Beta-triazole derivative as well as synthesis method and application thereof

Abstract

The invention discloses a high-selectivity beta-triazole (beta-triazole trifluoromethyl, beta-triazole ketone, beta-triazole sulfo and beta-triazole seleno) derivative as well as a synthesis method and application thereof.The high-selectivity beta-triazole (beta-triazole trifluoromethyl, beta-triazole ketone, beta-triazole sulfo and beta-triazole seleno) derivative is prepared from a triazole compound, an alkyl compound / aldehyde / disulfide / diselenide and styrene as raw materials in an oxidizing agent, an additive and an organic solvent in a one-pot reaction mode, and the high-selectivity beta-triazole (beta-triazole trifluoromethyl, beta-triazole ketone, beta-triazole sulfo and beta-triazole seleno) derivative is obtained. The product can be obtained with high selectivity and high yield through one-step reaction. The method provided by the invention has the advantages of good selectivity, mild reaction conditions, high yield, simple and safe operation, high efficiency and the like. The beta-triazolone derivative compound provided by the invention is of a brand new structure and has good anti-osteosarcoma activity, and biological activity analysis shows that part of the compound can achieve 99% inhibition rate on osteosarcoma (OS) cell lines 143B, MNG / HOS and SJSA-1 under the concentration of 10 [mu] M. Therefore, the compound can be used as an important intermediate of medicine and chemical industry, and has a wide application prospect in the field of medicine.

Description

Technical Field

[0001] The invention belongs to the field of synthetic pharmaceutical chemicals, and specifically relates to a β-triazole derivative and a synthesis method and application thereof. Background Art

[0002] The difunctionalization of olefins is a powerful and economical method for synthesizing complex and diverse compounds, which has attracted great interest from organic synthetic chemists. However, despite extensive efforts over the past few decades, the catalytic intermolecular difunctionalization of olefins 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 effectively established the difunctionalization of olefins by 1,2-carbon amination via covalently attached directing group strategies. However, the need for directing groups greatly limits the chemical space available for its practical application. The free radical reaction of difunctionalization of olefins was subsequently developed as another effective strategy to construct compounds with different complex structures through a tandem radical relay strategy, in which the secondary carbon-centered radical generated by the relay can be captured by other radicals or oxidized to carbocations and then captured by other nucleophiles. However, these methods are still limited to aromatic nitrogen heterocycles with broad biological activities in the pharmaceutical and medical fields, such as 1,2,3-triazoles, which are much less nucleophilic, more stable, and more difficult to generate the corresponding nitrogen-centered radicals compared with aliphatic amines. To the best of our knowledge, there are no examples of 1,2-carbazolylation of olefins via coupling of aromatic nitrogen heterocyclic radicals with secondary carbon-centered radicals in a radical relay reaction to construct β-triazole scaffolds. Summary of the invention

[0003] Here, the present invention proposes the first effective strategy for the formation of β-triazoles by free radical relay reaction of alkyl compounds or aldehydes or disulfides or diselenides with olefins and N-sulfonyl-1,2,3-triazoles. Preliminary mechanistic studies show that the reaction proceeds through a similar S N 2 is carried out by a tandem free radical relay desulfonylation process. The obtained novel β-triazolone skeleton compounds showed good selective inhibitory activity against osteosarcoma (OS) 143B, MNNG / HOS and SJSA-1 cell lines, and some compounds had an inhibition rate of up to 99% at 10 μM. In contrast, the control compounds without β-triazolyl or carbonyl groups had no inhibitory activity against 143B cancer cells. These results demonstrate that the β-triazolone skeleton has broad application prospects in the pharmaceutical or medical fields.

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

[0005]

[0006] R1 is alkyl, carbonyl, thio or seleno; R 2 is an aryl group, an aryl group substituted with an electron-donating group (wherein the electron-donating group is selected from alkyl, alkoxy, amino, and hydroxy), an aryl group substituted with an electron-withdrawing group (wherein the electron-withdrawing group is selected from halogen, trifluoromethyl, and trifluoromethoxy), or a heterocyclic aryl group; R 3 It is an alkyl group, an aryl group, an aryl group substituted with an electron donating group (wherein the electron donating group is selected from an alkyl group and an alkoxy group), an aryl group substituted with an electron withdrawing group (wherein the electron withdrawing group is selected from a halogen group, a trifluoromethyl group and a trifluoromethoxy group), a benzothiophene heterocyclic group, a benzofuran heterocyclic group and a thiophene heterocyclic group.

