CN116969871A - Synthesis method of difluoromethyl seleno ether compound - Google Patents
Synthesis method of difluoromethyl seleno ether compound Download PDFInfo
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- -1 difluoromethyl seleno Chemical group 0.000 title claims abstract description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 150000001875 compounds Chemical class 0.000 title claims abstract description 33
- 238000001308 synthesis method Methods 0.000 title claims abstract description 15
- 238000005286 illumination Methods 0.000 claims abstract description 13
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 11
- UEEXRMUCXBPYOV-UHFFFAOYSA-N iridium;2-phenylpyridine Chemical compound [Ir].C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1 UEEXRMUCXBPYOV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 6
- HGVLQMWHKAMCMG-UHFFFAOYSA-N difluoromethylphosphane Chemical class FC(F)P HGVLQMWHKAMCMG-UHFFFAOYSA-N 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 34
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 20
- 238000004440 column chromatography Methods 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 239000012074 organic phase Substances 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 11
- 239000003208 petroleum Substances 0.000 claims description 11
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 9
- 238000010189 synthetic method Methods 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 7
- 239000002274 desiccant Substances 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 238000007865 diluting Methods 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000013375 chromatographic separation Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000005561 phenanthryl group Chemical group 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- JPBJMYVOQWDQNS-UHFFFAOYSA-N silirane Chemical compound C1C[SiH2]1 JPBJMYVOQWDQNS-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 16
- 239000000758 substrate Substances 0.000 abstract description 13
- 239000000126 substance Substances 0.000 abstract description 11
- 239000011669 selenium Substances 0.000 abstract description 8
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052711 selenium Inorganic materials 0.000 abstract description 7
- 231100000086 high toxicity Toxicity 0.000 abstract description 5
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000000203 mixture Substances 0.000 description 10
- WNPMJTVOWUTTSY-UHFFFAOYSA-M difluoromethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(F)F)C1=CC=CC=C1 WNPMJTVOWUTTSY-UHFFFAOYSA-M 0.000 description 7
- 150000003958 selenols Chemical class 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 6
- VDMJCVUEUHKGOY-JXMROGBWSA-N (1e)-4-fluoro-n-hydroxybenzenecarboximidoyl chloride Chemical compound O\N=C(\Cl)C1=CC=C(F)C=C1 VDMJCVUEUHKGOY-JXMROGBWSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- 229940065287 selenium compound Drugs 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000003343 selenium compounds Chemical class 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000011941 photocatalyst Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 2
- YWBHROUQJYHSOR-UHFFFAOYSA-N $l^{1}-selanylbenzene Chemical compound [Se]C1=CC=CC=C1 YWBHROUQJYHSOR-UHFFFAOYSA-N 0.000 description 1
- WBRZELCGPCKRBO-UHFFFAOYSA-N $l^{1}-selanylmethylbenzene Chemical compound [Se]CC1=CC=CC=C1 WBRZELCGPCKRBO-UHFFFAOYSA-N 0.000 description 1
- UHIPSWQNPNQBQY-UHFFFAOYSA-K 2-pyridin-2-ylpyridine trichlororuthenium hexahydrate Chemical compound O.O.O.O.O.O.Cl[Ru](Cl)Cl.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1 UHIPSWQNPNQBQY-UHFFFAOYSA-K 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- USQXCHKPROJEPR-UHFFFAOYSA-N difluoromethylselanyl(difluoro)methane Chemical compound FC(F)[Se]C(F)F USQXCHKPROJEPR-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- OIKHZBFJHONJJB-UHFFFAOYSA-N dimethyl(phenyl)silicon Chemical compound C[Si](C)C1=CC=CC=C1 OIKHZBFJHONJJB-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 150000003346 selenoethers Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a difluoromethyl seleno ether compound. The invention provides a synthesis method of a difluoromethyl seleno ether compound, which comprises the steps of mixing tris (2-phenylpyridine) iridium, seleno sulfonate compounds shown in a formula (I), difluoromethyl phosphonium compounds shown in a formula (I) and a reaction solvent, and reacting under illumination conditions to obtain the difluoromethyl seleno ether compound shown in a formula (II);. The inventionThe synthesis method is simple and convenient to operate, and has wide applicable substrate range, and a high-toxicity selenium source and equivalent strong alkaline substances are not needed.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of a difluoromethyl seleno ether compound.
