CN109111406A - The synthetic method of perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds - Google Patents

The synthetic method of perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds Download PDF

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CN109111406A
CN109111406A CN201811244795.5A CN201811244795A CN109111406A CN 109111406 A CN109111406 A CN 109111406A CN 201811244795 A CN201811244795 A CN 201811244795A CN 109111406 A CN109111406 A CN 109111406A
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difluoromethyl
perfluoroalkyl
methylene chloride
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CN109111406B (en
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翁志强
吴伟
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Fuzhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/707—1,2,3- or 1,2,4-triazines; Hydrogenated 1,2,3- or 1,2,4-triazines
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Abstract

The invention discloses a kind of copper catalysis one pot process perfluoroalkyl or difluoromethyls -1,2, the method of 4- triazineon compounds, it is using mantoquita as catalyst, 2,2 '-dipyridyl derivatives are ligand, nitrine, alkynes, perfluorocarboxylic acid acid anhydride or difluoroacetic acid acid anhydride are raw material, in the environment that tetrahydrofuran, n-hexane/tetrahydrofuran or methylene chloride are solvent, after being stirred 1-30 hours at 30-60 DEG C, is handled through column chromatographic purifying, obtain the perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds.Synthetic method of the present invention has many advantages, such as that catalyst is inexpensive, be easy to get and small toxicity, yield are high, easy to operate, functional group's universality is good；Meanwhile gained has preferable inhibitory activity to germs such as cucumber downy mildews containing perfluorochemical, can be used as a kind of novel fungicide.

Description

The synthetic method of perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds
Technical field
The invention belongs to the chemosynthesis technical fields of Organic fluoride, and in particular to a kind of copper catalyzes and synthesizes perfluoroalkyl or two The method of methyl fluoride -1,2,4- triazineon compounds.
Background technique
Fluoro-containing group is introduced into organic molecule, can greatly change intramolecular physicochemical property and biological property, Such as enhance molecule it is fat-soluble, improve drug bioavilability, be pharmaceutical chemistry structure of modification important research strategy it One.Therefore, how research efficiently and selectively introduces perfluoroalkyl or difluoromethyl into organic active molecule, becomes synthesis One of the research hotspot of chemistry.1,2,4- triazinone is as heterocycle compound, in desinsection, sterilization, anticancer, antiulcer, plant Preferable bioactivity is shown in object growth regulating.Perfluoroalkyl or difluoro first are introduced on toward 1,2,4- triazineon compounds Base, it is possible to enhance its bioactivity, show the feature different with non-fluorine organic molecule, there is important theoretical significance And practical application value.We report a kind of copper before and catalyze and synthesize Trifluoromethyl-1, the method for 2,4- triazineon compounds (Chinese patent 201710259314.7), we continue to expand the application range of reaction on this basis, report that a kind of synthesis is complete The method of fluoroalkyl or difluoromethyl -1,2,4- triazineon compounds.
Summary of the invention
The purpose of the present invention is to provide a kind of copper to catalyze and synthesize perfluoroalkyl or difluoromethyl -1,2,4- triazinone chemical combination The method of object, the catalyst and raw material that this method utilizes are cheap and easy to get, and yield is generally higher, and the adaptability of functional group is fine, and Its reaction condition is mild, easy to operate, and gained has preferable inhibitory activity to germs such as cucumber downy mildews containing perfluorochemical, can As a kind of novel fungicide.
To achieve the above object, the present invention adopts the following technical scheme:
A kind of perfluoroalkyl or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds, are using mantoquita as catalyst 2, 2 '-bipyridyliums derivatives be ligand, nitrine (), alkynes () and perfluorocarboxylic acid acid anhydride or difluoroacetic acid acid anhydride For raw material, the perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds are made through one kettle way；Its reaction equation are as follows:
。
Wherein, the mantoquita is cuprous iodide, CuBr, CuCl, Cu (OTf)2、Cu(CH3CN)4BF4With it is any in CuCN It is a kind of.
The 2,2 '-bipyridyliums derivative is 2,2 '-bipyridyls, 5,5 '-dimethyl -2,2 '-bipyridyl, 4,4 '-two 2,2 '-bipyridyl of methyl -, 4,4 '-di-t-butyl -2, any one in 2 '-bipyridyls (dtbpy), preferably 4,4 '-two uncles Butyl -2,2 '-bipyridyl.