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

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

[0009] In a specific embodiment, preferably, the β-triazole derivatives include the following compounds:

[0010]

[0011] The present invention also provides a method for synthesizing a β-triazole derivative, which uses an alkyl compound / aldehyde / disulfide / diselenide, styrene and a triazole compound as raw materials, adds an oxidant and an additive in an organic solvent, and reacts to obtain a β-triazole derivative shown in formula (I); the reaction process is shown in reaction formula (II):

[0012]

[0013] Wherein, 1 is an alkyl radical, carbonyl radical, sulfide radical, or seleno radical generated by an alkyl compound / aldehyde / disulfide / diselenide under the action of an oxidant and an additive; R 1 , R2 , R 3 The definition of R is the same as that of formula (I). 4 It is methylsulfonyl and p-toluenesulfonyl.

[0014] In the synthesis reaction of the present invention, the molar ratio of the alkyl compound / aldehyde / disulfide / diselenide, 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, iodine ketone, sodium iodide, elemental iodine, etc.; preferably, it is copper tetraacetonitrile hexafluorophosphate.

[0016] Wherein, the oxidant is selected from one or more of tert-butyl peroxide, dibenzoyl peroxide, 2,3-dichloro-5,6-dicyanobenzoquinone, potassium persulfate, ammonium persulfate, etc.; preferably, it is tert-butyl peroxide.

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

[0018] Wherein, the amount of the oxidant used is 100-150% of the molar amount of the alkyl compound / aldehyde / disulfide / diselenide based on the alkyl compound / aldehyde / disulfide / diselenide; preferably, the amount of the oxidant used is 120% of the molar amount of the alkyl compound / aldehyde / disulfide / diselenide based on the alkyl compound / aldehyde / disulfide / diselenide.

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

[0020] The amount of the organic solvent is based on the triazole compound shown in substrate 3, so 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 50° C. The reaction time is 18-24 h, preferably 20 h.

[0022] The method of the present invention specifically comprises the following steps: taking a 4 mL two-necked bottle, first adding a solid, then replacing nitrogen three times, and finally dissolving a liquid compound in an organic solvent and adding the solution to a two-necked bottle protected by nitrogen, and reacting the solution at 50-90° C. for 18-24 hours to obtain a β-triazole derivative represented by formula (I).

[0023] The method further comprises the step of separating and purifying the compound obtained by the reaction; the separation and purification is performed 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 the present invention is shown in the following formula (III):

[0025]

[0026] Among them, R 1 , R 2 , R 3 The same as defined in formula (I).

[0027] Mechanism description: Alkyl compounds / aldehydes / disulfides / diselenides generate R under the action of oxidants and additives. 1 Free radical, R 1 The free radical then adds to the olefin to generate the secondary free radical 2i, which then attacks the N2 position of the triazole and simultaneously triggers the departure of the triazole sulfonyl group, ultimately generating compound 4. Due to the steric hindrance effect of the triazole N1, 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 use of the beta-triazolone derivative in the preparation of an anti-tumor cell active drug.

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

[0030] The β-triazole derivatives of the present invention include β-triazole trifluoromethyl, β-triazolone, β-triazole thio and β-triazole seleno derivatives.

[0031] The beneficial effects of the present invention are as follows: a synthesis method and application of β-triazole derivatives are provided, wherein triazole compounds, styrene and alkyl compounds / aldehydes / disulfide / diselenide are used as raw materials, Cu(CH 3 CN) 4 PF 6 Or NaI is used as an additive, tert-butyl peroxide or ammonium persulfate is used as an oxidant, and in an organic solvent, a one-step reaction can be performed with high selectivity (100% N 2 ), and obtain β-triazole derivatives with high yield (50-90%). The triazole skeleton contained in the β-triazolone derivatives involved in the present invention is an important structural fragment of many complex natural products with biological activity. Therefore, this type of compound can be used as an important intermediate in medicine and chemical industry and has broad application prospects in the field of medicine. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

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

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

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

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

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

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

[0040] Fig. 9 The product obtained in Example 4 of the present invention 19 Schematic diagram of F NMR.

[0041] Fig.10 The product obtained in Example 4 of the present invention 13 Schematic diagram of C NMR.

[0042] Fig.11 The product obtained in Example 5 of the present invention 1 Schematic diagram of H NMR.

[0043] Fig.12 The product obtained in Example 5 of the present invention 13 Schematic diagram of C NMR.

[0044] Fig.13 The product obtained in Example 6 of the present invention 1 Schematic diagram of H NMR.