Background
The incorporation of fluorine-containing groups into molecules is of great value for regulating chemical reactivity, lipophilicity, metabolic stability, and the like. Fluorochemical compounds have been considered as attractive candidate molecules in the development of pharmaceuticals, materials and agrochemicals. At present, difluoromethyl compounds have shown important application value in pharmaceutical chemistry research, because difluoromethyl is suitable for serving as a bioelectrode isostere with stronger lipophilicity of hydroxyl, sulfhydryl or amino groups and the like, and can serve as an effective hydrogen bond donor.
The organic selenium compound has a plurality of important biological functions of anti-inflammatory, anti-tumor, anti-oxidation and the like. Thus, the development of new synthetic strategies for difluoromethyl selenoether (R-SeCF 2H) compounds would provide more options for biomedical and chemical research. However, the existing methods for synthesizing difluoromethyl seleno ether compounds have limited quantity and serious defects. Selenol is the most commonly used selenizing reagent for preparing difluoromethyl selenoethyl compound, and selenol is a highly toxic compound with pungent smell, and has poor stability and easy volatilization, so that the selenol can be synthesized under strict protective environment and has complex operation.
Vaibhav P.Mehta uses phenylselenol, requires high temperature and continuous heating in the preparation of difluoromethyl seleno ether compound by adding potassium carbonate, and has only 65% yield (Org. Lett.2013,15, 5036-5039). Studer describes one example of benzyl selenol and [ Ph ] under UV irradiation 3 PCF 2 H]Examples of free radical difluoromethylation of Br (org. Lett.2017,19, 4150-4153) but the use of selenol and uv irradiation limits the application of this method. Recently, the group Xiao reported RSeCN and [ Ph ] formed in situ 3 PCF 2 H]Nucleophilic difluoromethylation of Br to synthesize difluoromethyl selenoethyl compound (J.org.chem.2021, 86, 13153-13159), but this strategy requires the use of toxic selenium source of potassium selenocyanate and equivalent amount of strongly basic substance (cesium carbonate), resulting in poor safety of the synthesized product, applicable only to methyl, methylene, and methine carbon atomsThe selenium compound substrate is replaced on the seed, the aryl selenium compound substrate is not contained, the highest synthesis yield is 83%, and the strong alkaline substance can generate strong corrosiveness to influence the application of the substrate. Therefore, in the prior art, a toxic selenium source (selenol or potassium selenocyanate) is required to be used, the operation is complex or a strong alkaline substance is used, the applicable substrate range is relatively narrow, and the large-scale popularization and application are very unfavorable.
Therefore, a method for synthesizing the difluoromethyl seleno ether compound needs no high-toxicity seleno source such as selenol or potassium selenocyanate and equivalent strong alkaline substances, is simple to operate and has wide applicable substrate range, so that the difluoromethyl seleno ether compound can be popularized and applied on a large scale.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to overcome the defects that the prior art for preparing the difluoromethyl seleno ether compound uses high-toxicity selenium sources such as selenol or potassium selenocyanate and the like, equivalent strong alkaline substances, the operation is complex, and the applicable substrate range is relatively narrow, thereby providing a novel synthesis method of the difluoromethyl seleno ether compound.
The invention provides a synthesis method of a difluoromethyl seleno ether compound, which comprises the following steps:
mixing tris (2-phenylpyridine) iridium, selenosulfonate compounds shown in a formula (I), difluoromethylphosphonium compounds shown in a formula (II) and a reaction solvent, and reacting under the condition of illumination to obtain difluoromethyl seleno-ether compounds shown in a formula (II);
wherein L is selected from single bond, C1-C10 alkylene;
R 1 selected from OR 4 、Si(R 5 )(R 6 )(R 7 ) Substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C10 heterocyclyl;
R 2 selected from C6-C20 aryl;
R 3 selected from C6-C20 aryl;
R 4 selected from the group consisting of substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C20 alkyl;
R 5 -R 7 each independently selected from C6-C20 aryl, C1-C20 alkyl;
W - selected from BF 4 - 、OTf - 、Cl - 、Br - 、I - 。
Preferably, the substituted C6-C20 aryl, substituted C1-C20 alkyl, substituted C3-C10 heterocyclyl contains 1-3 substituents selected from halogen, cyano, -COOR 8 、-S(O) 2 R 9 C1-C4 alkyl, C6-C20 aryl; r is R 8 Selected from C1-C4 alkyl, R 9 Selected from aryl groups containing 6 to 10 carbon atoms.
