for [C 21 H 15 F3NO] + requires354.1100, found 354.1087.

[0140] Example 16

[0141] Example 16 provides a 3-hydro-3-arylindolone derivative, named 2o, with the following structural formula:

[0142]

[0143] The preparation method of compound 2o is basically the same as that of Example 1, except that compound 1a in Example 1 is replaced with compound 1o.

[0144] In this embodiment, the yield of compound 2o was 68%. 1 H NMR (400 MHz, Chloroform-d) δ 7.62 (d,J = 8.2 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.34 – 7.26 (m, 5H), 7.24 (d, J =7.7 Hz, 1H), 7.16 (d, J = 7.3 Hz, 1H), 7.06 (td, J = 7.5, 1.0 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H), 5.03 – 4.87 (m, 2H), 4.78 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 175.4, 143.7, 140.8, 135.8, 130.0 (q, 2 J C-F = 32.6 Hz), 129.0,128.9, 128.0, 127.9, 127.5, 126.0 (q, 3 J C-F = 3.8 Hz), 125.2, 124.2 (q, 1 J C-F=273.7 Hz), 123.1, 109.6, 51.8, 44.2. 19 F NMR (376 MHz, Chloroform-d) δ -62.44.HRMS (ESI): m / z [M+H] + calcd for [C 22 H 17 F3NO] + requires 368.1257, found 368.1256.

[0145] Example 17

[0146] Example 17 provides a 3-hydroxy-3-arylindolone derivative, named 3a, whose synthesis process includes the following steps:

[0147]

[0148] Under an oxygen atmosphere, α-aryldiazoamide 1a (0.1 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.2 mmol) were weighed and placed in a reaction tube. 1 mL of anhydrous acetonitrile was added and the mixture was stirred until homogeneous to obtain a mixed solution. The mixed solution was irradiated with a 15 W, 460 nm blue LED lamp for 12 h, and the solvent was removed by rotary evaporation. Then, the solution was separated and purified by thin-layer chromatography (PE:EA = 10:1) to obtain 3-hydroxy-3-arylindolone derivative 3a with a yield of 94%. 1 H NMR (400 MHz, Chloroform-d) δ 7.54 (d, J = 8.3 Hz, 1H), 7.46 (d, J = 8.9 Hz, 2H), 7.37 (td,J = 7.8, 1.3 Hz, 1H), 7.22 (dd, J = 7.4, 1.3 Hz, 1H), 7.09 (td, J = 7.6, 1.0Hz, 1H), 6.92 (d, J = 7.9 Hz, 1H), 4.51 (s, 1H), 3.22 (s, 3H). 13 C NMR (101MHz, Chloroform-d) δ 177.3, 144.2, 143.4, 131.4, 130.4 (q, 2 J C-F = 32.4 Hz),130.3, 126.0, 125.6 (q, 3 J C-F= 3.8 Hz), 125.0, 124.1 (q, 1 J C-F = 272.2 Hz),124.0, 109.1, 78.0, 26.7. 19 F NMR (376 MHz, Chloroform-d) δ -62.51. HRMS(ESI): m / z [M+H] + calcd for [C 16 H 13 F3NO2] + requires 308.0893, found 308.0897.

[0149] Example 18

[0150] Example 18 provides a 3-hydroxy-3-arylindolone derivative, named 3b, with the following structural formula:

[0151]

[0152] The preparation method of compound 3b is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1b.

[0153] In this embodiment, the yield of compound 3b was 70%. 1 H NMR (400 MHz, Chloroform-d) δ 7.61 (m,J = 8.5 Hz, 2H), 7.48 (m, J = 8.6 Hz, 2H), 7.40 (td, J = 7.7, 1.3 Hz, 1H),7.24 – 7.20 (m, 1H), 7.11 (td, J = 7.5, 1.0 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 3.63 (s, 1H), 3.26 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 176.6,145.3, 143.5, 132.5, 130.8, 130.6, 126.4, 125.0, 124.1, 118.6, 112.3, 109.2,77.8, 26.8. HRMS (ESI): m / z [M+Na] + calcd for [C 16 H 12 [N2NaO2] +requires 287.0791, found 287.0792.

