A beta-triazole derivative, its synthesis method and application

Abstract

The application discloses a kind of high selectivity β-triazole (β-triazole trifluoromethyl, β-triazole ketone, β-triazole thio, β-triazole selenide) Derivative and its synthesis method and application, with triazole compound, alkyl compound / aldehyde / dithioether / diselenide and styrene as raw material, in oxidant, additive and organic solvent, through one step reaction can high selectivity, high yield product is obtained.The method of the application has the advantages of good selectivity, mild reaction condition, high yield, simple and safe operation and high efficiency etc.The β-triazole ketone derivative compound involved in the application is a kind of new structure, has good anti-osteosarcoma activity, biological activity analysis shows that part of compounds can reach 99% inhibition rate to osteosarcoma (OS) cell line 143B, MNG / HOS and SJSA-1 at 10 μM concentration.Therefore, the compound can be used as important pharmaceutical and chemical intermediates, and has wide application prospect in the field of medicine.

Description

Technical Field

[0001] This invention belongs to the field of synthetic pharmaceutical and chemical engineering, specifically relating to a β-triazole derivative, its synthesis method, and its application. Background Technology

[0002] Bifunctionalization of alkenes is a powerful and economical method for synthesizing complex and diverse compounds, attracting great interest from organic synthetic chemists. However, despite extensive efforts over the past few decades, catalytically achieving intermolecular bifunctionalization of alkenes remains a challenge due to the difficulty in controlling the chemical activation and regioselectivity of olefins. For example, in recent years, Pd or Ni catalysis has efficiently established 1,2-carbon amination bifunctionalization of alkenes via covalently linked directing groups. However, the need for directing groups significantly limits the chemical space available for its practical applications. Radical reactions for bifunctionalization of alkenes have subsequently been developed as another efficient strategy, constructing compounds with different complex structures through tandem radical relay strategies. In these cases, the secondary carbon-center radical generated can be captured by other radicals or oxidized to a carbocation, which is then captured by other nucleophiles. However, these methods remain limited to aromatic nitrogen heterocycles with broad bioactivity in the pharmaceutical and medical fields, such as 1,2,3-triazoles. Compared to aliphatic amines, aromatic nitrogen heterocycles are much less nucleophilic, more stable, and more difficult to generate the corresponding nitrogen-center radicals. To the best of our knowledge, there are no examples of 1,2-carbon triazoleization of olefins to construct β-triazole scaffolds by coupling aromatic nitrogen heterocyclic radicals with secondary carbon center radicals in radical relay reactions. Summary of the Invention

[0003] Here, the present invention proposes a first effective example of a strategy for generating β-triazole via a free radical relay reaction of alkyl compounds, aldehydes, disulfides, or diselenes with alkenes and N-sulfonyl-1,2,3-triazoles. Preliminary mechanistic studies indicate that the reaction proceeds via a similar S... N The tandem radical relay desulfonation process was carried out. The novel β-triazolone skeleton compounds obtained exhibited good selective inhibitory activity against osteosarcoma (OS) 143B, MNNG / HOS, and SJSA-1 cell lines, with some compounds showing inhibition rates as high as 99% at 10 μM. In contrast, control compounds without β-triazolyl or carbonyl groups showed no inhibitory activity against 143B cancer cells. These results demonstrate the broad application prospects of the β-triazolone skeleton in the pharmaceutical and medical fields.

[0004] This invention proposes a β-triazole derivative, the structural formula of which is shown in formula (I):

[0005]

[0006] R1 For alkyl, carbonyl, thio, and selenyl groups; R 2 Aryl, electron-donating substituted aryl (wherein the electron-donating group is selected from alkyl, alkoxy, amino, hydroxyl), electron-withdrawing substituted aryl (wherein the electron-withdrawing group is selected from halogen, trifluoromethyl, trifluoromethoxy), heterocyclic aryl; R 3 It is an alkyl, aryl, electron-donating group-substituted aryl group (wherein the electron-donating group is selected from alkyl, alkoxy), electron-withdrawing group-substituted aryl group (wherein the electron-withdrawing group is selected from halogen, trifluoromethyl, trifluoromethoxy), benzothiophene heterocyclic group, benzofuran heterocyclic group, and thiophene heterocyclic group.

[0007] Preferably, R 1 It can be carbonyl, thio, or selenyl. R 2 It is an aryl group, an electron-donating substituted aryl group (wherein the electron-donating group is selected from methyl, methoxy, amino, hydroxyl), an electron-withdrawing substituted aryl group (wherein the electron-withdrawing group is selected from fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy), or a naphthyl group. 3 It is a C1-20 alkyl, aryl, electron-donating substituted aryl (wherein the electron-donating group is selected from methyl, methoxy, n-butyl, n-pentyl), electron-withdrawing substituted aryl (wherein the electron-withdrawing group is selected from fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy), benzothiophene heterocyclic, benzofuran heterocyclic, and thiophene heterocyclic.

[0008] More preferably, R 1 It is benzoyl, phenylthio, or phenylselenoyl. R 2 It is phenyl, p-tolyl, p-chlorophenyl, p-fluorophenyl, or naphthyl. R 3 It can be phenyl, n-butyl, n-pentyl, benzothiophene heterocyclic, benzofuran heterocyclic, or thiophene heterocyclic.

[0009] In a specific implementation, preferably, the β-triazole derivative includes the following compounds:

[0010]

[0011] This invention also proposes a method for synthesizing β-triazole derivatives, using alkyl compounds / aldehydes / disulfides / diselenes, styrene, and triazole compounds as raw materials. An oxidant and additives are added to an organic solvent to react and obtain the β-triazole derivative shown in formula (I); the reaction process is shown in reaction formula (II).

[0012]

[0013] Wherein, 1 represents alkyl radicals, carbonyl radicals, thio radicals, and selenyl radicals generated by alkyl compounds / aldehydes / disulfides / diselenes under the action of oxidants and additives; R 1 R2 R 3 The definition is the same as in formula (I). R 4 It is methylsulfonyl or p-toluenesulfonyl.

[0014] In the synthesis reaction of this invention, the molar ratio of the alkyl compound / aldehyde / disulfide / diselenoether, styrene and triazole compound is (1.2-2):(1.2-2):1; preferably, it is 1.5:1.5:1.

[0015] The additive is selected from one or more of copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile hexafluoroborate, copper bromide, ketone iodide, sodium iodide, and elemental iodine; preferably, it is copper tetraacetonitrile hexafluorophosphate.

[0016] The oxidant is selected from one or more of the following: peroxytert-butanol, benzoyl peroxide, 2,3-dichloro-5,6-dicyanophenyl quinone, potassium persulfate, and ammonium persulfate; preferably, it is peroxytert-butanol.

[0017] The amount of the additive is based on the triazole compound and is 5–20% of the molar amount of the triazole compound; preferably, the amount of the additive is based on the triazole compound and is 10% of the molar amount of the triazole compound.

[0018] The amount of oxidant used is based on the alkyl compound / aldehyde / disulfide / diselenoether, and is 100–150% of the molar amount of the alkyl compound / aldehyde / disulfide / diselenoether; preferably, the amount of oxidant used is based on the alkyl compound / aldehyde / disulfide / diselenoether, and is 120% of the molar amount of the alkyl compound / aldehyde / disulfide / diselenoether.

[0019] The organic solvent is selected from one or more of DCM, DCE, EA, toluene, acetonitrile, etc.; preferably, it is DCE.

[0020] The amount of organic solvent is based on the triazole compound shown in substrate 3, such that the concentration of the triazole compound in the organic solvent is in the range of 0.05M-0.15M; preferably, the concentration of the triazole compound in the organic solvent is in the range of 0.10M.

[0021] The reaction temperature is 50–90°C; preferably, it is 50°C. The reaction time is 18–24 hours; preferably, it is 20 hours.

[0022] The method of the present invention specifically includes the following steps: take a 4 mL two-necked flask, add the solid first, then replace the nitrogen gas three times, and finally dissolve the liquid compound in an organic solvent and add it to the two-necked flask under nitrogen protection. Place it at 50–90℃ for 18–24 h to obtain the β-triazole derivative shown in formula (I).

[0023] The reaction process includes a separation and purification step after obtaining the compound; the separation and purification is carried out by column chromatography using a solution with a volume ratio of ethyl acetate:petroleum ether = 1:20 to 1:30.