[0045] Fig.14 The product obtained in Example 6 of the present invention 13 Schematic diagram of C NMR.

[0046] Fig.15 The product obtained in Example 7 of the present invention 1 Schematic diagram of H NMR.

[0047] Fig.16 The product obtained in Example 7 of the present invention 13 Schematic diagram of C NMR.

[0048] Fig.17 The product obtained in Example 8 of the present invention 1 Schematic diagram of H NMR

[0049] Fig.18 The product obtained in Example 8 of the present invention 13 Schematic diagram of C NMR.

[0050] Fig.19 The product obtained in Example 9 of the present invention 1 Schematic diagram of H NMR.

[0051] Fig. 20 The product obtained in Example 9 of the present invention 13 Schematic diagram of C NMR.

[0052] Fig.21 The product obtained in Example 10 of the present invention 1 Schematic diagram of H NMR.

[0053] Fig. 22 The product obtained in Example 10 of the present invention 13 Schematic diagram of C NMR.

[0054] Fig.23 The product obtained in Example 11 of the present invention 1 Schematic diagram of H NMR.

[0055] Fig.24 The product obtained in Example 11 of the present invention 13 Schematic diagram of C NMR.

[0056] Fig.25 The product obtained in Example 12 of the present invention 1 Schematic diagram of H NMR.

[0057] Fig.26 The product obtained in Example 12 of the present invention 13 Schematic diagram of C NMR.

[0058] Fig. 27 The product obtained in Example 13 of the present invention1 Schematic diagram of H NMR.

[0059] Fig.28 The product obtained in Example 13 of the present invention 13 Schematic diagram of C NMR.

[0060] Fig.29 The product obtained in Example 14 of the present invention 1 Schematic diagram of H NMR.

[0061] Fig.30 The product obtained in Example 14 of the present invention 13 Schematic diagram of C NMR.

[0062] Fig.31 The product obtained in Example 15 of the present invention 1 Schematic diagram of H NMR.

[0063] Fig.32 The product obtained in Example 15 of the present invention 19 Schematic diagram of F NMR.

[0064] Fig.33 The product obtained in Example 15 of the present invention 13 Schematic diagram of C NMR.

[0065] Fig.34 The product obtained in Example 16 of the present invention 1 Schematic diagram of H NMR.

[0066] Fig.35 The product obtained in Example 16 of the present invention 13 Schematic diagram of C NMR.

[0067] Fig.36 The product obtained in Example 17 of the present invention 1 Schematic diagram of H NMR.

[0068] Fig.37 The product obtained in Example 17 of the present invention 13 Schematic diagram of C NMR.

[0069] Fig.38 The product obtained in Example 18 of the present invention 1 Schematic diagram of H NMR.

[0070] Fig.39 The product obtained in Example 18 of the present invention 19 Schematic diagram of F NMR.

[0071] Fig.40 The product obtained in Example 18 of the present invention 13 Schematic diagram of C NMR.

[0072] Fig.41 The product obtained in Example 19 of the present invention 1 Schematic diagram of H NMR.

[0073] Fig.42 The product obtained in Example 19 of the present invention 13 Schematic diagram of C NMR.

[0074] Fig.43 The product obtained in Example 20 of the present invention 1 Schematic diagram of H NMR.

[0075] Fig.44 The product obtained in Example 20 of the present invention 13 Schematic diagram of C NMR.

[0076] Fig.45 The product obtained in Example 21 of the present invention 1 Schematic diagram of H NMR.

[0077] Fig.46 The product obtained in Example 21 of the present invention 13 Schematic diagram of C NMR.

[0078] Fig.47 The product obtained in Example 22 of the present invention 1 Schematic diagram of H NMR.

[0079] Fig.48 The product obtained in Example 22 of the present invention 13 Schematic diagram of C NMR.

[0080] Fig.49 The product obtained in Example 23 of the present invention 1 Schematic diagram of H NMR.

[0081] Fig.50 The product obtained in Example 23 of the present invention 13 Schematic diagram of C NMR.

[0082] Fig.51 The product obtained in Example 24 of the present invention 1 Schematic diagram of H NMR.

[0083] Fig.52 The product obtained in Example 24 of the present invention 13 Schematic diagram of C NMR.

[0084] Fig.53 The product obtained in Example 25 of the present invention 1 Schematic diagram of H NMR.

[0085] Fig.54 The product obtained in Example 25 of the present invention 13 Schematic diagram of C NMR.