The nitrineIn R ' group be following formula 1- formula 23 in any one:
。
The alkynesIn R ' ' group be following formula 24- formula 41 in any one:
。
Specific step is as follows for the synthetic method of the perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds: In nitrogen atmosphere, to magnetic stirring apparatus container in be added mantoquita, 2,2 '-bipyridyliums derivatives, nitrine, alkynes, Perfluorocarboxylic acid acid anhydride or difluoroacetic acid acid anhydride, triethylamine and solvent, shut plug after mixing, place it at 30-60 DEG C It after continuing stirring 1-30 hours, is filtered with 100-200 mesh silica gel, methylene chloride rinses, and merges organic phase, and then revolving removes and has Solvent；Obtained crude product is by silica gel column chromatography, using pentane-methylene chloride or pentane-ethyl acetate as eluant, eluent It is eluted, obtains the perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds.
The solvent is n-hexane/tetrahydrofuran mixed solvent, any one in methylene chloride, preferably n-hexane/ Tetrahydrofuran mixed solvent or dichloromethane solvent.
Mantoquita used, 2,2 '-bipyridyliums derivatives, alkynes, nitrine, perfluorocarboxylic acid acid anhydride, triethylamine and n-hexane, four The molar ratio of hydrogen furans 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)；Mantoquita used, 2,2 '-bipyridyliums derivatives, alkynes, nitrine, difluoroacetic acid acid anhydride, three The molar ratio of ethylamine and methylene chloride is (0.01-0.05): (0.005-0.025): (0.2-1): (0.4-2): (0.4-2): (0.3-1.5):(23-117)。
Gained perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds have preferably suppression to germs such as cucumber downy mildews System activity can be used as a kind of novel fungicide.
The beneficial effects of the present invention are:
(1) present invention is to urge with mantoquita with nitrine cheap and easy to get, alkynes, perfluorocarboxylic acid acid anhydride or difluoroacetic acid acid anhydride etc. for raw material Agent, 2,2 '-bipyridyliums derivatives are ligand, through one pot process perfluoroalkyl or difluoromethyl -1,2,4- triazine assimilation Object is closed, compound yield is higher, and the adaptability of functional group is fine, and its reaction condition is mild, and it is easy to operate, have good Prospects for commercial application.
(2) gained has preferable inhibitory activity to germs such as cucumber downy mildews containing perfluorochemical, can be used as a kind of novel Fungicide.
Detailed description of the invention
Fig. 1 is the reacting flow chart of synthetic reaction of the present invention.
Fig. 2 is 3- (pentafluoroethyl group) -6- phenyl -4- (3- phenyl propyl) -1,2,4- triazine -5 made from embodiment 14 (4H) -one mono-crystalline structures figure.
Specific embodiment
In order to make content of the present invention easily facilitate understanding, With reference to embodiment to of the present invention Technical solution is described further, but the present invention is not limited only to this.
Embodiment 1
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.3 mmol phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, is cooled to room temperature, with trifluoro after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths Methoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, Revolving removes organic solvent and obtains crude product, and crude product is washed by silica gel column chromatography with pentane and methylene chloride (1:1, v/v) It is de-, obtain 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 2
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous bromide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol are just Hexane, 0.3 mmol phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 Mmol triethylamine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with trifluoro methoxy Base benzene is internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 98%. NMR data is shown in embodiment 1.
Embodiment 3
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 mmol Cu(CH3CN)4BF4, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 Mmol n-hexane, 0.3 mmol phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, finally plus Enter 0.45 mmol triethylamine, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with three Fluorine methoxyl group benzene is internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield It is 51%.NMR data is shown in embodiment 1.
Embodiment 4
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous cyanide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol are just Hexane, 0.3 mmol phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 Mmol triethylamine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with trifluoro methoxy Base benzene is internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 57%. NMR data is shown in embodiment 1.
Embodiment 5
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 mmol Cu(OTf)2, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.3 mmol phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, is cooled to room temperature, with trifluoro after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths Methoxybenzene is internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 49%.NMR data is shown in embodiment 1.
