CN110903319A - Preparation method of 2-phosphonothioflavonoid compound - Google Patents
Preparation method of 2-phosphonothioflavonoid compound Download PDFInfo
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- CN110903319A CN110903319A CN201911097576.3A CN201911097576A CN110903319A CN 110903319 A CN110903319 A CN 110903319A CN 201911097576 A CN201911097576 A CN 201911097576A CN 110903319 A CN110903319 A CN 110903319A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 22
- -1 diaryl phosphine oxide Chemical compound 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000007800 oxidant agent Substances 0.000 claims abstract description 3
- 230000001590 oxidative effect Effects 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 239000000047 product Substances 0.000 claims description 14
- 239000003960 organic solvent Substances 0.000 claims description 12
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 claims description 11
- PHVMRDUYJACTLD-UHFFFAOYSA-N P(=O)(O)(O)C1(OC2=CC=CC=C2C(C1)=S)C1=CC=CC=C1 Chemical compound P(=O)(O)(O)C1(OC2=CC=CC=C2C(C1)=S)C1=CC=CC=C1 PHVMRDUYJACTLD-UHFFFAOYSA-N 0.000 claims description 11
- 239000012074 organic phase Substances 0.000 claims description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 8
- 239000012295 chemical reaction liquid Substances 0.000 claims description 8
- 239000012043 crude product Substances 0.000 claims description 8
- 238000010898 silica gel chromatography Methods 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 6
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 claims description 2
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims description 2
- 125000002560 nitrile group Chemical group 0.000 claims description 2
- 238000007789 sealing Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 238000009987 spinning Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 abstract description 5
- 238000007363 ring formation reaction Methods 0.000 abstract description 5
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 4
- 230000001699 photocatalysis Effects 0.000 abstract description 4
- 238000013032 photocatalytic reaction Methods 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052741 iridium Inorganic materials 0.000 abstract description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 abstract description 2
- 239000012071 phase Substances 0.000 abstract description 2
- 229910052707 ruthenium Inorganic materials 0.000 abstract description 2
- AWYYABCIESYFJD-UHFFFAOYSA-N CSC1=C(C=CC=C1)C(C#C)C(=O)C(C#C)C1=C(C=CC=C1)SC Chemical compound CSC1=C(C=CC=C1)C(C#C)C(=O)C(C#C)C1=C(C=CC=C1)SC AWYYABCIESYFJD-UHFFFAOYSA-N 0.000 abstract 1
- 238000006555 catalytic reaction Methods 0.000 abstract 1
- 238000005286 illumination Methods 0.000 abstract 1
- 229910000510 noble metal Inorganic materials 0.000 abstract 1
- 238000007146 photocatalysis Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- ZVGPMCFSHYYVBH-UHFFFAOYSA-N 1-(2-methylsulfanylphenyl)propan-2-one Chemical compound CSC1=CC=CC=C1CC(C)=O ZVGPMCFSHYYVBH-UHFFFAOYSA-N 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 238000004679 31P NMR spectroscopy Methods 0.000 description 6
- LAQPNDIUHRHNCV-UHFFFAOYSA-N isophthalonitrile Chemical compound N#CC1=CC=CC(C#N)=C1 LAQPNDIUHRHNCV-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000010276 construction Methods 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655363—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a six-membered ring
- C07F9/655372—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a preparation method of 2-phosphono sulfo-flavonoid compounds, which is a method for synthesizing by utilizing the aqueous phase visible light catalysis thereof. The invention takes tetracarbazole m-diphenylnitrile (4-CzIPN) as a photosensitizer, lauroyl peroxide as an oxidant, 2-methylthio-phenylpropargyl ketone and diaryl phosphine oxide as initial raw materials, water as a solvent, and the target product is obtained by illumination reaction for 24 hours at room temperature under the protection of nitrogen. The invention provides a method for preparing 2-phosphono-thioflavonoid compound by water phase photocatalysis and serial cyclization reaction of radicals. Compared with the traditional method, the method does not need to use the traditional noble metal (such as ruthenium, iridium and the like) organic photosensitizer, and can be used for quickly and efficiently synthesizing the 2-phosphonothioflavonoid compound under extremely mild and green reaction conditions, so that the method has great potential application value in the fields of green synthetic chemistry, photocatalytic reaction for constructing heterocyclic compounds and pharmaceutical chemistry.