[0024] The chemical mechanism involved in the synthesis method of this invention is shown in equation (III) below:

[0025]

[0026] Among them, R 1 R 2 R 3 The definition is the same as that of formula (I).

[0027] Mechanism explanation: Alkyl compounds / aldehydes / disulfides / diselenes generate R under the action of oxidants and additives. 1 Free radical, R 1 The free radical then adds to the olefin to generate a secondary free radical 2i. This secondary free radical 2i then attacks the N2 position of the triazole, simultaneously initiating the departure of the triazole sulfonyl group, ultimately generating compound 4. Due to the steric hindrance effect of the triazole N1 position, the secondary free radical 2i will not attack the N1 position of the triazole to generate compound 4'.

[0028] The present invention also proposes the application of the β-triazolone derivative in the preparation of antitumor cell-active drugs.

[0029] The tumor cells are one or more of the following: MNG / HOS type osteosarcoma cells, HCT 116 type colon cancer cells, SJSA-1 type osteosarcoma cells, and 143B type osteosarcoma cells.

[0030] The β-triazole derivatives of this invention include β-triazole trifluoromethyl, β-triazole ketone, β-triazole thio, and β-triazole selenide derivatives.

[0031] The beneficial effects of this invention are as follows: It provides a method for synthesizing and applying β-triazole derivatives, using triazole compounds, styrene, and alkyl compounds / aldehydes / disulfides / diselenes as raw materials, Cu(CH3CN)4PF6 or NaI as additives, and tert-butanol peroxide or ammonium persulfate as oxidants. In an organic solvent, a one-step reaction can achieve high selectivity (100% N). 2 β-triazole derivatives were obtained in high yields (50-90%). The triazole skeleton contained in the β-triazole ketone derivatives involved in this invention is an important structural fragment of many complex natural products with biological activity. Therefore, such compounds can serve as important pharmaceutical and chemical intermediates and have broad application prospects in the pharmaceutical field. Attached Figure Description

[0032] Figure 1 The product obtained in Example 1 of this invention 1 Schematic diagram of H NMR.

[0033] Figure 2 The product obtained in Example 1 of this invention 13 Schematic diagram of C NMR.

[0034] Figure 3 The product obtained in Example 2 of this invention 1 Schematic diagram of H NMR.

[0035] Figure 4 The product obtained in Example 2 of this invention 19 Schematic diagram of F NMR.

[0036] Figure 5 The product obtained in Example 2 of this invention 13 Schematic diagram of C NMR.

[0037] Figure 6 The product obtained in Example 3 of this invention 1 Schematic diagram of H NMR.

[0038] Figure 7 The product obtained in Example 3 of this invention 13 Schematic diagram of C NMR.

[0039] Figure 8 The product obtained in Example 4 of this invention 1 Schematic diagram of H NMR.

[0040] Figure 9 The product obtained in Example 4 of this invention 19 Schematic diagram of F NMR.

[0041] Figure 10 The product obtained in Example 4 of this invention 13 Schematic diagram of C NMR.

[0042] Figure 11 The product obtained in Example 5 of this invention 1 Schematic diagram of H NMR.

[0043] Figure 12 The product obtained in Example 5 of this invention 13 Schematic diagram of C NMR.

[0044] Figure 13 The product obtained in Example 6 of this invention 1 Schematic diagram of H NMR.

[0045] Figure 14 The product obtained in Example 6 of this invention13 Schematic diagram of C NMR.

[0046] Figure 15 The product obtained in Example 7 of this invention 1 Schematic diagram of H NMR.

[0047] Figure 16 The product obtained in Example 7 of this invention 13 Schematic diagram of C NMR.

[0048] Figure 17 The product obtained in Example 8 of this invention 1 H NMR schematic diagram

[0049] Figure 18 The product obtained in Example 8 of this invention 13 Schematic diagram of C NMR.

[0050] Figure 19 The product obtained in Example 9 of this invention 1 Schematic diagram of H NMR.

[0051] Figure 20 The product obtained in Example 9 of this invention 13 Schematic diagram of C NMR.

[0052] Figure 21 The product obtained in Example 10 of this invention 1 Schematic diagram of H NMR.

[0053] Figure 22 The product obtained in Example 10 of this invention 13 Schematic diagram of C NMR.

[0054] Figure 23 The product obtained in Example 11 of this invention 1 Schematic diagram of H NMR.

[0055] Figure 24 The product obtained in Example 11 of this invention 13 Schematic diagram of C NMR.

[0056] Figure 25 The product obtained in Example 12 of this invention 1 Schematic diagram of H NMR.

[0057] Figure 26 The product obtained in Example 12 of this invention 13 Schematic diagram of C NMR.

[0058] Figure 27 The product obtained in Example 13 of this invention 1 Schematic diagram of H NMR.

[0059] Figure 28 The product obtained in Example 13 of this invention 13 Schematic diagram of C NMR.

[0060] Figure 29 The product obtained in Example 14 of this invention 1 Schematic diagram of H NMR.

[0061] Figure 30 The product obtained in Example 14 of this invention 13 Schematic diagram of C NMR.

[0062] Figure 31 The product obtained in Example 15 of this invention 1 Schematic diagram of H NMR.

[0063] Figure 32 The product obtained in Example 15 of this invention 19 Schematic diagram of F NMR.

[0064] Figure 33 The product obtained in Example 15 of this invention 13 Schematic diagram of C NMR.

[0065] Figure 34 The product obtained in Example 16 of this invention 1 Schematic diagram of H NMR.

[0066] Figure 35 The product obtained in Example 16 of this invention 13 Schematic diagram of C NMR.

[0067] Figure 36 The product obtained in Example 17 of this invention 1 Schematic diagram of H NMR.

[0068] Figure 37 The product obtained in Example 17 of this invention 13 Schematic diagram of C NMR.

[0069] Figure 38 The product obtained in Example 18 of this invention 1 Schematic diagram of H NMR.

[0070] Figure 39 The product obtained in Example 18 of this invention 19 Schematic diagram of F NMR.

[0071] Figure 40 The product obtained in Example 18 of this invention 13 Schematic diagram of C NMR.

[0072] Figure 41The product obtained in Example 19 of this invention 1 Schematic diagram of H NMR.

[0073] Figure 42 The product obtained in Example 19 of this invention 13 Schematic diagram of C NMR.

[0074] Figure 43 The product obtained in Example 20 of this invention 1 Schematic diagram of H NMR.

[0075] Figure 44 The product obtained in Example 20 of this invention 13 Schematic diagram of C NMR.

[0076] Figure 45 The product obtained in Example 21 of this invention 1 Schematic diagram of H NMR.

[0077] Figure 46 The product obtained in Example 21 of this invention 13 Schematic diagram of C NMR.

[0078] Figure 47 The product obtained in Example 22 of this invention 1 Schematic diagram of H NMR.

[0079] Figure 48 The product obtained in Example 22 of this invention 13 Schematic diagram of C NMR.

[0080] Figure 49 The product obtained in Example 23 of this invention 1 Schematic diagram of H NMR.

[0081] Figure 50 The product obtained in Example 23 of this invention 13 Schematic diagram of C NMR.

[0082] Figure 51 The product obtained in Example 24 of this invention 1 Schematic diagram of H NMR.

[0083] Figure 52 The product obtained in Example 24 of this invention 13 Schematic diagram of C NMR.

[0084] Figure 53 The product obtained in Example 25 of this invention 1 Schematic diagram of H NMR.

[0085] Figure 54 The product obtained in Example 25 of this invention 13Schematic diagram of C NMR.

[0086] Figure 55 The product obtained in Example 26 of this invention 1 Schematic diagram of H NMR.

[0087] Figure 56 The product obtained in Example 26 of this invention 13 Schematic diagram of C NMR.

[0088] Figure 57 The product obtained in Example 27 of this invention 1 Schematic diagram of H NMR.

[0089] Figure 58 The product obtained in Example 27 of this invention 13 Schematic diagram of C NMR.

[0090] Figure 59 The product obtained in Example 28 of this invention 1 Schematic diagram of H NMR.

[0091] Figure 60 The product obtained in Example 28 of this invention 13 Schematic diagram of C NMR.

[0092] Figure 61 The product obtained in Example 29 of this invention 1 Schematic diagram of H NMR.

[0093] Figure 62 The product obtained in Example 29 of this invention 13 Schematic diagram of C NMR.

[0094] Figure 63 The product obtained in Example 30 of this invention 1 Schematic diagram of H NMR.