Embodiment 6
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.015mmol is added Stannous chloride, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol just oneself Alkane, 0.3 mmol phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 Mmol triethylamine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with trifluoro methoxy Base benzene is internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 48%. NMR data is shown in embodiment 1.
Embodiment 7
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075mmol 4,4 '-dimethyl -2,2 '-bipyridyl, 12 mmol tetrahydrofurans, 0.3 mmol benzene second Alkynes, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, in It is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 93%.NMR data is shown in embodiment 1。
Embodiment 8
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.015mmol is added Cuprous iodide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 11.7 mmol methylene chloride, 0.3 mmol benzene second Alkynes, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, in It is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, measures 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 93%.NMR data is shown in embodiment 1。
Embodiment 9
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 9.4 mmol methylene chloride, 0.3 mmol benzene Acetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, It is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, surveys Obtain 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 69%.NMR data is shown in implementation Example 1.
Embodiment 10
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 7.6 mmol methylene chloride, 0.3 mmol benzene Acetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, It is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, surveys Obtain 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 68%.NMR data is shown in implementation Example 1.
Embodiment 11
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 12.5 mmol methylene chloride, 0.3 mmol Phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethyl group Amine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, Measure 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield is 61%.NMR data is shown in reality Apply example 1.
Embodiment 12
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 12.3 mmol tetrahydrofurans, 0.3 mmol Phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethyl group Amine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, Measure 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield yield is 94%.NMR data See embodiment 1.
Embodiment 13
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 15.6 mmol methylene chloride, 0.3 mmol Phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethyl group Amine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, using trifluomethoxybenzene as internal standard, Measure 3- (pentafluoroethyl group) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one19F yield yield is 68%.NMR number According to seeing embodiment 1.
Embodiment 14
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol (3- nitrine propyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, is cooled to room temperature, with trifluoro after being stirred to react 15 h in a closed system under the conditions of 60 DEG C of oil baths Methoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, Revolving removes organic solvent and obtains crude product, and crude product is washed by silica gel column chromatography with pentane and methylene chloride (1:1, v/v) It is de-, obtain 3- (pentafluoroethyl group) -6- phenyl -4- (3- phenyl propyl) -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 15
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 12.3 mmol tetrahydrofurans, 0.30 Mmol phenylacetylene, 0.36 mmol (3- nitrine propyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol tri- Ethylamine, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 60 DEG C of oil baths, is with trifluomethoxybenzene Internal standard measures 3- (pentafluoroethyl group) -6- phenyl -4- (3- phenyl propyl) -1,2,4- triazine -5 (4H) -one19F yield 92%. NMR data is shown in embodiment 14.
Embodiment 16
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol 4- cyano phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, most After 0.45 mmol triethylamine is added, be cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 60 DEG C of oil baths, Using trifluomethoxybenzene as internal standard, measure19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, dichloromethane Alkane rinses, and revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1: 2, v/v) it elutes, obtains 4- (5- oxo -3- (pentafluoroethyl group) -4- phenethyl -4,5- dihydro -1,2,4- triazine -6- base) benzene first Nitrile (separation yield 99%).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)。
Embodiment 17
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 12.3 mmol tetrahydrofurans, 0.30 Mmol 4- cyano phenylacetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 Mmol triethylamine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 60 DEG C of oil baths, with trifluoro methoxy Base benzene is internal standard, measures 4- (5- oxo -3- (pentafluoroethyl group) -4- phenethyl -4,5- dihydro -1,2,4- triazine -6- base) benzene first Nitrile19F yield is 75%.NMR data is shown in embodiment 16.
Embodiment 18
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol 2- chlorobenzene acetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 40 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride Rinse, revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1:1, V/v it) elutes, obtains 6- (2- chlorphenyl) -3- (pentafluoroethyl group) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 19
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 12.3 mmol tetrahydrofurans, 0.30 Mmol 2- chlorobenzene acetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 Mmol triethylamine is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 40 DEG C of oil baths, with trifluoro methoxy Base benzene is internal standard, measures 6- (2- chlorphenyl) -3- (pentafluoroethyl group) -4- phenethyl -1,2,4- triazine -5 (4H) -one19F yield Greater than 92%.NMR data is shown in embodiment 18.
