CN109111406B

CN109111406B - Synthesis method of perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound

Info

Publication number: CN109111406B
Application number: CN201811244795.5A
Authority: CN
Inventors: 翁志强; 吴伟
Original assignee: Fuzhou University
Current assignee: Fuzhou University
Priority date: 2018-10-24
Filing date: 2018-10-24
Publication date: 2021-12-17
Anticipated expiration: 2038-10-24
Also published as: CN109111406A

Abstract

The invention discloses a copper-catalyzed one-pot method for synthesizing perfluoroalkyl or difluoromethyl-1,2,4-triazinone compounds, which uses copper salts as catalysts, 2,2'-bipyridine Derivatives are ligands, azide, alkyne, perfluorocarboxylic acid anhydride or difluoroacetic anhydride are raw materials, and in the environment of tetrahydrofuran, n-hexane/tetrahydrofuran or dichloromethane as solvents, stir at 30-60 ° C for 1- After 30 hours, the perfluoroalkyl or difluoromethyl-1,2,4-triazinone compound is obtained through column chromatography purification. The synthesis method of the invention has the advantages of cheap catalyst, easy availability, low toxicity, high yield, simple operation, good functional group universality and the like; at the same time, the obtained perfluorinated compound has better inhibitory activity against cucumber downy mildew and other pathogens , can be used as a new type of fungicide.

Description

Synthesis method of perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound

Technical Field

The invention belongs to the technical field of chemical synthesis of organic fluorine, and particularly relates to a method for synthesizing a perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound by copper catalysis.

Background

The introduction of fluorine-containing groups into organic molecules can greatly change the physicochemical properties and biological properties of the molecules, such as enhancing the lipid solubility of the molecules, improving the bioavailability of drugs and the like, and is one of the important research strategies for the modification of the chemical structure of drugs. Therefore, it is one of the research hotspots of synthetic chemistry to research how to efficiently and selectively introduce perfluoroalkyl or difluoromethyl into organic active molecules. 1,2, 4-triazone as a heterocyclic compound shows better biological activity in the aspects of killing insects, sterilizing, resisting cancers, resisting ulcers and regulating plant growth. The perfluoroalkyl group or difluoromethyl group is introduced into the 1,2, 4-triazone compound, so that the bioactivity of the compound can be enhanced, the compound has different characteristics from non-fluorine organic molecules, and the compound has important theoretical research significance and practical application value. We have previously reported a method for copper-catalyzed synthesis of trifluoromethyl-1, 2, 4-triazinone compounds (Chinese patent 201710259314.7), and on the basis of the method, we continue to expand the application range of the reaction and report a method for synthesizing perfluoroalkyl or difluoromethyl-1, 2, 4-triazinone compounds.

Disclosure of Invention

The invention aims to provide a method for synthesizing perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compounds by copper catalysis, which utilizes catalysts and raw materials which are cheap and easy to obtain, has generally higher yield, good adaptability of functional groups, mild reaction conditions and simple and convenient operation, and the obtained compounds containing perfluoro have better inhibitory activity on pathogens such as cucumber downy mildew and the like, and can be used as a novel bactericide.

In order to achieve the purpose, the invention adopts the following technical scheme:

a process for synthesizing perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound includes such steps as preparing copper salt as catalyst, preparing 2, 2' -bipyridine derivative as ligand, and preparing azide(s)

) Alkyne (a)

) The perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound is prepared by a one-pot method with perfluorocarboxylic anhydride or difluoroacetic anhydride as raw materials; the reaction formula is as follows:

。

wherein the copper salt is cuprous iodide, CuBr, CuCl, Cu (OTf)₂、Cu(CH₃CN)₄BF₄And CuCN.

The 2,2 '-bipyridine derivative is any one of 2, 2' -bipyridine, 5 '-dimethyl-2, 2' -bipyridine, 4 '-dimethyl-2, 2' -bipyridine and 4,4 '-di-tert-butyl-2, 2' -bipyridine (dtbpy), and is preferably 4,4 '-di-tert-butyl-2, 2' -bipyridine.

The azide

Wherein the R' group is any one of the following formulas 1 to 23:

。

the alkyne

The group R '' in (A) is any one of the following formulae 24 to 41:

。

the synthesis method of the perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound comprises the following specific steps: adding copper salt, 2' -bipyridine derivatives, azide, alkyne, perfluorocarboxylic anhydride or difluoroacetic anhydride, triethylamine and a solvent into a container with a magnetic stirring device in a nitrogen atmosphere, uniformly mixing, closing a plug, putting the container at 30-60 ℃, continuously stirring for 1-30 hours, filtering by using 100-200-mesh silica gel, washing by using dichloromethane, combining organic phases, and then removing the organic solvent by rotary evaporation; and (3) carrying out silica gel column chromatography on the obtained crude product, and eluting by using n-pentane-dichloromethane or n-pentane-ethyl acetate as an eluent to obtain the perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound.

The solvent is any one of a n-hexane/tetrahydrofuran mixed solvent and dichloromethane, and preferably a n-hexane/tetrahydrofuran mixed solvent or a dichloromethane solvent.

The molar ratio of the used copper salt, 2' -bipyridine derivative, alkyne, azide, perfluorocarboxylic anhydride, triethylamine, n-hexane and tetrahydrofuran is (0.015-0.05): (0.0075-0.025): (0.3-1): 0.36-1.2): 0.39-1.3): 0.45-1.5): 0-13): 6-20; the molar ratio of the copper salt, the 2, 2' -bipyridine derivative, alkyne, azide, difluoroacetic anhydride, triethylamine and dichloromethane is (0.01-0.05): (0.005-0.025): 0.2-1): 0.4-2): 0.3-1.5): 23-117.

The obtained perfluoroalkyl group or difluoromethyl-1, 2, 4-triazone compound has good inhibitory activity on pathogens such as cucumber downy mildew and the like, and can be used as a novel bactericide.

The invention has the beneficial effects that:

(1) the invention takes cheap and easily obtained azide, alkyne, perfluorocarboxylic anhydride or difluoroacetic anhydride and the like as raw materials, takes copper salt as a catalyst and 2, 2' -bipyridine derivatives as ligands, and synthesizes perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compounds by a one-pot method, and the compounds have the advantages of higher yield, good adaptability of functional groups, mild reaction conditions, simple and convenient operation and good industrial application prospect.

(2) The obtained perfluoro-compound has better inhibitory activity to pathogens such as cucumber downy mildew and the like, and can be used as a novel bactericide.

Drawings

FIG. 1 is a reaction scheme of the synthesis reaction of the present invention.

FIG. 2 shows 3- (pentafluoroethyl) -6-phenyl-4- (3-phenylpropyl) -1,2, 4-triazine-5 (4) prepared in example 14H) -single crystal structure diagram of ketones.

Detailed Description

In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.