Description
Technical Field
The invention relates to the field of organic chemical synthesis, in particular to a water-phase photocatalytic preparation method of a 2-phosphonothio-flavonoid compound.
Background
Researchers in various fields increasingly pay more attention to how to reduce the influence of research behaviors on the environment to the maximum extent so as to ensure sustainable development. Especially for organic chemistry, the development of environmentally friendly and green sustainable synthetic means is a necessary way for the development of organic chemistry. One of the adverse effects of classical organic synthesis on the environment is the use of organic solvents, and since chemical reactions often require heating, the liquid or vapor of organic solvents may cause severe combustion or even explosion under such conditions, and further cause corresponding safety and pollution problems, which are rare. For this reason, the academic community proposed the concept of "green chemistry" in 1991, aiming to guide the chemical research process and to avoid or reduce the use and production of dangerous substances and pollutants as much as possible. The use of "safe solvents" as reaction medium is explicitly proposed in its twelve principles. As a natural liquid with abundant reserves, the water has the advantages of no toxicity, low price, easy obtainment, safety, environmental protection and the like. The water used as a reaction medium instead of the traditional organic solvent can effectively avoid potential pollution and safety risks in chemical processes. The development of aqueous organic synthetic chemistry has therefore become a consensus in the field. Meanwhile, the chemical reaction induced by visible light becomes a research hotspot due to novel innovativeness and great application value, and great progress is made in many aspects. However, at present, photo-oxidation-reduction catalytic systems are almost all carried out in organic media, and there are only reports about aqueous phase photo-catalytic organic reactions, so that the development of a photo-catalytic synthesis strategy using water as a green solvent to replace a traditional organic solvent is urgently needed.
The phosphorus-containing compound, especially the heterocyclic organic phosphine compound, has wide application in the fields of organic synthesis, material chemistry and pharmaceutical chemistry. After some heterocyclic compounds are connected with phosphorus-containing groups, the biological response can be enhanced, the curative effect of the medicine is improved or the material performance is improved. Therefore, the construction of carbon-phosphorus bond has been receiving extensive attention from academia in the last decades, and at present, the construction of carbon-phosphorus bond mainly depends on the traditional cross-coupling reaction and the radical series cyclization reaction emerging in recent years, but the reactions often need to use peroxide, transition metal (manganese, silver, copper, iron, ruthenium, iridium and the like) and higher reaction temperature, thereby limiting the practical application of the reaction.
The invention provides a novel method for preparing 2-phosphonothioflavone compounds by using easily-obtained 2-methylthiophenylproparganone and diphenylphosphine oxide as starting materials and performing visible light-induced aqueous-phase free radical serial cyclization reaction. Compared with the traditional method, the method avoids the traditional metal organic photosensitizer, quickly and efficiently constructs the target compound under extremely mild and green reaction conditions, and has great potential application value in the fields of green synthetic chemistry, construction of heterocyclic compounds by photocatalytic reaction and pharmaceutical and chemical industry
Disclosure of Invention
The invention provides a novel method for synthesizing 2-phosphono-thioflavonoid compounds by visible light-induced aqueous phase free radical serial cyclization reaction.
The technical scheme for realizing the invention is as follows:
a method for preparing 2-phosphono-thioflavonoid compounds comprises the following steps: sequentially adding 2-methylthio phenylpropargyl ketone, diaryl phosphine oxide, lauroyl peroxide and tetracarbazole m-diphenylnitrile into a reaction bottle, then adding water into the reaction system, sealing the reaction bottle after introducing nitrogen, stirring at room temperature under the irradiation of a white light-emitting diode until the 2-methylthio phenylpropargyl ketone is completely converted, extracting the reaction solution by using ethyl acetate, combining organic phases, drying by using anhydrous sodium sulfate, removing the organic solvent by spinning, and purifying the crude product by silica gel column chromatography to obtain a 2-phosphonothioflavone product.
