An α-trifluoromethyl diazosulfonium salt compound and its applications

Abstract

This invention discloses an α-trifluoromethyldiazonium sulfonium salt compound and its applications, belonging to the field of organic synthesis technology. The α-trifluoromethyldiazonium sulfonium salt compound is obtained by mixing and reacting a high-valent iodine reagent, a thioether, and an organic solvent. An organic solvent, a rhodium catalyst, N-heteroaromatic hydrocarbons, nitrile compounds, a base, and the α-trifluoromethyldiazonium sulfonium salt compound are mixed to undergo a [2+1+2] tandem cyclization reaction, yielding imidazo[N-heteroaromatic] compounds. This invention has found that these compounds possess certain inhibitory activity against tumor cell growth and are expected to be used as anti-tumor drugs, providing a basis for the research of imidazo[N-heteroaromatic] skeletal polycyclic compounds in the field of medicinal chemistry.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to an α-trifluoromethyl diazosulfonium salt compound and its applications. Background Technology

[0002] Fluorine has a small atomic radius, low orbital energy, and high electronegativity. Therefore, introducing fluorine atoms or fluorine-containing groups into organic compounds does not cause changes in steric hindrance. However, its inductive, pseudo-effect, blocking, lipophilic, and hydrogen bonding effects can significantly alter the physicochemical properties and biological activities of the molecule. Trifluoromethyl groups, as important fluorine-containing groups, are widely used in biomedicine, agrochemicals, and materials science, for example, in drugs such as celecoxib, efavirenz, and etofenamate, and pesticides such as picoxystrobin and fluazinam. However, natural products containing trifluoromethyl groups are extremely rare. Therefore, developing corresponding synthetic methods to introduce trifluoromethyl groups into molecules to enhance their biological activity is a significant undertaking.

[0003] Furthermore, heterocyclic compounds, as an important class of skeletons, are widely present in drug molecules. They can not only affect drug-receptor interactions but also increase the water solubility of drug molecules and reduce their lipophilicity. Imidazolon N-heteroaromatics, as an important nitrogen-containing heterocycle, have also received extensive attention and research in the field of medicinal chemistry. They have been studied as NK1 receptor ligands, benzodiazepine receptor ligands, and PDE10A inhibitors. Currently reported synthetic methods for imidazon N-heteroaromatic compounds mainly include tandem cyclization reactions of 2-substituted quinolines with alkylamines or amino acids via electrocatalysis or other oxidation pathways, denitrification cyclization reactions of quinoline triazoles, and Vilsmeier-type cyclization. However, most of these methods rely on some prefunctionalized substrates and require additional chemical oxidants or high-temperature conditions. Currently, it remains quite difficult to achieve one-pot synthesis of trifluoromethylimidazo-N-heteroaromatic compounds using readily available raw materials. Therefore, exploring a simpler method to achieve one-step synthesis of trifluoromethylimidazo-N-heteroaromatic compounds based on readily available commercial raw materials is of great significance in the fields of organic chemistry and medicinal chemistry. Summary of the Invention

[0004] To address the aforementioned problems in the prior art, this invention provides an α-trifluoromethyldiazosulfonium salt compound and its applications.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] One of the technical solutions of the present invention: an α-trifluoromethyldiazonium sulfonate compound having the structure shown in formula (I):

[0007]

[0008] The second technical solution of the present invention: a method for preparing the above-mentioned α-trifluoromethyldiazonium sulfonium salt compound, comprising the following steps: mixing and reacting a high-valent iodine reagent, a thioether, and an organic solvent to obtain the α-trifluoromethyldiazonium sulfonium salt compound.

[0009] Further, the high-valent iodine is one of iodophenyl diacetic acid, [bis(trifluoroacetyl)iodine]pentafluorobenzene, [bis(trifluoroacetoxy)iodine]benzene, bis(acetyl-O)(3-methoxy)iodine, iodo-m-trimethylbenzene diacetate, bis(tert-butylcarbonyloxy)iodobenzene, 4-iodide toluene diacetate, and 1-[bis(trifluoroacetoxy)iodine]-4-methylbenzene; the sulfide is dimethyl sulfide; the organic solvent is one of dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, benzene, and toluene; the molar ratio of the high-valent iodine reagent to the sulfide is 1:(1-5); the reaction temperature is -50 to 50°C, and the time is 2 to 48 h.

[0010] The third technical solution of the present invention: the application of the above-described α-trifluoromethyl diazosulfonium salt compound in the preparation of imidazo-N-heteroaromatic compounds.

[0011] The fourth technical solution of the present invention: an imidazo-N-heteroaromatic compound having the general structural formula shown in formula (II):

[0012]

[0013] In equation (II), when X = N, Y = C, Z = C, R 1 R 2 R 3 R 4 R 5 R 6 Each is independently selected from H, halogen, nitro, cyano, C1-C10 alkyl, C1-C10 alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl or alkoxy-substituted phenyl, and correspondingly, R 7 Selected from trifluoromethyl; correspondingly, R 8 Selected from methyl, phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, benzyloxyphenyl or [1,3]dioxanephenyl;

[0014] When X = C, Y = N, Z = C, R 1 R 2 R 3 R4 R 5 R 6 Each is independently selected from H, halogen, nitro, cyano, C1-C10 alkyl, C1-C10 alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl or alkoxy-substituted phenyl, and correspondingly, R 7 Selected from methyl, phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, benzyloxyphenyl, or [1,3]dioxanephenyl, correspondingly, R 8 Selected from trifluoromethyl;

[0015] When X = N, Y = C, Z = N, or when X = N, Y = C, Z = N, R 1 R 2 R 3 R 4 R 6 Each is independently selected from H, halogen, nitro, cyano, C1-C10 alkyl, C1-C10 alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl or alkoxy-substituted phenyl, and correspondingly, R 7 Selected from trifluoromethyl, correspondingly, R 8 Selected from methyl, phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, benzyloxyphenyl or [1,3]dioxanephenyl.

[0016] The fifth technical solution of the present invention: The preparation method of the imidazo-N-heteroaromatic compound described above includes the following steps: mixing an organic solvent, a rhodium catalyst, an N-heteroaromatic hydrocarbon, a nitrile compound, a base and the α-trifluoromethyl diazonium sulfonate salt compound of claim 1, and undergoing a [2+1+2] tandem cyclization reaction to obtain the imidazo-N-heteroaromatic compound.

[0017] Further, the rhodium catalyst is any one of bis[(α,α,α′,α′-tetramethyl-1,3-phenylenediamine)rhodium], dipolyacetate rhodium, dipolytrifluoroacetate rhodium, tetracaprolactam dirhodium, tetra(triphenylacetic acid) dirhodium, and dipolyoctanoate rhodium; the base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, and sodium acetate; the organic solvent is any one of acetonitrile, 1,2-dichloroethane, dichloromethane, chloroform, carbon tetrachloride, benzene, and toluene.

[0018] Furthermore, the structure of the N-heteroaromatic hydrocarbon is shown in formulas (Ⅲ) to (Ⅵ):

[0019]

[0020] In equations (Ⅲ) to (Ⅵ), R 1 ~R 4Each group is independently selected from H, halogen, nitro, cyano, C1-C10 alkyl, C1-C10 alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl, or alkoxy-substituted phenyl.

[0021] Furthermore, the structure of the nitrile compound is shown in formula (VII):

[0022] In equation (Ⅶ), R 5 Each is independently selected from methyl, phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, benzyloxyphenyl or [1,3]dioxanephenyl.

[0023] Furthermore, the molar ratio of the N-heteroaromatic hydrocarbon, α-trifluoromethyl diazosulfonium salt compound, nitrile compound, base and rhodium catalyst is 1:(1-4):(1-4):(1-4):(0.01-0.05); the temperature of the [2+1+2] tandem cyclization reaction is -50 to 80°C, and the time is 1 to 48 h.

[0024] The sixth technical solution of the present invention: the application of the above-mentioned imidazo-N-heteroaromatic compounds in the preparation of drugs for the prevention and treatment of tumor diseases.

