CN113548936A - Aroyldifluoromethyl olefin and preparation method thereof - Google Patents
Aroyldifluoromethyl olefin and preparation method thereof Download PDFInfo
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- CN113548936A CN113548936A CN202110787649.2A CN202110787649A CN113548936A CN 113548936 A CN113548936 A CN 113548936A CN 202110787649 A CN202110787649 A CN 202110787649A CN 113548936 A CN113548936 A CN 113548936A
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- olefin
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- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 150000001336 alkenes Chemical class 0.000 title claims abstract description 10
- 238000006772 olefination reaction Methods 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 101
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 30
- -1 difluoromethyl olefin Chemical class 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 229940125904 compound 1 Drugs 0.000 claims abstract description 7
- 229940126214 compound 3 Drugs 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 156
- 238000000605 extraction Methods 0.000 claims description 83
- 239000007788 liquid Substances 0.000 claims description 54
- 239000003480 eluent Substances 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 239000000460 chlorine Substances 0.000 claims description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 238000010828 elution Methods 0.000 claims description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- LAXRNWSASWOFOT-UHFFFAOYSA-J (cymene)ruthenium dichloride dimer Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ru+2].[Ru+2].CC(C)C1=CC=C(C)C=C1.CC(C)C1=CC=C(C)C=C1 LAXRNWSASWOFOT-UHFFFAOYSA-J 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N CHCl3 Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 3
- UKODFQOELJFMII-UHFFFAOYSA-N pentamethyldiethylenetriamine Chemical compound CN(C)CCN(C)CCN(C)C UKODFQOELJFMII-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 229910052707 ruthenium Inorganic materials 0.000 abstract description 3
- 238000003756 stirring Methods 0.000 abstract description 3
- 239000000575 pesticide Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 138
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 239000007858 starting material Substances 0.000 description 33
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 23
- 238000004293 19F NMR spectroscopy Methods 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 239000003208 petroleum Substances 0.000 description 23
- UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 13
- RXBQTZHAUYILQJ-UHFFFAOYSA-N 2,2-difluoro-2-iodo-1-phenylethanone Chemical compound FC(F)(I)C(=O)C1=CC=CC=C1 RXBQTZHAUYILQJ-UHFFFAOYSA-N 0.000 description 10
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NJXYTXADXSRFTJ-UHFFFAOYSA-N 1,2-Dimethoxy-4-vinylbenzene Chemical compound COC1=CC=C(C=C)C=C1OC NJXYTXADXSRFTJ-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- ALZAWWLALHIZLQ-ZHACJKMWSA-N (E)-2,2-difluoro-4-(4-fluorophenyl)-1-phenylbut-3-en-1-one Chemical group O=C(C(/C=C/C(C=C1)=CC=C1F)(F)F)C1=CC=CC=C1 ALZAWWLALHIZLQ-ZHACJKMWSA-N 0.000 description 1
- OVVJULDKHKNKTD-VAWYXSNFSA-N (E)-2,2-difluoro-4-(4-methoxyphenyl)-1-phenylbut-3-en-1-one Chemical compound COC1=CC=C(/C=C/C(C(C2=CC=CC=C2)=O)(F)F)C=C1 OVVJULDKHKNKTD-VAWYXSNFSA-N 0.000 description 1