[0086] Fig.55 The product obtained in Example 26 of the present invention 1 Schematic diagram of H NMR.

[0087] Fig.56 The product obtained in Example 26 of the present invention 13 Schematic diagram of C NMR.

[0088] Fig.57 The product obtained in Example 27 of the present invention 1 Schematic diagram of H NMR.

[0089] Fig.58 The product obtained in Example 27 of the present invention 13 Schematic diagram of C NMR.

[0090] Fig.59 The product obtained in Example 28 of the present invention 1 Schematic diagram of H NMR.

[0091] Fig.60 The product obtained in Example 28 of the present invention 13 Schematic diagram of C NMR.

[0092] Fig.61 The product obtained in Example 29 of the present invention 1 Schematic diagram of H NMR.

[0093] Fig.62 The product obtained in Example 29 of the present invention 13 Schematic diagram of C NMR.

[0094] Fig.63 The product obtained in Example 30 of the present invention 1 Schematic diagram of H NMR.

[0095] Fig.64 The product obtained in Example 30 of the present invention 13 Schematic diagram of C NMR.

[0096] Fig.65 The product obtained in Example 31 of the present invention 1 Schematic diagram of H NMR.

[0097] Fig.66 The product obtained in Example 31 of the present invention 19 Schematic diagram of F NMR.

[0098] Fig.67 The product obtained in Example 31 of the present invention13 Schematic diagram of C NMR.

[0099] Fig.68 The product obtained in Example 32 of the present invention 1 Schematic diagram of H NMR.

[0100] Fig.69 The product obtained in Example 32 of the present invention 13 Schematic diagram of C NMR.

[0101] Fig.70 The product obtained in Example 33 of the present invention 1 Schematic diagram of H NMR.

[0102] Fig.71 The product obtained in Example 33 of the present invention 13 Schematic diagram of C NMR.

[0103] Fig.72 The product obtained in Example 34 of the present invention 1 Schematic diagram of H NMR.

[0104] Fig.73 The product obtained in Example 34 of the present invention 13 Schematic diagram of C NMR.

[0105] Fig.74 The product obtained in Example 35 of the present invention 1 Schematic diagram of H NMR.

[0106] Fig.75 The product obtained in Example 35 of the present invention 13 Schematic diagram of C NMR.

[0107] Fig.76 The product obtained in Example 36 of the present invention 1 Schematic diagram of H NMR.

[0108] Fig.77 The product obtained in Example 36 of the present invention 13 Schematic diagram of C NMR.

[0109] Fig.78 The product obtained in Example 37 of the present invention 1 Schematic diagram of H NMR.

[0110] Fig.79 The product obtained in Example 37 of the present invention 13 Schematic diagram of C NMR.

[0111] Fig.80 The product obtained in Example 38 of the present invention 1 Schematic diagram of H NMR.

[0112] Fig.81 The product obtained in Example 38 of the present invention 13 Schematic diagram of C NMR.

[0113] Fig.82 The product obtained in Example 39 of the present invention 1 Schematic diagram of H NMR.

[0114] Fig.83 The product obtained in Example 39 of the present invention 13 Schematic diagram of C NMR.

[0115] Fig.84 The product obtained in Example 40 of the present invention 1 Schematic diagram of H NMR.

[0116] Fig.85 The product obtained in Example 41 of the present invention 19 Schematic diagram of FNMR.

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

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

[0119] Fig.88 is the inhibition rate of β-triazolone compounds on colon cancer cells HCT116. DETAILED DESCRIPTION

[0120] The present invention is further described in detail in conjunction with the following specific embodiments and drawings, and the protection content of the present invention is not limited to the following embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the claims.

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

[0122]

[0123] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6(0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4a with a yield of 68%. 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 N 3 O(M+H) + 354.1603,Found:354.1606.

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

[0125]

[0126] Take a 4 mL two-necked bottle, add 4-(3-fluorophenyl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4b with a yield of 72%. 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 FN 3 O(M+H) + 372.1497,Found:372.1502.

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

[0128]

[0129] Take a 4 mL two-necked bottle, add 4-(3-chlorophenyl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4c with a yield of 70%.1 H 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 C1N 3 O(M+H) + 388.1248,Found:388.1247.

[0130] Example 4 3-(4-(4-Fluorophenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4d)

[0131]

[0132] Take a 4 mL two-necked bottle, add 4-(4-fluorophenyl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4d with a yield of 73%. 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 FN 3 O(M+H) + 372.1497,Found:372.1505.