[0025] Furthermore, the tumor diseases mentioned are human leukemia, lung cancer, liver cancer, breast cancer, and colon cancer.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] This invention utilizes the domino [2+1+2] cycloaddition reaction of α-trifluoromethyl diazonium sulfonium salt with N-heteroaromatics and nitrile compounds to provide a series of novel trifluoromethyl imidazo-N-heteroaromatic polycyclic compounds. These synthesized compounds contain a potentially biologically active trifluoromethyl group and an imidazo-N-heteroaromatic skeleton, providing a source of compounds for bioactivity screening and possessing significant application value in drug screening and the pharmaceutical industry. Furthermore, this invention screened the tumor growth inhibitory activity of these compounds against five tumor cell lines: human leukemia cells (HL-60), human lung cancer cells (A549), human liver cancer cells (SMMC-7721), human breast cancer cells (MDA-MB-231), and human colon cancer cells (SW480). The results showed that these compounds exhibit certain inhibitory activity against tumor cell growth and are expected to be used as anti-tumor drugs, providing a basis for research on these imidazo-N-heteroaromatic skeleton polycyclic compounds in the field of medicinal chemistry. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 Compound 1 obtained in Example 1 of this invention 1 H NMR spectrum;

[0030] Figure 2 Compound 1 obtained in Example 1 of this invention 13 C NMR spectrum;

[0031] Figure 3 Compound 1 obtained in Example 1 of this invention 19 F NMR spectrum;

[0032] Figure 4 Single-crystal diffraction structure of compound 1 obtained in Example 1 of this invention;

[0033] Figure 5 Compound 4d obtained in Example 5 of this invention 1 H NMR spectrum;

[0034] Figure 6 Compound 4d obtained in Example 5 of this invention 13 C NMR spectrum;

[0035] Figure 7 Compound 4d obtained in Example 5 of this invention 19 F NMR spectrum;

[0036] Figure 8 This is a single-crystal diffraction structure diagram of compound 4d obtained in Example 5 of the present invention. Detailed Implementation

[0037] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention. It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the present invention.

[0038] Furthermore, regarding the numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included within this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0039] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0040] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0041] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0042] In the following examples, all raw materials used are commercially available.

[0043] Example 1

[0044] The preparation steps of the α-trifluoromethyl diazosulfonium salt compound are as follows:

[0045] (1) Preparation of trifluorodiazoethane, the reaction equation is as follows:

[0046]

[0047] Under an argon atmosphere, trifluoroethylamine hydrochloride (20 mmol, 2.71 g) and sodium nitrite (22 mmol, 1.53 g) were dissolved in 40 mL of dichloromethane and stirred in an ice-water bath. Then, 4 mL of water was added dropwise to the mixture, and after stirring in the ice-water bath for 2 hours, the reaction flask was transferred to room temperature and stirring continued for 1 hour. After the reaction was complete, the reaction solution was frozen overnight at -20°C. The next day, anhydrous potassium carbonate (10 g) was added to the reaction flask, and after standing for 2 hours, a yellow trifluorodiazoethane-dichloromethane solution was obtained.

[0048] (2) Preparation of high-valent iodine reagent, the reaction equation is as follows:

[0049]

[0050] Add diacetoxyiodobenzene (DIP) to a 100.0 mL double-necked round-bottom flask equipped with a magnetic stirrer. 1.6 g (5.0 mmol), ultra-dry dichloromethane (20.0 mL), and trimethyl trifluoromethanesulfonate (0.90 mL, 5.0 mmol) were added dropwise to the reaction system. Nitrogen gas was gradually observed to escape. After the addition was complete, the reaction was stirred continuously at room temperature for 1 h. After the reaction was complete, the solvent was removed by vacuum concentration, and the crude product was recrystallized at -18 °C using a 5:1 mixture of diethyl ether and dichloromethane to obtain the yellow solid, which is the corresponding high-valent iodine reagent.

[0051] (3) Preparation of α-trifluoromethyl diazosulfonium salt compound: The high-valent iodine reagent prepared in step (2) was added sequentially to a 50.0 mL dry round-bottom flask equipped with a magnetic stirrer. 2.31 g (5.0 mmol) and ultra-dry dichloromethane (20.0 mL) were added. Then, under ice bath stirring, dimethyl sulfide (310.7 mg, 6.5 mmol) was added to the reaction solution all at once. The reaction solution gradually changed from orange to colorless and transparent, and a white solid was formed. The reaction was carried out at 0°C with continuous stirring for 3 hours. After the reaction was complete, the solvent was removed by vacuum concentration. The crude product was collected and recrystallized with a dichloromethane / ethyl acetate mixture. A large amount of white crystals precipitated within 30 minutes. The mother liquor was removed, and the recrystallized product was washed several times with cold diethyl ether. Finally, after vacuum drying, a white needle-like solid was obtained, namely the α-trifluoromethyldiazonium sulfonium salt compound, denoted as product 1.

[0052] The preparation reaction formula is as follows:

[0053]

[0054] Product 1 characterization data: White solid, 0.88 g, yield 55%, mp 68.9–70.4 °C; 1 H NMR (400M Hz, DMSO-d6) δ3.78 (s, 6H). 13 C NMR (101MHz, DMSO-d6) δ 123.60 (q, J = 273.4Hz), 120.73 (q, J = 323.5Hz), 28.86. 19 F NMR(376MHz,DMSO-d6)δ-48.53(s,3F),-74.09(s,3F).HRMS(ESI-TOF):calcd.For C4H6F3N2S + [M-OTf] + 171.0198; found 171.0195.

[0055] Compound 1 1 H NMR spectrum as shown Figure 1 As shown, 13 The C NMR spectrum is as follows Figure 2 As shown, 19 F NMR spectrum as shown Figure 3 As shown, the single-crystal diffraction structure pattern is as follows: Figure 4 As shown.

[0056] Example 2

[0057] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0058] Rh2(esp)2 (0.004 mmol, 3.0 mg), sodium carbonate (0.4 mmol, 42.4 mg), N-heteroaryl:quinoline (0.2 mmol), and acetonitrile (2 mL) were added sequentially to a dry 10 mL reaction tube. Then, α-trifluoromethyldiazosulfonium salt (0.4 mmol, 128 mg) was weighed and dissolved in acetonitrile (2 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography (petroleum ether:ethyl acetate (5:1) as the developing solvent) to obtain product 4a.

[0059] Characterization data of product 4a: White solid, 42.0 mg, 84% yield, mp 151.5–153.2 °C; 1 HNMR (400MHz, CDCl3) δ8.20(d,J=8.6Hz,1H),7.68(dd,J=7.8,1.6Hz,1H),7.57(t,J=8.0Hz,1H),7.49–7.38(m,2H),7.13(d,J=9.6Hz,1H),3.06(s,3H). 13 C NMR (101MHz, CDCl3) δ140.5, 132.7, 129.2, 129.0, 128.9, 125.9, 125.1, 124.5, 122.9 (q, J = 268.0Hz), 120.7 (q, J = 38.4Hz), 116.3, 115.5, 19.8. 19 F NMR(376MHz, CDCl3)δ-59.57(s,3F).HRMS(ESI-TOF):calcd.For C 13 H9F3N2[M+H] +251.0791; found 251.0795.

[0060] Examples 3-27

[0061] The preparation of imidazo N-heteroaromatic compounds 4b-4z follows the same steps as in Example 2, except that the types of N-heteroaromatic compounds added are different, as shown in Table 1:

[0062] Table 1

[0063]

[0064] The structural formulas of products 4b to 4z are shown below:

[0065]

[0066] Product 4b characterization data: The product was separated by silica gel column chromatography with a polar developing solvent ranging from petroleum ether:ethyl acetate (5:1) to dichloromethane (100%). White solid, 43.8 mg, 83% yield, mp 188.4–189.3 °C; 1 H NMR (400MHz, CDCl3) δ8.11(d,J=8.6Hz,1H),7.48(s,1H),7.45–7.35(m,2H),7.10(d,J=9.6Hz,1H),3.06(s,3H),2.48(s,3H). 13 C NMR(101MHz, CDCl3)δ140.3,135.7,130.7,130.0,129.1,129.0(q,J=3.0Hz),125.1,12 4.4, 123.0 (q, J = 268.0Hz), 120.6 (q, J = 38.4Hz), 116.2, 115.4 (d, J = 1.4Hz), 21.0, 19.7. 19 F NMR(376MHz, CDCl3)δ-59.51(s,3F).HRMS(ESI-TOF):calcd.For C 14 H 11 F3N2[M+H] + 265.0947; found 265.0965.