Preferably, L is selected from single bond, C1-C4 alkylene;
preferably, L is selected from single bond, methylene, ethylene, propylene, butylene.
Preferably, R 1 Selected from OR 4 、Si(R 5 )(R 6 )(R 7 ) Substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C3-C10 heterocyclyl;
and/or C6-C20 aryl is selected from phenyl, naphthyl, biphenyl, terphenyl, phenanthryl;
and/or C1-C20 alkyl is selected from methyl, ethyl, propyl, butyl;
and/or, a C3-C10 heterocyclic group contains at least 1 nitrogen atom;
preferably, the C3-C10 heterocyclyl is selected from the group consisting of silacyclopropane, silacyclobutane, and silacyclohexane.
Preferably, the substituted C6-C20 aryl, substituted C1-C20 alkyl and substituted C3-C10 heterocyclic groups contain 1-3 substituents, and the substituents are selected from cyano groups and COOR groups 8 、-S(O) 2 R 9 Methyl, ethyl, propyl, butyl, phenyl, naphthyl, biphenyl, terphenyl; r is R 8 Selected from methyl, ethyl, propyl, butyl, R 9 Selected from phenyl, p-methylphenyl.
Preferably, R 2 Selected from phenyl;
and/or R 3 Selected from phenyl;
and/or W - Selected from Br - 。
Preferably, the selenosulfonate compound represented by formula (I) is selected from
The invention is that Ts is p-toluenesulfonyl and Me is methyl.
The selenobenzenesulfonate compound used in the invention is an existing compound or can be prepared by an existing conventional method, and can be obtained by adopting literature Fang, Y.; li, X; liu, c; tang, j.; the synthesis was prepared as described in Chen, Z.J.org.Chem.2021,86,18081-18093.
Preferably, the molar ratio of the selenosulfonate compound shown in the formula (I), the difluoromethylphosphonium compound shown in the formula (II) and the tris (2-phenylpyridine) iridium is 1: (1.0-3.0): (0.001-0.050);
and/or the ratio of the selenosulfonate compound shown in the formula (I) to the reaction solvent is 1: (2-10), in mmol: and (3) mL. For example, when the molar amount of the selenosulfonate compound represented by formula (I) is 1mmol, 2mL of the reaction solvent is used; when the molar amount of the selenosulfonate compound shown in the formula (I) is 1mmol, 5mL of the reaction solvent is used; when the molar amount of the selenosulfonate compound represented by the formula (I) is 1mmol, 10mL of the reaction solvent is used.
Preferably, the illumination is visible light with the wavelength range of 400-480 nm;
optionally, the visible light is LED visible light.
Preferably, the reaction temperature of the reaction is 10-40 ℃, the stirring speed of the reaction is 400-500r/min, and the reaction time is 4-7h.
Preferably, the reaction is carried out under a nitrogen atmosphere.
Preferably, the reaction solvent is an organic solvent;
preferably, the organic solvent is at least one of acetonitrile, tetrahydrofuran, dichloromethane, ethylene glycol dimethyl ether, N-methylpyrrolidone, N-dimethylformamide and N, N-dimethylacetamide.
Preferably, after the reaction is finished, the method further comprises a step of separation and purification;
the separation and purification step comprises the steps of diluting the reaction liquid, washing and collecting an organic phase, drying and separating by column chromatography.
Preferably, the diluted diluting solvent is selected from ethyl acetate;
and/or the washing solvent of the washing is selected from saline solution;
and/or the drying agent is selected from anhydrous sodium sulfate;
and/or, the column chromatography separation comprises mixing an organic phase and column chromatography silica gel powder, concentrating to remove a solvent, and performing column chromatography separation on a concentrated product;
and/or, the column chromatographic separation adopts ethyl acetate and/or petroleum ether as eluent.
Optionally, the volume ratio of the diluent solvent to the mixed solution after the reaction is finished is (100-200): (0.1-8);
optionally, the saline solution is saturated saline;
optionally, the volume of the detergent for single use is 50-100mL, and the washing times are 2-3 times;
optionally, the mass ratio of the total mass of the mixed solution to the mass of the column chromatography silica gel powder after the reaction is finished is (145-400): (800-1000);
the concentration mode is not particularly limited, and the solvent can be removed by rotary evaporation to achieve the concentration purpose.
Optionally, the volume ratio of ethyl acetate to petroleum ether in the eluent is 1: (5-60).