[0154] Example 19

[0155] Example 19 provides a 3-hydroxy-3-arylindolone derivative, named 3c, with the following structural formula:

[0156]

[0157] The preparation method of compound 3c is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1c.

[0158] In this embodiment, the yield of compound 3c was 92%. 1 H NMR (400 MHz, Chloroform-d) δ 7.45 –7.41 (m, 2H), 7.36 (td, J = 7.7, 1.3 Hz, 1H), 7.24 (m, J = 2.2 Hz, 2H), 7.22(m, J = 2.0 Hz, 1H), 7.09 (td, J = 7.5, 1.0 Hz, 1H), 6.91 (d, J = 7.9 Hz, 1H), 3.81 (s, 1H), 3.23 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 177.3,143.4, 139.3, 131.8, 131.3, 130.2, 127.3, 124.9, 123.9, 122.5, 109.0, 77.7,26.7. HRMS (ESI): m / z [M+H] + calcd for [C 15 H 13 BrNO2] + requires 318.0124, found 318.0128.

[0159] Example 20

[0160] Example 20 provides a 3-hydroxy-3-arylindolone derivative, named 3d, with the following structural formula:

[0161]

[0162] The preparation method of compound 3d is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1d.

[0163] In this embodiment, the yield of compound 3d was 80%. 1 H NMR (400 MHz, Chloroform-d) δ 7.40 –7.33 (m, 2H), 7.26 – 7.22 (m, 4H), 7.10 (td, J = 7.6, 1.0 Hz, 1H), 6.92 (d, J= 7.8 Hz, 1H), 3.49 (s, 1H), 3.25 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ177.3, 143.4, 142.3, 134.6, 131.4, 130.2, 123.0, 128.5, 125.8, 125.0, 123.9,123.8, 109.0, 77.7, 26.7. HRMS (ESI): m / z [M+K] + calcd for [C 15 H 12 ClKNO2] + requires 312.0188, found 312.0198.

[0164] Example 21

[0165] Example 21 provides a 3-hydroxy-3-arylindolone derivative, named 3e, with the following structural formula:

[0166]

[0167] The preparation method of compound 3e is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1e.

[0168] In this embodiment, the yield of compound 3e was 78%. 1 H NMR (400 MHz, Chloroform-d) δ 7.38(td, J = 7.8, 1.3 Hz, 1H), 7.35 – 7.29 (m, 2H), 7.26 (dd, J = 7.3, 1.4 Hz,1H), 7.21 (dt, J = 8.0, 1.3 Hz, 1H), 7.17 – 7.07 (m, 2H), 6.93 (d, J = 7.9Hz, 1H), 3.69 (s, 1H), 3.25 (s, 3H). 13C NMR (101 MHz, Chloroform-d) δ 177.2,149.5, 143.4, 142.7, 131.2, 130.3, 130.0, 125.0, 123.9, 123.9, 120.6, 120.5(q, 1 J C-F = 258.6 Hz), 118.5, 109.0, 77.7, 26.7. 19 F NMR (376 MHz, Chloroform-d) δ -57.59. HRMS (ESI): m / z [M+H] + calcd for [C 16 H 13 F3NO3] + requires 324.0842, found 324.0836.

[0169] Example 22

[0170] Example 22 provides a 3-hydroxy-3-arylindolone derivative, named 3f, with the following structural formula:

[0171]

[0172] The preparation method of compound 3f is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1f.

[0173] In this embodiment, the yield of compound 3f was 46%. 1 H NMR (400 MHz, Chloroform-d) δ 7.35(td, J = 7.8, 1.3 Hz, 1H), 7.30 – 7.27 (m, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.08 (td, J = 7.6, 0.9 Hz, 1H), 7.03 – 7.00 (m, 1H), 6.92 – 6.86 (m, 2H), 6.83 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), 3.78 (s, 3H), 3.37 (s, 1H), 3.25 (s,3H). 13C NMR (101 MHz, Chloroform-d) δ 177.5, 159.9, 143.6, 141.7, 131.5,130.0, 129.8, 125.0, 123.7, 117.6, 113.7, 111.4, 108.8, 78.0, 55.4, 26.6.HRMS (ESI): m / z [M+H] + calcd for [C 16 H 16 NO3] + requires 270.1125, found270.1127.