[0095] Figure 64 The product obtained in Example 30 of this invention 13 Schematic diagram of C NMR.

[0096] Figure 65 The product obtained in Example 31 of this invention 1 Schematic diagram of H NMR.

[0097] Figure 66 The product obtained in Example 31 of this invention 19 Schematic diagram of F NMR.

[0098] Figure 67 The product obtained in Example 31 of this invention 13 Schematic diagram of C NMR.

[0099] Figure 68 The product obtained in Example 32 of this invention 1 Schematic diagram of H NMR.

[0100] Figure 69 The product obtained in Example 32 of this invention 13 Schematic diagram of C NMR.

[0101] Figure 70 The product obtained in Example 33 of this invention 1 Schematic diagram of H NMR.

[0102] Figure 71 The product obtained in Example 33 of this invention 13 Schematic diagram of C NMR.

[0103] Figure 72 The product obtained in Example 34 of this invention 1 Schematic diagram of H NMR.

[0104] Figure 73 The product obtained in Example 34 of this invention 13 Schematic diagram of C NMR.

[0105] Figure 74 The product obtained in Example 35 of this invention 1 Schematic diagram of H NMR.

[0106] Figure 75 The product obtained in Example 35 of this invention 13 Schematic diagram of C NMR.

[0107] Figure 76 The product obtained in Example 36 of this invention 1 Schematic diagram of H NMR.

[0108] Figure 77 The product obtained in Example 36 of this invention 13 Schematic diagram of C NMR.

[0109] Figure 78 The product obtained in Example 37 of this invention 1 Schematic diagram of H NMR.

[0110] Figure 79 The product obtained in Example 37 of this invention 13 Schematic diagram of C NMR.

[0111] Figure 80 The product obtained in Example 38 of this invention 1 Schematic diagram of H NMR.

[0112] Figure 81The product obtained in Example 38 of this invention 13 Schematic diagram of C NMR.

[0113] Figure 82 The product obtained in Example 39 of this invention 1 Schematic diagram of H NMR.

[0114] Figure 83 The product obtained in Example 39 of this invention 13 Schematic diagram of C NMR.

[0115] Figure 84 The product obtained in Example 40 of this invention 1 Schematic diagram of H NMR.

[0116] Figure 85 The product obtained in Example 41 of this invention 19 Schematic diagram of FNMR.

[0117] Figure 86 The inhibition rate of β-triazolone compounds on osteosarcoma cell lines 143B, SJSA-1, and MNG / HOS is given.

[0118] Figure 87 The inhibition rate of β-triazolone compounds on osteosarcoma cell lines 143B, SJSA-1, and MNG / HOS is given.

[0119] Figure 88 The inhibition rate of β-triazolone compounds against HCT116 colon cancer cells. Detailed Implementation

[0120] The present invention will be further described in detail below with reference to the specific embodiments and accompanying drawings. The scope of protection of the present invention is not limited to the following embodiments. All variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention and are protected by the claims.

[0121] Example 11,3-Diphenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one 4a

[0122]

[0123] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4a in 68% yield. 1 H NMR (400MHz, Chloroform-d) δ8.00(d,J=7.7Hz,2H),7.82(s,1H),7.72(d,J=7.5Hz,2H),7.56(t,J=7.3Hz,1H),7.45(t,J =7.4Hz,2H),7.41–7.27(m,8H),6.51(dd,J=8.2,5.5Hz,1H),4.56(dd,J=17.7,9.0Hz,1H),3.72(dd,J=17.8,4.9Hz,1H). 13 CNMR(101MHz,Chloroform-d)δ195.9,147.6,139.5,136.4,133.5,131.1,130.4,128. 9,128.7,128.7,128.3,128.3,128.2,126.7,126.1,64.2,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 20 N3O(M+H) + 354.1603, Found: 354.1606.

[0124] Example 23-(4-(3-fluorophenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one 4b

[0125]

[0126] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(3-fluorophenyl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4b in 72% yield. 1H NMR(400MHz,Chloroform-d)δ8.01(d,J=7.9Hz,2H),7.82(s,1H),7.58(t,J=7.3Hz,1H),7.51–7.42(m,4H),7.39(d,J=7.6Hz,2H), 7.37–7.29(m,4H),6.99(t,J=8.4Hz,1H),6.51(dd,J=9.1,4.9Hz,1H),4.57(dd,J=17.7,9.2Hz,1H),3.71(dd,J=17.7,4.9Hz,1H). 19 F NMR (376MHz, Chloroform-d) δ-112.75 (d, J=3.3Hz). 13 C NMR(101MHz,Chloroform-d)δ195.8,163.1(d,J=245.6Hz),146.5(d,J=2.8Hz),139.3,136.4,133.5,132.6(d,J=8.4Hz),131.2,130.3(d,J= 8.4Hz),128.9,128.7,128.4,128.2,126.7,121.5(d,J=2.9Hz),115.1(d,J=21.2Hz),112.9(d,J=22.9Hz),64.4,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19 FN3O(M+H) + 372.1497, Found: 372.1502.

[0127] Example 33-(4-(3-chlorophenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4c)

[0128]

[0129] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(3-chlorophenyl)-1-(methylsulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the nitrogen atmosphere three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 70% yield of β-triazolone 4c. 1H NMR(400MHz,Chloroform-d)δ8.01(d,J=7.8Hz,2H),7.82(s,1H),7.74(s,1H),7.58(t,J=6.5Hz,2H),7.47(t,J=7.5 Hz,2H),7.41–7.27(m,7H),6.50(dd,J=9.0,4.9Hz,1H),4.57(dd,J=17.7,9.2Hz,1H),3.72(dd,J=17.7,4.9Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.8,146.3,139.2,136.4,134.7,133.5,132.2,131.2,130. 0,128.9,128.7,128.4,128.3,128.2,126.7,126.0,124.0,64.4,44.0.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19 ClN3O(M+H) + 388.1248, Found: 388.1247.

[0130] Example 43 -(4-(4-fluorophenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4d)

[0131]

[0132] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(4-fluorophenyl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the nitrogen atmosphere three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4d in 73% yield. 1H NMR(400MHz,Chloroform-d)δ8.01(d,J=7.7Hz,2H),7.78(s,1H),7.69(dd,J=8.1,5.6Hz,2H),7.58(t,J=7.3Hz,1H),7.47(t,J=7.6Hz, 2H),7.41–7.28(m,5H),7.06(t,J=8.6Hz,2H),6.50(dd,J=9.0,4.9Hz,1H),4.56(dd,J=17.7,9.2Hz,1H),3.71(dd,J=17.7,4.9Hz,1H). 19 F NMR(376MHz,Chloroform-d)δ-113.27. 13 C NMR (101MHz, Chloroform-d) δ195.9, 162.7 (d, J = 247.6Hz), 146.8, 139.4, 136.4, 133.5, 130.8, 128. 9,128.7,128.3,128.2,127.7,127.7,126.7,115.7(d,J=21.7Hz),64.2,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19 FN3O(M+H) + 372.1497, Found: 372.1505.

[0133] Example 53 -(4-(4-ethylphenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4e)

[0134]

[0135] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(4-ethylphenyl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone in 71% yield for 4d. 1H NMR(400MHz,Chloroform-d)δ8.00(d,J=7.8Hz,2H),7.80(s,1H),7.64(d,J=7.7Hz ,2H),7.56(t,J=7.3Hz,1H),7.45(t,J=7.6Hz,2H),7.38(d,J=7.6Hz,2H),7.36–7.2 6(m,3H),7.20(d,J=7.8Hz,2H),6.50(dd,J=8.7,5.2Hz,1H),4.55(dd,J=17.7,8.9 Hz, 1H), 3.72 (dd, J=17.7, 5.1Hz, 1H), 2.64 (q, J=7.6Hz, 2H), 1.23 (t, J=7.6Hz, 3H). 13 C NMR(101MHz,Chloroform-d)δ195.9,147.7,144.6,139.6,136.5,133.4,130.9,128 .8,128.7,128.2,127.8,126.7,126.0,64.2,44.1,28.7,15.6.HRMS(ESI)m / z:[M+H] + Calcd for C 25 H 24 N3O(M+H) + 382.1918, Found: 382.1919.