The technical scheme of the invention has the following advantages:
1. the invention provides a synthesis method of a difluoromethyl seleno ether compound, which comprises the following steps: mixing tris (2-phenylpyridine) iridium, selenosulfonate compounds shown in a formula (I), difluoromethylphosphonium compounds shown in a formula (II) and a reaction solvent, and reacting under the condition of illumination to obtain difluoromethyl seleno-ether compounds shown in a formula (II);
. According to the invention, the selenosulfonate compound shown in the formula (I) is used as a selenium source to perform catalytic reaction under a specific photocatalyst, so that the toxicity of the selenium source is relatively low, and a selenol compound or potassium selenocyanate with unstable property and high toxicity is not required, so that strict environmental requirements are not required, and the operation is simple; the synthesis method of the invention has wide applicable substrate range, is not only suitable for substituting selenium compound substrates on carbon atoms of methyl, methylene and methine, but also is suitable for aryl selenium compound substrates; the synthetic method has no introduction of equivalent strong alkaline substances, reduces the corrosiveness of the synthetic reaction to equipment and simultaneously reduces the universality of applicable substrates due to the influence of the strong alkaline substances. According to the invention, the difluoromethyl seleno ether compound is synthesized by using the seleno sulfonate compound and the difluoromethyl phosphonium compound under specific photocatalyst and illumination conditions, a high-toxicity selenium source and equivalent strong alkaline substances are not needed, the operation is convenient and simple, and the application substrate range is wide.
2. The synthesis strategy has the advantages of wider substrate universality, high synthesis yield, no need of high-temperature heating treatment, capability of being carried out at room temperature, reduction of operation difficulty and improvement of operation safety by common light treatment relative to ultraviolet irradiation treatment, realization of large-scale synthesis, and hopeful realization of large-scale production and application.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
FIG. 1 shows a nuclear magnetic resonance spectrum of (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether in example 1 of the present invention;
FIG. 2 is a nuclear magnetic resonance spectrum of (difluoromethyl) (2- (4-cyanophenoxy) ethyl) selenoether in example 2 of the present invention;
FIG. 3 is a nuclear magnetic resonance spectrum of (difluoromethyl) ((dimethyl (phenyl) silyl) methyl) selenide in example 3 according to the invention;
FIG. 4 is a nuclear magnetic resonance spectrum of methyl 4- ((difluoromethyl) seleno) benzoate in example 4 of the present invention;
FIG. 5 nuclear magnetic resonance spectrum of 4- ((difluoromethyl) seleno) -1-p-toluenesulfonylpiperidine in example 5 of the present invention.
Detailed Description
The following examples are provided for a better understanding of the present invention and are not limited to the preferred embodiments described herein, but are not intended to limit the scope of the invention, any product which is the same or similar to the present invention, whether in light of the present teachings or in combination with other prior art features, falls within the scope of the present invention.
The specific experimental procedures or conditions are not noted in the examples and may be followed by the operations or conditions of conventional experimental procedures described in the literature in this field. The reagents or apparatus used were conventional reagent products commercially available without the manufacturer's knowledge.
Example 1: preparation of (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether
The present example provides a method for synthesizing (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether (3 a), which comprises the following steps:
the specific synthesis steps are as follows:
taking a clean 8mL screw reaction bottle, and placing the bottle into a magnetic force of 5 mm or 10mmSe- (2- (4-phenylphenoxy) ethyl) selenophenyl sulfonate (1 a,83.5mg,0.20 mmol), triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) and Ir (ppy) were added sequentially under nitrogen atmosphere with stirring 3 (2.62 mg, 0.04 mmol). N, N-dimethylacetamide (1 mL) was then added and mixed, and after capping, the mixture was stirred at a temperature of 25deg.C under illumination of 460nm LED lamp (rotation speed 400 rpm) and reacted for 4 hours. After the reaction was completed, the reaction system was transferred to a separating funnel, diluted with 100mL of ethyl acetate, and the organic phase was collected by washing with a saturated saline solution twice (50 ml×2), and the collected organic phase was dried over anhydrous sodium sulfate. Then filtering to remove the drying agent, adding 800mg of column chromatography silica gel powder, removing the solvent by rotary evaporation, and then performing column chromatography separation by taking petroleum ether as a leaching agent to obtain a target product (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether 3a. The target product was a white solid, yield: 94%.