[0067] Product 4C characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate as the developing solvent (5:1 to 3:1). White solid, 53.4 mg, 95% yield, mp 131.5–132.8 °C; 1H NMR (400MHz, CDCl3) δ8.07(d,J=9.2Hz,1H),7.38(d,J=9.6Hz,1H),7.10(dd,J=9.2,3.0Hz,1H),7.07–7.01(m,2H),3.89(s,3H),2.99(s,3H). 13 C NMR(101MHz, CDCl3)δ156.9,139.9,128.6(q,J=3.0Hz),126.9,126.4,124.2,122.9(q, J=268.3Hz), 120.6 (q, J=38.4Hz), 117.6, 116.6, 115.8 (d, J=2.0Hz), 111.0, 55.7, 19.5. 19 F NMR(376MHz, CDCl3)δ-59.42(s,3F).HRMS(ESI-TOF):calcd.F or C 14 H 11 F3N2O[M+H] + 281.0896; found 281.0893.

[0068] Product characterization data for 4 days: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (5:1). White solid, 48.4 mg, 90% yield, mp 173.2–175.5℃; 1 H NMR (400MHz, CDCl3) δ8.19 (dd, J=9.4, 4.4Hz, 1H), 7.47 (d, J=9.6Hz, 1H), 7.35 (dd,J=8.4,3.0Hz,1H),7.33–7.25(m,1H),7.08(d,J=9.6Hz,1H),3.05(s,3H). 13 C N R(101MHz, CDCl3)δ159.7(d,J=247.5Hz),140.4,129.1(d,J=2.0Hz),128.6(q,J=2.7Hz),126.9(d,J=8.1Hz),123.6(d,J=3.0Hz),1 22.7(q,J=268.0Hz), 121.3(q,J=38.7Hz), 118.2(d,J=9.1Hz), 116.8(d,J=2.0Hz), 116.4(d,J=24.2Hz), 114.4(d,J=23.2Hz), 19.7. 19F NMR(376MHz, CDCl3)δ-59.67(s,3F),-115.31(s,1F).HRMS(ESI-TOF):calcd.For C 13 H8F4N2[M+H] + 269.0696; found269.0694.

[0069] Compound 4d 1 H NMR spectrum as shown Figure 5 As shown, 13 The C NMR spectrum is as follows Figure 6 As shown, 19 F NMR spectrum as shown Figure 7 As shown, the single-crystal diffraction structure pattern is as follows: Figure 8 As shown.

[0070] Product 4e characterization data: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (5:1 to 3:1). White solid, 44.4 mg, 78% yield, mp 184.8–185.8 °C; 1 H NMR(400MH z, CDCl3) δ 8.14 (d, J = 9.0Hz, 1H), 7.65 (d, J = 2.4Hz, 1H), 7.52 (dd, J = 9.0, 2.4Hz, 1H), 7.47 (d, J = 9.0Hz, 1H), 7.05 (d, J = 9.6Hz, 1H), 3.04 (s, 3H). 13 C NMR(101MHz, CDCl3)δ140.7,131.4,131.1,128.8,128.6(q,J=2.5Hz),128.3,126.5, 123.3, 122.7 (q, J = 268.3Hz), 121.4 (q, J = 38.4Hz), 117.8, 116.8 (d, J = 2.0Hz), 19.7. 19 F NMR(376MHz, CDCl3)δ-59.71(s,3F).HRMS(ESI-TO F):calcd.For C 13 H8ClF3N2[M+H] + 285.0401; found 285.0403.

[0071] Product 4f characterization data: The product was separated by silica gel column chromatography with a polar solvent ranging from petroleum ether:ethyl acetate (5:1) to dichloromethane (100%). Light yellow solid, 45.4 mg, 69% yield, mp 185.4–187.4 °C; 1HNMR(400MHz, CDCl3)δ8.09(d,J=9.0Hz,1H),7.82(d,J=2.4Hz,1H),7.66(dd, J=9.0,2.2Hz,1H),7.48(d,J=9.4Hz,1H),7.06(d,J=9.6Hz,1H),3.05(s,3H). 13 C NMR (101MHz, CDCl3) δ140.7, 131.6, 131.5, 131.3, 128.6 (q, J = 2.7Hz), 126.8, 123.1, 122.6 (q, J = 268.3Hz), 121.4 (q, J = 38.7Hz), 119.1, 117.9, 116.8 (d, J = 2.0Hz), 19.7. 19 F NMR(376MHz, CDCl3)δ-59.72(s,3F); HRMS(ESI-TOF):calcd.For C 13 H8BrF3N2[M+H] + 328.9896; found 328.9896.

[0072] Characterization data for 4g of product: The product was separated by silica gel column chromatography, with the developing solvent being a polarity of petroleum ether:ethyl acetate (5:1) to dichloromethane (100%). White solid, 55.2mg, 73% yield, mp 169.7–171.3℃; 1 HN MR(400MHz, CDCl3) δ7.99(d,J=2.0Hz,1H),7.92(d,J=9.0Hz,1H),7.82(dd,J=9.0,2.0Hz,1H),7.43(d,J=8.2Hz,1H),7.00(d,J=9.6Hz,1H),3.02(s,3H). 13 C NMR(101MHz,CDCl3)δ140.7,137.5,137.4,132.1,128.6(q,J=3.0Hz),127.0, 123.0, 122.6 (q, J = 268.3Hz), 121.4 (q, J = 38.4Hz), 118.0, 116.6, 90.0, 19.7. 19 F NMR(376MHz, CDCl3)δ-59.70(s,3F).HRMS(ESI-TOF):ca lcd.For C 13 H8F3IN2[M+H] + 376.9757; found 376.9756.

[0073] Product characterization data over 4 hours: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate as the developing solvent (5:1 to 3:1). Yellow solid, 42.6 mg, 72% yield, mp 236.0–237.1 °C; 1 H NMR (400MHz, DMSO-d6) δ8.86(d,J=2.6Hz,1H),8.56(d,J=9.4Hz,1H),8.41(dd,J=9.4,2.8Hz,1H),7.67–7.61(m,2H),3.06(s,3H). 13 C NMR (101MHz, DMSO-d6) δ144.1, 142.4, 135.5, 128.5, 125.0, 124.6, 124.1, 123.4, 122.6 (q, J = 268.2Hz), 119.6 (q, J = 37.9Hz), 118.6, 116.5, 19.2. 19 F NMR(376MHz,DMSO-d6)δ-57.81(s,3F).HRMS(ESI-TOF):calcd.For C 13 H8F3N3O2[M+H] + 296.0641; found 296.0640.

[0074] Product 4i characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (5:1) as the developing solvent. White solid, 57.4 mg, 89% yield, mp 182.6–183.5 °C; 1 H NMR (400MHz, CDCl3) δ8.34 (s, 1H), 8.27–8.15 (m, 2H), 7.46 (d, J = 9.6Hz, 1H), 7. 18(d,J=9.6Hz,1H),4.43(q,J=7.2Hz,2H),3.08(s,3H),1.43(t,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3) δ165.4,141.1,135.3,130.7,129.6,129.0(q,J=2.7Hz),127.8,124.8,12 4.3, 122.6 (q, J = 268.3Hz), 121.3 (q, J = 38.7Hz), 116.4, 116.3 (d, J = 2.0Hz), 61.6, 19.8, 14.4. 19 F NMR(376MHz, CDCl3)δ-59.81(s,3F).HRMS(ESI-TOF):calcd.For C16 H 13 F3N2O2[M+H] + 323.1002; found 323.1003.