[0136] Example 63-(4-(4-methoxyphenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4f)

[0137]

[0138] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(4-methoxyphenyl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 70% yield of β-triazolone 4f. 1H NMR(400MHz,Chloroform-d)δ8.00(d,J=7.7Hz,2H),7.75(s,1H),7.65(d,J=8.1Hz,2H),7.57(t,J=7.3Hz,1H),7.46(t,J=7.5Hz,2H),7.39(d,J=7.5H z,2H),7.36–7.24(m,3H),6.90(d,J=8.1Hz,2H),6.49(dd,J=8.5,5.3Hz,1H ),4.55(dd,J=17.7,8.9Hz,1H),3.81(s,3H),3.71(dd,J=16.6,5.5Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.9,159.7,147.5,139.6,136.5,133.4,130.5,128. 8,128.6,128.2,127.3,126.7,123.1,114.1,64.1,55.3,44.1.HRMS(ESI)m / z:[M+H] + Calcdfor C 24 H 22 N3O2(M+H) + 384.1716, Found: 384.1712.

[0139] Example 73 -(4-([1,1'-biphenyl]-4-yl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4g)

[0140]

[0141] Take a 4 mL two-necked flask, add 0.2 mmol of 4-([1,1'-biphenyl]-4-yl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4 g of β-triazole ketone in 76% yield. 1H NMR(400MHz,Chloroform-d)δ8.02(d,J=7.8Hz,2H),7.86(s,1H),7.80(d,J=7.7Hz,2H),7.64–7.54(m,5H),7.50–7.3 8(m,6H),7.38–7.27(m,4H),6.53(dd,J=8.8,5.1Hz,1H),4.58(dd,J=17.7,9.0Hz,1H),3.74(dd,J=17.7,5.0Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.9,147.3,141.1,140.6,139.5,136.5,133.5,131.1,129.4,128. 9,128.8,128.7,128.3,128.2,127.4,127.4,127.0,126.7,126.3,64.3,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 29 H 24 N3O(M+H) + 429.1836, Found: 429.1839.

[0142] Example 83 - (4-Butyl-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4h)

[0143]

[0144] Take a 4 mL two-necked flask, add 0.2 mmol of 4-butyl-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone in 58% yield for 4 h. 1H NMR(400MHz,Chloroform-d)δ8.00–7.97(m,2H),7.56(t,J=7.4Hz,1H),7.45(t,J=7.7Hz,2H),7.35–7.27(m,6H),6.41(dd,J=8.8,5.3Hz,1H), 4.47(dd,J=17.7,8.8Hz,1H),3.68(dd,J=17.7,5.3Hz,1H),2.62(t,J=8.0Hz,2H),1.62–1.53(m,2H),1.37–1.25(m,2H),0.88(t,J=7.3Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ196.0,148.7,139.8,136.5,133.4,132.5,128.8,12 8.6,128.2,128.1,126.6,63.7,44.1,31.3,25.2,22.3,13.8.HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 24 N3O(M+H) + 334.1635, Found: 334.1643.

[0145] Example 93 -(4-(tert-butyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4i)

[0146]

[0147] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(tert-butyl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4i in 56% yield. 1H NMR(400MHz,Chloroform-d)δ7.98(d,J=7.6Hz,2H),7.56(t,J=7.4Hz,1H),7.45(t,J=7.6Hz,2H),7.36(s,1H),7.33 –7.25(m,5H),6.41(dd,J=8.7,5.4Hz,1H),4.46(dd,J=17.4,8.8Hz,1H),3.63(dd,J=17.4,5.3Hz,1H),1.25(s,9H). 13 CNMR(101MHz,Chloroform-d)δ196.3,157.4,139.9,136.7,133.3,130.5,128.7,128.6,128.2,128.1,126.7,63.9,30.8,30.3.HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 24 N3OS(M+H) + 333.1865, Found: 333.1873.

[0148] Example 101,3-Diphenyl-3-(4-(thiophen-3-yl)-2H-1,2,3-triazol-2-yl)prop-1-one (4j)

[0149]

[0150] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-(thiophen-3-yl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4j in 63% yield. 1 H NMR(400MHz,Chloroform-d)δ7.93(d,J=7.7Hz,2H),7.65(s,1H),7.53–7.46(m,2H),7.39(t,J=7.4Hz,2H), 7.33–7.21(m,7H),6.42(dd,J=8.8,5.1Hz,1H),4.47(dd,J=17.7,9.0Hz,1H),3.64(dd,J=17.7,5.0Hz,1H). 13C NMR(101MHz,Chloroform-d)δ195.9,143.8,139.4,136.4,133.4,131.7,131.2,128. 8,128.6,128.3,128.2,126.7,126.2,126.0,121.5,64.1,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 18 N3OS(M+H) + 360.1165, Found: 360.1171.

[0151] Example 113-(4-(benzothiophene-2-yl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4k)

[0152]

[0153] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(benzothiophene-2-yl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4k in 67% yield. 1 H NMR (400MHz, Chloroform-d) δ8.02(d,J=7.7Hz,2H),7.84(s,1H),7.81(d,J=7.7Hz,1H),7.74(d,J=7.1Hz,1H),7.61–7.54(m,2H),7.48(t,J= 7.6Hz,2H),7.42(d,J=7.4Hz,2H),7.38–7.29(m,5H),6.52(dd,J=8.8,5.1Hz,1H),4.56(dd,J=17.8,9.0Hz,1H),3.75(dd,J=17.8,5.1Hz,1H). 13C NMR(101MHz,Chloroform-d)δ195.8,142.8,139.9,139.5,139.1,136.4,133.5,132.8,131.4,128. 9,128.7,128.4,128.2,126.8,124.7,124.5,123.7,122.3,121.0,64.4,44.0.HRMS(ESI)m / z:[M+H] + Calcd for C 25 H 20 N3OS(M+H) + 410.1266, Found: 410.1260.

[0154] Example 123-(4-(benzofuran-2-yl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylprop-1-one (4l)

[0155]

[0156] Take a 4 mL two-necked flask, add 0.2 mmol of 4-(benzofuran-2-yl)-1-(methanesulfonyl)-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4 L of β-triazolone in 65% yield. 1 H NMR(400MHz,Chloroform-d)δ8.01(d,J=7.8Hz,2H),7.94(s,1H),7.57(d,J=7.6Hz,2H),7.51–7.45(m,2H),7.42(d,J=7.5Hz,2H),7.35(t,J=7.3H z,2H),7.32–7.28(m,2H),7.28–7.20(m,2H),7.05(s,1H),6.56(dd,J=8. 7,5.2Hz,1H),4.56(dd,J=17.9,8.9Hz,1H),3.79(dd,J=17.9,5.0Hz,1H). 13CNMR(101MHz,Chloroform-d)δ195.7,154.7,147.7,139.9,139.0,136.3,133.5,131.9,128.9,1 28.7,128.4,128.2,126.7,124.7,123.1,121.1,111.3,103.5,64.5,44.0.HRMS(ESI)m / z:[M+H] + Calcd for C 25 H 20 N3OS(M+H) + 394.1556, Found: 394.1547.

[0157] Example 131-(3-bromophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4m)

[0158]

[0159] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace the gas with nitrogen three times. Finally, dissolve 3-bromobenzaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4 mL of β-triazole ketone in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ8.13(s,1H),7.92(d,J=7.7Hz,1H),7.83(s,1H),7.71(dd,J=14.5,7.9Hz,3H) ,7.41–7.28(m,9H),6.48(dd,J=8.8,4.9Hz,1H),4.54(dd,J=17.7,9.2Hz,1H),3.65(dd,J=17.7,4.7Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ194.7,147.7,139.2,138.2,136.3,131.3,131.1,130.4,130. 3,128.9,128.8,128.4,128.3,126.7,126.6,126.1,123.1,64.1,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19BrN3O(M+H) + 432.0730, Found: 432.0721.

[0160] Example 141-(3,5-dichlorophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4n)

[0161]

[0162] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace with nitrogen three times. Finally, dissolve 3,4-dichlorobenzaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react at 50 °C for 18 h to obtain β-triazolone 4n in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ8.09(s,1H),7.82(d,J=6.0Hz,2H),7.72(d,J=7.4Hz,2H),7.55(d,J=8.3Hz,1H ),7.42–7.28(m,8H),6.47(dd,J=8.9,4.6Hz,1H),4.53(dd,J=17.6,9.3Hz,1H),3.62(dd,J=17.6,4.5Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ193.9,147.7,139.1,138.1,136.1,133.4,131.2,130.8,130. 3,130.2,128.9,128.8,128.4,128.4,127.2,126.6,125.9,64.1,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 18 Cl2N3O(M+H) + 422.0837, Found: 422.0827.