The target product is characterized by electrospray mass spectrometry (EI-MS) and nuclear magnetic resonance, and the characterization data are as follows (the nuclear magnetic hydrogen spectrum of the target product is shown in figure 1):
1 H NMR(400MHz,CDCl 3 )δ7.59–7.54(m,4H),7.47–7.43(m,2H),7.36–7.32(m,1H),7.32(t,J＝56.0Hz,1H),7.04–6.96(m,2H),4.36(t,J＝6.6Hz,2H),3.23(t,J＝6.5Hz,2H).
13 C NMR(150MHz,CDCl 3 )δ157.9,140.8,134.6,128.9,128.4,126.9,126.9,115.3(t,J＝285Hz),115.1,68.3,21.4(t,J＝3.0Hz).
19 F NMR(565MHz,CDCl 3 )δ-91.1.
HRMS(EI)m/z[M] + theoretical value C 15 H 14 F 2 OSe + 328.0178, experimental 328.0173.
Example 2: preparation of (difluoromethyl) (2- (4-cyanophenoxy) ethyl) selenoether
The embodiment provides a synthesis method of (difluoromethyl) (2- (4-cyanophenoxy) ethyl) selenoether (3 b), which comprises the following synthesis routes:
the specific synthesis steps are as follows:
a clean 8mL screw flask was placed in a 5 x 10mm magnetic stirrer and Se- (2- (4-cyanophenoxy) ethyl) selenophensulfonate (1 b,73.3mg,0.20 mmol), triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) and Ir (ppy) were added sequentially under nitrogen atmosphere 3 (2.62 mg, 0.04 mmol) of N, N-dimethylacetamide (1 mL) was then added, the cap was closed, and the mixture was stirred at a temperature of 25deg.C under light irradiation of a 460nm LED lamp (rotation speed 400 rpm), after the reaction was completed, the reaction system was transferred to a separating funnel, 100mL of ethyl acetate was added to dilute the reaction system, and the organic phase was collected by washing with a saturated saline solution twice (50 mL. Times.2), the collected organic phase was dried over anhydrous sodium sulfate, then the drying agent was removed by filtration, 800mg of column chromatography silica gel powder was added, the solvent was removed by spin evaporation, and then column chromatography was performed using a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether=1:10, v/v) as a eluting agent to obtain the objective product (difluoromethyl) (2- (4-cyanophenoxy) ethyl) selenoethyl 3b as a pale yellow oily liquid, the yield: 95%.
The target product is characterized by electrospray mass spectrometry (EI-MS) and nuclear magnetic resonance, and the characterization data are as follows (the nuclear magnetic hydrogen spectrum of the target product is shown in figure 2):
1 H NMR(600MHz,CDCl 3 )δ7.61–7.56(m,2H),7.27(t,J＝54.0Hz,1H),6.97–6.92(m,2H),4.33(t,J＝6.6Hz,2H),3.21(t,J＝6.6Hz,2H).
13 C NMR(150MHz,CDCl 3 )δ161.5,134.2,119.1,115.4,115.1(t,J＝285Hz),104.7,68.4,20.7(t,J＝3.0Hz).
19 F NMR(565MHz,CDCl 3 )δ-91.1.
HRMS(EI)m/z[M] + theoretical value C 10 H 9 F 2 NOSe + 276.9817, experimental 276.9815.
Example 3: (difluoromethyl) ((dimethyl (phenyl) silyl) methyl) selenoether
The present example provides a method for synthesizing (difluoromethyl) ((dimethyl (phenyl) silyl) methyl) selenoether (3 c), which comprises the following synthetic routes:
the specific synthesis steps are as follows:
a clean 8mL screw flask was placed in a 5 x 10mm magnetic stirrer and Se- ((dimethyl (phenyl) silyl) methyl) selenophensulfonate (1 c,71.1mg,0.20 mmol), triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) and Ir (ppy) were added sequentially under nitrogen atmosphere 3 (2.62 mg, 0.04 mmol) was then added and mixed with N, N-dimethylacetamide (1 mL), after capping, the mixture was stirred at a temperature of 25deg.C under illumination with a 460nm LED lamp (rotation speed 400 rpm), after the reaction was completed, the reaction system was transferred to a separating funnel, 100mL of ethyl acetate was added to dilute the reaction system, and the organic phase was collected by washing with a saturated saline solution twice (50 mL. Times.) and dried over anhydrous sodium sulfate, then a drying agent was removed by filtration, 800mg of silica gel powder was added, the solvent was removed by spin evaporation, and then column chromatography was performed with petroleum ether as a eluting agent to obtain the objective product (difluoromethyl) ((dimethyl (phenyl) silicon-based) methyl) selenoether 3c as a pale yellow oily liquid in 95% yield.