[0075] Product 4j characterization data: The product was separated by silica gel column chromatography, with the developing solvent polarity ranging from petroleum ether:ethyl acetate (5:1) to dichloromethane (100%). White solid, 59.4 mg, 92% yield, mp 141.8–143.2 °C; 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.8Hz,1H),7.61(d,J=2.2Hz,1H),7.51(dd,J=8.8,2.2Hz ,1H),7.43(d,J=8.2Hz,1H),7.12(d,J=9.6Hz,1H),3.76(s,2H),3.73(s,3H),3.06(s,3H). 13 C NMR (101MHz, CDCl3) δ171.6,140.5,131.79,131.76,130.0,129.7,128.9(q,J=3.0Hz),125.3,1 24.3, 122.8 (q, J = 268.3Hz), 120.8 (q, J = 38.9Hz), 116.6, 115.8 (d, J = 2.0Hz), 52.4, 40.4, 19.7. 19 F NMR(376MHz, CDCl3)δ-59.58(s,3F).HRMS(ESI-TOF):calcd.For C 16 H 13 F3N2O2[M+H] + 323.1002; found 323.1000.

[0076] Product characterization data: The product was separated by silica gel column chromatography, with the developing solvent polarity ranging from petroleum ether:ethyl acetate (5:1) to dichloromethane (100%). White solid, 39.9 mg, 56% yield, mp 167.0–168.1 °C; 1 H NMR (400MHz, CDCl3) δ8.10(d,J=9.2Hz,1H),7.51–7.32(m,6H),7.24–7.15(m,2H),7.04(d,J=9.6Hz,1H),5.15(s,2H),3.02(s,3H). 13C NMR (101MHz, CDCl3) δ156.1,139.9,136.4,128.8,128.6(q,J=2.7Hz),128.4,127.6,127.1,126.5,12 4.2,122.9(q,J=268.0Hz),120.7(q,J=38.4Hz),117.7,117.3,115.9(d,J=2.0Hz),112.3,70.5,19.6. 19 F NMR(376MHz, CDCl3)δ-59.43(s,3F).HRMS(ESI-TOF):calcd.For C 20 H 15 F3N2O[M+H] + 357.1209; found 357.1216.

[0077] Product 4L characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (8:1) as the developing solvent. White solid, 65.9 mg, 96% yield, mp 212.6–213.3℃; 1 H NMR (400MHz, CDCl3) δ8.03(s,1H),7.81(s,1H),7.38(d,J=9.6Hz,1H),7.00(d,J=9.6Hz,1H),3.05(s,3H),2.56(s,3H). 13 C NMR (101MHz, CDCl3) δ140.5,138.9,131.9,131.7,128.8(q,J=2.5Hz),124.6,123.0,12 2.7(q,J=268.3Hz),121.9,121.1(q,J=38.4Hz),118.1,115.8(d,J=1.5Hz),24.1,19.8. 19 F NMR(376MHz,C DCl3)δ-59.68(s,3F).HRMS(ESI-TOF):calcd.For C 14 H 10 BrF3N2[M+H] + 343.0052; found 343.0057.

[0078] Product characterization data (4m): The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (5:1) as the developing solvent. White solid, 46.7 mg, 82% yield, mp 178.0–181.0 °C; 1H NMR (400MHz, CDCl3) δ8.17(d,J=8.4Hz,1H),8.07(d,J=8.0Hz,1H),7.64(t,J=7.8Hz,1H),7.55–7.46(m,2H),3.03(s,3H). 13 C NMR (101MHz, CDCl3) δ140.8,132.7,130.1,128.4,127.8(q,J=2.5Hz),126.5,126.3,122.54,122.52(q,J=268.3H z), 120.8 (q, J = 38.7Hz), 116.4, 114.9 (d, J = 1.6Hz), 19.9. 19 F NMR(376MHz, CDCl3)δ-59.80(s,3F).HRMS(ESI-TOF):calcd.ForC 13 H8ClF3N2[M+H] + 285.0401; found 285.0402.

[0079] Product 4n characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (10:1) as the developing solvent. White solid, 31.7 mg, 60% yield, mp 164.9–165.7 °C; 1 H NMR (400MHz, CDCl3) δ8.12(d,J=8.4Hz,1H),7.54(d,J=7.8Hz,1H),7.47(t,J=8.0Hz,1H),7.38(t,J=7.6Hz,1H),6.87(s,1H),3.01(s,3H),2.48(s,3H). 13 C NMR (101MHz, CDCl3) δ139.3, 131.5, 129.7 (q, J = 4.0Hz), 128.0, 127.9, 125.7, 125.5 (d, J = 2.0H z), 125.3, 124.3, 122.9 (q, J = 268.0Hz), 121.2 (q, J = 38.7Hz), 116.0, 20.0, 19.6 (q, J = 5.1Hz). 19 F NMR(376MHz, CDCl3)δ-53.55(s,3F).HRM S(ESI-TOF):calcd.For C 14 H 11 F3N2[M+H] + 265.0947; found 265.0946.

[0080] Product characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (10:1) as the developing solvent. White solid, 27.4 mg, 48% yield, mp 189.3–190.3 °C; 1 H NMR (400MHz, CDCl3) δ8.22(d,J=8.2Hz,1H),7.54(ddd,J=8.4,5.6,3.2Hz,1H),7.48–7.39(m,2H),6.87(s,1H),3.03(s,3H). 13 C NMR (101MHz, CDCl3) δ139.0,129.9(q,J=3.0Hz),129.1,128.6,128.5,126.3,124.5( q,J=5.1Hz),123.1,122.9(q,J=268.3Hz),122.1(q,J=38.9Hz),121.9,115.8,19.1. 19 F NMR(376MHz,CDC l3)δ-59.72(s,3F).HRMS(ESI-TOF):calcd.For C 13 H8ClF3N2[M+H] + 285.0401; fo und 285.0403.

[0081] Product 4p characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (10:1) as the developing solvent. White solid, 36.3 mg, 50% yield, mp 131.8–134.6 °C; 1 H NMR (400MHz, CDCl3) δ8.05(d,J=8.8Hz,1H),7.62(dd,J=8.8,2.0Hz,1H),7.58(d,J=2.0Hz,1H),6.78(s,1H),3.04(s,3H). 13 C NMR (101MHz, CDCl3) δ139.5, 132.1, 129.9, 129.2 (q, J = 2.5Hz), 128.7, 126.0 (q, J = 5. 4Hz), 124.5, 122.7 (q, J = 268.7Hz), 122.6, 122.5 (q, J = 39.1Hz), 120.7, 114.6, 19.2. 19 F NMR(376MHz, CDCl3)δ-59.93(s,3F).HRMS(ESI-TOF):calcd.For C 13 H7BrClF3N2[M+H] +362.9506; fou nd 362.9510.

[0082] Product 4q characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (10:1) as the developing solvent. White solid, 27.9 mg, 42% yield, mp 175.5–176.4 °C; 1 H NMR (400MHz, CDCl3) δ8.23 (d, J = 8.2Hz, 1H), 7.60–7.51 (m, 1H), 7.51–7.40 (m, 2H), 7.11 (s, 1H), 3.08 (s, 3H). 13 C NMR(101MHz, CDCl3)δ139.6,130.0(q,J=3.0Hz),129.2,128.7,128.6,126.2,124.5( q, J=5.4Hz), 122.9 (q, J=268.7Hz), 122.3, 121.8 (q, J=38.7Hz), 120.9, 109.8, 19.7. 19 F NMR(376MHz, CDCl3)δ-59.73(s,3F).HRMS(ESI-TOF):calcd.For C 13 H8BrF3N2[M+H] + 328.9896; found 328.9890.

[0083] Product 4R characterization data: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (5:1 to 3:1). Light yellow solid, 40.8 mg, 77 yield %, mp 185.5–186.8 °C; 1 H NMR (400MHz, CDCl3) δ8.23–8.06(m,1H),8.02–7.81(m,1H),7.65–7.44(m,2H),3.09(s,3H),2.82(s,3H). 13 C NMR (101MHz, CDCl3) δ152.3,140.6,136.6,129.8,128.2,127.3,125.7,125.3(q,J= 39.1Hz), 123.1 (q, J = 3.0Hz), 121.9 (q, J = 268.7Hz), 115.5, 24.0 (q, J = 4.4Hz), 19.1. 19 FNMR(376MHz, CDCl3)δ-55.73(s,3F).HRMS(ESI-TOF):calcd.For C 13 H10 F3N3[M+H] + 266.0900; found 266.0906.