[0133] Example 5 3-(4-(4-ethylphenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4e)

[0134]

[0135] Take a 4 mL two-necked bottle, add 4-(4-ethylphenyl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4d with a yield of 71%. 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 N 3 O(M+H) + 382.1918,Found:382.1919.

[0136] Example 6 3-(4-(4-methoxyphenyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4f)

[0137]

[0138] Take a 4 mL two-necked bottle, add 4-(4-methoxyphenyl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4f with a yield of 70%. 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 N 3 O 2 (M+H) + 384.1716,Found:384.1712.

[0139] Example 7 3-(4-([1,1'-biphenyl]-4-yl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4 g)

[0140]

[0141] Take a 4 mL two-necked bottle, add 4-([1,1'-biphenyl]-4-yl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain 4g of β-triazolone with a yield of 76%. 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 N 3 O(M+H) + 429.1836,Found:429.1839.

[0142] Example 8 3-(4-Butyl-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4h)

[0143]

[0144] Take a 4 mL two-necked bottle, add 4-butyl-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone with a yield of 58%. 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 N 3 O(M+H) + 334.1635,Found:334.1643.

[0145] Example 9 3-(4-(tert-butyl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4i)

[0146]

[0147] Take a 4 mL two-necked bottle, add 4-(tert-butyl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4i with a yield of 56%. 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 N 3 OS(M+H) + 333.1865,Found:333.1873.

[0148] Example 10 1,3-Diphenyl-3-(4-(thiophen-3-yl)-2H-1,2,3-triazol-2-yl)propan-1-one (4j)

[0149]

[0150] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-(thiophen-3-yl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4j with a yield of 63%. 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).13 C 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 N 3 OS(M+H) + 360.1165,Found:360.1171.

[0151] Example 11 3-(4-(Benzothiophene-2-yl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (4k)

[0152]

[0153] Take a 4 mL two-necked bottle, add 4-(benzothiophen-2-yl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4k with a yield of 67%. 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 N 3 OS(M+H) + 410.1266,Found:410.1260.

[0154] Example 12 3-(4-(Benzofuran-2-yl)-2H-1,2,3-triazol-2-yl)-1,3-diphenylpropan-1-one (41)

[0155]

[0156] Take a 4 mL two-necked bottle, add 4-(benzofuran-2-yl)-1-(methylsulfonyl)-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4l with a yield of 65%. 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 N 3 OS(M+H) + 394.1556,Found:394.1547.

[0157] Example 13 1-(3-bromophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4m)

[0158]

[0159] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, 3-bromobenzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4m with a yield of 72%. 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 19 Bn 3 O(M+H) + 432.0730,Found:432.0721.

[0160] Example 14 1-(3,5-dichlorophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4n)

[0161]

[0162] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, 3,4-dichlorobenzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4n with a yield of 72%. 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 Cl 2 N 3 O(M+H) + 422.0837,Found:422.0827.

[0163] Example 15 1-(4-Fluorophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4o)

[0164]

[0165] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, p-fluorobenzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4o with a yield of 68%. 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 FN 3 O(M+H) + 372.1497,Found:372.1502.

[0166] Example 16 1-(4-chlorophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4p)

[0167]

[0168] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, p-chlorobenzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4p with a yield of 71%. 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 C1N 3 O(M+H) + 388.1321,Found:388.1328.

[0169] Example 17 1-(4-bromophenyl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4q)

[0170]

[0171] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6(0.02mol) and then replaced with nitrogen three times. Finally, p-bromobenzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4q with a yield of 68%. 1 H 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 for C 23 H 19 Bn 3 O(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)propan-1-one (4r)

[0173]

[0174] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, p-trifluoromethoxybenzaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4r with a yield of 74%. 1H 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 F 3 N 3 O 2 (M+H) + 438.1421,Found:438.1429.

[0175] Example 19 3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)-1-(p-tolyl)propan-1-one (4s)

[0176]

[0177] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, p-anisaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4s with a yield of 74%. 1H 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 C 24 H 22 F 3 N 3 O 2 (M+H) + 384.1712,Found:384.1716.

[0178] Example 20 3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)-1-(thiophen-2-yl)propan-1-one (4t)

[0179]

[0180] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, thiophene-2-carboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4s with a yield of 73%. 1H 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 for C 21 H 18 N 3 OS(M+H) + 360.1165,Found:360.1171.