Embodiment 20
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol 3- bromobenzene acetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 30 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride Rinse, revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1:1, V/v it) elutes, obtains 6- (3- bromophenyl) -3- (pentafluoroethyl group) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 21
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol 2- acetenyl naphthalene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride Rinse, revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1:1, V/v it) elutes, obtains 6- (2- naphthalene) -3- (pentafluoroethyl group) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 22
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol 3- ethynyl pyridine, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, most After 0.45 mmol triethylamine is added, be cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 40 DEG C of oil baths, Using trifluomethoxybenzene as internal standard, measure19F yield is 83%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride Rinse, revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and ethyl acetate (1:1, V/v it) elutes, obtains 3- (pentafluoroethyl group) -4- phenethyl -6- (pyridin-3-yl) -1,2,4- triazines -5 (4H) -one (separation 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)。
Embodiment 23
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol 3- thiophene acetylene, 0.36 mmol (2- azidoethyl) benzene, 0.39 mmol pentafluoropropionic anhydride, most After 0.45 mmol triethylamine is added, be cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, Using trifluomethoxybenzene as internal standard, measure19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, dichloromethane Alkane rinses, and revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1: 1, v/v) it elutes, obtains 3- (pentafluoroethyl group) -4- phenethyl -6- (3- thienyl) -1,2,4- triazine -5 (4H) (separation produces -one Rate 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)。
Embodiment 24
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol 1- nitrine normal octane, 0.39 mmol pentafluoropropionic anhydride, are eventually adding 0.45 mmol triethylamine, is cooled to room temperature, with trifluoro after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths Methoxybenzene is internal standard, is measured19F yield is 93%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, rotation Organic solvent is evaporated off and obtains crude product, crude product is washed by silica gel column chromatography with pentane and methylene chloride (1:1, v/v) It is de-, obtain 4- n-octyl -3- (pentafluoroethyl group) -6- phenyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 25
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol 6- nitrine hexyl -1- alkene, 0.39 mmol pentafluoropropionic anhydride, finally plus Enter 0.45 mmol triethylamine, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with three Fluorine methoxyl group benzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride punching It washes, revolving removes organic solvent and obtains crude product, and crude product is by silica gel column chromatography, with pentane and methylene chloride (1:1, v/ V) it elutes, obtains 4- (5- alkene n-hexyl) -3- (pentafluoroethyl group) -6- phenyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 26
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol 2- (2- azidoethyl) thiophene, 0.39 mmol pentafluoropropionic anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 40 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride Rinse, revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1:1, V/v it) elutes, obtains 3- (pentafluoroethyl group) -6- phenyl -4- (2- (2- thienyl) ethyl) -1,2,4- triazines -5 (4H) -one (point From 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)。
Embodiment 27
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol 1- azido-methyl -3- bromobenzene, 0.60 mmol pentafluoropropionic anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 40 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield 78% merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, Revolving removes organic solvent and obtains crude product, and crude product is washed by silica gel column chromatography with pentane and methylene chloride (1:1, v/v) It is de-, obtain 4- (3- bromobenzyl) -3- (pentafluoroethyl group) -6- phenyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 28
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 6.0 mmol tetrahydrofurans, 3.9 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol 4- azido-methyl methyl benzoate, 0.60 mmol pentafluoropropionic anhydride, most After 0.45 mmol triethylamine is added, be cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 40 DEG C of oil baths, Using trifluomethoxybenzene as internal standard, measure19F yield is 54%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride Rinse, revolving removes organic solvent and obtains crude product, crude product by silica gel column chromatography, with pentane and methylene chloride (1:2, V/v it) elutes, obtains 4- ((5- oxo -3- (pentafluoroethyl group) -6- phenyl -1,2,4- triazine -4 (5H)-yl) methyl) benzoic acid first Ester (separation 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)。