[0084] Product 4S characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (5:1) as the developing solvent. White solid, 46.7 mg, 88% yield, mp 141.0–142.4 °C; 1 H NMR (400MHz, CDCl3) δ8.93(s,1H),7.94(d,J=8.2Hz,1H),7.43(t,J=7.8Hz,1H),7.39(d,J=7.4Hz,1H),3.04(s,3H),2.69(s,3H). 13 C NMR (101MHz, CDCl3) δ142.0 (q, J = 2.0Hz), 141.8, 139.4, 135.1, 128.54, 128.48, 126.5 ,124.7(q,J=39.7Hz),123.3(q,J=2.0Hz),121.9(q,J=269.0Hz),113.4,19.00,18.7. 19 F NMR(376MHz, CDCl3)δ-60.07(s,3F).HRMS(ESI-TOF):calcd.For C 13 H 10 F3N3[M+H] + 266.0900; found 266.0900.

[0085] Product characterization data: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (5:1 to 3:1). White solid, 44.8 mg, 68% yield, mp 138.5–141.3℃; 1 H NMR (400MHz, CDCl3) δ9.01 (s, 1H), 8.13 (d, J = 8.4Hz, 1H), 7.82 (d, J = 8.0Hz, 1H), 7.43 (t, J = 8.2Hz, 1H), 3.09 (s, 3H). 13 C NMR (101MHz, CDCl3) δ144.2, 142.4, 134.6, 131.6, 129.4, 127.7, 126.1, 125.7 (q, J = 40.1Hz), 123.3 (q, J = 2.5Hz), 121.5 (q, J = 269.3Hz), 115.2, 19.1. 19F NMR(376MHz, CDCl3)δ-56.15(s,3F).H RMS(ESI-TOF):calcd.For C 12 H7BrF3N3[M+H] + 329.9848; found 329.9852.

[0086] Product characterization data (4u): The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (2:1) as the developing solvent. White solid, 40.3 mg, 65% yield, mp 133.6–134.9 °C; 1 H NMR (400MHz, CDCl3) δ9.06 (s, 1H), 8.29 (d, J = 8.4Hz, 1H), 7.74 (d, J = 7.4Hz, 1H), 7.63 (t, J = 8.0Hz, 1H), 4.00 (s, 3H), 3.10 (s, 3H). 13 C NMR(101MHz, CDCl3)δ167.6,144.4(q,J=2.0Hz),142.3,134.4,133.8,128.6,126 .9,126.7,125.8(q,J=40.1Hz),122.9,121.6(q,J=269.0Hz),118.1,53.0,18.9. 19 F NMR(376MHz, CDCl3)δ-60.33(s,3F).HRMS(ESI-TOF):calcd.For C 14 H 10 F3N3O2[M+H] + 310.0798; found 310.0794.

[0087] Product characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (5:1) as the developing solvent. White solid, 36.9 mg, 72% yield, mp 153.0–153.6 °C; 1 H NMR (400MHz, CDCl3) δ7.67(d,J=8.2Hz,1H),7.56(d,J=8.0Hz,1H),7.40(t,J=7.2Hz,1H),7.32(t,J=7.6Hz,1H),2.78(s,3H). 13C NMR (101MHz, CDCl3) δ138.9, 132.9, 131.6, 129.5 (q, J = 3.5Hz), 126.4, 125.9, 124.3, 122.0 (q, J = 267.0Hz), 118.7 (q, J = 41.1Hz), 113.7, 15.6. 19 F NMR(376MHz, CDCl3)δ-61.11(s,3F).HRMS(ESI-TOF):calcd.For C 11 H7F3N2S[M+H] + 257.0355; found 257.0357.

[0088] Product characterization data (4W): The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (5:1 to 2:1). Light yellow solid, 48.1 mg, 84% yield, mp 106.2–107.1 °C; 1 H NMR (400MHz, CDCl3) δ7.53(d,J=9.0Hz,1H),7.03(d,J=2.4Hz,1H),6.90(dd,J=9.0,2.6Hz,1H),3.83(s,3H),2.74(s,3H). 13 C NMR (101MHz, CDCl3) δ157.7, 138.4, 134.4, 129.2 (q, J = 3.4Hz), 125.7, 122.0 (q, J = 267.0Hz), 118.7 (q, J = 41.1Hz), 114.2, 113.2, 108.5, 55.9, 15.3. 19 FNMR(376MHz, CDCl3)δ-61.05(s,3F).HRMS(ESI-TOF):calcd.For C 12 H9F3N2OS[M+H] + 287.0460; found 287.0461.

[0089] Product 4x characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (5:1) as the developing solvent. White solid, 47.4 mg, 86% yield, mp 224.5–225.6 °C; 1 H NMR (400MHz, Acetone-d6) δ8.01(dd,J=9.0,5.2Hz,1H),7.89(dd,J=9.2,2.4Hz,1H),7.37(td,J=9.0,2.4Hz,1H),2.92(s,3H).13 C NMR (101MHz, Acetone-d6) δ162.4(d,J=244.4Hz),140.9,133.4(d,J=12.1Hz),131.5,128.8(d,J=3.0Hz),126 .8(d,J=10.1Hz), 123.2(q,J=266.3Hz), 118.7(d,J=40.4Hz), 114.3(d,J=24.2Hz), 103.7(d,J=29.3Hz), 15.3. 19 F NMR(376MHz, Acetone-d6)δ-60.63(s,3F),-114.38(s,1F).HRMS(ESI-TOF):calcd.For C 11 H6F4N2S[M+H] + 275.0261; found 275.0261.

[0090] Product characterization data (4 years): The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate (10:1) as the developing solvent. White solid, 58.4 mg, 87% yield, mp 221.4–222.2 °C; 1 H NMR (400MHz, CDCl3)

[0091] δ7.87(s,1H),7.51(s,2H),2.85(s,3H). 13 C NMR (101MHz, CDCl3) δ139.2, 132.8, 132.3, 129.8 (q, J = 3.0Hz), 129.1, 125.6, 121.8 (q, J = 267.0Hz), 119.8, 119.3 (q, J = 41.4Hz), 117.2, 15.8. 19 F NMR(376MHz, CDCl3)δ-61.32(s,3F).HRMS(ESI-TOF):calcd.ForC 11 H6BrF3N2S[M+H] + 334.9460; found 334.9460.

[0092] Product characterization data: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (5:1 to 2:1). Yellow solid, 50.0 mg, 83% yield, mp 269.4–271.0 °C; 1H NMR (400MHz, DMSO-d6) δ9.06–9.03(m,1H),8.39–8.33(m,1H),8.18(d,J=9.0Hz,1H),2.84(s,3H). 13 C NMR(101MHz,DMSO-d6)δ144.7,140.9,135.5,133.9,131.0

[0093] (d, J=3.8Hz), 122.6, 122.0 (q, J=266.6Hz), 121.3, 117.2 (q, J=39.7Hz), 115.3, 15.1. 19 F NMR(376MHz,DMSO-d6)δ-55.14(s,3F).HRMS(ESI-TOF):calcd.ForC 11 H6F3N3O2S[M+H] + 302.0206; found 302.0208.

[0094] Example 28

[0095] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0096] Rh2(esp)2 (0.006 mmol, 4.5 mg), sodium carbonate (0.6 mmol, 63.6 mg), quinoxaline (0.2 mmol), and acetonitrile (2 mL) were added sequentially to a dry 10 mL reaction tube. Then, α-trifluoromethyldiazonium salt (0.6 mmol, 192 mg) was weighed and dissolved in acetonitrile (3 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4aa.