[0174] Example 23

[0175] Example 23 provides a 3-hydroxy-3-arylindolone derivative, named 3g, with the following structural formula:

[0176]

[0177] The preparation method of compound 3g is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1g.

[0178] In this embodiment, the yield of compound 3g was 69%. 1 H NMR (400 MHz, Chloroform-d) δ 7.57 (d,J = 8.2 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.08 (td, J = 8.8, 2.6 Hz, 1H), 6.98 (dd, J = 7.5, 2.6 Hz, 1H), 6.87 (dd, J = 8.5, 4.0 Hz, 1H), 4.16 (s, 1H), 3.24 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 177.0, 159.9 (d, 1 J C-F = 243.3Hz), 143.6, 139.3 (d, 4 J C-F = 2.4 Hz), 132.7 (d, 3 J C-F = 7.8 Hz), 130.8 (d, 2 J C-F = 32.3 Hz), 125.8, 125.8 (q,3 J C-F = 3.6 Hz), 124.0 (q, 1 J C-F = 273.7 Hz), 116.7 (d, 2 J C-F = 23.5 Hz), 113.2 (d, 2 J C-F = 25.0 Hz), 109.8 (d, 3 J C-F = 7.9 Hz), 78.0, 77.3, 26.9. 19 F NMR (376 MHz, Chloroform-d) δ -62.60, -118.22. HRMS(ESI): m / z [M+Na] + calcd for [C 16 H 11 F4NNaO2] + requires 348.0618, found 348.0612.

[0179] Example 24

[0180] Example 24 provides a 3-hydroxy-3-arylindolone derivative, named 3h, with the following structural formula:

[0181]

[0182] The preparation method of compound 3h is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1h.

[0183] In this example, the yield of compound 3h was 65%. 1 H NMR (400 MHz, Chloroform-d) δ 7.57 (d,J = 8.2 Hz, 2H), 7.44 (d, J = 8.2 Hz, 2H), 7.34 (dd, J = 8.3, 2.1 Hz, 1H), 7.20 (d, J = 2.2 Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H), 4.04 (s, 1H), 3.23 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 176.78, 143.46, 141.93, 132.74, 130.8(d, 2 JC-F = 32.3 Hz), 130.28, 129.41, 125.83, 125.8 (d, 3 J C-F = 4.0 Hz), 125.55, 124.0 (d, 1 J C-F = 273.7 Hz), 110.11, 77.84, 26.87. 19 F NMR (376 MHz,Chloroform-d) δ -62.62. HRMS (ESI): m / z [M+Na] + calcd for [C 16 H 11 ClF3NNaO2] + requires 364.0323, found 364.0318.

[0184] Example 25

[0185] Example 25 provides a 3-hydroxy-3-arylindolone derivative, named 3i, with the following structural formula:

[0186]

[0187] The preparation method of compound 3i is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1i.

[0188] The yield of compound 3i in this embodiment was 78%. 1 H NMR (400 MHz, Chloroform-d) δ 7.58 (d,J = 8.3 Hz, 2H), 7.50 (dd, J = 8.3, 2.0 Hz, 1H), 7.45 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 2.0 Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 3.98 (s, 1H), 3.23 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 176.7, 143.5, 142.4, 133.2, 133.1,130.8 (q, 2 J C-F = 32.3 Hz), 128.3, 125.9, 125.8, 125.8 (q, 3 J C-F= 3.6 Hz), 123.9 (q, 1 J C-F = 273.7 Hz), 116.6, 110.6, 77.8, 53.5, 26.8. 19 F NMR (376 MHz,Chloroform-d) δ -62.58. HRMS (ESI): m / z [M+Na] + calcd for [C 16 H 11 BrF3NNaO2] + requires 407.9817, found 407.9830.

[0189] Example 26

[0190] Example 26 provides a 3-hydroxy-3-arylindolone derivative, named 3j, with the following structural formula:

[0191]

[0192] The preparation method of compound 3j is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1j.