[0181] Example 21 3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)-1-(thiophen-3-yl)propan-1-one (4u)

[0182]

[0183] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, thiophene-3-carboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4u with a yield of 72%. 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 for C 21 H 18 N 3 OS(M+H) + 360.1165,Found:360.1171.

[0184] Example 22 1-(Benzothiophen-2-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4v)

[0185]

[0186] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzothiophene-2-carboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4v with a yield of 70%. 1 H 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 N 3 OS(M+H) + 410.1357,Found:410.1348.

[0187] Example 23 1-(Benzofuran-2-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4w)

[0188]

[0189] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzofuran-2-carboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into a two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4w with a yield of 69%. 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). 13 C 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 N 3 O 2 (M+H) + 394.1548,Found:394.1556.

[0190] Example 24 1-(Benzo[d][1,3]dihydroxy-5-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4x)

[0191]

[0192] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, piperonal (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into a two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4x with a yield of 68%. 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 N 3 O 2 (M+H) + 398.1512,Found:398.1505.

[0193] Example 25 1-Cyclopropyl-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4y)

[0194]

[0195] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, cyclopropanecarboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4y with a yield of 72%. 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(101MHz,Chloroform-d)δ206.6,147.5,139.3,131.0,130.4,128.9,128.8, 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 N 3 O(M+H) + 318.1598,Found:318.1606.

[0196] Example 26 1-cyclobutyl-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4z)

[0197]

[0198] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6(0.02mol) and then replaced nitrogen three times. Finally, cyclobutanecarboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4z with a yield of 72%. 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 N 3 O(M+H) + 332.1773,Found:332.1777.

[0199] Example 27 1-Cyclopentyl-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4aa)

[0200]

[0201] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, cyclopentanecarboxaldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4aa with a yield of 72%. 1H 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 N 3 O(M+H) + 346.1919,Found:346.1909.

[0202] Example 28 1-phenyl-1-(4-phenyl-2H-1,2,3-triazol-2-yl)hexan-3-one (4ab)

[0203]

[0204] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced with nitrogen three times. Finally, n-butyraldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4ab with a yield of 72%. 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 N 3 O(M+H) + 320.1716,Found:320.1725.

[0205] Example 29 1-phenyl-1-(4-phenyl-2H-1,2,3-triazol-2-yl)heptan-3-one (4ac)

[0206]

[0207] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, n-valeraldehyde (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4ac with a yield of 72%. 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 N 3 O 334.1917,Found:334.1919.

[0208] Example 30 1-phenyl-1-(4-phenyl-2H-1,2,3-triazol-2-yl)decan-3-one (4ad)

[0209]

[0210] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, n-dodecanal (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into a two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4ad with a yield of 72%. 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 N 3 O(M+H) + 376.2399,Found:376.2404.

[0211] Example 31 3-(4-Fluorophenyl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4ae)

[0212]

[0213] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), p-fluorostyrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4ae with a yield of 68%. 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 FN 3 O 372.1491,Found:372.1497.

[0214] Example 32 3-(4-chlorophenyl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4af)

[0215]

[0216] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), p-chlorostyrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4af with a yield of 70%. 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 C1N 3 O(M+H) + 387.1123,Found:387.1128.

[0217] Example 33 3-([1,1'-biphenyl]-4-yl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4ag)

[0218]

[0219] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), p-phenylethylene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into a two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4ag with a yield of 62%. 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 N 3 O(M+H) + 430.1945,Found:430.1949.

[0220] Example 34 1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)-3-(p-tolyl)propan-1-one (4ah)

[0221]

[0222] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), p-methylstyrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into a two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4ah with a yield of 72%. 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 N 3 O(M+H) + 368.1748,Found:368.1742.

[0223] Example 35 3-(Naphthalen-2-yl)-1-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4ai)

[0224]

[0225] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), naphthalene styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4ai with a yield of 66%. 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 N 3 O(M+H) + 404.1767,Found:404.1763.

[0226] Example 36 1,2,3-Triphenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4aj)

[0227]

[0228] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, benzaldehyde (0.4mmol), diphenylethylene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazolone 4aj with a yield of 50%. 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 N 3 O(M+H) + 429.1887,Found:429.1881.

[0229] Example 37 1-(Naphthalen-2-yl)-3-phenyl-3-(4-phenyl-2H-1,2,3-triazol-2-yl)propan-1-one (4ak)

[0230]

[0231] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, 2-naphthaldehyde (0.4mmol), diphenylethylene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was reacted at 50℃ for 18h to obtain β-triazolone 4ak with a yield of 40%. 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 N 3 O(M+H) + 404.1767,Found:404.1763.