[0097] Product 4aa characterization data: The product was separated by silica gel column chromatography with a petroleum ether:ethyl acetate (1:1) polar solvent. Light yellow solid, 36.8 mg, 49% yield. 1 H NMR (400MHz, CDCl3) δ8.12 (dd, J=6.6, 3.6Hz, 2H), 7.54 (dd, J=6.4, 3.4Hz, 2H), 3.00 (s, 6H). 13C NMR (101MHz, CDCl3) δ144.0,127.3,125.2,122.6,119.9,118.3,117.9,19.6. 19 F NMR(376MH z,CDCl3)δ-61.95(s,6F).HRMS(ESI-TOF):calcd.For C 16 H 10 F6N4[M+H] + 373.0882; found 373.0884.

[0098] Example 29

[0099] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0100] Rh2(esp)2 (0.006 mmol, 4.5 mg), sodium carbonate (0.6 mmol, 63.6 mg), 6-methoxyquinoxaline (0.2 mmol), and acetonitrile (2 mL) were added sequentially to a dry 10 mL reaction tube. Then, α-trifluoromethyldiazonium salt (0.6 mmol, 192 mg) was weighed and dissolved in acetonitrile (3 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ab.

[0101] Characterization data of product 4ab: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (2:1 to 1:1). Light yellow solid, 37.4 mg, 46% yield, mp 195.0–196.4 °C; 1 H NMR (400MHz, CDCl3) δ7.99(d,J=9.2Hz,1H),7.59(d,J=2.6Hz,1H),7.01(dd,J=9.3,2.6Hz,1H),3.92(s,3H),2.98(s,3H),2.93(s,3H). 13 C NMR (101MHz, CDCl3) δ158.0, 143.8, 143.2, 126.4 (q, J = 39.1Hz), 126.3, 125.3, 122.6, 120 .0,118.9,118.8,118.6(d,J=2.0Hz),117.8(d,J=2.0Hz),111.3,104.6,56.0,19.6,19.3. 19F NMR(376MHz, CDCl3)δ-61.88(dt,J=42.3,12.8Hz,6F).HR MS(ESI-TOF):calcd.For C 17 H 12 F6N4O[M+H] + 403.0988; found 403.0990.

[0102] Example 30

[0103] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0104] Rh2(esp)2 (0.006 mmol, 4.5 mg), sodium carbonate (0.6 mmol, 63.6 mg), 6-bromoquinoxaline (0.2 mmol), and acetonitrile (2 mL) were added sequentially to a dry 10 mL reaction tube. Then, α-trifluoromethyldiazosulfonium salt (0.6 mmol, 192 mg) was weighed and dissolved in acetonitrile (3 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ac.

[0105] Product 4ac characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate as the developing solvent (3:1 to 2:1). Yellow solid, 55.2 mg, 61% yield, mp 218.6–219.5 °C; 1 H NMR (400M Hz, CDCl3) δ8.22(s,1H),7.98(d,J=9.0Hz,1H),7.64(dd,J=9.0,2.0Hz,1H),2.99(s,3H),2.96(s,3H). 13 C NMR (101MHz, CDCl3) δ144.0,143.9,130.1,126.2,124.2,122.4,120.9,120.3,119.7,119.1,118.2,118.0,19.50,19.47. 19 F NMR(376MHz, CDCl3)δ-62.07–-62.15(m,6F).HRMS(ESI-TOF):calcd.For C 16 H9BrF6N4[M+H] + 450.9988; found 450.9990.

[0106] Example 31

[0107] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0108] Rh2(esp)2 (0.006 mmol, 4.5 mg), sodium carbonate (0.6 mmol, 63.6 mg), methyl quinoxaline-6-carboxylate (0.2 mmol), and acetonitrile (2 mL) were added sequentially to a dry 10 mL reaction tube. Then, α-trifluoromethyldiazonium salt (0.6 mmol, 192 mg) was weighed and dissolved in acetonitrile (3 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ad.

[0109] Product 4ad characterization data: The product was separated by silica gel column chromatography with petroleum ether:ethyl acetate as the developing solvent (2:1 to 1:1). White solid, 51.7 mg, 60% yield, mp 195.9–196.8 °C; 1 H NMR (400MH z, CDCl3) δ8.79(s,1H),8.17(s,2H),4.01(s,3H),3.05(s,3H),3.02(s,3H). 13 C NMR (101MHz, CDCl3) δ165.0,144.4,144.3,128.8,128.3,128.1,125.2,122.4,119.7,119.1,118.5,118.1,117.7,53.2,19.7,19.5. 19 F NMR(376MHz,CDC l3)δ-62.06–-62.32(m,6F).HRMS(ESI-TOF):calcd.For C 18 H 12 F6N4O2[M+H] + 431.0937; found 431.0936.

[0110] Example 32

[0111] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0112] To a dry 10 mL reaction tube, sodium carbonate (0.4 mmol, 42.4 mg), quinoline (0.2 mmol), benzonitrile (2.0 mmol), α-trifluoromethyldiazonium sulfonate (0.6 mmol, 192 mg), and 1,2-dichloroethane (2 mL) were added sequentially. Then, Rh₂(esp)₂ (0.004 mmol, 3.0 mg) was weighed and dissolved in 1,2-dichloroethane (2 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ae.

[0113] Product 4ae characterization data: The product was separated by silica gel column chromatography with a polarity of petroleum ether:ethyl acetate (2:1) to dichloromethane (100%). White solid, 31.2 mg, 50% yield, mp 137.1–139.0 °C (lit). 5 (mp135–136℃); 1 H NMR (400MHz, CDCl3) δ7.69(d,J=7.8Hz,1H),7.63(d,J=7.8Hz,2H),7.57–7.49(m,5H),7.39(t,J=7.6Hz,1H),7.28–7.23(m,2H). 13 C NMR (101MHz, CDCl3) δ142.5,132.7,132.0,130.1,129.9,129.1,128.5,126.1,125 .2,125.1,122.9(q,J=268.3Hz),122.4(q,J=38.7Hz),117.6,115.4(d,J=2.0Hz). 19 F NMR(376MHz, CDCl3)δ-59.53(s,3F).HRMS(ESI-T OF):calcd.For C 18 H 11 F3N2[M+H] + 313.0947; found 313.0949.

[0114] Example 33

[0115] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0116] To a dry 10 mL reaction tube, sodium carbonate (0.4 mmol, 42.4 mg), quinoline (0.2 mmol), p-methoxybenzonitrile (2.0 mmol), α-trifluoromethyldiazonium salt compound (0.6 mmol, 192 mg), and 1,2-dichloroethane (2 mL) were added sequentially. Then, Rh₂(esp)₂ (0.004 mmol, 3.0 mg) was weighed and dissolved in 1,2-dichloroethane (2 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4af.

[0117] Product characterization data (4af): The product was separated by silica gel column chromatography with a polar solvent ranging from petroleum ether:ethyl acetate (2:1) to dichloromethane (100%). White solid, 41.7 mg, 61% yield, mp 165.5–166.9 °C (lit). 5 (mp163–164℃); 1 H NMR (400MHz, CDCl3) δ7.69(d,J=7.8Hz,1H),7.61–7.50(m,4H),7.40(t,J=7.6Hz,1H),7.27(t,J=10.6Hz,2H),7.08(d,J=8.4Hz,2H),3.93(s,3H). 13 CNMR (101MHz, CDCl3) δ160.9, 142.5, 132.1, 131.2, 129.04, 128.95 (q, J = 2.7Hz), 128.4, 126.0, 125. 1,125.0,124.8,122.9(q,J=268.3Hz),122.1(q,J=38.4Hz),117.5,115.4(d,J=2.0Hz),114.5,55.5. 19 F NMR(376MHz, CDCl3)δ-59.47(s,3F).HRMS(ESI-TOF):calcd.For C 19 H 13 F3N2O[M+H] + 343.1053; found 343.1053.

[0118] Example 34

[0119] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0120] To a dry 10 mL reaction tube, sodium carbonate (0.4 mmol, 42.4 mg), quinoline (0.2 mmol), p-fluorobenzonitrile (2.0 mmol), α-trifluoromethyldiazonium salt compound (0.6 mmol, 192 mg), and 1,2-dichloroethane (2 mL) were added sequentially. Then, Rh₂(esp)₂ (0.004 mmol, 3.0 mg) was weighed and dissolved in 1,2-dichloroethane (2 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain 4 ag of product.