[0163] Example 151-(4-fluorophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4o)

[0164]

[0165] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of p-fluorobenzaldehyde, 0.4 mmol of styrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4o in 68% yield. 1 H NMR(400MHz,Chloroform-d)δ8.06–8.01(m,2H),7.83(s,1H),7.72(d,J=7.5Hz,2H),7.34(dq,J=19.9,7.2Hz,8H ), 7.13 (t, J = 8.0Hz, 2H), 6.49 (dd, J = 8.7, 5.0Hz, 1H), 4.54 (dd, J = 17.6, 9.1Hz, 1H), 3.67 (dd, J = 17.6, 4.8Hz, 1H). 19 F NMR(376MHz,Chloroform-d)δ-104.43. 13 C NMR(101MHz,Chloroform-d)δ194.3,165.9(d,J=255.3Hz),147.6,139.4,132.9(d,J=2.9Hz),131.1,130.9,130. 9,130.4,128.9,128.7,128.3(d,J=2.3Hz),126.7,125.9,115.8(d,J=21.9Hz),64.2,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19 FN3O(M+H) + 372.1497, Found: 372.1502.

[0166] Example 161-(4-chlorophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4p)

[0167]

[0168] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace with nitrogen three times. Finally, dissolve p-chlorobenzaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react at 50 °C for 18 h to obtain β-triazolone 4p in 71% yield. 1 H NMR(400MHz,Chloroform-d)δ7.94(d,J=8.6Hz,2H),7.82(s,1H),7.74–7.70(m,2H),7.43(d,J=8.6Hz,2H),7.40–7.3 5(m,5H),7.35–7.28(m,3H),6.49(dd,J=9.1,5.0Hz,1H),4.53(dd,J=17.7,9.2Hz,1H),3.66(dd,J=17.7,5.0Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ194.8,147.7,139.9,139.3,134.8,131.1,130.3,1 29.6,129.1,128.9,128.7,128.4,126.6,125.9,64.2,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19 ClN3O(M+H) + 388.1321, Found: 388.1328.

[0169] Example 171-(4-bromophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4q)

[0170]

[0171] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of p-bromobenzaldehyde, 0.4 mmol of styrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4q in 68% yield. 1H NMR(400MHz,Chloroform-d)δ7.86(d,J=7.6Hz,2H),7.82(s,1H),7.72(d,J=7.4Hz,2H),7.60(d,J=7.6Hz,2H ),7.40–7.27(m,8H),6.48(dd,J=8.6,4.9Hz,1H),4.53(dd,J=17.6,9.1Hz,1H),3.65(dd,J=17.6,4.6Hz,1H). 13 CNMR(101MHz,Chloroform-d)δ195.1,147.7,139.3,135.2,132.1,131.1,130.3,12 9.7,128.9,128.7,128.7,128.4,126.6,125.9,64.21,44.05.HRMS(ESI)m / z:[M+H] + Calcd forC 23 H 19 BrN3O(M+H) + 432.0730, Found: 432.0721.

[0172] Example 18: 3-Phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)-1-(4-(trifluoromethoxy)phenyl)prop-1-one (4r)

[0173]

[0174] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace the gas with nitrogen three times. Finally, dissolve p-trifluoromethoxybenzaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4r in 74% yield. 1 H NMR(400MHz,Chloroform-d)δ8.07(d,J=8.4Hz,2H),7.83(s,1H),7.72(d,J=7.6Hz,2H),7.41–7.2 7(m,10H),6.49(dd,J=8.9,4.9Hz,1H),4.56(dd,J=17.6,9.2Hz,1H),3.67(dd,J=17.7,4.7Hz,1H). 19 F NMR(376MHz,Chloroform-d)δ-57.57.13 C NMR(101MHz,Chloroform-d)δ194.52,152.89(d,J=2.0Hz),147.71,139.29,134.68,131.17,130.33, 128.95,128.79,128.43,126.67,125.96,121.57,120.46,118.99,64.21,44.12.HRMS(ESI)m / z:[M+H] + Calcd for C 24 H 19 F3N3O2(M+H) + 438.1421, Found: 438.1429.

[0175] Example 193 - Phenylacetyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)-1-(p-tolyl)prop-1-one (4s)

[0176]

[0177] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of p-methoxybenzaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4s in 74% yield. 1 H NMR(400MHz,Chloroform-d)δ7.99(d,J=8.3Hz,2H),7.82(s,1H),7.74(d,J=7.8Hz,2H),7.41–7.27(m,8H),6.93(d, J=8.3Hz,2H),6.51(dd,J=8.6,5.3Hz,1H),4.50(dd,J=17.4,8.9Hz,1H),3.86(s,3H),3.69(dd,J=17.5,5.1Hz,1H). 13 CNMR(101MHz,Chloroform-d)δ194.3,163.7,147.6,139.6,131.1,130.5,130.5,129.5, 128.8,128.7,128.3,128.2,126.7,126.1,113.8,64.3,55.5,43.7.HRMS(ESI)m / z:[M+H] + Calcd for C24 H 22 F3N3O2(M+H) + 384.1712, Found: 384.1716.

[0178] Example 203-Phenylacetyl-3-(4-Phenylacetyl-2H-1,2,3-triazol-2-yl)-1-(thiophen-2-yl)prop-1-one (4t)

[0179]

[0180] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace with nitrogen three times. Finally, dissolve thiophene-2-carboxaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react at 50 °C for 18 h to obtain β-triazolone 4s in 73% yield. 1 H NMR(400MHz,Chloroform-d)δ7.83(s,2H),7.73(d,J=7.7Hz,2H),7.65(d,J=4.9Hz,1H),7.41–7.28(m,8H),7 .14(t,J=4.0Hz,1H), 6.48(dd,J=8.8,5.4Hz,1H), 4.46(dd,J=17.1,9.0Hz,1H), 3.69(dd,J=17.1,5.2Hz,1H). 13 CNMR(101MHz,Chloroform-d)δ188.6,147.7,143.6,139.2,134.2,132.4,131.1,1 30.4,128.8,128.7,128.3,128.2,126.7,125.9,64.2,44.7.HRMS(ESI)m / z:[M+H] + Calcd forC 21 H 18 N3OS(M+H) + 360.1165, Found: 360.1171.

[0181] Example 213-Phenylacetyl-3-(4-Phenylacetyl-2H-1,2,3-triazol-2-yl)-1-(thiophene-3-yl)prop-1-one (4u)

[0182]

[0183] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace the gas with nitrogen three times. Finally, dissolve thiophene-3-carboxaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4 u of β-triazole ketone in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ8.16(s,1H),7.83(s,1H),7.73(d,J=7.6Hz,2H),7.56(d,J=5.0Hz,1H),7. 42–7.28(m,9H),6.48(dd,J=8.8,5.3Hz,1H),4.44(dd,J=17.4,9.0Hz,1H),3.66(dd,J=17.4,5.2Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ190.1,147.6,141.7,139.4,132.6,131.1,130.4,128. 8,128.7,128.3,128.3,126.9,126.7,126.5,125.9,64.1,45.2.HRMS(ESI)m / z:[M+H] + Calcd forC 21 H 18 N3OS(M+H) + 360.1165, Found: 360.1171.

[0184] Example 221-(benzothiophene-2-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4v)

[0185]

[0186] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace with nitrogen three times. Finally, dissolve benzothiophene-2-carboxaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react at 50 °C for 18 h to obtain β-triazolone 4v in 70% yield. 1H NMR(400MHz,Chloroform-d)δ8.09(s,1H),7.92–7.80(m,3H),7.72(d,J=7.2Hz,2H),7.50–7 .25(m,10H),6.55–6.47(m,1H),4.58(dd,J=17.0,9.0Hz,1H),3.78(dd,J=17.1,4.7Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ190.2,147.7,143.0,142.7,139.1,139.0,131.2,130.3,129.8,128. 9,128.7,128.4,128.4,127.6,126.7,126.0,126.0,125.1,123.0,64.2,44.6.HRMS(ESI)m / z:[M+H] + Calcdfor C 25 H 20 N3OS(M+H) + 410.1357, Found: 410.1348.