Embodiment 29
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 3.7 mmol tetrahydrofurans, 4.6 mmol N-hexane, 0.30 mmol phenylacetylene, 0.36 mmol 2- azidoethyl benzene, 0.39 mmol heptafluorobutyric anhydride, are eventually adding 0.45 mmol triethylamine, is cooled to room temperature, with trifluoro after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths Methoxybenzene is internal standard, is measured19F yield is greater than 99%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, Revolving removes organic solvent and obtains crude product, and crude product is washed by silica gel column chromatography with pentane and methylene chloride (3:2, v/v) It is de-, obtain 3- (seven fluorine butyl) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 30
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 3.7 mmol tetrahydrofurans, 4.6 mmol N-hexane, 0.30 mmol 4- cyano phenylacetylene, 0.36 mmol 2- azidoethyl benzene, 0.39 mmol heptafluorobutyric anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield is 79%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride punching It washes, revolving removes organic solvent and obtains crude product, and crude product is by silica gel column chromatography, with pentane and methylene chloride (1:1, v/ V) it elutes, obtains 4- (5- oxo -3- (heptafluoropropyl) -4- phenethyl -4,5- dihydro -1,2,4- triazine -6- base) benzonitrile and (divide From 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)。
Embodiment 31
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.015 Mmol cuprous iodide, 0.0075 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 3.7 mmol tetrahydrofurans, 4.6 mmol N-hexane, 0.30 mmol 4- thiophene acetylene, 0.36 mmol 2- azidoethyl benzene, 0.39 mmol heptafluorobutyric anhydride, finally 0.45 mmol triethylamine is added, is cooled to room temperature after being stirred to react 15 h in a closed system under the conditions of 50 DEG C of oil baths, with Trifluomethoxybenzene is internal standard, is measured19F yield is 98%, merges organic phase, is filtered with 100-200 mesh silica gel, methylene chloride punching It washes, revolving removes organic solvent and obtains crude product, and crude product is by silica gel column chromatography, with pentane and methylene chloride (3:2, v/ V) it elutes, obtains 3- (heptafluoropropyl) -4- phenethyl -6- (3- thienyl) -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 32
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol Phenylacetylene, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol triethyl group Amine is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 30 DEG C of oil baths, using trifluomethoxybenzene as internal standard, It measures19F yield is 62%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic solvent Crude product is obtained, crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 3- (difluoro first Base) -4- phenethyl -6- phenyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 33
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 3- bromobenzene acetylene, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol, tri- second Base amine is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 60 DEG C of oil baths, is interior with trifluomethoxybenzene Mark, measures19F yield is 36%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic molten Agent obtains crude product, and crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 6- (3- bromine Phenyl) -3- (difluoromethyl) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 34
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 4- Methoxy-phenylacetylene, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol Triethylamine is cooled to room temperature, with trifluomethoxybenzene after being stirred to react 30 h in a closed system under the conditions of 30 DEG C of oil baths For internal standard, measure19F yield is 91%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving, which removes, to be had Solvent obtains crude product, and crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 3- (difluoromethyl) -6- (4- methoxyphenyl) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 35
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 4- phenyl ethynyl phenyl, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol tri- Ethylamine, is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 30 DEG C of oil baths, is with trifluomethoxybenzene Internal standard measures19F yield is 55%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic Solvent obtains crude product, and crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 6- Three azepine -5 (4 of ([1,1'- xenyl -4- base) -3- (difluoromethyl) -4- phenethyl -1,2,4-H) -one] (separation 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)。
Embodiment 36
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 2- chlorobenzene acetylene, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol, tri- second Base amine is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 50 DEG C of oil baths, is interior with trifluomethoxybenzene Mark, measures19F yield is 48%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic molten Agent obtains crude product, and crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 3- (difluoro Methyl) -6- (2- chlorphenyl) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 37