[0121] Product characterization data (4ag): The product was separated by silica gel column chromatography, with the developing solvent being a polarity of petroleum ether:ethyl acetate (2:1) to dichloromethane (100%). White solid, 27.7 mg, 42% yield, mp 181.6–183.3 °C (lit). 5 (mp173–174℃); 1 H NMR (400MHz, CDCl3) δ7.70 (d, J=7.8Hz, 1H), 7.62 (dd, J=8.4, 5.4Hz, 2H), 7.55 (d ,J=9.6Hz,1H),7.48(d,J=8.6Hz,1H),7.41(t,J=7.6Hz,1H),7.33–7.19(m,4H). 13 C NMR (101MHz, CDCl3) δ163.8 (d, J = 252.5Hz), 141.4, 131.94 (d, J = 9.1Hz), 131.87, 129.3, 129.2(q,J=2.7Hz),128.8(d,J=4.0Hz),128.6,126.2,125.3,125.1,122.8(q,J=268.7H z), 122.4 (q, J = 38.7Hz), 117.4, 116.4 (d, J = 22.2Hz), 115.4 (d, J = 2.0Hz). 19 F NMR(376MHz, CDCl3)δ-59.61(s,3F),-109.94(s,1F).HRMS(ESI-TOF):calcd.For C 18 H 10 F4N2[M+H] + 331.0853; found 331.0859.

[0122] Example 35

[0123] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0124] To a dry 10 mL reaction tube, sodium carbonate (0.4 mmol, 42.4 mg), quinoline (0.2 mmol), 4-benzyloxybenzonitrile (2.0 mmol), α-trifluoromethyldiazonium salt compound (0.6 mmol, 192 mg), and 1,2-dichloroethane (2 mL) were added sequentially. Then, Rh₂(esp)₂ (0.004 mmol, 3.0 mg) was weighed and dissolved in 1,2-dichloroethane (2 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ah.

[0125] Product characterization data (4Ah): The product was separated by silica gel column chromatography, with the developing solvent ranging from petroleum ether:ethyl acetate (1:1) to dichloromethane (100%). White solid, 33.4 mg, 40% yield, mp 148.3–149.8 °C; 1 HN MR(400MHz, CDCl3)δ7.68(d,J=7.8Hz,1H),7.62–7.52(m,4H),7.50(d,J=7.2Hz ,2H),7.46–7.34(m,4H),7.31–7.22(m,2H),7.15(d,J=8.8Hz,2H),5.18(s,2H). 13 C NMR (101MHz, CDCl3) δ160.0,142.5,136.5,132.0,131.2,129.0,128.9(q,J=2.4Hz),128.7,128.4,128.2,1 27.6,126.0,125.1,125.0,124.9,122.9(q,J=268.7Hz),122.1(q,J=38.9Hz),117.5,115.40,115.36,70.2. 19 F NMR(376MHz, CDCl3)δ-59.40(s,3F).HRMS(ESI-TOF):calcd.For C 25 H 17 F3N2O[M+H] + 419.1366; found 419.1361.

[0126] Example 36

[0127] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0128] To a dry 10 mL reaction tube, sodium carbonate (0.4 mmol, 42.4 mg), quinoline (0.2 mmol), piperonitrile (2.0 mmol), α-trifluoromethyldiazonium sulfonate (0.6 mmol, 192 mg), and 1,2-dichloroethane (2 mL) were added sequentially. Then, Rh₂(esp)₂ (0.004 mmol, 3.0 mg) was weighed and dissolved in 1,2-dichloroethane (2 mL), and this solution was slowly added dropwise to the reaction mixture under ice bath conditions. The reaction was carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction was complete, the reaction mixture was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ai.

[0129] Product characterization data: The product was separated by silica gel column chromatography, with the developing solvent ranging from petroleum ether:ethyl acetate (1:1) to dichloromethane (100%). White solid, 45.6 mg, 64% yield, mp 133.4–135.0 °C; 1 HN MR(400MHz,DMSO-d6)δ7.86(d,J=7.4Hz,1H),7.52(q,J=9.8Hz,2H),7.45–7.38(m,3H),7.20(s,1H),7.12(s,2H),6.18(s,2H). 13 C NMR(101MHz,DM SO-d6)δ148.8,147.8,141.8,131.4,129.3,128.8,128.6(q,J=2.7Hz),126.1,125.9,125.7, 124.5, 124.0, 123.0 (q, J = 268.3Hz), 120.0 (q, J = 38.0Hz), 116.9, 114.4, 109.9, 108.9, 101.8. 19 F NMR(376MHz,DMSO-d6)δ-53.38(s,3F).HR MS(ESI-TOF):calcd.For C 19 H 11 F3N2O2[M+H] + 357.0845; found 357.0845.

[0130] Example 37

[0131] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0132] Taking the preparation of the quinoxalic acid fungicide derivative 1-(5-(difluoromethyl)-4-(4-fluorobenzene)-1-methyl-1H-pyrazole)-3-(4-fluorophenyl)urea 4aj as an example, the raw materials and preparation method are as follows: Rh2(esp)2 (0.004 mmol, 3.0 mg), sodium carbonate (0.4 mmol, 42.4 mg), quinoxalic acid (0.2 mmol), and acetonitrile (2 mL) are added sequentially to a dry 10 mL reaction tube. Then, α-trifluoromethyl diazonium sulfonium salt (0.4 mmol, 128 mg) is weighed and dissolved in acetonitrile (2 mL), and the solution is slowly added dropwise to the reaction solution under ice bath conditions. The reaction is carried out at 0 °C for 1 hour under argon protection, followed by heating in an oil bath at 50 °C for 1 hour. After the reaction, the reaction solution is evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4aj.

[0133] Product 4aj characterization data: The product was separated by silica gel column chromatography with dichloromethane (100%) as the developing solvent. White solid; 37.0 mg, 43% yield; mp 178.2–180.0 °C; 1 H NMR (400MHz, CDCl3) δ8.22(s,1H),7.59(s,1H),7.11(t,J=8.4Hz,2H),7.06–7.02(m,2H),6.78(s,1H),3.09(s,3H). 13 CNMR(101MHz, CDCl3)δ159.6(d,J=244.4Hz),151.2(d,J=2.0Hz),149.5,140.5,135.7,135.2,132.6,129.8,128.2(q,J= 3.0Hz), 122.5 (q, J = 267.7Hz), 120.7 (d, J = 8.1Hz), 120.1 (q, J = 38.4Hz), 117.2, 117.0 (d, J = 24.2Hz), 116.0, 101.8, 20.3. 19 F NMR(376MHz, CDCl3)δ-59.98(s,3F),-118.24(septet,J=4.1Hz,1F).HRMS(ESI-TOF):calcd.ForC 19 H 10 C l2 F4N2O[M+H] + 429.0179; found 429.0181.

[0134] Example 38

[0135] Imidazolones N-heteroaromatic compounds The preparation steps are as follows:

[0136] Taking the preparation of the PDE10A drug analog 1-(5-(difluoromethyl)-4-(4-fluorobenzene)-1-methyl-1H-pyrazole)-3-(4-fluorophenyl)urea 4ak with the above structural formula as an example, the raw materials and preparation method are as follows: Sodium carbonate (16.0 mmol, 1.70 g), o-methylbenzonitrile (9.37 g, 80.0 mmol), 2-methylquinoxaline (1.18 g, 8.0 mmol), α-trifluoromethyldiazosulfonium salt compound (5.12 g, 16.0 mmol), and ultra-dry 1,2-dichloroethane (40 mL) are added sequentially to a dry 100 mL double-necked round-bottom flask. Then, Rh2(esp)2 (121.4 mg, 0.16 mmol) is weighed and dissolved in 1,2-dichloroethane (15 mL), and the above solution is slowly added dropwise to the reaction solution under ice bath conditions. The reaction was carried out at 0°C for 1 hour under argon protection, followed by heating in an oil bath at 50°C for another hour. After the reaction was completed, the reaction solution was evaporated to dryness, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain product 4ak.