Furthermore, the structural formula of the 2-methylthio phenylproparganone is as follows:
wherein R is1Is mono-or polysubstituted with one of the following groups: hydrogen, methyl, ethyl, tert-butyl, methoxy,Fluorine, chlorine, bromine, trifluoromethyl and nitrile group.
Also, the diarylphosphine oxide has the following structural formula:
wherein R is2Is one of the following groups: phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 2-naphthyl;
furthermore, the structural formula of the 2-phosphonothioflavonoid compound is as follows:
wherein R is1Is one of the following groups: hydrogen, 4-methyl, 4-ethyl, 4-tert-butyl, 4-methoxy, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, 4-nitrile, 3-methyl, 3-fluoro, 2-bromo; wherein R is2Is one of the following groups: phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 2-naphthyl.
Furthermore, the preparation equation of the target product 2-phosphonothioflavone product is as follows:
in addition, the method takes 2-methylthio phenylpropargyl ketone and diphenyl phosphine oxide as initial raw materials, lauroyl peroxide as an oxidant and tetracarbazole m-diphenylnitrile as a photosensitizer, wherein the ratio of 2-methylthio phenylpropargyl ketone: diphenyl phosphine oxide: lauroyl peroxide: the feeding mmol ratio of the tetracarbazole m-diphenylnitrile is 1:1-2:1-3: 1-10%, the adding amount of water as a solvent is 2.5mL, the reaction is carried out at room temperature, a white light-emitting diode is irradiated for 24 hours under the protection of nitrogen, after the raw materials are completely consumed, ethyl acetate is used for extracting reaction liquid, an organic phase is removed by rotation, and a series of target products, namely 2-phosphonothioflavonoid compounds are obtained by column chromatography separation.
The invention has the advantages and effects that:
the invention provides a novel method for preparing 2-phosphonothioflavonoid compounds by using easily-obtained 2-methylthio phenylproparganone and diphenylphosphine oxide as starting materials and inducing aqueous-phase free radical serial cyclization reaction by visible light. Compared with the traditional method, the method does not need to use the traditional metal organic photosensitizer, quickly and efficiently constructs the target compound under extremely mild and green reaction conditions, and has great potential application value in the fields of green synthetic chemistry, construction of heterocyclic compounds through photocatalytic reaction and pharmaceutical and chemical industry
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without inventive effort based on the embodiments of the present invention, are within the scope of the present invention.
Example 1
The preparation method of the phosphonothioflavone compound 1 comprises the following steps:
2-methylthiophenylpropanone (0.2mmol), diphenylphosphine oxide (0.4mmol), lauroyl peroxide (2.0 equiv) and tetracarbazole isophthalonitrile (5 mol%) are sequentially added into a 10mL reaction bottle, then 2.5mL of water is added into the reaction system, the reaction bottle is sealed after nitrogen is introduced, the mixture is stirred for 24 hours at room temperature under the irradiation of a white light-emitting diode until the 2-methylthiophenylpropanone is completely converted, ethyl acetate (3X 5mL) is used for extracting reaction liquid, organic phases are combined and dried by anhydrous sodium sulfate, an organic solvent is removed by rotation, and a crude product is purified by silica gel column chromatography to obtain a 2-phosphonothioflavone product 1.