[0193] In this embodiment, the yield of compound 3j was 87%. 1 H NMR (400 MHz, Chloroform-d) δ 7.59 –7.52 (m, 2H), 7.51 – 7.46 (m, 1H), 7.44 – 7.40 (m, 1H), 7.30 (t, J = 7.8 Hz,0.5H), 7.11 (d, J = 7.6 Hz, 0.5H), 6.94 – 6.86 (m, 1H), 6.82 – 6.74 (m, 1H), 3.68 (s, 1H), 3.24 (s, 1.5H), 3.21 (s, 1.5H), 2.41 (s, 1.5H), 2.06 (s, 1.5H). 13 C NMR (101 MHz, Chloroform-d) δ 177.57, 177.22, 144.52, 143.69, 143.50,143.26, 140.76, 136.64, 130.3 (q, 2 J C-F = 32.3 Hz), 130.2 (q, 2 J C-F= 32.3 Hz),130.18, 129.02, 128.50, 126.08, 126.05, 125.92, 125.52 (q, 3 J C-F = 4.0 Hz), 125.51 (q, 3 J C-F = 4.0 Hz), 124.73, 124.44, 124.14 (q, 1 J C-F = 273.7 Hz), 124.12(q, 1 J C-F = 273.7 Hz), 109.95, 106.44, 78.43, 77.86, 26.74, 26.65, 22.02,17.57. 19 F NMR (376 MHz, Chloroform-d) δ -62.50, -62.54. HRMS (ESI): m / z [M+H] + calcd for [C 17 H 15 F3NO2] + requires 322.1049, found 322.1052.

[0194] Example 27

[0195] Example 27 provides a 3-hydroxy-3-arylindolone derivative, named 3j′, with the following structural formula:

[0196]

[0197] The preparation method of compound 3j′ is exactly the same as that of Example 26. It is a regioisomer of compound 3j, and the regioisomer ratio rr = 1:1.

[0198] Example 28

[0199] Example 28 provides a 3-hydroxy-3-arylindolone derivative, named 3k, with the following structural formula:

[0200]

[0201] The preparation method of compound 3k is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1k.

[0202] The yield of compound 3k in this embodiment was 54%. 1H NMR (400 MHz, Chloroform-d) δ 7.59 –7.55 (m, 2H), 7.53 – 7.43 (m, 2H), 7.20 (dd, J = 8.0, 1.8 Hz, 1H), 7.12 –7.03 (m, 1H), 6.85 (d, J = 7.9 Hz, 1H), 3.78 (s, 1H), 3.24 (s, 3H), 2.60 (q,J = 7.6 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ177.18, 144.4, 141.3, 140.3, 131.3, 130.4 (q, 2 J C-F = 32.3 Hz), 129.5, 126.0,125.6 (q, 3 J C-F = 3.7 Hz), 124.6, 124.1 (q, 1 J C-F = 273.7 Hz), 108.9, 78.1,28.6, 26.7, 15.8. 19 F NMR (376 MHz, Chloroform-d) δ -62.54. HRMS (ESI): m / z [M+Na] + calcd for [C 18 H 16 F3NNaO2] + requires 358.1025, found 358.1033.

[0203] Example 29

[0204] Example 29 provides a 3-hydroxy-3-arylindolone derivative, named 3l, with the following structural formula:

[0205]

[0206] The preparation method of compound 3l is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1l.

[0207] In this embodiment, the yield of compound 3l was 69%. 1H NMR (400 MHz, Chloroform-d) δ 7.58 (d,J = 8.3 Hz, 2H), 7.49 (d, J = 8.3 Hz, 2H), 7.24 (dd, J = 8.0, 1.9 Hz, 1H), 7.12 (d, J = 1.8 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 3.65 (s, 1H), 3.24 (s,3H), 2.87 (p, J = 6.9 Hz, 1H), 1.20 (dd, J = 6.9, 5.6 Hz, 6H). 13 C NMR (101MHz, Chloroform-d) δ 177.2, 145.1, 144.4, 141.3, 131.2, 130.4 (q, 2 J C-F = 32.7Hz), 128.0, 126.0, 125.6 (q, 1 J C-F = 3.8 Hz), 124.1(q, 3 J C-F = 272.7 Hz), 123.2,108.8, 78.1, 33.9, 26.7, 24.3, 24.1. 19 F NMR (376 MHz, Chloroform-d) δ -62.53.HRMS (ESI): m / z [M+H] + calcd for [C 19 H 19 F3NO2] + requires 350.1362, found 350.1373.