[0187] Example 231-(benzofuran-2-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4w)

[0188]

[0189] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzofuran-2-carboxaldehyde, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4 w of β-triazolone in 69% yield. 1 H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.71(t,J=6.8Hz,3H),7.58(d,J=8.6Hz,2H),7.49(t,J=7.8Hz,1H),7.42(d,J =7.8Hz,2H),7.39–7.28(m,7H),6.51(dd,J=9.0,5.4Hz,1H),4.54(dd,J=17.4,9.2Hz,1H),3.76(dd,J=17.4,5.3Hz,1H). 13C NMR(101MHz,Chloroform-d)δ186.9,155.7,152.2,147.7,139.1,131.2,130.3,128.9,128.7,128. 5,128.4,128.3,127.0,126.7,125.9,124.0,123.4,113.4,112.5,63.9,44.3.HRMS(ESI)m / z:[M+H] + Calcd for C 25 H 20 N3O2(M+H) + 394.1548, Found: 394.1556.

[0190] Example 241-(benzo[d][1,3]dihydroxy-5-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4x)

[0191]

[0192] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then change the atmosphere with nitrogen three times. Finally, dissolve piperonal (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4x in 68% yield. 1 H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.74(d,J=7.7Hz,2H),7.64(d,J=8.2Hz,1H),7.45(s,1H),7.41–7.28(m,8H),6 .85(d,J=8.1Hz,1H),6.49(dd,J=8.8,5.1Hz,1H),6.03(s,2H),4.47(dd,J=17.5,9.0Hz,1H),3.65(dd,J=17.5,5.0Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ193.9,152.1,148.2,147.6,139.5,131.3,131.0,130.4,128.8,1 28.7,128.3,128.2,126.7,125.9,124.6,108.0,107.9,101.9,64.3,43.8.HRMS(ESI)m / z:[M+H]+ Calcd for C 25 H 20 N3O2(M+H) + 398.1512, Found: 398.1505.

[0193] Example 251 - Cyclopropyl-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4y)

[0194]

[0195] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace the gas with nitrogen three times. Finally, dissolve cyclopropane (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4y in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ7.84(s,1H),7.78(d,J=7.7Hz,2H),7.40(t,J=7.5Hz,2H),7.36–7.26(m,6H),6.29(dd,J=9.1,5.3Hz,1H),4.06(dd ,J=17.3,9.2Hz,1H),3.35(dd,J=17.4,5.2Hz,1H),1.98(tt,J=8.0,4.6H z,1H),1.08–1.01(m,1H),1.01–0.94(m,1H),0.87(q,J=5.1,4.2Hz,2H). 13 C NMR (101 MHz, Chloroform-d)δ

[0196] 206.6,147.5,139.3,131.0,130.4,128.9,128.8,128.3,128.2,126.6,125.9,64.1,48.1,21.1,11.0,10.9.HRMS(ESI)m / z:[M+H] + Calcd for C 20 H 20 N3O(M+H) + 318.1598, Found: 318.1606.

[0197] Example 261 - Cyclobutyl-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4z)

[0198]

[0199] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then change the atmosphere with nitrogen three times. Finally, dissolve cyclobutanaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4z in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.77(d,J=7.2Hz,2H),7.40(t,J=7.5Hz,2H),7.35–7.25(m,6H),6.30(dd,J=9.3,5.3Hz,1H),3 .87(dd,J=17.5,9.3Hz,1H),3.32(q,J=8.5Hz,1H),3.14(dd,J=17.5,5.3Hz,1H),2.31–2.06(m,4H),2.01–1.90(m,1H),1.82–1.71(m,1H). 13 C NMR(101MHz,Chloroform-d)δ207.4,147.6,139.4,131.1,130.5,128.8,128.8,12 8.4,128.3,126.6,125.9,64.1,45.7,45.3,24.2,23.9,17.7.HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 22 N3O(M+H) + 332.1773, Found: 332.1777.

[0200] Example 271 - Cyclopentyl-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4aa)

[0201]

[0202] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then change the atmosphere with nitrogen three times. Finally, dissolve cyclopentanaldehyde (0.4 mmol), styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4aa in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.76(d,J=7.4Hz,2H),7.40(t,J=7.5Hz,2H),7.35–7.23(m,6H),6.31(dd,J=9.2,5.2Hz,1H), 3.98(dd,J=17.6,9.3Hz,1H),3.22(dd,J=17.6,5.2Hz,1H),2.95–2.90(m,1H),1.84–1.78(m,2H),1.73–1.67(m,2H),1.61–1.53(m,4H). 13 C NMR(101MHz,Chloroform-d)δ208.7,147.6,139.5,131.1,130.5,128.8,128.8,128.4 ,128.2,126.6,125.9,64.1,51.8,46.9,28.6,28.4,25.9,25.9.HRMS(ESI)m / z:[M+H] + Calcd for C 22 H 24 N3O(M+H) + 346.1919, Found: 346.1909.

[0203] Example 281-Pheny-1-(4-Pheny-2H-1,2,3-triazol-2-yl)hex-3-one (4ab)

[0204]

[0205] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the nitrogen atmosphere three times. Finally, dissolve 0.4 mmol of n-butyraldehyde, 0.4 mmol of styrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4ab in 72% yield. 1H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.76(d,J=7.2Hz,2H),7.40(t,J=7.4Hz,2H),7.35–7.26(m,8H),6.28(dd,J=9.4,5.1 Hz,1H),3.93(dd,J=17.4,9.4Hz,1H),3.16(dd,J=17.4,5.1Hz,1H),2.55–2.37(m,2H),1.64–1.54(m,2H),0.86(t,J=7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ206.8,147.6,139.4,131.1,130.5,128.8,128.8, 128.4,128.3,126.6,125.9,64.1,47.8,45.2,17.1,13.6.HRMS(ESI)m / z:[M+H] + Calcd for C 20 H 22 N3O(M+H) + 320.1716, Found: 320.1725.

[0206] Example 291 - Phenylacetyl-1-(4-phenyl-2H-1,2,3-triazol-2-yl)hepta-3-one (4ac)

[0207]

[0208] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the nitrogen atmosphere three times. Finally, dissolve 0.4 mmol of n-pentanal, 0.4 mmol of styrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4ac in 72% yield. 1H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.77(d,J=7.8Hz,2H),7.41(t,J=7.5Hz,2H),7.35–7.28(m,6H),6.28(dd,J=9.4,5.1Hz,1H),3 .94(dd,J=17.4,9.4Hz,1H),3.17(dd,J=17.4,5.1Hz,1H),2.58–2.39(m,2H),1.59–1.49(m,2H),1.32–1.20(m,2H),0.86(t,J=7.3Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ206.9,147.5,139.3,131.0,130.4,128.8,128.8,12 8.3,128.2,126.6,125.9,64.1,47.7,43.0,25.6,22.2,13.8.HRMS(ESI)m / z:[M+H] + Calcd for C 21 H 24 N3O 334.1917, Found: 334.1919.

[0209] Example 301 - Phenylacetyl-1-(4-phenyl-2H-1,2,3-triazol-2-yl)dec-3-one (4ad)

[0210]

[0211] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of dodecaldehyde, 0.4 mmol of styrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain β-triazolone 4ad in 72% yield. 1H NMR(400MHz,Chloroform-d)δ7.83(s,1H),7.76(d,J=7.2Hz,2H),7.40(t,J=7.5Hz,2H),7.35–7.26(m,6H),6.28(dd,J=9.4,5.1Hz,1H),3 .93(dd,J=17.3,9.4Hz,1H),3.16(dd,J=17.3,5.1Hz,1H),2.56–2.38(m,2H),1.59–1.50(m,2H),1.29–1.15(m,8H),0.85(t,J=6.8Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ206.9,147.6,139.4,131.1,130.5,128.9,128.8,128.4,128. 3,126.6,125.9,64.1,47.8,43.4,31.7,29.1,29.1,23.6,22.6,14.1.HRMS(ESI)m / z:[M+H] + Calcd for C 24 H 30 N3O(M+H) + 376.2399, Found: 376.2404.