The specific results are as follows:
1H NMR(400MHz,Chloroform-d)δ8.23(dd,J＝8.1,1.1Hz,1H),7.78-7.72(m,4H),7.65-7.61(m,1H),7.57-7.55(m,1H),7.52-7.48(m,1H),7.44-7.41(m,3H),7.40-7.34(m,5H),7.33-7.28(m,3H)；13C NMR(101MHz,Chloroform-d)δ181.0(d,J＝7.3Hz),166.6(d,J＝9.0Hz),136.9,136.0(d,J＝5.1Hz),135.1,134.0,132.2,131.4,131.3,131.2(d,J＝4.0Hz),131.1(d,J＝2.9Hz),130.3,128.9,128.7,128.5,128.1,128.0,128.0,127.6,126.7,125.5；31P NMR(162MHz,Chloroform-d)δ25.90.HRMS Calcd for C27H20O2PS[M+H]+:439.0916,found:439.0918
example 2
The preparation method of the phosphonothioflavone compound 2 comprises the following steps:
2-methylthiophenylpropanone (0.2mmol), diphenylphosphine oxide (0.4mmol), lauroyl peroxide (2.0 equiv) and tetracarbazole isophthalonitrile (5 mol%) are sequentially added into a 10mL reaction bottle, then 2.5mL of water is added into the reaction system, the reaction bottle is sealed after nitrogen is introduced, the mixture is stirred for 24 hours at room temperature under the irradiation of a white light-emitting diode until the 2-methylthiophenylpropanone is completely converted, ethyl acetate (3X 5mL) is used for extracting reaction liquid, organic phases are combined and dried by anhydrous sodium sulfate, an organic solvent is removed by rotation, and a crude product is purified by silica gel column chromatography to obtain a 2-phosphonothioflavone product 2.
The specific results are as follows:
1H NMR(400MHz,Chloroform-d)δ8.23(dd,J＝8.1,1.4Hz,1H),7.81-7.75(m,4H),7.65-7.61(m,1H),7.57(d,J＝7.4Hz,1H),7.53-7.48(m,1H),7.46-7.42(m,2H),7.39-7.35(m,6H),7.13(d,J＝7.9Hz,2H),2.37(s,3H)；13C NMR(101MHz,Chloroform-d)δ181.2(d,J＝7.3Hz),166.8(d,J＝8.9Hz),140.7,137.0,135.2,134.1,133.3(d,J＝5.1Hz),132.1,131.4,131.3,131.2(d,J＝4.0Hz),131.0(d,J＝2.9Hz),128.9,128.8,128.7,128.4,128.1,127.9,127.3,126.3,125.5,21.5；31P NMR(162MHz,Chloroform-d)δ26.20.HRMSCalcd for C28H22O2PS[M+H]+:453.1073,found:453.1074
example 3
The preparation method of the phosphonothioflavone compound 3 comprises the following steps:
2-methylthiophenylpropanone (0.2mmol), diphenylphosphine oxide (0.4mmol), lauroyl peroxide (2.0 equiv) and tetracarbazole isophthalonitrile (5 mol%) are sequentially added into a 10mL reaction bottle, then 2.5mL of water is added into the reaction system, the reaction bottle is sealed after nitrogen is introduced, the mixture is stirred for 24 hours at room temperature under the irradiation of a white light-emitting diode until the 2-methylthiophenylpropanone is completely converted, ethyl acetate (3X 5mL) is used for extracting reaction liquid, organic phases are combined and dried by anhydrous sodium sulfate, an organic solvent is removed by rotation, and a crude product is purified by silica gel column chromatography to obtain a 2-phosphonothioflavone product 3.
The specific results are as follows:
1H NMR(400MHz,Chloroform-d)δ8.21(dd,J＝8.1,1.3Hz,1H),7.77-7.72(m,4H),7.65-7.61(m,1H),7.55(d,J＝7.6Hz,1H),7.52-7.48(m,1H),7.44-7.40(m,4H),7.38–7.33(m,4H),7.01-6.96(m,2H)；13C NMR(101MHz,Chloroform-d)δ181.0(d,J＝7.2Hz),166.3–164.0(m),162.7,136.7,134.9,133.8,132.3,132.0(dd,J＝5.2,3.4Hz),131.4,131.3,131.2(d,J＝2.8Hz),131.1,131.0(d,J＝8.8Hz),128.8,128.6,128.2,128.0,127.1,125.5,115.3,115.1；31P NMR(162MHz,Chloroform-d)δ26.05；19F NMR(376MHz,Chloroform-d)δ-109.80.HRMS Calcd for C27H19FO2PS[M+H]+:457.0822,found:457.0825
example 4
The preparation method of phosphonothioflavone compound 4 comprises the following steps:
2-methylthiophenylpropanone (0.2mmol), diphenylphosphine oxide (0.4mmol), lauroyl peroxide (2.0 equiv) and tetracarbazole isophthalonitrile (5 mol%) are sequentially added into a 10mL reaction bottle, then 2.5mL of water is added into the reaction system, the reaction bottle is sealed after nitrogen is introduced, the mixture is stirred for 24 hours at room temperature under the irradiation of a white light-emitting diode until the 2-methylthiophenylpropanone is completely converted, ethyl acetate (3X 5mL) is used for extracting reaction liquid, organic phases are combined and dried by anhydrous sodium sulfate, an organic solvent is removed by rotation, and a crude product is purified by silica gel column chromatography to obtain a 2-phosphonothioflavone product 4.