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 3- thiophene acetylene, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol tri- Ethylamine, is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 60 DEG C of oil baths, is with trifluomethoxybenzene Internal standard measures19F yield is 43%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic Solvent obtains crude product, and crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 3- (two Methyl fluoride) -6- (3- thienyl) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 38
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol Cyclopropyl acetylene, 0.40 mmol (2- azidoethyl) benzene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol triethyl group Amine is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 40 DEG C of oil baths, using trifluomethoxybenzene as internal standard, It measures19F yield is 38%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic solvent Crude product is obtained, crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 6- cyclopropyl- 3- (difluoromethyl) -4- phenethyl -1,2,4- triazine -5 (4H) -one (separation 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)。
Embodiment 39
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 4- methyl phenylacetylene, 0.40 mmol nitrine hexamethylene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol triethyl group Amine is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 40 DEG C of oil baths, using trifluomethoxybenzene as internal standard, It measures19F yield is 75%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, and revolving removes organic solvent Crude product is obtained, crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 4- cyclohexyl- - 5 (4H) -one of 3- (difluoromethyl) -4- (p-methylphenyl) -1,2,4- triazine (separation 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)。
Embodiment 40
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 4- methyl phenylacetylene, 0.40 mmol nitrine hexamethylene, 0.40 mmol difluoroacetic acid acid anhydride, are eventually adding 0.30 mmol triethyl group Amine is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 60 DEG C of oil baths, using trifluomethoxybenzene as internal standard, It measures19F yield is 72%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, revolving removes organic solvent Crude product is obtained, crude product is eluted with pentane and methylene chloride (1:5, v/v) by silica gel column chromatography, obtains 6- (3- (two Methyl fluoride) -5- oxo -6- (p-methylphenyl) -1,2,4- triazine -4 (5H)-yl] ethyl hexanoate (separation 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)。
Embodiment 41
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, is added 0.010 Mmol cuprous iodide, 0.0050 mmol 4,4 '-di-t-butyl -2,2 '-bipyridyl, 23 mmol methylene chloride, 0.20 mmol 4- methyl phenylacetylene, 0.40 mmol 2- (2- azidoethyl) -1,3-dioxolane, 0.40 mmol difluoroacetic acid acid anhydride, finally plus Enter 0.30 mmol triethylamine, is cooled to room temperature after being stirred to react 30 h in a closed system under the conditions of 50 DEG C of oil baths, with three Fluorine methoxyl group benzene is internal standard, is measured19F yield is 62%, merges organic phase, is filtered with 100-200 mesh silica gel, and methylene chloride rinses, Revolving removes organic solvent and obtains crude product, and crude product is washed by silica gel column chromatography with pentane and methylene chloride (1:5, v/v) It is de-, obtain 4- (2- (1,3- dioxolyl -2- ethyl) ethyl) -3- (difluoromethyl) -6- (p-methylphenyl) -1,2,4- Triazine -5 (4H) -one (separation 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)。
Bactericidal activity test
1. accurately weigh the compound of the preparation of embodiment 14, water is added and 0.1% Tween-80 is configured to the medical fluid of 400 mg/L 20 mL are measured for bactericidal activity.Use crops sprayer carry out spraying treatment (sprayer type be solid crops sprayer, Atomisation pressure is 1.5 kg/cm2, spouting liquid is about 675 L/hm2).
The consistent two leaves phase cucumber of growth cultivated in greenhouse is taken, natural air drying is inoculated with pathogen after 24 h.It is specifically Using inoculator by bacterium of downy mildew of cucumber sporangia suspension (5 × 105A/ml) it sparges on host crop, then move into people Work climatic chamber culture (24 DEG C, RH > 90, no light).After 24 h, test material shifting is investigated after greenhouse normal management, 4-7 d The bactericidal activity of test specimen.
According to the occurring degree of control, using visual method, the bactericidal activity of experimental investigation sample, as a result with 100-0 come It indicates, represented with " 100 " grade disease-free, " 0 " grade represents the occurring degree of most serious.Calculate the inhibiting rate to bacterium of downy mildew of cucumber It is 45%.
2. accurately weighing the compound of the preparation of embodiment 1, it is configured to the dichloromethane solution 5mL of 1g/L, filter paper is taken to soak Enter wherein, takes out and killed after air-drying for Escherichia coli (Gram-negative bacteria), staphylococcus aureus (gram-positive bacteria) Bacterium determination of activity.