[0208] Example 30

[0209] Example 30 provides a 3-hydroxy-3-arylindolone derivative, named 3m, with the following structural formula:

[0210]

[0211] The preparation method of compound 3m is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1m.

[0212] In this embodiment, the yield of compound 3m was 59%. 1H NMR (400 MHz, Chloroform-d) δ 7.57 (d,J = 8.3 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.37 (td, J = 7.8, 1.3 Hz, 1H), 7.24 (dd, J = 7.4, 1.3 Hz, 1H), 7.09 (td, J = 7.6, 0.9 Hz, 1H), 6.96 (d, J =7.9 Hz, 1H), 3.79 (dh, J = 21.4, 7.1 Hz, 2H), 3.66 (s, 1H), 1.32 (t, J = 7.2Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 176.8, 144.4, 142.5, 131.6, 130.4(q, 2 J C-F = 32.3 Hz), 130.3, 125.8, 125.6 (q, 3 J C-F = 3.7 Hz), 125.2, 124.1 (q, 1 J C-F = 273.7 Hz), 123.8, 109.2, 77.9, 35.2, 12.6. 19 F NMR NMR (376 MHz,Chloroform-d) δ -62.52. HRMS (ESI): m / z [M+H] + calcd for [C 17 H 15 F3NO2] + requires322.1049, found 322.1053.

[0213] Example 31

[0214] Example 31 provides a 3-hydroxy-3-arylindolone derivative, named 3n, with the following structural formula:

[0215]

[0216] The preparation method of compound 3n is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1n.

[0217] In this embodiment, the yield of compound 3n was 49%. 1H NMR (400 MHz, ) δ 7.64 (d, J = 8.4 Hz,1H), 7.54 (td, J = 7.1, 2.6 Hz, 1H), 7.48 – 7.41 (m, 3H), 7.33 – 7.27 (m,4H), 7.23 (d, J = 7.2 Hz, 1H), 7.17 – 7.10 (m, 1H), 6.91 (d, J = 8.0 Hz, 1H), 4.87 (s, 0H). 13 C NMR (101 MHz, Chloroform-d) δ 176.5, 144.4, 143.5, 133.8,131.04, 130.60 (q, 2 J C-F = 32.5 Hz), 130.2, 129.9, 128.6, 126.5, 126.0, 125.7(q, 3 J C-F = 3.8 Hz), 125.3, 124.4, 124.1(q, 1 J C-F = 273.7 Hz), 110.4, 78.0. 19 FNMR NMR (376 MHz, Chloroform-d) δ -63.20. HRMS (ESI): m / z [M+H] + calcd for[C 21 H 15 F3NO2] + requires 370.1049, found 370.1047.

[0218] Example 32

[0219] Example 32 provides a 3-hydroxy-3-arylindolone derivative, named 3o, with the following structural formula:

[0220]

[0221] The preparation method of compound 3o is basically the same as that of Example 17, except that compound 1a in Example 17 is replaced with compound 1o.

[0222] In this embodiment, the yield of compound 3o was 76%. 1H NMR (400 MHz, Chloroform-d) δ 7.56 (d,J = 8.3 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.35 – 7.27 (m, 5H), 7.25 – 7.20(m, 2H), 7.04 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 5.08 – 4.75 (m,2H), 3.32 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 177.2, 142.6, 135.3,131.3, 130.5 (q, 2 J C-F = 32.4 Hz), 130.3, 129.1, 128.1, 127.4, 125.9, 125.7(q, 3 J C-F = 3.8 Hz), 125.1, 124.1 (q, 1 J C-F = 273.7 Hz), 124.0, 110.1, 77.9,44.3. 19 F NMR (376 MHz, Chloroform-d) δ -62.50.HRMS (ESI): m / z [M+H] + calcdfor [C 22 H 17 F3NO2] + requires 384.1206, found 384.1211.