The target product is characterized by electrospray mass spectrometry (EI-MS) and nuclear magnetic resonance, and the characterization data are as follows (the nuclear magnetic hydrogen spectrum of the target product is shown in figure 3):
1 H NMR(400MHz,CDCl 3 )δ7.58–7.52(m,2H),7.44–7.36(m,3H),7.07(t,J＝56.0Hz,1H),2.23(s,2H),0.43(s,6H).
13 C NMR(150MHz,CDCl 3 )δ137.1,133.7,129.8,128.2,115.2(t,J＝285Hz),5.1,-2.7.
19 F NMR(565MHz,CDCl 3 )δ-93.2.
HRMS(EI)m/z[M] + theoretical value C 10 H 14 F 2 SiSe + 279.9998, experimental 279.9999.
EXAMPLE 4- ((difluoromethyl) seleno) benzoic acid methyl ester
This example provides a method for synthesizing methyl 4- ((difluoromethyl) seleno) benzoate (3 d), which comprises the following synthetic routes:
the specific synthesis steps are as follows:
a clean 8mL screw flask was placed in a 5 x 10mm magnetic stirrer and Se- ((4-methoxycarbonyl) phenyl) selenophenyl sulfonate (1 d,71.1mg,0.20 mmol), triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) and Ir (ppy) were added sequentially under nitrogen atmosphere 3 (2.62 mg, 0.04 mmol) was then added and mixed with N, N-dimethylacetamide (1 mL), after capping, the mixture was stirred at a temperature of 25deg.C under illumination with a 460nm LED lamp (rotation speed 400 rpm), after the reaction was completed, the reaction system was transferred to a separating funnel, 100mL of ethyl acetate was added to dilute the reaction system, and the organic phase was collected by washing with a saturated aqueous solution of sodium chloride twice (50 mL. Times.) and dried over anhydrous sodium sulfate, then the drying agent was removed by filtration, 800mg of silica gel powder was added, the solvent was distilled off by spin evaporation, and then column chromatography was performed with a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether=1:20, v/v) as a eluting agent to obtain methyl benzoate 3d as the objective product, 4- ((difluoromethyl) seleno) as a colorless oily liquid, the objective product was 79%.
The target product is characterized by electrospray mass spectrometry (EI-MS) and nuclear magnetic resonance, and the characterization data are as follows (the nuclear magnetic hydrogen spectrum of the target product is shown in figure 4):
1 H NMR(400MHz,CDCl 3 )δ8.03–7.97(m,2H),7.75–7.68(m,2H),7.22(t,J＝56.0Hz,1H),3.93(s,3H).
13 C NMR(100MHz,CDCl 3 )δ166.5,135.6,131.0,130.5,129.8(t,J＝3.0Hz),116.8,52.5.
19 F NMR(376MHz,CDCl 3 )δ-89.9.
HRMS(EI)m/z[M] + theoretical value C 9 H 8 F 2 O 2 Se + 265.9658, experimental 265.9666.
EXAMPLE 5 4- ((difluoromethyl) seleno) -1-p-toluenesulfonylpiperidine
The present example provides a method for synthesizing 4- ((difluoromethyl) seleno) -1-p-toluenesulfonylpiperidine (3 e), which is depicted in the synthetic route:
the specific synthesis steps are as follows:
a clean 8mL screw flask was placed in a 5 x 10mm magnetic stirrer and Se- (1-p-toluenesulfonylpiperidin-4-yl) selenophene sulfonate (1 e,91.7mg,0.20 mmol), triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) and Ir (ppy) were added sequentially under nitrogen atmosphere 3 (2.62 mg, 0.04 mmol) was then added and mixed with N, N-dimethylacetamide (1 mL), after capping, the reaction was stirred at a temperature of 25deg.C under illumination with a 460nm LED lamp (rotation speed 400 rpm) and after the reaction was completed, the reaction system was transferred to a separating funnel, 100mL ethyl acetate was added to dilute the reaction system, and the organic phase was collected by washing with a saturated aqueous solution of sodium chloride twice (50 mL. 2), the collected organic phase was dried over anhydrous sodium sulfate, then the drying agent was removed by filtration, 800mg of silica gel powder was added, the solvent was distilled off by spin evaporation, and then column chromatography was performed with a mixture of ethyl acetate and petroleum ether (ethyl acetate: petroleum ether=1:10, v/v) as a eluting agent to obtain the objective product 4- ((difluoromethyl) seleno) -1-p-toluenesulfonylpiperidine 3e as an off-white solid in a yield of 95%.