[0232] Example 38 4-phenyl-2-(1-phenyl-2-(phenylthio)ethyl)-2H-1,2,3-triazole (4al)

[0233]

[0234] Take a 4mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2mmol), NaI (0.02mol), then replace nitrogen three times, and finally add diphenyl sulfide (0.4mmol), styrene (0.4mmol), (NH 4 ) 2 S 2 O 4 (0.6mmol) was dissolved in 2ml of dichloroethane, then injected into a two-necked bottle with a syringe, and finally reacted at 80℃ for 18h 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.

[0235] Example 39 4-phenyl-2-(1-phenyl-2-(phenylseleno)ethyl)-2H-1,2,3-triazole (4am)

[0236]

[0237] Take a 4mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2mmol), NaI (0.02mol), then replace nitrogen three times, and finally add diphenyl selenide (0.4mmol), styrene (0.4mmol), (NH 4 ) 2 S 2 O 4 (0.6mmol) was dissolved in 2ml of dichloroethane, then injected into a two-necked bottle with a syringe, and finally reacted at 80℃ for 18h to obtain 83% yield of β-triazole seleno compound 4am. 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.

[0238] Example 40 4-phenyl-2-(3,3,3-trifluoro-1-phenylpropyl)-2H-1,2,3-triazole (4an)

[0239]

[0240] Take a 4 mL two-necked bottle, add 1-(methylsulfonyl)-4-phenyl-1H-1,2,3-triazole (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (0.02mol) and then replaced nitrogen three times. Finally, sodium trifluoromethanesulfonate (0.4mmol), styrene (0.4mmol), and TBHP (0.6mmol) were dissolved in 2ml of dichloroethane and then injected into the two-necked bottle with a syringe. Finally, it was placed at 50℃ for 18h to obtain β-triazole 4an with a yield of 50%. 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.

[0241] Example 41 Anti-tumor cell activity test experiment:

[0242] 1. Inoculation of cells:

[0243] 1) A single cell suspension was prepared using DMEM culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and 2500 MNG / HOS osteosarcoma cells were inoculated into a 96-well cell culture plate in each well, with a volume of 100 μL per well.

[0244] 2) A single cell suspension was prepared using RPMI1640 culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and 2500 SJSA-1 osteosarcoma cells were inoculated into a 96-well cell culture plate in each well, with a volume of 100 μL per well.

[0245] 3) A single cell suspension was prepared using McCoy's 5A culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and 2500 HCT116 osteosarcoma cells were seeded into a 96-well cell culture plate in each well, with a volume of 100 μl per well.

[0246] 4) A single cell suspension was prepared using MEM culture medium containing 10% fetal bovine serum, 1% penicillin and streptomycin, and 2500 143B osteosarcoma cells were inoculated into a 96-well cell culture plate in each well, with a volume of 100 μl per well.

[0247] 2. Administration: The compound of formula (I) synthesized in the above examples of the present invention was prepared into a stock solution with a final concentration of 10 mM using DMSO, diluted to 10 μM using complete culture medium, and applied to the cells in three replicate wells.

[0248] 3. Cultivation: Cultivate in an incubator with 5% CO2 and 37°C saturated humidity for 72 hours.

[0249] 4. Color development: After 72 hours of culture, aspirate the culture medium, add 100 μL complete culture medium and 10 μL CCK8 to each well, and incubate at 37°C for 2-4 hours.

[0250] 5. Colorimetry: Select 620nm and 450nm wavelengths, measure the optical density (OD) value of each well on the microplate reader, and record the results.

[0251] 6. For the same well, the absorbance value at 450 nm minus the absorbance value at 620 nm (background absorbance value) is used as the final absorbance and substituted into the following formula.

[0252] 7. Cell proliferation activity (%) = [A(drug added) - A(blank)] / [A(no drug added) - A(blank)] × 100%.

[0253] A (drug addition): absorbance of wells with osteosarcoma cells, CCK8 solution (Cell Counting Kit-8, a rapid and highly sensitive detection reagent for cell proliferation and cytotoxicity based on WST-8 (chemical name: 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfonylbenzene)-2H-tetrazolyl monosodium salt)) and drug solution (drug solution refers to DMSO solution of the compound sample to be tested)

[0254] A (blank): absorbance of wells with culture medium and CCK8 solution but no cells

[0255] A (no drug added): absorbance of the well with cells and CCK8 solution but no drug solution 8. The experimental results show that under the action of the compound of formula (I) of the present invention at a concentration of 10 μM, the survival rates of four different subtypes of osteosarcoma cells are as follows: Figures 86-88 As shown:

[0256] The results showed that compounds 4e and 4x showed good inhibitory activity against osteosarcoma cells MNG / HOS; compounds 4c, 4e, 4u, 4x, and 4ak showed 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 showed good inhibitory activity against osteosarcoma cells HCT116; compounds 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4l, 4n, 4o, 4r, 4t, 4u, 4w, 4x, and 4ae showed relatively good inhibitory activity against osteosarcoma cells 143B.