The specific results are as follows:
1H NMR(400MHz,Chloroform-d)δ8.25(dd,J＝8.1,1.0Hz,1H),7.66-7.60(m,5H),7.58-7.55(m,1H),7.53-7.49(m,1H),7.43-7.37(m,3H),7.33-7.26(m,2H),7.16(dd,J＝8.0,2.8Hz,4H),2.35(s,6H)；13C NMR(101MHz,Chloroform-d)δ181.1(d,J＝7.4Hz),166.2(d,J＝8.9Hz),141.3(d,J＝3.0Hz),137.0,136.2(d,J＝5.1Hz),132.1,131.9,131.5,131.4,131.2(d,J＝3.9Hz),130.8,130.2,128.88,128.86,128.77,128.72,128.4,128.0,127.9,127.0,125.4,21.6；31P NMR(162MHz,Chloroform-d)δ26.49.HRMS Calcd forC29H24O2PS[M+H]+:467.1229,found:467.1230
example 5
The preparation method of phosphonothioflavone compound 5 comprises the following steps:
2-methylthiophenylpropanone (0.2mmol), diphenylphosphine oxide (0.4mmol), lauroyl peroxide (2.0 equiv) and tetracarbazole isophthalonitrile (5 mol%) are sequentially added into a 10mL reaction bottle, then 2.5mL of water is added into the reaction system, the reaction bottle is sealed after nitrogen is introduced, the mixture is stirred for 24 hours at room temperature under the irradiation of a white light-emitting diode until the 2-methylthiophenylpropanone is completely converted, ethyl acetate (3X 5mL) is used for extracting reaction liquid, organic phases are combined and dried by anhydrous sodium sulfate, an organic solvent is removed by rotation, and a crude product is purified by silica gel column chromatography to obtain a 2-phosphonothioflavone product 5.
The specific results are as follows:
1H NMR(400MHz,CDCl3)δ9.46(s,1H),8.23–7.99(m,4H),7.88–7.77(m,2H),7.60–7.45(m,3H),4.30–4.23(m,2H),1.43(t,J＝7.0Hz,3H).13C NMR(101MHz,CDCl3)δ151.52(s),149.92(s),146.42(s),146.17(s),142.83–142.38(m),132.88(d,J＝2.8Hz),132.41(d,J＝10.0Hz),132.00(s),130.70(s),130.33(d,J＝1.2Hz),129.50(d,J＝1.9Hz),128.61(d,J＝13.4Hz),62.26(d,J＝6.3Hz),16.57(d,J＝6.3Hz).31P NMR(162MHz,CDCl3)δ24.24(s).
example 6
The preparation method of phosphonothioflavone compound 6 comprises the following steps:
2-methylthiophenylproparganone (0.2mmol), dinaphthylphosphine oxide (0.4mmol), lauroyl peroxide (2.0 equiv.), and tetracarbazole isophthalonitrile (5 mol%) are sequentially added into a 10mL reaction bottle, then 2.5mL of water is added into the reaction system, the reaction bottle is sealed after nitrogen is introduced, the mixture is stirred for 24 hours at room temperature under the irradiation of a white light-emitting diode until the 2-methylthiophenylproparganone is completely converted, ethyl acetate (3X 5mL) is used for extracting reaction liquid, organic phases are combined and dried by anhydrous sodium sulfate, an organic solvent is removed by rotation, and a crude product is purified by silica gel column chromatography to obtain a 2-phosphonothioflavone product 6.