[0223] Examples 33-57

[0224] The contents of Examples 33-57 are basically the same as those of Example 17. The differences and the yield of compound 3a are shown in Table 1.

[0225] Table 1

[0226]

[0227] Examples 58-65

[0228] The contents of Examples 58-65 are basically the same as those of Example 1. The differences and the yield of compound 2a are shown in Table 2.

[0229] Table 2

[0230]

[0231] Experimental Example

[0232] This invention also provides the application of some 3-arylindolone derivatives in food antibacterial applications, with specific experiments as follows:

[0233] Sixteen 3-hydroxy-3-arylindolone derivatives and two 3-hydro-3-arylindolone derivatives were selected as test samples to detect their antibacterial activity against Gram-negative bacteria Escherichia coli.

[0234] 1. Activation and proliferation of the tested bacterial strains

[0235] Gram-negative Escherichia coli cultured to the logarithmic growth phase was selected, mixed thoroughly with 20% glycerol and 80% MHB broth, and stored at -80 ℃. During the experiment, the mixture was thawed at room temperature, shaken, and inoculated onto TSA solid medium, and incubated upside down at 37 ℃ for 12 h. Single TSA colonies were picked and inoculated into sterile broth, and cultured at 37 ℃ and 150 rpm for 4-6 h until the logarithmic growth phase, ready for use.

[0236] 2. Antibacterial activity test

[0237] Preparation of LB broth: Dissolve 20 g of commercially available LB broth in 1000 mL of distilled water, boil to dissolve, then dispense into containers and autoclave at 121 °C for 15 min. Take 15 3-hydroxy-3-arylindolone derivatives and 2 3-hydro-3-arylindolone derivatives as test samples, weigh 1 mg of each, and add 200 μL DMSO and 800 μL broth to prepare 1 mL of test solution. Dissolve PBS powder and bring to volume, sterilize at 121 °C for 20 min, cool, and store at 4 °C for washing and dilution of the bacterial suspension. Take 1 mL of the cultured bacterial suspension in a shaker, centrifuge and discard the supernatant, wash with PBS and centrifuge 3 times; dilute the centrifuged bacterial suspension to the reading of an ultra-micro UV-Vis spectrophotometer (OD). 600 =1.0, approximately 10 9 (CFU / mL), then diluted 100 times with LB broth to 1000 CFU / mL. 7 CFU / mL, shake to mix thoroughly, and use as the test bacterial solution.

[0238] Antibacterial concentration determination

[0239] ① 96-well plate loading: Add 100 μL LB broth to wells 2-8 in rows 2-4; add 100 μL DMSO to well 5; add 100 μL broth to wells 2-9 in row 7; and add 200 μL broth to wells 2-9 in row 8, serving as solvent control, bacterial control, and blank control, respectively. ② Serial dilution of drug: Add the test drug solution to well 2 in rows 2-4, mix well, and then serially dilute 2-fold to well 9. ③ Bacterial addition and contamination prevention: Add 100 μL of bacterial solution to each well (final volume 200 μL) except for the blank group. Add ultrapure water to the wells around the plate to prevent contamination. ④ Incubation and detection: Incubate at 37 ℃ for 12 h, observe the clarity with the naked eye, and measure the OD value at 600 nm using a microplate reader.

[0240] The formula for calculating bacterial survival rate in a 96-well plate is:

[0241]

[0242] Among them, OD e : Groups containing only microorganisms and culture medium, reflecting the normal growth of microorganisms; OD O Add the group of the sample to be tested; OD p : Groups containing only culture medium, used to eliminate the influence of the absorbance value of the culture medium itself.

[0243] 3. Experimental Results and Analysis

[0244] The experimental results for 15 3-hydroxy-3-arylindolone derivatives 3a-3o are shown in [reference]. Figures 1-5 Experimental results showed that the antibacterial rate of compound 3a-3o increased in a concentration-dependent manner, exhibiting good antibacterial effect at a concentration of 250 μg / mL, and was able to kill most bacteria. Among them, compounds with electron-withdrawing groups on the C3 aryl ring of indole, compounds with electron-withdrawing groups on the aniline aryl ring, and N-benzyl-substituted indole derivatives had relatively higher antibacterial rates.