The target product is characterized by electrospray mass spectrometry (EI-MS) and nuclear magnetic resonance, and the characterization data are as follows (the nuclear magnetic hydrogen spectrum of the target product is shown in figure 5):
1 H NMR(400MHz,CDCl 3 )δ7.66–7.58(m,2H),7.32(d,J＝8.0Hz,2H),7.15(t,J＝56.0Hz,1H),3.51–3.41(m,2H),3.37–3.30(m,1H),2.64(ddd,J＝12.4,9.8,3.0Hz,2H),2.42(s,3H),2.15(dq,J＝13.1,4.0Hz,2H),1.92(dtd,J＝13.7,10.0,3.8Hz,2H).
13 C NMR(150MHz,CDCl 3 )δ143.8,133.2,129.8,127.7,115.5(t,J＝285Hz),46.2,35.3(t,J＝3.0Hz),33.3,21.6.
19 F NMR(565MHz,CDCl 3 )δ-90.6.
HRMS(EI)m/z[M] + theoretical value C 13 H 17 F 2 NO 2 SSe + 369.0113, experimental 369.0112.
Comparative example 1
The embodiment provides a synthesis method of (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether, which comprises the following specific synthesis steps:
a clean 8mL screw flask was placed in a 5 x 10mm magnetic stirrer and Se- (2- (4-phenylphenoxy) ethyl) selenophenyl sulfonate (1 a,83.5mg,0.20 mmol), triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) and Ir (ppy) were added sequentially under nitrogen atmosphere 3 (2.62 mg, 0.04 mmol. Then N, N-dimethylacetamide (1 mL) was added and mixed, after the cap was closed, the mixture was stirred at a rotation speed of 400 rpm at 25℃without light, and after the reaction was completed, the reaction was performed for 4 hours, and then, the reaction was performed by thin plate chromatography, whereby no target product was formed.
Comparative example 2
The embodiment provides a synthesis method of (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether, which comprises the following specific synthesis steps:
a clean 8mL screw flask was placed in a 5 x 10mm magnetic stirrer and Se- (2- (4-phenylphenoxy) ethyl) selenophenyl sulfonate (1 a,83.5mg,0.20 mmol) and triphenyl (difluoromethyl) phosphonium bromide (2, 141.6mg,0.36 mmol) were added sequentially under nitrogen. N, N-dimethylacetamide (1 mL) was then added and mixed, and after capping, the mixture was stirred at a temperature of 25deg.C under illumination of 460nm LED lamp (rotation speed 400 rpm) and reacted for 4 hours. After the reaction is finished, no target product is generated by thin plate chromatography detection.
Comparative example 3
The comparative example provides a synthesis method of (difluoromethyl) (2- (4-phenylphenoxy) ethyl) selenoether, which comprises the following specific synthesis steps:
a clean 8mL screw reactor was placed in a 5X 10mm magnetic stirrer, se- (2- (4-phenylphenoxy) ethyl) selenophenyl sulfonate (1 a,83.5mg,0.20 mmol), triphenylphosphonium (difluoromethyl) bromide (2, 141.6mg,0.36 mmol) and tris (2, 2-bipyridine) ruthenium chloride hexahydrate (3.0 mg, 0.04 mmol) were added in sequence under a nitrogen atmosphere, then N, N-dimethylacetamide (1 mL) was added and mixed, and after capping, the mixture was stirred at a temperature of 25℃under illumination of a 460nm LED lamp (rotation speed 400 rpm) for 4 hours. After the reaction is finished, no target product is generated by thin plate chromatography detection.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.