The broth bouillon of 25g/L is made of sterilizing hot water, LB agar and technology agar powder in superclean bench, by meat Soup culture medium pours into surface plate while hot, and solid medium is made after air drying, and by bacterium, (ultraviolet-uisible spectrophotometer is measured Bacterial concentration: light absorption value=0.04) it uniformly is applied to solid culture primary surface, take control filter paper (blank assay) and sample filter The scraps of paper are respectively placed in surface plate, are then sealed, and surface plate is placed in 37 DEG C of electro-heating standing-temperature cultivators and is cultivated for 24 hours, investigation The bactericidal activity of test specimen.
According to the sterility of control, using the bactericidal activity of visual method experimental investigation sample, the results show that control filter Scraps of paper bacterium energy normal growth, and show the compound of the preparation of embodiment 1 to large intestine bar without bacterial growth around sample filter paper Bacterium and staphylococcus aureus have strong bactericidal activity.
3. accurately weighing the compound of the preparation of embodiment 23, it is configured to the dichloromethane solution 5mL of 1g/L, takes filter paper It is immersed, takes out and killed after air-drying for Escherichia coli (Gram-negative bacteria), staphylococcus aureus (gram-positive bacteria) Bacterium determination of activity.
The broth bouillon of 25g/L is made of sterilizing hot water, LB agar and technology agar powder in superclean bench, by meat Soup culture medium pours into surface plate while hot, and solid medium is made after air drying, and by bacterium, (ultraviolet-uisible spectrophotometer is measured Bacterial concentration: light absorption value=0.04) it uniformly is applied to solid culture primary surface, take control filter paper (blank assay) and sample filter The scraps of paper are respectively placed in surface plate, are then sealed, and surface plate is placed in 37 DEG C of electro-heating standing-temperature cultivators and is cultivated for 24 hours, investigation The bactericidal activity of test specimen.
According to the sterility of control, using the bactericidal activity of visual method experimental investigation sample, the results show that control filter Scraps of paper bacterium energy normal growth, and the breeding of sample filter paper surrounding bacterial is slowly, shows the compound of the preparation of embodiment 23 to big Enterobacteria and staphylococcus aureus have bactericidal activity.
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with Modification, is all covered by the present invention.

Claims (9)

1. a kind of perfluoroalkyl or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds, it is characterised in that: be with mantoquita Catalyst, 2,2 '-bipyridyliums derivatives are ligand, nitrine, alkynesWith perfluorocarboxylic acid acid anhydride or difluoro Acetic anhydride is raw material, and the perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds are made through one kettle way；
The structural formula of the perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds are as follows:, wherein RF= C2F5、n-C3F7、CF2H。
2. perfluoroalkyl according to claim 1 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: the mantoquita is cuprous iodide, CuBr, CuCl, Cu (OTf)2、Cu(CH3CN)4BF4With any one in CuCN.
3. perfluoroalkyl according to claim 1 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: the 2,2 '-bipyridyliums derivative is 2,2 '-bipyridyls, 5,5 '-dimethyl -2,2 '-bipyridyl, 4,4 '-diformazans Any one in base -2,2 '-bipyridyl, 4,4 '-di-t-butyls -2,2 '-bipyridyl.
4. perfluoroalkyl according to claim 1 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: the nitrineIn R ' group be following formula 1- formula 23 in any one:
。
5. perfluoroalkyl according to claim 1 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: the alkynesIn R ' ' group be following formula 24- formula 41 in any one:
。
6. perfluoroalkyl according to claim 1 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: its specific synthesis step is as follows: in nitrogen atmosphere, mantoquita, 2 are added into the container with magnetic stirring apparatus, 2 '-bipyridyliums derivatives, nitrine, alkynes, perfluorocarboxylic acid acid anhydride or difluoroacetic acid acid anhydride, triethylamine and solvent are uniformly mixed After shut plug, place it at 30-60 DEG C continue stirring 1-30 hour after, with 100-200 mesh silica gel filter, methylene chloride rush It washes, merges organic phase, then revolving removes organic solvent；Obtained crude product is by silica gel column chromatography, with pentane-dichloromethane Alkane or pentane-ethyl acetate are that eluant, eluent is eluted, and obtain the perfluoroalkyl or difluoromethyl -1,2,4- triazine assimilation Close object.
7. perfluoroalkyl according to claim 6 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: the solvent is n-hexane/tetrahydrofuran mixed solvent, any one in methylene chloride.