[0212] Example 313-(4-fluorophenyl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4ae)

[0213]

[0214] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace with nitrogen three times. Finally, dissolve benzaldehyde (0.4 mmol), p-fluorostyrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react at 50 °C for 18 h to obtain β-triazolone 4ae in 68% yield. 1H NMR(400MHz,Chloroform-d)δ8.00(d,J=7.5Hz,2H),7.83(s,1H),7.73(d,J=7.4Hz,2H),7.58(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),7.43–7.3 5(m,4H),7.31(t,J=7.3Hz,1H),7.02(t,J=8.6Hz,2H),6.49(dd,J=8.3,5.8Hz,1H),4.49(dd,J=17.7,8.5Hz,1H),3.76(dd,J=17.7,5.7Hz,1H). 19 F NMR(376MHz,Chloroform-d)δ-113.63. 13 C NMR (101MHz, Chloroform-d) δ 195.7, 162.6 (d, J = 247.2Hz), 147.8, 136.4, 135.3 (d, J = 3.2Hz), 133.6, 131.2, 130. 3,128.8,128.7(d,J=1.6Hz),128.6,128.5,128.2,125.9,115.8(d,J=21.7Hz),63.6,44.1.HRMS(ESI)m / z:[M+H] + Calcdfor C 23 H 19 FN3O 372.1491, Found: 372.1497.

[0215] Example 323-(4-chlorophenyl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4af)

[0216]

[0217] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of p-chlorostyrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 70% yield of β-triazolone 4af. 1H NMR (400MHz, Chloroform-d) δ8.00(d,J=7.6Hz,2H),7.83(s,1H),7.73(d,J=7.3Hz,2H),7.58(t,J=7.3Hz,1H),7.46(t,J =7.6Hz,2H),7.41–7.27(m,7H),6.48(dd,J=8.2,5.8Hz,1H),4.49(dd,J=17.7,8.4Hz,1H),3.75(dd,J=17.7,5.7Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.6,147.9,137.9,136.3,134.3,133.6,131.3,130. 3,129.1,128.8,128.8,128.5,128.3,128.2,126.0,63.6,44.0.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 19 ClN3O(M+H) + 387.1123, Found: 387.1128.

[0218] Example 333-([1,1'-biphenyl]-4-yl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4ag)

[0219]

[0220] Take a 4 mL two-necked flask, add 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then change the atmosphere with nitrogen three times. Finally, dissolve benzaldehyde (0.4 mmol), p-styrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4 ag of β-triazole ketone in 62% yield. 1H NMR(400MHz,Chloroform-d)δ8.03(d,J=7.7Hz,2H),7.85(s,1H),7.75(d,J=7.5Hz,2H),7.56(q,J=7.8,7.3Hz,5H),7.48(t,J=6.8Hz, 4H),7.44–7.36(m,4H),7.33(t,J=7.3Hz,2H),6.56(dd,J=8.6,5.3Hz,1H),4.58(dd,J=17.7,8.8Hz,1H),3.79(dd,J=17.7,5.2Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.9,147.7,141.3,140.5,138.4,136.5,133.5,131.2,130.4,128. 8,128.8,128.7,128.4,128.3,127.6,127.5,127.2,127.1,126.0,64.0,44.1.HRMS(ESI)m / z:[M+H] + Calcdfor C 29 H 23 N3O(M+H) + 430.1945, Found: 430.1949.

[0221] Example 341-Phenylacetyl-3-(4-Phenylacetyl-2H-1,2,3-triazol-2-yl)-3-(p-Tolyl)prop-1-one (4ah)

[0222]

[0223] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of p-methylstyrene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 4ah of β-triazolone in 72% yield. 1H NMR(400MHz,Chloroform-d)δ8.01(d,J=7.7Hz,2H),7.81(s,1H),7.72(d,J=7.5Hz,2H),7.57(t,J=7.3Hz,1H),7.46(t,J=7.6Hz,2H),7.37(t,J=7.4H z,2H),7.33–7.27(m,3H),7.14(d,J=7.8Hz,2H),6.47(dd,J=8.7,5.3Hz,1H ), 4.53(dd,J=17.7,8.9Hz,1H), 3.73(dd,J=17.7,5.3Hz,1H), 2.31(s,1H). 13 C NMR(101MHz,Chloroform-d)δ196.0,147.6,138.1,136.6,136.5,133.4,131.1,130.5,1 29.5,128.7,128.7,128.3,128.3,126.7,126.00,64.1,44.1,21.1.HRMS(ESI)m / z:[M+H] + Calcd for C 24 H 22 N3O(M+H) + 368.1748, Found: 368.1742.

[0224] Example 353-(naphthyl-2-yl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4ai)

[0225]

[0226] Take a 4 mL two-necked flask, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol) and Cu(CH3CN)4PF6 (0.02 mol), then replace with nitrogen three times. Finally, dissolve benzaldehyde (0.4 mmol), naphthalenestyrene (0.4 mmol), and TBHP (0.6 mmol) in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react at 50 °C for 18 h to obtain β-triazole 4ai in 66% yield. 1H NMR(400MHz,Chloroform-d)δ8.02(d,J=7.5Hz,2H),7.85(s,2H),7.83–7.77(m,3H),7.74(d,J=7.4Hz,2H),7.60–7.51(m,2H),7.49–7.43(m ,4H),7.37(t,J=7.4Hz,2H),7.30(t,J=7.3Hz,1H),6.68(dd,J=8.7,5.2Hz,1H),4.64(dd,J=17.7,8.8Hz,1H),3.83(dd,J=17.7,5.2Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.9,147.7,136.8,136.5,133.5,133.3,133.1,131.2,130.5,128.8,128. 7,128.7,128.4,128.3,128.2,127.7,126.4,126.4,126.1,126.0,124.3,64.5,44.1.HRMS(ESI)m / z:[M+H] + Calcd for C 27 H 22 N3O(M+H) + 404.1767, Found: 404.1763.

[0227] Example 361,2,3-Triphenyl-3-(4-Pheny-2H-1,2,3-triazol-2-yl)prop-1-one (4aj)

[0228]

[0229] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of benzaldehyde, 0.4 mmol of stilbene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 50% yield of β-triazole 4aj. 1H NMR(400MHz,Chloroform-d)δ8.02(d,J=7.5Hz,2H),7.78(s,1H),7.61(d,J=7.0Hz,2H),7.50(t,J=7.4Hz,1H) ,7.40(t,J=7.6Hz,2H),7.35–7.25(m,4H),7.23–7.11(m,9H),6.53(d,J=11.2Hz,1H),5.95(d,J=11.2Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ197.3,147.3,137.4,136.6,134.2,133.0,131.1,130.4,129.3,128. 9,128.7,128.7,128.5,128.3,128.2,128.0,127.8,127.4,125.9,70.8,58.5.HRMS(ESI)m / z:[M+H] + Calcd for C 29 H 24 N3O(M+H) + 429.1887, Found: 429.1881.

[0230] Example 371-(naphthyl-2-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)prop-1-one (4ak)

[0231]

[0232] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the atmosphere with nitrogen three times. Finally, dissolve 0.4 mmol of 2-naphthaldehyde, 0.4 mmol of stilbene and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 40% yield of β-triazolone 4ak. 1H NMR (400MHz, Chloroform-d) δ8.55 (s, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.96 (d, J = 8. 0Hz,1H),7.86(dd,J=13.5,6.4Hz,3H),7.72(d,J=7.6Hz,2H),7.63–7.50(m,2H ),7.43(d,J=7.5Hz,2H),7.35(t,J=7.3Hz,4H),7.30(d,J=7.0Hz,2H),6.57(dd ,J=8.6,5.2Hz,1H),4.70(dd,J=17.6,9.0Hz,1H),3.85(dd,J=17.6,5.0Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ195.8,147.7,139.5,135.7,133.8,132.5,131.1,130.4,130.1,129.6,1 28.9,128.7,128.7,128.5,128.3,127.8,126.9,126.7,126.0,123.8,64.4,44.2.HRMS(ESI)m / z:[M+H] + Calcd for C 27 H 22 N3O(M+H) + 404.1767, Found: 404.1763.

[0233] Example 384-Phenylacetyl-2-(1-Phenylacetyl-2-(phenylthio)ethyl)-2H-1,2,3-triazole (4al)

[0234]

[0235] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of NaI, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of diphenyl sulfide, 0.4 mmol of styrene, and 0.6 mmol of (NH4)2S2O4 in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the mixture at 80 °C for 18 h to obtain 70% yield of β-triazole thio compound 4ak. 1H NMR (400MHz, Chloroform-d) δ7.84 (s, 1H), 7.76 (d, J = 7.6Hz, 2H), 7.38 (d, J = 7.7Hz, 6H), 7.28 (dt, J = 15. 1,8.2Hz,6H),7.19(t,J=7.2Hz,1H),5.86–5.73(m,1H),4.17–4.05(m,1H),3.66(dd,J=14.1,4.8Hz,1H). 13 C NMR (101MHz, Chloroform-d) δ147.8,138.3,134.7,131.2,131.1,130.5,129.2,128.8,128.6,128.4,127.1,127.1,126.1,68.6,40.1.