Example 1

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.45 mmol of triethylAmine, stirring and reacting for 15 h in a closed system under the condition of 50 ℃ oil bath, cooling to room temperature, taking trifluoromethoxybenzene as an internal standard, and measuring¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 8.40 (d, J = 7.5 Hz, 2H), 7.58 (dt, J = 25.9, 7.4 Hz, 3H), 7.44-7.30 (m, 5H), 4.36 (t, J = 8.0 Hz, 2H), 3.11 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.7 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 158.5 (s), 151.7 (s), 142.7 (t, J = 28.0 Hz), 136.6 (s), 132.2 (s), 131.5 (s), 129.7 (s), 129.0 (s), 128.9 (s), 128.5 (s), 127.3 (s), 122.3 (t, J = 33.6 Hz), 119.4 (t, J = 33.7 Hz), 116.6 (t, J = 33.6 Hz), δ 113.7 (t, J = 33.7 Hz), 113.3 (q, J = 38.6 Hz), 110.7 (q, J = 38.3 Hz), 108.1 (q, J = 38.5 Hz), 47.0 (t, J = 4.8 Hz), 34.2 (s)。

Example 2

Under the protection of nitrogen, 0.015mmol of cuprous bromide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.45 mmol of triethylamine is finally added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 98%. NMR data are given in example 1.

Example 3

Under the protection of nitrogen, 0.015mmol of Cu (CH) is added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirring bar₃CN)₄BF₄0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride, finally adding 0.45 mmol of triethylamine, stirring and reacting in a closed system under the condition of 50 ℃ oil bath for 15 hours, cooling to room temperature, and measuring to obtain 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4)H) Of-ketones¹⁹The yield of F was 51%. NMR data are given in example 1.

Example 4

Under the protection of nitrogen, 0.015mmol of cuprous cyanide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.45 mmol of triethylamine is finally added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 57%. NMR data are given in example 1.

Example 5

Under the protection of nitrogen, 0.015mmol of Cu (OTf) is added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirring bar₂0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride, finally adding 0.45 mmol of triethylamine, stirring and reacting in a closed system under the condition of 50 ℃ oil bath for 15 hours, cooling to room temperature, and measuring to obtain 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4)H) Of-ketones¹⁹The yield of F was 49%. NMR data are given in example 1.

Example 6

Under the protection of nitrogen, 0.015mmol of cuprous chloride, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine and 6.0 mmol of cuprous chloride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrerl tetrahydrofuran, 3.9 mmol n-hexane, 0.3 mmol phenylacetylene, 0.36 mmol (2-azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, and finally 0.45 mmol triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, and then the mixture is cooled to room temperature, and 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4) is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 48%. NMR data are given in example 1.

Example 7

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-dimethyl-2, 2' -bipyridine, 12 mmol of tetrahydrofuran, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system for 15 hours under the condition of 50 ℃ oil bath, then the mixture is cooled to room temperature, and 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4-pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 (4) is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 93%. NMR data are given in example 1.

Example 8

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 11.7 mmol of dichloromethane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system at the temperature of 50 ℃ for 15 hours, then the mixture is cooled to room temperature, and the 3- (pentafluoroethyl) -4-phenylethyl-6-phenyl-1, 2, 4-triazine-5 (4- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 93%. NMR data are given in example 1.

Example 9

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 9.4 mmol of dichloromethane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene, 0.39 mmol of pentafluoropropionic anhydride and finally 0.45 mmol of triethylamine are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirring barStirring and reacting for 15 h in a closed system under the condition of 50 ℃ oil bath, cooling to room temperature, and measuring to obtain 3- (pentafluoroethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4) by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 69%. NMR data are given in example 1.

Example 10

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 7.6 mmol of dichloromethane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system at the temperature of 50 ℃ for 15 hours, then the mixture is cooled to room temperature, and the 3- (pentafluoroethyl) -4-phenylethyl-6-phenyl-1, 2, 4-triazine-5 (4- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 68%. NMR data are given in example 1.

Example 11

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 12.5 mmol of dichloromethane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system at the temperature of 50 ℃ for 15 hours, then the mixture is cooled to room temperature, and the 3- (pentafluoroethyl) -4-phenylethyl-6-phenyl-1, 2, 4-triazine-5 (4- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F was 61%. NMR data are given in example 1.

Example 12

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 12.3 mmol of tetrahydrofuran, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ in an oil bath for 15 hours, then the mixture is cooled to room temperature, and 3- (pentafluoroethyl) -4-phenylethyl-6-phenylethyl is measured by taking trifluoromethoxybenzene as an internal standard-phenyl-1, 2, 4-triazine-5 (4)H) Of-ketones¹⁹Yield of F was 94%. NMR data are given in example 1.

Example 13

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 15.6 mmol of dichloromethane, 0.3 mmol of phenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system at the temperature of 50 ℃ for 15 hours, then the mixture is cooled to room temperature, and the 3- (pentafluoroethyl) -4-phenylethyl-6-phenyl-1, 2, 4-triazine-5 (4- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹Yield of F was 68%. NMR data are given in example 1.

Example 14

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of (3-azidopropyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.36 mmol of (3-azidopropyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added, finally 0.45 mmol of triethylamine are added, the mixture is stirred and reacted in a closed system under the oil bath condition of 60 ℃ for 15 hours, then the mixture is cooled to room temperature, and trifluoromethoxybenzene is taken as an internal standard, and the measured result shows that the content of the trifluoromethoxybenzene is high¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 3- (pentafluoroethyl) -6-phenyl-4- (3-phenylpropyl) -1,2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 8.38 (d, J = 7.5 Hz, 2H), 7.56 (dt, J = 26.9, 7.5 Hz, 3H), 7.35 (t, J = 7.2 Hz, 2H), 7.26 (d, J = 7.0 Hz, 3H), 4.23-4.13 (t, J = 7.5 Hz, 2H), 2.81 (t, J = 7.5 Hz, 2H), 2.22-2.09 (m, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -110.0 (s, 2F).¹³C NMR (101 MHz, CDCl₃) δ 158.3 (s), 151.6 (s), 142.8 (t, J = 27.7 Hz), 139.9 (s), 132.1 (s), 131.5 (s), 129.7 (s), 128.6 (s), 128.5 (s), 128.2 (s), 126.5 (s), 122.3 (t, J = 33.8 Hz), 119.4 (t, J = 33.8 Hz), 116.6 (t, J = 33.8 Hz), 113.7 (t, J = 33.9 Hz), 113.2 (q, J = 38.4 Hz), 110.6 (q, J = 38.3 Hz), 108.0 (q, J = 38.4 Hz), 45.5 (t, J= 4.9 Hz), 33.1 (s), 29.2 (s)。

Example 15

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 12.3 mmol of tetrahydrofuran, 0.30 mmol of phenylacetylene, 0.36 mmol of (3-azidopropyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 60 ℃ in an oil bath for 15 hours, then the mixture is cooled to room temperature, and the 3- (pentafluoroethyl) -6-phenyl-4- (3-phenylpropyl) -1,2, 4-triazine-5 (4-trifluoromethylbenzene is used as an internal standard to measureH) Of-ketones¹⁹F yield was 92%. NMR data are given in example 14.