[0137] Product 4ak characterization data: The product was separated by silica gel column chromatography with a polar developing solvent of petroleum ether:dichloromethane (10:1 to 5:1). Yellow solid; 1.94 g, 71% yield; mp 178.7–180.1 °C; 1 H NMR(400MHz, CDCl3)δ7.91(d,J=8.6Hz,1H),7.51(t,J=7.4Hz,1H),7.47–7.41(m ,2H),7.38(dd,J=7.6,3.6Hz,2H),7.21–7.14(m,2H),2.91(s,3H),2.02(s,3H). 13 C NMR (101MHz, CDCl3) δ152.2 (d, J = 2.0Hz), 141.7, 138.4, 136.5, 131.3, 131.0, 130.8, 130.4, 129.7, 128.3, 127.5, 126. 8,126.2(q,J=38.9Hz),125.1,122.6(q,J=2.7Hz),121.9(q,J=269.3Hz),115.3,24.1(q,J=4.4Hz),19.6(d,J=2.0Hz). 19F NMR(376MHz, CDCl3)δ-55.62(s,3F).HRMS(ESI-TOF):calcd.For C 19 H 14 F3N3[M+H] + 342.1213; found 342.1212.

[0138] Effect verification

[0139] The imidazo N-heteroaryl compounds obtained in the examples were subjected to cytotoxicity tests on human leukemia cells (HL-60), human lung cancer cells (A549), human liver cancer cells (SMMC-7721), human breast cancer cells (MDA-MB-231), and human colon cancer cells (SW480).

[0140] 1. Cell seeding: Prepare a single-cell suspension using culture medium (DMEM or RMPI1640) containing 10% fetal bovine serum. Seed 3,000 to 15,000 cells per well into a 96-well plate, with a volume of 100 μL per well. The cells should be seeded and cultured 12 to 24 hours in advance.

[0141] 2. Add the solution of the compound to be tested: Dissolve the compound in DMSO, and screen the compound at concentrations of 40 μM, 8 μM, 1.6 μM, 0.32 μM and 0.064 μM. The final volume of each well is 200 μl, and each treatment has 3 replicates.

[0142] 3. Color development: After culturing at 37°C for 48 hours, discard the culture medium in the wells of adherent cells, and add 20 μL of MTS solution and 100 μL of culture medium to each well; discard 100 μL of culture supernatant in the wells of suspended cells, and add 20 μL of MTS solution to each well; set up 3 blank replicates (a mixture of 20 μL of MTS solution and 100 μL of culture medium), and continue incubation for 2-4 hours to allow the reaction to proceed fully before measuring the absorbance.

[0143] 4. Colorimetric analysis: Select a wavelength of 492 nm, use a multi-microplate reader (MULTISKAN FC) to read the absorbance values ​​of each well, record the results, and after data processing, plot the cell growth curve with concentration as the x-axis and cell viability as the y-axis. Calculate the IC50 value of the compound using the Reed and Muench method.

[0144] 5. Positive control compound: Cisplatin (DDP) was set as the positive control compound in each experiment. Cell growth curves were plotted with concentration on the x-axis and cell viability on the y-axis. The IC50 value of the compound was calculated using the Reed and Muench method.

[0145] As shown in Table 2, the IC50 of compound 4ac against HL-60 cells was tested using the above method, and the result was 16.45 ± 0.21 μm. The IC50 of the positive control cisplatin against HL-60 tumor cells was 10.25 ± 0.73 μm.

[0146] The IC50 of compound 4ac against A549 cells was tested using the above method, and the result was 19.27 ± 0.24 μm. In contrast, the IC50 of the positive control cisplatin against HL-60 tumor cells was 25.03 ± 1.40 μm.

[0147] The IC50 values ​​of compounds 4e, 4j, 4ac, and 4s against SMMC-7721 cells were tested using the above method, and the results were 12.63±0.82 μm, 30.09±0.96 μm, 2.243±0.141 μm, and 21.89±1.41 μm, respectively. The IC50 of the positive control cisplatin against SMMC-7721 tumor cells was 23.86±1.49 μm.

[0148] The IC50 values ​​of compounds 4ac and 4s against MDA-MB-231 cells were tested using the above method, and the results were 20.48±0.29 μm and 31.02±1.19 μm, respectively. The IC50 of the positive control cisplatin against MDA-MB-231 tumor cells was 21.31±1.74 μm.

[0149] The IC50 values ​​of compounds 4ac and 4s against SW480 cells were tested using the above method, and the results were 12.57±0.80 μm and 31.69±0.93 μm, respectively. The IC50 of the positive control cisplatin against SW480 tumor cells was 19.95±1.71 μm.

[0150] Table 2

[0151]

[0152] The above description is merely a preferred embodiment of the present invention, and the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. An α-trifluoromethyldiazonium sulfonate compound, characterized in that, It has the structure shown in equation (I): （I）。 2. A method for preparing the α-trifluoromethyldiazonium sulfonium salt compound according to claim 1, characterized in that, Includes the following steps: Will Dimethyl sulfide is mixed with an organic solvent and reacted to obtain the α-trifluoromethyl diazosulfonium salt compound.

3. The preparation method according to claim 2, characterized in that, The organic solvent is one of dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, benzene, and toluene; the molar ratio of the high-valent iodine reagent to the thioether is 1:(1-5); the reaction temperature is -50~50℃, and the time is 2~48h.

4. The use of the α-trifluoromethyl diazosulfonium salt compound of claim 1 in the preparation of imidazo-N-heteroaromatic compounds.

5. A method for preparing an imidazo-N-heteroaromatic compound, characterized in that, The process includes the following steps: mixing an organic solvent, a rhodium catalyst, an N-heteroaromatic hydrocarbon, a nitrile compound, a base, and the α-trifluoromethyl diazosulfonate salt compound of claim 1, and subjecting them to a [2+1+2] tandem cyclization reaction to obtain the product; The imidazo-N-heteroaromatic compound has the general structural formula shown in formula (II): （Ⅱ）； In equation (II), when X=N, Y=C, Z=C, R 1 R 2 R 3 R 4 R 5 R 6 Each is independently selected from H, halogen, nitro, cyano, C1-C10 alkyl, C1-C10 alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl or alkoxy-substituted phenyl, and correspondingly, R 7 Selected from trifluoromethyl; correspondingly, R 8 Selected from methyl, phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, benzyloxyphenyl or [1,3]dioxanephenyl; When X=N, Y=C, Z=N, R 1 R 2 R 3 R 4 R 6 Each is independently selected from H, halogen, nitro, cyano, C1-C10 alkyl, C1-C10 alkoxy, aldehyde, ester, amino, heteroaryl, phenyl, alkyl-substituted phenyl or alkoxy-substituted phenyl, and correspondingly, R 7 Selected from trifluoromethyl, correspondingly, R 8 Selected from methyl, phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl, benzyloxyphenyl or [1,3]dioxanephenyl.

6. The preparation method according to claim 5, characterized in that, The rhodium catalyst is any one of bis[(α,α,α′,α′-tetramethyl-1,3-phenylpropionic acid)rhodium], dipolyacetate rhodium, dipolytrifluoroacetate rhodium, tetracaprolactam dirhodium, tetra(triphenylacetic acid) dirhodium, and dipolyoctanoate rhodium; the base is any one of sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, and sodium acetate; the organic solvent is any one of acetonitrile, 1,2-dichloroethane, dichloromethane, chloroform, carbon tetrachloride, benzene, and toluene.

7. The preparation method according to claim 5, characterized in that, The molar ratio of the N-heteroaromatic hydrocarbon, α-trifluoromethyl diazosulfonium salt compound, nitrile compound, base and rhodium catalyst is 1:(1-4):(1-4):(1-4):(0.01-0.05); the temperature of the [2+1+2] tandem cyclization reaction is -50~80℃ and the time is 1~48h.

8. The use of the imidazo-N-heteroaromatic compound of claim 5 in the preparation of drugs for the prevention and treatment of liver cancer, breast cancer, or colon cancer.

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