Claims (14)
1. The synthesis method of the difluoromethyl seleno ether compound is characterized by comprising the following steps of:
mixing tris (2-phenylpyridine) iridium, selenosulfonate compounds shown in a formula (I), difluoromethylphosphonium compounds shown in a formula (II) and a reaction solvent, and reacting under the condition of illumination to obtain difluoromethyl seleno-ether compounds shown in a formula (II);
wherein L is selected from single bond, C1-C10 alkylene;
R 1 selected from OR 4 、Si(R 5 )(R 6 )(R 7 ) Substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted C3-C10 heterocyclyl;
R 2 selected from C6-C20 aryl;
R 3 selected from C6-C20 aryl;
R 4 selected from the group consisting of substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C20 alkyl;
R 5 -R 7 each independently selected from C6-C20 aryl, C1-C20 alkyl;
W - selected from BF 4 - 、OTf - 、Cl - 、Br - 、I - 。
2. The method according to claim 1, wherein the substituted C6-C20 aryl, substituted C1-C20 alkyl, and substituted C3-C10 heterocyclic group has 1-3 substituents selected from halogen, cyano, and COOR 8 、-S(O) 2 R 9 C1-C4 alkyl, C6-C20 aryl; r is R 8 Selected from C1-C4 alkyl, R 9 Selected from aryl groups containing 6 to 10 carbon atoms.
3. The synthetic method according to claim 1 or 2, characterized in that L is selected from single bonds, C1-C4 alkylene groups;
preferably, L is selected from single bond, methylene, ethylene, propylene, butylene.
4. A synthetic method according to any one of claims 1 to 3, wherein R 1 Selected from OR 4 、Si(R 5 )(R 6 )(R 7 ) Substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C3-C10 heterocyclyl;
and/or C6-C20 aryl is selected from phenyl, naphthyl, biphenyl, terphenyl, phenanthryl;
and/or C1-C20 alkyl is selected from methyl, ethyl, propyl, butyl;
and/or, a C3-C10 heterocyclic group contains at least 1 nitrogen atom;
preferably, the C3-C10 heterocyclyl is selected from the group consisting of silacyclopropane, silacyclobutane, and silacyclohexane.
5. Root of Chinese characterThe method according to any one of claims 1 to 4, wherein the substituted C6-C20 aryl, substituted C1-C20 alkyl, substituted C3-C10 heterocyclyl contains 1 to 3 substituents selected from cyano, -COOR 8 、-S(O) 2 R 9 Methyl, ethyl, propyl, butyl, phenyl, naphthyl, biphenyl, terphenyl; r is R 8 Selected from methyl, ethyl, propyl, butyl, R 9 Selected from phenyl, p-methylphenyl.
6. The synthetic method of any one of claims 1-5 wherein R 2 Selected from phenyl;
and/or R 3 Selected from phenyl;
and/or W - Selected from Br - 。
7. The method according to any one of claims 1 to 6, wherein the selenosulfonate compound represented by formula (I) is selected from
8. The synthetic method according to any one of claims 1 to 7, wherein the molar ratio of the selenosulfonate compound represented by formula (I), the difluoromethylphosphonium compound represented by formula (ii), and tris (2-phenylpyridine) iridium is 1: (1.0-3.0): (0.001-0.050);
and/or the ratio of the selenosulfonate compound shown in the formula (I) to the reaction solvent is 1: (2-10), in mmol: and (3) mL.
9. The method of any one of claims 1-8, wherein the illumination is visible light in the wavelength range of 400-480 nm;
optionally, the visible light is LED visible light.
10. The method according to any one of claims 1 to 9, wherein the reaction temperature of the reaction is 10 to 40 ℃, the stirring speed of the reaction is 400 to 500r/min, and the reaction time is 4 to 7 hours.
11. The synthetic method of any one of claims 1 to 10 wherein the reaction is carried out under a nitrogen atmosphere.
12. The synthetic method according to any one of claims 1 to 11, wherein the reaction solvent is an organic solvent;
preferably, the organic solvent is at least one of acetonitrile, tetrahydrofuran, dichloromethane, ethylene glycol dimethyl ether, N-methylpyrrolidone, N-dimethylformamide and N, N-dimethylacetamide.
13. The synthetic method of any one of claims 1 to 12 further comprising the step of separation and purification after the reaction is completed;
preferably, the step of separating and purifying comprises the steps of diluting the reaction liquid, washing and collecting an organic phase, drying and separating by column chromatography.
14. The synthetic method of claim 13 wherein the diluted diluting solvent is selected from the group consisting of ethyl acetate;
and/or the washing solvent of the washing is selected from saline solution;
and/or the drying agent is selected from anhydrous sodium sulfate;
and/or, the column chromatography separation comprises mixing an organic phase and column chromatography silica gel powder, concentrating to remove a solvent, and performing column chromatography separation on a concentrated product;
and/or, the column chromatographic separation adopts ethyl acetate and/or petroleum ether as eluent.
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