Example 16

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of 4-cyanobenzene acetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the oil bath condition of 60 ℃ for 15 hours, then the mixture is cooled to room temperature, and trifluoromethoxybenzene is taken as an internal standard to measure the content¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 2, v/v) to obtain 4- (5-oxo-3- (pentafluoroethyl) -4-phenethyl-4, 5-dihydro-1, 2, 4-triazin-6-yl) benzonitrile (the separation yield is 99 percent).¹H NMR (400 MHz, CDCl₃) δ 8.51 (d, J = 8.0 Hz, 2H), 7.80 (d, J= 8.0 Hz, 2H), 7.43-7.29 (m, 5H), 4.38 (t, J = 8.0 Hz, 2H), 3.11 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.8 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 157.0 (s), 151.4 (s), 143.6 (t, J = 27.9 Hz), 136.3 (s), 135.5 (s), 132.1 (s), 130.1 (s), 129.1 (s), 128.9 (s), 127.5 (s), 122.2 (t, J = 33.5 Hz), 119.3 (t, J = 33.6 Hz), 118.1 (s), 116.5 (t, J = 33.7 Hz), 115.4 (s), 113.6 (t, J = 33.6 Hz), 113.1 (q, J = 38.4 Hz), 110.5 (q, J = 38.6 Hz), 107.9 (q, J = 38.4 Hz), 47.3 (t, J = 4.8 Hz), 34.2 (s)。

Example 17

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 12.3 mmol of tetrahydrofuran, 0.30 mmol of 4-cyanobenzene acetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.45 mmol of triethylamine is finally added, the mixture is stirred and reacted in a closed system under the condition of oil bath at 60 ℃ for 15 hours, then the mixture is cooled to room temperature, and the 4- (5-oxo-3- (pentafluoroethyl) -4-phenethyl-4, 5-dihydro-1, 2, 4-triazine-6-yl) benzonitrile is measured by taking trifluoromethoxybenzene as an internal standard¹⁹The yield of F was 75%. NMR data are given in example 16.

Example 18

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of 2-chlorophenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.36 mmol of (2-azidoethyl) benzene and 0.45 mmol of triethylamine are added, the mixture is stirred and reacted in a closed system under the condition of oil bath at 40 ℃ for 15 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard, so that the measured result is that¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 6- (2-chlorphenyl) -3- (pentafluoroethyl) -4-phenethyl-1,2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 7.60-7.54 (m, 2H), 7.48 (dd, J = 19.3, 7.3 Hz, 2H), 7.43-7.31 (m, 5H), 4.37 (t, J = 8.0 Hz, 2H), 3.12 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.8 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 161.6 (s), 151.0 (s), 143.9 (t, J = 27.9 Hz), 136.5 (s), 133.5 (s), 132.0 (s), 131.3 (s), 131.1 (s), 130.0 (s), 129.0 (s), 128.9 (s), 127.4 (s), 127.1 (s), 122.3 (t, J = 33.6 Hz), 119.4 (t, J = 33.7 Hz), 116.6 (t, J = 33.7 Hz), δ 113.7 (t J = 33.6 Hz), 113.2 (q, J = 38.6 Hz), 110.6 (q, J = 38.4 Hz), 108.1 (q, J = 38.1 Hz), 47.2 (t, J = 4.5 Hz), 34.1 (s)。

Example 19

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 12.3 mmol of tetrahydrofuran, 0.30 mmol of 2-chloroacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 40 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and the 6- (2-chlorophenyl) -3- (pentafluoroethyl) -4-phenethyl-1, 2, 4-triazine-5 (4-phenylethyl-1, 2, 4-triazine-5 (4) is measured by taking trifluoromethoxybenzene as an internal standardH) Of-ketones¹⁹The yield of F is more than 92%. NMR data are given in example 18.

Example 20

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of 3-bromophenylacetylene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.45 mmol of triethylamine is finally added, the mixture is stirred and reacted in a closed system under the condition of oil bath at the temperature of 30 ℃ for 15 hours, then the mixture is cooled to the room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is more than 99 percent, and the organic phases are combined and treated by 100-200Filtering silica gel, washing with dichloromethane, removing organic solvent by rotary evaporation to obtain crude product, purifying the crude product by silica gel column chromatography, eluting with n-pentane and dichloromethane (1: 1, v/v) to obtain 6- (3-bromophenyl) -3- (pentafluoroethyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 8.58 (s, 1H), 8.36 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.43-7.30 (m, 6H), 4.35 (t, J = 8.0 Hz, 2H), 3.09 (t, J= 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.7 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 157.0 (s), 151.3 (s), 143.1 (t, J = 27.8 Hz), 136.5 (s), 135.1 (s), 133.3 (s), 132.5 (s), 130.0 (s), 129.0 (s), 128.9 (s), 128.3 (s), 127.4 (s), 122.6 (s), 122.2 (t, J = 33.5 Hz), 119.4 (t, J = 33.6 Hz), 116.6 (t, J = 33.7 Hz), 113.7 (t, J = 33.7 Hz), 113.2 (q, J = 38.4 Hz) 110.6 (q, J = 38.4 Hz), 108.0 (q, J = 38.4 Hz), 47.08 (t, J = 4.7 Hz), 34.22 (s)。

Example 21

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of 2-ethynylnaphthalene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.45 mmol of triethylamine is finally added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 6- (2-naphthyl) -3- (pentafluoroethyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 9.16 (s, 1H), 8.45 (d, J = 8.7 Hz, 1H), 8.03 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.60 (dt, J = 15.0, 6.9 Hz, 2H), 7.44-7.32 (m, 5H), 4.39 (t, J = 8.0 Hz, 2H), 3.13 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.3 (s, 3F), -109.5 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 157.9 (s), 151.7 (s), 142.5 (t, J = 27.8 Hz), 136.6 (s), 135.0 (s), 132.8 (s), 131.8 (s), 129.7 (s), 129.0 (s), 128.9 (s), 128.9 (s), 128.4 (s), 128.3 (s), 127.7 (s), 127.4 (s), 126.7 (s), 125.2 (s), 122.3 (t, J = 33.7 Hz), 119.4 (t, J = 33.6 Hz), 116.6 (t, J = 33.8 Hz), 113.8 (t, J= 33.6 Hz), 113.3 (q, J = 38.2 Hz), 110.7 (q, J = 38.5 Hz), 108.2 (q, J = 38.1 Hz), 47.0 (t, J = 4.8 Hz), 34.3 (s)。