Claims

1. A β-triazole derivative, characterized in that: Its structure is shown in formula (I): Among them, R 1 is alkyl, carbonyl, thio or seleno; R 2 is an aryl group, an aryl group substituted with an electron donating group, an aryl group substituted with an electron withdrawing group, or a heterocyclic aryl group; R 3 It is an alkyl group, an aryl group, an aryl group substituted with an electron donating group, an aryl group substituted with an electron withdrawing group, a benzothiophene heterocyclic group, a benzofuran heterocyclic group, or a thiophene heterocyclic group.

2. The β-triazole derivative according to claim 1, characterized in that R 1 It is carbonyl, thio, seleno; R 2 is aryl, aryl substituted with an electron donating group, aryl substituted with an electron withdrawing group, or naphthyl; R 3 It is a C1-20 alkyl group, an aryl group, an aryl group substituted with an electron donating group, an aryl group substituted with an electron withdrawing group, a benzothiophene heterocyclic group, a benzofuran heterocyclic group, or a thiophene heterocyclic group.

3. The β-triazole derivative according to claim 1, characterized in that The compounds included are as follows:

4. A method for synthesizing a β-triazole derivative, characterized in that: An alkyl compound / aldehyde / disulfide / diselenide, styrene and a triazole compound are used as raw materials, an oxidant and an additive are added in an organic solvent, and a β-triazole derivative represented by formula (I) is obtained by reaction; the reaction process is shown in reaction formula (II): Wherein, 1 is an alkyl radical, carbonyl radical, sulfide radical, or seleno radical generated by an alkyl compound / aldehyde / disulfide / diselenide under the action of an oxidant and an additive; R 1 is alkyl, carbonyl, thio or seleno; R 2 is an aryl group, an aryl group substituted with an electron-donating group, an aryl group substituted with an electron-withdrawing group, or a heterocyclic aryl group; R 3 is an alkyl group, an aryl group, an aryl group substituted with an electron-donating group, an aryl group substituted with an electron-withdrawing group, a benzothiophene heterocyclic group, a benzofuran heterocyclic group, or a thiophene heterocyclic group; R 4 It is methylsulfonyl and p-toluenesulfonyl.

5. The synthesis method according to claim 4, characterized in that The reaction temperature is 50-90°C; and / or the reaction time is 18-24h.

6. The synthesis method according to claim 4, characterized in that The molar ratio of the alkyl compound / aldehyde / disulfide / diselenide, 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 alkyl compound / aldehyde / disulfide / diselenide based on the alkyl compound / aldehyde / disulfide / diselenide.

7. The synthesis method according to claim 4, characterized in that The oxidant is selected from one or more of tert-butyl peroxide, dibenzoyl peroxide, 2,3-dichloro-5,6-dicyanobenzoquinone, potassium persulfate, and ammonium persulfate; and / or, the additive is selected from one or more of tetraacetonitrile copper hexafluorophosphate, tetraacetonitrile copper hexafluoroborate, copper bromide, iodine ketone, sodium iodide, and elemental iodine; and / or, The organic solvent is selected from one or more of DCM, DCE, EA, toluene and acetonitrile; and / or, the amount of the organic solvent is based on the substrate triazole compound, so that the concentration of the triazole compound in the organic solvent ranges from 0.05M to 0.15M.

8. The synthesis method according to claim 4, characterized in that Furthermore, the β-triazole derivative obtained by the reaction is separated and purified; the separation and purification is performed by column chromatography using a solution with a volume ratio of ethyl acetate: petroleum ether = 1:30 to 1:

20.

9. Use of the β-triazole derivative according to any one of claims 1 to 3 in the preparation of a drug having anti-tumor cell activity.

10. The use according to claim 9, characterized in that The tumor cells are one or more of MNG / HOS osteosarcoma cells, HCT116 osteosarcoma cells, SJSA-1 osteosarcoma cells, and 143B osteosarcoma cells.

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