[0236] Example 394 - Phenylacetyl-2-(1-Phenylacetyl-2-(phenylselenoyl)ethyl)-2H-1,2,3-triazole (4am)

[0237]

[0238] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of NaI, then replace the gas with nitrogen three times. Finally, dissolve 0.4 mmol of diphenylselenoether, 0.4 mmol of styrene, and 0.6 mmol of (NH4)2S2O4 in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the mixture at 80 °C for 18 h to obtain 4am, a β-triazole selenized compound, in 83% yield. 1 H NMR(400MHz,Chloroform-d)δ7.83(d,J=1.5Hz,1H),7.79–7.75(m,2H),7.53–7.49(m,2H),7.40(t,J=7. 7Hz,2H),7.37–7.26(m,6H),7.25–7.22(m,3H),5.86–5.80(m,1H),4.09–4.01(m,1H),3.66–3.57(m,1H). 13 C NMR (101MHz, Chloroform-d) δ147.7,138.8,133.9,131.1,130.5,129.2,129.2,128.8,128.8,128.5,128.4,127.6,126.9,126.1,69.3,32.9.

[0239] Example 404 - Phenylacetyl-2-(3,3,3-trifluoro-1-phenylpropyl)-2H-1,2,3-triazole (4an)

[0240]

[0241] Take a 4 mL two-necked flask, add 0.2 mmol of 1-(methanesulfonyl)-4-phenyl-1H-1,2,3-triazole and 0.02 mol of Cu(CH3CN)4PF6, then change the nitrogen atmosphere three times. Finally, dissolve 0.4 mmol of sodium trifluoromethanesulfonate, 0.4 mmol of styrene, and 0.6 mmol of TBHP in 2 mL of dichloroethane, then inject the solution into the two-necked flask using a syringe. Finally, react the solution at 50 °C for 18 h to obtain 50% yield of β-triazole 4an. 1 H NMR(400MHz,Chloroform-d)δ7.87(s,1H),7.79(d,J=7.5Hz,2H),7.43(t,J=7.2Hz,4H), 7.36(d,J=7.5Hz,4H), 6.05(dd,J=9.1,4.7Hz,1H), 3.75–3.62(m,1H), 3.09–2.92(m,1H). 19 F NMR(376MHz,Chloroform-d)δ-65.01.

[0242] Example 41: Antitumor cell activity test experiment:

[0243] 1. Cell inoculation:

[0244] 1) Prepare a single-cell suspension using DMEM culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and seed 2500 MNG / HOS osteosarcoma cells per well into a 96-well cell culture plate, with a volume of 100 μL per well.

[0245] 2) Prepare a single-cell suspension using RPMI 1640 culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and seed 2500 SJSA-1 osteosarcoma cells per well into a 96-well cell culture plate, with a volume of 100 μL per well.

[0246] 3) Prepare a single-cell suspension using McCoy's 5A culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and seed 2500 HCT116 colon cancer cells per well into a 96-well cell culture plate, with a volume of 100 μl per well.

[0247] 4) Prepare a single-cell suspension using MEM culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and seed 2500 143B osteosarcoma cells per well into a 96-well cell culture plate, with a volume of 100 μl per well.

[0248] 2. Administration: The compound of formula (I) synthesized in the foregoing embodiments of the present invention was prepared into a stock solution with a final concentration of 10 mM using DMSO, diluted to 10 μM with complete culture medium, and applied to cells in three replicates.

[0249] 3. Incubation: Incubate for 72 hours in a 5% CO2, 37℃ saturated humidity incubator.

[0250] 4. Color development: After 72 hours of incubation, aspirate the culture medium, add 100 μL of complete culture medium and 10 μL of CCK8 to each well, and incubate at 37°C for 2-4 hours.

[0251] 5. Colorimetric analysis: Select wavelengths of 620 nm and 450 nm, measure the optical density (OD) value of each well on the microplate reader, and record the results.

[0252] 6. The absorbance value at 450nm and the absorbance value at 620nm (background absorbance value) of the same well are used as the final absorbance and substituted into the following formula.

[0253] 7. Cell proliferation activity (%) = [A(drug-treated) - A(blank)] / [A(no drug-treated) - A(blank)] × 100%.

[0254] A (Drug Addition): Absorbance of wells containing osteosarcoma cells, CCK8 solution (Cell Counting Kit-8, a rapid and highly sensitive assay for cell proliferation and cytotoxicity based on WST-8 (chemical name: 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonylbenzene)-2H-tetrazole monosodium salt) and drug solution (drug solution refers to the DMSO solution of the compound sample to be tested).

[0255] A (Blank): Absorbance of wells containing culture medium and CCK8 solution but without cells.

[0256] A (Untreated): Absorbance of the pore containing cells and CCK8 solution but no drug solution. 8. Experimental results show that under the action of the compound of formula (I) of this invention at a concentration of 10 μM, the survival rate of four different subtypes of osteosarcoma cells is as follows: Figures 86-88 As shown:

[0257] This indicates that compounds 4e and 4x exhibit good inhibitory activity against osteosarcoma cells MNG / HOS; compounds 4c, 4e, 4u, 4x, and 4ak exhibit relatively good inhibitory activity against osteosarcoma cells SJSA-1; compounds 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4l, 4n, 4o, 4r, 4t, 4v, 4w, 4ae, and 4ai exhibit good inhibitory activity against colon cancer cells HCT116; and compounds 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4l, 4n, 4o, 4r, 4t, 4u, 4w, 4x, and 4ae exhibit relatively good inhibitory activity against osteosarcoma cells 143B.

Claims

1. A β-triazole derivative, characterized in that, which is selected from the group consisting of:

2. A method of synthesizing a β-triazole derivative, characterized by, The reaction is carried out in an organic solvent, and an oxidant and an additive are added to obtain a β-triazole derivative shown in formula (I); the reaction process is shown in reaction formula (II): wherein 1 is a carbonyl radical generated from an aldehyde under the action of an oxidizing agent and an additive; R 1 is a benzoyl group; R 2 is a phenyl group, a phenyl group substituted with an electron-donating group, a phenyl group substituted with an electron-withdrawing group, a naphthyl group; R 3 is a C1-20 alkyl group, a phenyl group, a phenyl group substituted with an electron-donating group, a phenyl group substituted with an electron-withdrawing group, a benzo-thiophene heterocyclic group, a benzo-furan heterocyclic group, a thiophene heterocyclic group; R 4 is a methylsulfonyl group, a p-toluenesulfonyl group; wherein the electron-withdrawing group is selected from halogen, trifluoromethyl, trifluoromethoxy, and the electron-donating group is selected from an alkyl group, an alkoxy group; The oxidant is selected from tert-butyl hydroperoxide; and the additive is selected from tetraethylammonium copper hexafluorophosphate.

3. The method of synthesis of claim 2, wherein, The reaction temperature is 50-90℃; and / or, the reaction time is 18-24h.

4. The method of synthesis of claim 2, wherein, The molar ratio of the aldehyde, styrene and triazole compound is (1.2-2):(1.2-2):1; and / or, the amount of the additive is 5-20% of the molar amount of the triazole compound based on the triazole compound; The amount of the oxidant is 100-150% of the molar amount of the aldehyde based on the aldehyde.

5. The method of synthesis of claim 2, wherein, The organic solvent is selected from one or more of DCM, DCE, EA, toluene, acetonitrile; and / or, the amount of the organic solvent is 0.05M-0.15M of the concentration of the triazole compound in the organic solvent based on the substrate triazole compound.

6. The method of synthesis of claim 2, wherein, Further, the β-triazole derivative obtained by the reaction is separated and purified; the separation and purification is carried out by column chromatography using a solution of ethyl acetate: petroleum ether = 1:30-1:20 by volume.

7. Use of the β-triazole derivative according to claim 1 for the manufacture of a medicament for anti-tumor cell activity, characterized in that, The tumor cells are one or more of HOS type osteosarcoma cells, HCT 116 type colon cancer cells, SJSA-1 type osteosarcoma cells, and 143B type osteosarcoma cells.

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