Example 22

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of 3-ethynylpyridine, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 40 ℃ oil bath for 15 hours, cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is 83 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and ethyl acetate (1: 1, v/v) to obtain 3- (pentafluoroethyl) -4-phenethyl-6- (pyridin-3-yl) -1,2, 4-triazine-5 (4)H) Ketone (isolated yield 79%).¹H NMR (400 MHz, CDCl₃) δ 9.40 (d, J = 292.8 Hz, 1H), 8.67 (d, J = 7.5 Hz, 1H), 7.54 (s, 1H), 7.44-6.87 (m, 6H), 4.35 (t, J = 8.0 Hz, 2H), 3.08 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.5 (s, 3F), -109.8 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 157.1 (s), 152.4 (br), 151.5 (s), 150.4 (br), 143.2 (t, J = 27.9 Hz), 136.6 (s), 136.3 (s), 129.0 (s), 128.9 (s), 127.4 (s), 122.2 (t, J = 33.6 Hz), 119.3 (t, J = 33.7 Hz), 116.5 (t, J = 33.7 Hz), 113.6 (t, J = 33.4 Hz), 113.1 (q, J = 38.3 Hz), 110.6 (q, J = 38.5 Hz), 108.0 (q, J= 38.3 Hz), 47.1 (t, J = 4.8 Hz), 34.2 (s)。

Example 23

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of 3-ethynylthiophene, 0.36 mmol of (2-azidoethyl) benzene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure the content¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 3- (pentafluoroethyl) -4-phenethyl-6- (3-thienyl) -1,2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 9.01-8.95 (m, 1H), 8.10 (d, J = 5.1 Hz, 1H), 7.54-7.21 (m, 6H), 4.35 (t, J = 8.0 Hz, 2H), 3.08 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.4 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 153.8 (s), 151.1 (s), 141.7 (t, J = 27.8 Hz), 136.6 (s), 133.8 (s), 133.3 (s), 129.0 (s), 128.9 (s), 127.5 (s), 127.3 (s), 125.9 (s), 122.3 (t, J = 33.7 Hz), 119.5 (t, J = 33.7 Hz), 116.6 (t, J = 33.7 Hz), 113.8 (t, J = 33.7 Hz), 113.3 (q, J = 38.3 Hz), 110.7 (q, J = 38.2 Hz), 108.2 (q, J = 38.3 Hz), 46.9 (t, J = 4.8 Hz), 34.2 (s)。

Example 24

Under the protection of nitrogen, in a 5mL magnetic stirring bar with polytetrafluoroethyleneAdding 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of 1-azido-octane and 0.39 mmol of pentafluoropropionic anhydride into a reaction tube, finally adding 0.45 mmol of triethylamine, stirring and reacting in a closed system under the condition of 50 ℃ oil bath for 15 hours, cooling to room temperature, taking trifluoromethoxybenzene as an internal standard, and measuring to obtain the product¹⁹The yield of F is 93 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 4-n-octyl-3- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 92%).¹H NMR (400 MHz, CDCl₃) δ 8.34 (d, J = 7.8 Hz, 2H), 7.55 (t, J = 8.0 Hz, 1H), 7.49 (t, J = 7.4 Hz, 2H), 4.13 (t, J = 8.0 Hz, 2H), 1.79 (dd, J = 14.7, 7.5 Hz, 2H), 1.49-1.26 (m, 10H), 0.91 (t, J = 6.0 Hz, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.6 (s, 3F), -110.1 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 158.2 (s), 151.6 (s), 142.9 (t, J = 27.7 Hz), 132.0 (s), 131.6 (s), 129.7 (s), 128.4 (s), 122.3 (t, J = 33.8 Hz), 119.4 (t, J = 33.8 Hz), 116.6 (t, J = 33.8 Hz), 113.7 (q, J = 33.8 Hz), 113.2 (q, J = 38.2 Hz), 110.6 (q, J = 38.3 Hz), 108.0 (q, J= 38.2 Hz), 45.8 (t, J = 4.8 Hz), 31.7 (s), 29.0 (s), 28.9 (s), 28.1 (s), 26.8 (s), 22.6 (s), 14.0 (s)。

Example 25

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of 6-azidohexyl-1-ene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.36 mmol of 6-azidohexyl-1-ene and 0.45 mmol of triethylamine are finally added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and trifluoromethoxybenzene is taken as an internal standard, and the measured result shows that¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated by rotary evaporation to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 4- (5-alkene-n-hexyl) -3- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 8.32 (d, J = 7.7 Hz, 2H), 7.50 (dt, J = 14.8, 7.2 Hz, 3H), 5.80 (td, J = 16.8, 6.7 Hz, 1H), 5.02 (dd, J = 19.7, 13.7 Hz, 2H), 4.11 (t, J = 8.0 Hz, 2H), 2.14 (q, J = 13.8, 6.8 Hz, 2H), 1.80 (s, 2H), 1.60-1.48 (m, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.6 (s, 3F), -110.1 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 158.18 (s), 151.54 (s), 142.79 (t, J = 27.7 Hz), 137.63 (s), 131.99 (s), 131.53 (s), 129.63 (s), 128.34 (s), 122.25 (t, J = 33.8 Hz), 119.40 (t, J = 33.8 Hz), 116.56 (t, J = 33.8 Hz), 115.25 (s), 113.82 (t, J = 33.8 Hz), 113.16 (q, J = 38.4 Hz), 110.59 (q, J = 38.2 Hz), 108.01 (q, J = 38.1 Hz), 45.54 (t, J = 4.7 Hz), 32.98 (s), 27.48 (s), 25.99 (s)。

Example 26

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of 2- (2-azidoethyl) thiophene and 0.39 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of oil bath at 40 ℃ for 15 hours, then the mixture is cooled to room temperature, and trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 3- (pentafluoroethyl) -6-phenyl-4- (2- (2-thienyl) ethyl) -1,2, 4-triazine-5 (4)H) Ketone (isolated yield 99%).¹H NMR (400 MHz, CDCl₃) δ 8.37 (d, J = 8.0 Hz, 2H), 7.56 (dt, J = 27.3, 7.4 Hz, 3H), 7.37-7.33 (m, 1H), 7.16 (s, 1H), 7.08 (d, J = 4.9 Hz, 1H), 4.35 (t, J = 8.0 Hz, 2H), 3.14 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.8 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 158.5 (s), 151.6 (s), 142.7 (t, J = 27.7 Hz), 136.6 (s), 132.2 (s), 131.5 (s), 129.7 (s), 128.5 (s), 127.9 (s), 126.5 (s), 122.6 (s), 122.2 (t, J = 33.3 Hz), 119.4 (t, J = 33.7 Hz), 116.5 (t, J = 33.7 Hz), 113.7 (t, J = 33.6 Hz), 113.2 (q, J = 38.6 Hz), 110.6 (q, J = 38.4 Hz), 108.1 (q, J = 38.4 Hz), 46.2 (t, J = 4.9 Hz), 28.6 (s)。

Example 27

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of 1-azidomethyl-3-bromobenzene and 0.60 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 40 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is 78 percent, organic phases are combined, the mixture is filtered by 100-mesh silica gel, washed by dichloromethane and rotary-evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 1, v/v) to obtain 4- (3-bromobenzyl) -3- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 75%).¹H NMR (400 MHz, CDCl₃) δ 8.36 (d, J = 7.6 Hz, 2H), 7.59 (t, J = 6.9 Hz, 1H), 7.55-7.42 (m, 4H), 7.25 (t, J = 7.5 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H), 5.38 (s, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -108.8 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 158.8 (s), 151.6 (s), 142.6 (t, J = 28.0 Hz), 135.7 (s), 132.4 (s), 131.63(s), 131.3 (s), 130.5 (s), 130.2 (s), 129.8 (s), 128.5 (s), 125.6 (s), 123.0 (s), 122.2 (t, J = 33.7 Hz), 119.3 (t, J = 33.7 Hz), 116.5 (t, J = 33.7 Hz), 113.6 (t, J = 33.3 Hz), 113.1 (q, J = 38.4 Hz), 110.5 (q, J = 38.4 Hz), 107.9 (q, J = 38.4 Hz), 47.6 (t, J = 5.2 Hz)。