8. perfluoroalkyl according to claim 7 or difluoromethyl -1,2, the synthetic method of 4- triazineon compounds is special Sign is: mantoquita, 2,2 '-bipyridyliums derivatives, alkynes, nitrine, perfluorocarboxylic acid acid anhydride, triethylamine and n-hexane and four used The molar ratio of hydrogen furans 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)；
Mantoquita used, 2,2 '-bipyridyliums derivatives, alkynes, nitrine, difluoroacetic acid acid anhydride, triethylamine and methylene chloride rub You are than being (0.01-0.05): (0.005-0.025): (0.2-1): (0.4-2): (0.4-2): (0.3-1.5): (23-117).
9. a kind of perfluoroalkyl or difluoromethyl -1,2,4- triazineon compounds such as the synthesis of claim 1-8 the method exists For as the application on fungicide.
CN201811244795.5A 2018-10-24 2018-10-24 Synthesis method of perfluoroalkyl or difluoromethyl-1, 2, 4-triazone compound Expired - Fee Related CN109111406B (en)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3159624A (en) * 1960-11-17 1964-12-01 Toyama Kagaku Kogyo Kabushiki Substituted pyruvic acid esters and 3-amino-5-hydroxy-6-(substituted ethenyl)-1, 2, 4-triazines prepared therefrom
US4081267A (en) * 1975-02-14 1978-03-28 Sumitomo Chemical Company, Limited Pyridyltriazinone herbicidal compositions
CN1474652A (en) * 2000-10-27 2004-02-11 �ݶ�ũ�����޹�˾ Substituted 4,5-dihydro-1,2,4-triazin -6-ones, 1,2,4-triazin-6-ones, and their use as fungicides and insecticides
CN1474694A (en) * 2000-10-27 2004-02-11 �ݶ�ũ�����޹�˾ Substituted 4,5-dihydro-1,2,4-triazin-3-ones, 1,2,4-triazin-3-ones, and their use as fungicides and insecticides
CN101189214A (en) * 2005-05-03 2008-05-28 美国陶氏益农公司 Substituted 4,5-dihydro-1,2,4-triazin-6-ones, 1,2,4-triazin-6-ones, and their use as fungicides
CN107118168A (en) * 2017-04-20 2017-09-01 福州大学 A kind of method that copper catalysis synthesizes the triazineon compounds of trifluoromethyl 1,2,4
CN107935955A (en) * 2017-11-22 2018-04-20 天津大学 A kind of 1,2,4 3 nitrogen piperazine of 5 aryl, 6 trifluoromethyl, 1,2,5,6 tetrahydrochysene, 3 formic acid ester compound and preparation method

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3159624A (en) * 1960-11-17 1964-12-01 Toyama Kagaku Kogyo Kabushiki Substituted pyruvic acid esters and 3-amino-5-hydroxy-6-(substituted ethenyl)-1, 2, 4-triazines prepared therefrom
US4081267A (en) * 1975-02-14 1978-03-28 Sumitomo Chemical Company, Limited Pyridyltriazinone herbicidal compositions
CN1474652A (en) * 2000-10-27 2004-02-11 �ݶ�ũ�����޹�˾ Substituted 4,5-dihydro-1,2,4-triazin -6-ones, 1,2,4-triazin-6-ones, and their use as fungicides and insecticides
CN1474694A (en) * 2000-10-27 2004-02-11 �ݶ�ũ�����޹�˾ Substituted 4,5-dihydro-1,2,4-triazin-3-ones, 1,2,4-triazin-3-ones, and their use as fungicides and insecticides
CN101189214A (en) * 2005-05-03 2008-05-28 美国陶氏益农公司 Substituted 4,5-dihydro-1,2,4-triazin-6-ones, 1,2,4-triazin-6-ones, and their use as fungicides
CN107118168A (en) * 2017-04-20 2017-09-01 福州大学 A kind of method that copper catalysis synthesizes the triazineon compounds of trifluoromethyl 1,2,4
CN107935955A (en) * 2017-11-22 2018-04-20 天津大学 A kind of 1,2,4 3 nitrogen piperazine of 5 aryl, 6 trifluoromethyl, 1,2,5,6 tetrahydrochysene, 3 formic acid ester compound and preparation method

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