[0245] The experimental results for the two 3-hydro-3-arylindolone derivatives, 2h and 2i, are shown in [reference needed]. Figure 6 The experimental results showed that the activity of the two compounds exhibited a significant concentration-dependent effect. At different concentrations, the antibacterial rate of the compounds initially increased and then decreased. The antibacterial rate was only about 1% at 250 μg / mL, reaching a peak at 31.25 μg / mL. However, the antibacterial effect of 3-hydro-3-arylindolone compounds was generally lower than that of 3-hydroxy-3-arylindolone compounds.

[0246] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.

Claims

1. A method for preparing a 3-arylindolone derivative, characterized in that, Includes the following steps: Under light conditions, in an air or oxygen atmosphere, α-aryldiazoamide of Formula I is reacted in a solvent as a raw material; by controlling whether or not a base catalyst is added, 3-arylindolone derivatives of Formula II are synthesized by divergent synthesis. When the reaction is carried out in the presence of a base-free catalyst, a 3-hydro-3-arylindolone derivative of formula II with R4 being H is obtained. When the reaction is carried out in the presence of a base catalyst, a 3-hydroxy-3-arylindolone derivative of formula II, in which R4 is OH, is obtained; R1 and R3 represent substituents at any position on the benzene ring, and each is independently selected from H, halogen atom, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, trifluoromethoxy, and cyano; R2 is selected from C1-C6 alkyl, phenyl, and benzyl.

2. The method for preparing the 3-arylindolone derivative according to claim 1, characterized in that, The illumination condition is visible light irradiation; the alkaline catalyst is at least one of triethylamine, dimethylaminopyridine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium pentanoate, potassium acetate, sodium oxalate, cesium fluoride, potassium phosphate, sodium carbonate, cesium carbonate, sodium methoxide, and sodium hydroxide.

3. The method for preparing the 3-arylindolone derivative according to claim 2, characterized in that, The wavelength of the visible light is 400–490 nm, and the power is 5–50 W.

4. The method for preparing the 3-arylindolone derivative according to claim 2, characterized in that, The amount of the base catalyst is 0.5 to 2.5 times that of α-aryldiazoamide, based on the molar amount of α-aryldiazoamide.

5. The method for preparing the 3-arylindolone derivative according to claim 1, characterized in that, The reaction is carried out at a temperature of 10–40 °C for a time of 0.5–12 h.

6. The method for preparing the 3-arylindolone derivative according to claim 1, characterized in that, The solvent is at least one of methanol, ethanol, tert-butanol, hexafluoroisopropanol, n-hexane, 1,4-dioxane, dichloromethane, 1,2-dichloroethane, toluene, water, N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, and tetrahydrofuran; the ratio of α-aryldiazoamide to solvent is 1 mmol: (5-50) mL.

7. The method for preparing the 3-arylindolone derivative according to claim 1, characterized in that, The α-aryldiazoamide shown in Formula I is prepared by reacting the amide compound shown in Formula III and the sulfonyl azide compound in acetonitrile in the presence of an organic base. R1 and R3 represent substituents at any position on the benzene ring, and each is independently selected from H, halogen atom, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, trifluoromethoxy, and cyano; R2 is selected from C1-C6 alkyl, phenyl, and benzyl.

8. The method for preparing the 3-arylindolone derivative according to claim 1, characterized in that, The sulfonyl azide compound is p-acetaminobenzenesulfonyl azide; the organic base is 1,8-diazabicyclo[5.4.0]undec-7-ene; the molar ratio of the amide compound, the sulfonyl azide compound and the organic base is 1:(1.5-3):(1.5-3); the reaction time is 4-12 h.

9. A 3-arylindolone derivative, characterized in that, The 3-arylindolone derivative is prepared by the method according to any one of claims 1 to 8, and is any one of the following compounds:

10. The use of the 3-arylindolone derivative of claim 9 in food antibacterial applications.

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