Example 28

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 6.0 mmol of tetrahydrofuran, 3.9 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of methyl 4-azidobenzoate and 0.60 mmol of pentafluoropropionic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.36 mmol of methyl 4-azidobenzoate and 0.60 mmol of pentafluoropropionic anhydride are added, and finally 0.45 mmol of triethylamine are added, the mixture is stirred and reacted in a closed system under the condition of oil bath at 40 ℃ for 15 hours, then the mixture is cooled to room temperature, and trifluoromethoxybenzene is taken as an internal standard, so that the measured result is that the product is obtained¹⁹The yield of F is 54 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 2, v/v) to obtain 4- ((5-oxo-3- (pentafluoroethyl) -6-phenyl-1, 2, 4-triazine-4 (5)H) -yl) methyl) benzoate (isolated yield 54%).¹H NMR (400 MHz, CDCl₃) δ 8.35 (d, J = 7.7 Hz, 2H), 8.04 (d, J= 7.8 Hz, 2H), 7.54 (dt, J = 33.4, 7.3 Hz, 3H), 7.32 (d, J = 7.9 Hz, 2H), 5.46 (s, 2H), 3.92 (s, 3H). ¹⁹F NMR (376 MHz, CDCl₃) δ -79.4 (s, 3F), -109.0 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 166.4 (s), 158.8 (s), 151.6 (s), 142.7 (t, J = 28.0 Hz), 138.5 (s), 132.4 (s), 131.2 (s), 130.2 (s), 130.2 (s), 129.7 (s), 128.5 (s), 126.8 (s), 122.2 (t, J = 33.6 Hz), 119.3 (t, J = 33.6 Hz), 116.5 (t, J = 33.6 Hz), 113.6 (t, J = 35.8 Hz), 113.1 (q, J = 38.6 Hz), 110.5 (q, J = 38.7 Hz), 107.9 (q, J = 38.7 Hz), 52.2 (s), 48.0 (t, J = 5.2 Hz)。

Example 29

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 3.7 mmol of tetrahydrofuran, 4.6 mmol of n-hexane, 0.30 mmol of phenylacetylene, 0.36 mmol of 2-azidoethylbenzene and 0.39 mmol of heptafluorobutyric anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.36 mmol of 2-azidoethylbenzene and 0.39 mmol of heptafluorobutyric anhydride are added, finally 0.45 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 hours, then the mixture is cooled to room temperature, and the interior standard of trifluoromethoxybenzene is measured¹⁹The yield of F is more than 99 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (3: 2, v/v) to obtain 3- (heptafluorobutyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 98%).¹H NMR (400 MHz, CDCl₃) δ 8.39 (d, J = 7.5 Hz, 2H), 7.58 (dt, J = 25.7, 7.3 Hz, 3H), 7.44-7.32 (m, 5H), 4.34 (t, J = 8.0 Hz, 2H), 3.09 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -78.5 (t, J = 10.4 Hz, 3F), -107.2 (q, J = 10.2 Hz, 2F), -122.2 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 158.4 (s), 151.7 (s), 142.9 (tt, J = 27.0, 2.6 Hz), 136.5 (s), 132.2 (s), 131.5 (s), 129.8 (s), 129.0 (s), 128.9 (s), 128.5 (s), 127.4 (s), 122.1 (t, J = 34.2 Hz), 119.3 (t, J = 33.7 Hz), 116.4 (t, J = 33.7 Hz), 114.7 (t, J = 30.6 Hz), 113.5 (t, J = 33.4 Hz), 112.1 (t, J = 30.5 Hz), 111.7 (q, J = 38.8 Hz), 111.5 (t, J = 33.0 Hz), 109.6 (t, J= 30.4 Hz), 109.2 (t, J = 33.7 Hz), 109.0 (q, J = 38.4 Hz), 108.8 (t, J = 34.0 Hz), 106.3 (q, J = 39.3 Hz), 106.2 (t, J = 17.3 Hz), 47.2 (t, J = 5.0 Hz), 34.3 (s)。

Example 30

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 ' -di-tert-butyl-2, 2 ' -bipyridine and 3 ' -dipyridyl are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer7 mmol tetrahydrofuran, 4.6 mmol n-hexane, 0.30 mmol 4-cyanophenylacetylene, 0.36 mmol 2-azidoethylbenzene, 0.39 mmol heptafluorobutyric anhydride, finally 0.45 mmol triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 15 h, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard, and the determination is carried out¹⁹The yield of F was 79%, the organic phases were combined, filtered through 100-mesh 200-mesh silica gel, washed with dichloromethane, and the organic solvent was removed by rotary evaporation to give a crude product, which was purified by silica gel column chromatography eluting with n-pentane and dichloromethane (1: 1, v/v) to give 4- (5-oxo-3- (heptafluoropropyl) -4-phenethyl-4, 5-dihydro-1, 2, 4-triazin-6-yl) benzonitrile (isolated yield 78%).¹H NMR (400 MHz, CDCl₃) δ 8.51 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.43-7.36 (m, 2H), 7.36-7.30 (m, 3H), 4.37 (q, J = 8.0 Hz, 2H), 3.10 (q, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -78.5 (t, J = 10.4 Hz, 3F), -107.4 (q, J = 10.2 Hz, 2F), -122.3 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 156.9 (s), 151.5 (s), 143.8 (tt, J = 27.1, 2.5 Hz), 136.2 (s), 135.5 (s), 132.1 (s), 130.1 (s), 129.1 (s), 128.9 (s), 127.5 (s), 122.0 (t, J = 32.8 Hz), 119.2 (t, J = 33.4 Hz), 118.1 (s), 116.3 (t, J = 33.5 Hz), 115.4 (s), 114.6 (t, J = 30.6 Hz), 113.4 (t, J = 34.3 Hz), 112.0 (t, J = 30.6 Hz), 109.3 (q, J = 20.2 Hz), 109.1 (t, J = 36.1 Hz), 108.9 (q, J = 38.2 Hz), 108.7 (t, J= 34.1 Hz), 106.2 (q, J = 38.4 Hz), 47.5 (t, J = 5.0 Hz), 34.3 (s)。