The specific results are as follows:
1H NMR(400MHz,Chloroform-d)δ8.66(d,J＝6.4Hz,2H),8.04(d,J＝8.0Hz,1H),7.94-7.67(m,6H),7.57-7.49(m,2H),7.45-7.35(m,9H),7.26(d,J＝9.2Hz,1H),7.16(t,J＝7.4Hz,2H)；13C NMR(101MHz,Chloroform-d)δ180.5(d,J＝6.8Hz),166.0(d,J＝9.1Hz),136.7,135.9(d,J＝4.9Hz),133.75,133.65,132.5,132.0,130.9(d,J＝3.8Hz),130.5,130.1,129.5,128.9,128.7,128.5,128.3,127.7,127.6,126.9,126.0,125.2,124.5,124.4；31P NMR(162MHz,Chloroform-d)δ34.25；HRMS Calcd for C35H24O2PS[M+H]+:539.1229,found:539.1236
the above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (6)
1. A preparation method of 2-phosphono-thioflavonoid compounds is characterized by comprising the following steps: the method comprises the following steps: sequentially adding 2-methylthio phenylpropargyl ketone, diaryl phosphine oxide, lauroyl peroxide and tetracarbazole m-diphenylnitrile into a reaction bottle, then adding water into the reaction system, sealing the reaction bottle after introducing nitrogen, stirring at room temperature under the irradiation of a white light-emitting diode until the 2-methylthio phenylpropargyl ketone is completely converted, extracting the reaction solution by using ethyl acetate, combining organic phases, drying by using anhydrous sodium sulfate, removing the organic solvent by spinning, and purifying the crude product by silica gel column chromatography to obtain a 2-phosphonothioflavone product.
2. The process for the preparation of 2-phosphonothioflavonoids according to claim 1, characterized in that: the structural formula of the 2-methylthio phenylproparganone is as follows:
wherein R is1Is mono-or polysubstituted with one of the following groups: hydrogen, methyl, ethyl, tert-butyl, methoxy, fluorine, chlorine, bromine, trifluoromethyl and nitrile group.
3. The process for the preparation of 2-phosphonothioflavonoids according to claim 1, characterized in that: the diaryl phosphine oxide has the following structural formula:
wherein R is2Is one of the following groups: phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 2-naphthyl.
4. A process for the preparation of 2-phosphonothioflavonoids according to any of claims 1 to 3, characterized in that: the structural formula of the 2-phosphonothioflavonoid compound is as follows:
wherein R is1Is one of the following groups: hydrogen, 4-methyl, 4-ethyl, 4-tert-butyl, 4-methoxy, 4-fluoro, 4-chloro, 4-bromo, 4-trifluoromethyl, 4-nitrile, 3-methyl, 3-fluoro, 2-bromo; wherein R is2Is one of the following groups: phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3, 5-dimethylphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 2-naphthyl.
5. The process for the preparation of 2-phosphonothioflavonoids according to any of claims 1 to 4, characterized in that: the preparation equation of the target product 2-phosphonothioflavone product is as follows:
6. the process for the preparation of 2-phosphonothioflavonoids according to any of claims 1 to 5, characterized in that: the method takes 2-methylthio phenylpropargyl ketone and diphenyl phosphine oxide as initial raw materials, lauroyl peroxide as an oxidant and tetracarbazole m-diphenylnitrile as a photosensitizer, wherein the ratio of 2-methylthio phenylpropargyl ketone: diphenyl phosphine oxide: lauroyl peroxide: the feeding mmol ratio of the tetracarbazole m-diphenylnitrile is 1:1-2:1-3: 1-10%, the adding amount of water as a solvent is 2.5mL, the reaction is carried out at room temperature, a white light-emitting diode is irradiated for 24 hours under the protection of nitrogen, after the raw materials are completely consumed, ethyl acetate is used for extracting reaction liquid, an organic phase is removed by rotation, and a series of target products, namely 2-phosphonothioflavonoid compounds are obtained by column chromatography separation.
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