Example 31

Under the protection of nitrogen, 0.015mmol of cuprous iodide, 0.0075mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 3.7 mmol of tetrahydrofuran, 4.6 mmol of n-hexane, 0.30 mmol of 4-ethynylthiophene, 0.36 mmol of 2-azidoethylbenzene and 0.39 mmol of heptafluorobutyric anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and the mixture is stirred and reacted in a closed system for 15 hours at the temperature of 50 ℃ in an oil bath, and then cooled to the roomWarm, with trifluoromethoxybenzene as an internal standard, and measures¹⁹The yield of F is 98 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (3: 2, v/v) to obtain 3- (heptafluoropropyl) -4-phenethyl-6- (3-thienyl) -1,2, 4-triazine-5 (4)H) -ketone (isolated yield 95%).¹H NMR (400 MHz, CDCl₃) δ 8.99 (d, J = 2.5 Hz, 1H), 8.10 (d, J = 5.1 Hz, 1H), 7.45-7.30 (m, 6H), 4.34 (t, J = 8.0 Hz, 2H), 3.08 (t, J = 8.0 Hz, 2H). ¹⁹F NMR (376 MHz, CDCl₃) δ -78.6 (t, J = 10.5 Hz, 3F), -107.0 (q, J = 10.3 Hz, 2F), -122.3 (s, 2F). ¹³C NMR (101 MHz, CDCl₃) δ 153.71 (s), 151.22 (s), 141.86 (tt, J = 26.3, 2.5 Hz), 136.57 (s), 133.83 (s), 133.22 (s), 128.98 (s), 128.86 (s), 127.55 (s), 127.33 (s), 125.90 (s), 122.15 (t, J = 33.6 Hz), 119.28 (t, J = 33.5 Hz), 116.41 (t, J = 33.8 Hz), 114.76 (t, J = 30.4 Hz), 113.55 (t, J = 33.4 Hz), 113.54 (t, J = 33.7 Hz), 112.17 (t, J = 30.5 Hz), 109.57 (t, J = 30.6 Hz), 108.97 (q, J = 76.9, 38.5 Hz), 106.48 (t, J = 34.1 Hz), 106.09 (t, J = 33.4 Hz), 47.11 (t, J = 5.0 Hz), 34.33 (s)。

Example 32

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of phenylacetylene, 0.40 mmol of (2-azidoethyl) benzene and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of oil bath at the temperature of 30 ℃ for 30 hours, then the mixture is cooled to the room temperature, and the trifluoromethoxybenzene is taken as an internal standard, so that the measurement is carried out¹⁹The yield of F is 62 percent, organic phases are combined, 100-mesh 200-mesh silica gel is used for filtering, dichloromethane is used for washing, organic solvent is removed by rotary evaporation to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain the compoundTo 3- (difluoromethyl) -4-phenethyl-6-phenyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 62%).¹H NMR (400 MHz, CDCl₃) δ 8.33 (d, J = 7.6 Hz, 2H), 7.57 (dq, J = 14.5, 7.2 Hz, 3H), 7.42-7.28 (m, 5H), 6.76 (t, J = 52.9 Hz, 1H), 4.39 (t, J = 8.4 Hz, 2H), 3.11 (t, J = 8.4 Hz, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -116.0 (d, 2F, J = 53.1 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 158.1 (s), 152.0 (s), 146.7 (t, J = 26.6 Hz), 136.9 (s), 131.8 (s), 131.8 (s), 129.5 (s), 129.0 (s), 128.9 (s), 128.4 (s), 127.2 (s), 113.6 (t, J= 246.5 Hz), 46.4 (t, J = 4.2 Hz), 34.3 (t, J = 1.4 Hz)。

Example 33

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 3-bromophenylacetylene, 0.40 mmol of (2-azidoethyl) benzene and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 60 ℃ in an oil bath for 30 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is 36 percent, organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and rotary-evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain 6- (3-bromophenyl) -3- (difluoromethyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 36%).¹H NMR (400 MHz, CDCl₃) δ 8.53 (s, 1H), 8.31 (d, J = 7.9 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.44-7.29 (m, 6H), 6.77 (t, J = 52.9 Hz, 1H), 4.39 (t, J = 8.0 Hz, 2H), 3.11 (t, J = 8.0 Hz, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -116.0 (d, 2F, J = 52.9 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 156.7 (s), 151.7 (s), 147.1 (t, J = 26.7 Hz), 136.8 (s), 134.7 (s), 133.7 (s), 132.3 (s), 129.9 (s), 128.9 (s), 128.1 (s), 127.3 (s), 122.5 (s), 113.4 (t, J = 246.8 Hz), 46.4 (t, J = 4.1 Hz), 34.3 (s)。

Example 34

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 4-methoxyphenylacetylene, 0.40 mmol of (2-azidoethyl) benzene and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of oil bath at the temperature of 30 ℃ for 30 hours, then the mixture is cooled to the room temperature, and the trifluoromethoxybenzene is taken as an internal standard to measure¹⁹The yield of F is 91 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain 3- (difluoromethyl) -6- (4-methoxyphenyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 90%).¹H NMR (400 MHz, CDCl₃) δ 8.42 (d, J = 8.9 Hz, 2H), 7.42-7.29 (m, 5H), 7.04 (d, J = 8.9 Hz, 2H), 6.75 (t, J = 53.0 Hz, 1H), 4.37 (t, J = 8.4 Hz, 2H), 3.92 (s, 3H), 3.10 (t, J = 8.4 Hz, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -115.8 (d, 2F, J = 53.0 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 162.7 (s), 157.1 (s), 152.1 (s), 146.1 (t, J = 26.4 Hz), 137.0 (s), 131.5 (s), 129.0 (s), 128.9 (s), 127.2 (s), 124.4 (s), 113.9 (s), 113.7 (t, J = 246.2 Hz), 55.5 (s), 46.2 (t, J = 4.1 Hz), 34.3 (s)。

Example 35

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 4-phenyl phenylacetylene, 0.40 mmol of (2-azidoethyl) benzene and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of oil bath at the temperature of 30 ℃ for 30 hours, and then the mixture is cooled to the room temperature to be prepared into the product by using trifluoromethylOxybenzene is used as an internal standard, and the measurement is carried out¹⁹The yield of F is 55 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain 6- ([1,1' -biphenyl-4-yl) -3- (difluoromethyl) -4-phenethyl-1, 2, 4-triaza-5 (4)H) -ketones](isolated yield 50%).¹H NMR (400 MHz, CDCl₃) δ 8.46 (d, J = 8.4 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 7.7 Hz, 2H), 7.51 (t, J = 7.5 Hz, 2H), 7.46-7.32 (m, 6H), 6.78 (t, J = 53.0 Hz, 1H), 4.41 (t, J = 8.4 Hz, 2H), 3.13 (t, J = 8.4 Hz, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -115.9 (d, 2F, J = 53.0 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 157.6 (s), 152.0 (s), 146.8 (t, J = 27.0 Hz), 144.5 (s), 140.1 (s), 136.9 (s), 130.9 (s), 130.7 (s), 130.0 (s), 129.0 (s), 128.9 (s), 128.1 (s), 127.3 (s), 127.2 (s), 127.1 (s), 113.6 (t, J = 246.5 Hz), 46.4 (t, J = 4.1 Hz), 34.3 (s)。

Example 36

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 2-chlorophenylacetylene, 0.40 mmol of (2-azidoethyl) benzene and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, 0.30 mmol of triethylamine is finally added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 30 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard, so that the measurement is carried out¹⁹The yield of F is 48 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain 3- (difluoromethyl) -6- (2-chlorophenyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 48%).¹H NMR (400 MHz, CDCl₃) δ 7.58-7.42 (m, 5H), 7.41-7.29 (m, 4H), 6.77 (t, J = 52.9 Hz, 1H), 4.39 (t, J = 8.4 Hz, 2H), 3.16-3.08 (t, J = 8.4 Hz, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -116.2 (d, 2F, J = 53.7 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 160.9 (s), 151.3 (s), 147.8 (t, J = 26.7 Hz), 136.8 (s), 133.5 (s), 131.7 (s), 131.6 (s), 131.0 (s), 130.0 (s), 129.0 (s), 128.9 (s), 127.2 (s), 127.0 (s), 113.4 (t, J = 247.2 Hz), 46.5 (t, J = 4.0 Hz), 34.2 (s)。

Example 37

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 3-ethynylthiophene, 0.40 mmol of (2-azidoethyl) benzene and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 60 ℃ oil bath for 30 hours, then the mixture is cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard, so that the measurement is carried out¹⁹The yield of F is 43 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain 3- (difluoromethyl) -6- (3-thienyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 38%).¹H NMR (400 MHz, CDCl₃) δ 8.94 (s, 1H), 8.10-8.05 (m, 1H), 7.50-7.21 (m, 6H), 6.76 (t, J= 52.9 Hz, 1H), 4.39 (t, J = 8.0 Hz, 2H), 3.15-3.05 (t, J = 8.0 Hz, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -115.7 (d, 2F, J = 53.0 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 153.5 (s), 151.5 (s), 145.8 (t, J = 26.5 Hz), 137.0 (s), 133.6 (s), 132.9 (s), 128.9 (s), 128.9 (s), 127.5 (s), 127.2 (s), 125.7 (s), 113.6 (t, J = 246.2 Hz), 46.3 (t, J = 4.1 Hz), 34.3 (s)。

Example 38

Under the protection of nitrogen, 0.010 mmol cuprous iodide and 0.0050 mmol 4, 4' -di-tert-butyl-2 are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of cyclopropylacetylene, 0.40 mmol of (2-azidoethyl) benzene, 0.40 mmol of difluoroacetic anhydride, and finally 0.30 mmol of triethylamine are added, the mixture is stirred in a closed system under the condition of 40 ℃ oil bath for reaction for 30 hours and then cooled to room temperature, and the interior standard of trifluoromethoxybenzene is determined¹⁹The yield of F is 38 percent, the organic phases are combined, filtered by 100-mesh silica gel, washed by dichloromethane and evaporated to remove the organic solvent to obtain a crude product, and the crude product is subjected to silica gel column chromatography and eluted by n-pentane and dichloromethane (1: 5, v/v) to obtain 6-cyclopropyl-3- (difluoromethyl) -4-phenethyl-1, 2, 4-triazine-5 (4)H) Ketone (isolated yield 38%).¹H NMR (400 MHz, CDCl₃) δ 7.35 (td, J = 14.3, 7.0 Hz, 5H), 6.64 (t, J = 52.9 Hz, 1H), 4.29 (t, J = 8.4 Hz, 2H), 3.06 (t, J = 8.4 Hz, 2H), 2.64 (dd, J = 7.0, 4.8 Hz, 1H), 1.36 (s, 2H), 1.27-1.20 (m, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -115.8 (d, 2F, J = 53.0 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 165.7 (s), 152.7 (s), 145.6 (t, J = 26.6 Hz), 137.0 (s), 128.9 (s), 128.9 (s), 127.1 (s), 113.8 (t, J = 246.1 Hz), 46.0 (t, J = 4.1 Hz), 34.2 (s), 12.3 (s), 10.6 (s)。

Example 39

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 4-methylphenylacetylene, 0.40 mmol of azidocyclohexane and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of oil bath at 40 ℃ for 30 hours, then cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard, so that the measurement result shows that the reaction temperature is high¹⁹The yield of F was 75%, the organic phases were combined, filtered through 100-mesh 200-mesh silica gel, washed with dichloromethane, and the organic solvent was removed by rotary evaporation to give a crude product, which was purified by column chromatography on silica gel eluting with n-pentane and dichloromethane (1: 5, v/v) to give 4-cyclohexyl-3- (difluoromethyl) -4- (p-tolyl) -1,2, 4-triazin-5 (4H) -one (isolated yield 75%).¹H NMR (400 MHz, CDCl₃) δ 8.18 (d, J = 7.5 Hz, 2H), 7.30 (d, J = 7.5 Hz, 2H), 6.73 (t, J = 53.3 Hz, 1H), 4.32 (t, J = 10.7 Hz, 1H), 2.68 (q, J = 11.7 Hz, 2H), 2.44 (s, 3H), 1.95 (d, J = 11.7 Hz, 2H), 1.82 (d, J = 11.8 Hz, 2H), 1.73 (d, J = 10.7 Hz, 1H), 1.37 (td, J = 25.4, 13.3 Hz, 3H).¹⁹F NMR (376 MHz, CDCl₃) δ -115.2 (d, 2F, J = 53.7 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 158.9 (s), 152.5 (s), 146.7 (t, J = 25.7 Hz), 142.0 (s), 129.5 (s), 129.2 (s), 129.0 (s), 114.3 (t, J = 247.1 Hz), 61.8 (t, J = 5.3 Hz), 28.1 (s), 26.0 (s), 24.8 (s), 21.5 (s)。

Example 40

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 4-methylphenylacetylene, 0.40 mmol of azidocyclohexane and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of oil bath at 60 ℃ for 30 hours, then cooled to room temperature, and the trifluoromethoxybenzene is taken as an internal standard, so that the measurement result shows that the reaction temperature is high¹⁹The yield of F was 72%, the organic phases were combined, filtered through 100-mesh 200-mesh silica gel, washed with dichloromethane, and the organic solvent was removed by rotary evaporation to give a crude product, which was purified by column chromatography on silica gel eluting with n-pentane and dichloromethane (1: 5, v/v) to give 6- (3- (difluoromethyl) -5-oxo-6- (p-tolyl) -1,2, 4-triazine-4 (5)H) -radical]Ethyl hexanoate (isolated yield 70%).¹H NMR (400 MHz, CDCl₃) δ 8.23 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 6.71 (t, J = 53.0 Hz, 1H), 4.19-4.11 (m, 4H), 2.44 (s, 3H), 2.35 (t, J = 7.3 Hz, 2H), 1.88-1.79 (m, 2H), 1.77-1.68 (m, 2H), 1.54-1.44 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H).¹⁹F NMR (376 MHz, CDCl₃) δ -116.1 (d, 2F, J = 53.0 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 173.3 (s), 157.7 (s), 152.0 (s), 146.5 (t, J = 26.5 Hz), 142.3 (s), 129.5 (s), 129.1 (s), 113.6 (t, J = 246.4 Hz), 60.3 (s), 44.7 (t, J = 4.1 Hz), 34.0 (s), 27.73 (s), 26.3 (s), 24.3 (s), 21.6 (s), 14.2 (s)。

EXAMPLE 41

Under the protection of nitrogen, 0.010 mmol of cuprous iodide, 0.0050 mmol of 4,4 '-di-tert-butyl-2, 2' -bipyridine, 23 mmol of dichloromethane, 0.20 mmol of 4-methylphenylacetylene, 0.40 mmol of 2- (2-azidoethyl) -1, 3-dioxolane and 0.40 mmol of difluoroacetic anhydride are added into a 5mL reaction tube provided with a polytetrafluoroethylene magnetic stirrer, and finally 0.30 mmol of triethylamine is added, the mixture is stirred and reacted in a closed system under the condition of 50 ℃ oil bath for 30 hours, then the mixture is cooled to room temperature, and the interior standard is determined by taking trifluoromethoxybenzene as an interior standard¹⁹The yield of F was 62%, the organic phases were combined, filtered through 100-mesh 200-mesh silica gel, washed with dichloromethane, and the organic solvent was removed by rotary evaporation to give a crude product, which was purified by column chromatography on silica gel eluting with n-pentane and dichloromethane (1: 5, v/v) to give 4- (2- (1, 3-dioxolanyl-2-ethyl) -3- (difluoromethyl) -6- (p-tolyl) -1,2, 4-triazine-5 (4)H) Ketone (isolated yield 59%).¹H NMR (400 MHz, CDCl₃) δ 8.26 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 6.73 (t, J = 52.9 Hz, 1H), 5.07 (s, 1H), 4.36 (t, J= 6.0 Hz, 2H), 4.04-3.86 (m, 4H), 2.45 (s, 3H), 2.22 (s, 2H).¹⁹F NMR (376 MHz, CDCl₃) δ -116.3 (d, 2F, J = 53.3 Hz).¹³C NMR (101 MHz, CDCl₃) δ 157.6 (s), 152.1 (s), 146.6 (t, J = 26.4 Hz), 142.3 (s), 129.5 (s), 129.1 (s), 113.4 (t, J = 246.4 Hz), 102.0 (s), 65.0 (s), 40.1 (t, J = 4.2 Hz), 31.8 (s), 29.7 (s), 21.6 (s)。

Test for fungicidal Activity

1. The compound prepared in example 14 was weighed out accurately, and 20 mL of 400 mg/L medicinal solution was prepared by adding water and 0.1% Tween-80 for bactericidal activity assay. Spraying with crop sprayer (sprayer type is stereoscopic crop sprayer, spraying pressure is 1.5 kg/cm)²The amount of the sprayed liquid is about 675L/hm²）。

And (3) taking the cucumbers with consistent growth in the two-leaf period cultured in the greenhouse, naturally drying the cucumbers in the two-leaf period, and inoculating pathogenic bacteria after 24 hours. Which is to adopt an inoculator to make cucumber downy mildew sporangium suspension (5 multiplied by 10)⁵One/ml) was sprayed onto the host crop and then transferred into a climatic chamber for cultivation (24 ℃ C., RH)>90, no light). After 24h, the test material was moved to a greenhouse for normal management, and the bactericidal activity of the test samples was investigated after 4-7 d.

The bactericidal activity of the test samples was investigated visually according to the degree of the control, and the results were expressed as 100-0, with "100" representing no disease and "0" representing the most severe degree of the disease. The inhibition rate of cucumber downy mildew is calculated to be 45%.

2. The compound prepared in example 1 was accurately weighed and prepared into 5mL of a 1g/L dichloromethane solution, and a filter paper sheet was immersed in the dichloromethane solution, taken out, air-dried, and used for the bactericidal activity assay of Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria).

Preparing a broth culture medium of 25g/L by using sterilized hot water, LB agar and technical agar powder in an ultra-clean workbench, pouring the broth culture medium into a surface dish while the broth culture medium is hot, preparing a solid culture medium after air drying, uniformly coating bacteria (the concentration of the bacteria is measured by an ultraviolet-visible spectrophotometer, and the light absorption value = 0.04) on the surface of the solid culture medium, respectively placing a control filter paper sheet (blank experiment) and a sample filter paper sheet into the surface dish, sealing, placing the surface dish into an electric heating constant temperature incubator at 37 ℃ for culturing for 24 hours, and investigating the bactericidal activity of a test sample.

The bactericidal activity of the test samples was investigated by visual inspection based on the degree of sterilization of the control, and the results showed that the control filter paper showed normal growth of bacteria, while no bacteria were grown around the sample filter paper, indicating that the compound prepared in example 1 had strong bactericidal activity against escherichia coli and staphylococcus aureus.

3. The compound prepared in example 23 was weighed out accurately and prepared into 5mL of a 1g/L dichloromethane solution, and a filter paper sheet was immersed in the dichloromethane solution, taken out, air-dried, and used for the bactericidal activity assay of Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria).

The bactericidal activity of the test samples was investigated by visual inspection based on the degree of sterilization of the control, and the results showed that the control filter paper showed normal growth of bacteria and the sample filter paper showed slow bacterial growth around the filter paper, indicating that the compound prepared in example 23 had bactericidal activity against E.coli and Staphylococcus aureus.

The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.

Claims

1. a perfluoroalkyl-1,2,4-triazinone compound, is characterized in that: its structural formula is:

, where R _F =C ₂ F ₅ ,

R' group is

, R'' group is

, or the R' group is

, R'' group is

, or the R' group is

, R'' group is

.

2. a kind of synthetic method of perfluoroalkyl-1,2,4-triazinone compound as claimed in claim 1 is characterized in that: with copper salt as catalyst, 2,2'-bipyridine derivatives is the ligand, azide

, alkyne

Using pentafluoropropionic anhydride as a raw material, the perfluoroalkyl-1,2,4-triazinone compound is prepared by a one-pot method;

Wherein, the 2,2'-bipyridine derivatives are among 4,4'-dimethyl-2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine any of the

The copper salt is any one of cuprous iodide, CuBr, CuCl, Cu(OTf) ₂ , Cu(CH ₃ CN) ₄ BF ₄ and CuCN.

3. the synthetic method of perfluoroalkyl-1,2,4-triazinone compound according to claim 2, is characterized in that: its concrete synthesis step is as follows: Add copper salt, 2,2'-bipyridine derivatives, azide, alkyne, pentafluoropropionic anhydride, triethylamine and solvent to the container, mix well, close the stopper, and place it at 30-60℃ After stirring continuously for 1-30 hours, filter with 100-200 mesh silica gel, rinse with dichloromethane, combine the organic phases, and then remove the organic solvent by rotary evaporation; Methane is used as an eluent for elution to obtain the perfluoroalkyl-1,2,4-triazinone compound.

4. the synthetic method of perfluoroalkyl-1,2,4-triazinone compound according to claim 3, is characterized in that: described solvent is any one in n-hexane/tetrahydrofuran mixed solvent, dichloromethane kind.