- OWCCBQWNYAHFJM-OUKQBFOZSA-N (E)-2,2-difluoro-4-naphthalen-2-yl-1-phenylbut-3-en-1-one Chemical compound O=C(C(/C=C/C1=CC2=CC=CC=C2C=C1)(F)F)C1=CC=CC=C1 OWCCBQWNYAHFJM-OUKQBFOZSA-N 0.000 description 1
- BFDHPQJEAJECLJ-ZHACJKMWSA-N (E)-4-(2-chlorophenyl)-2,2-difluoro-1-phenylbut-3-en-1-one Chemical group O=C(C(/C=C/C(C=CC=C1)=C1Cl)(F)F)C1=CC=CC=C1 BFDHPQJEAJECLJ-ZHACJKMWSA-N 0.000 description 1
- DQCKSAJBXFVPKN-ZHACJKMWSA-N (E)-4-(3,4-dimethoxyphenyl)-2,2-difluoro-1-phenylbut-3-en-1-one Chemical compound COC(C=CC(/C=C/C(C(C1=CC=CC=C1)=O)(F)F)=C1)=C1OC DQCKSAJBXFVPKN-ZHACJKMWSA-N 0.000 description 1
- OYFNSLNUHACVCK-MDZDMXLPSA-N (E)-4-(3-bromophenyl)-2,2-difluoro-1-phenylbut-3-en-1-one Chemical group O=C(C(/C=C/C1=CC(Br)=CC=C1)(F)F)C1=CC=CC=C1 OYFNSLNUHACVCK-MDZDMXLPSA-N 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- ZLPFRDJVNGJQQH-UHFFFAOYSA-N 1-(2-bromophenyl)-2,2-difluoro-2-iodoethanone Chemical compound O=C(C(F)(F)I)C(C=CC=C1)=C1Br ZLPFRDJVNGJQQH-UHFFFAOYSA-N 0.000 description 1
- TTZMREOQXNJLKI-UHFFFAOYSA-N 1-(difluoromethoxy)-4-[2-(4-pentylphenyl)ethynyl]benzene Chemical compound C1=CC(CCCCC)=CC=C1C#CC1=CC=C(OC(F)F)C=C1 TTZMREOQXNJLKI-UHFFFAOYSA-N 0.000 description 1
- KQJQPCJDKBKSLV-UHFFFAOYSA-N 1-bromo-3-ethenylbenzene Chemical compound BrC1=CC=CC(C=C)=C1 KQJQPCJDKBKSLV-UHFFFAOYSA-N 0.000 description 1
- CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 1
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 1
- QEDJMOONZLUIMC-UHFFFAOYSA-N 1-tert-butyl-4-ethenylbenzene Chemical compound CC(C)(C)C1=CC=C(C=C)C=C1 QEDJMOONZLUIMC-UHFFFAOYSA-N 0.000 description 1
- VKNWFPOBQOQCKK-UHFFFAOYSA-N 2,2-difluoro-1,4-diphenylpent-4-en-1-one Chemical compound C=C(CC(C(C1=CC=CC=C1)=O)(F)F)C1=CC=CC=C1 VKNWFPOBQOQCKK-UHFFFAOYSA-N 0.000 description 1
- ISRGONDNXBCDBM-UHFFFAOYSA-N 2-chlorostyrene Chemical compound ClC1=CC=CC=C1C=C ISRGONDNXBCDBM-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- KXYAVSFOJVUIHT-UHFFFAOYSA-N 2-vinylnaphthalene Chemical compound C1=CC=CC2=CC(C=C)=CC=C21 KXYAVSFOJVUIHT-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- XYLMUPLGERFSHI-UHFFFAOYSA-N alpha-Methylstyrene Chemical compound CC(=C)C1=CC=CC=C1 XYLMUPLGERFSHI-UHFFFAOYSA-N 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- GIRAMLXWTABMMK-CMDGGOBGSA-N ethyl (E)-2,2-difluoro-4-(4-methoxyphenyl)but-3-enoate Chemical compound CCOC(=O)C(F)(F)\C=C\c1ccc(OC)cc1 GIRAMLXWTABMMK-CMDGGOBGSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to an arylformyl difluoromethyl olefin and a preparation method thereof, wherein the method comprises the following steps: compound 1, ruthenium catalyst, olefin 2, alkali and solventMixing the agents in N2Under protection, stirring and reacting at normal temperature under the irradiation of visible light until the reaction is complete, and extracting and separating the obtained reaction liquid to obtain a compound 3 shown as the following formula, namely the arylformyl difluoromethyl olefin shown as the following formula:
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to arylformyl difluoromethyl olefin and a preparation method thereof.
Background
With the continuous development of fluorine-containing organic chemical synthesis methodology, chemists effectively introduce fluorine atoms or fluorine-containing groups into organic compound molecules and develop various reactions related to fluorine, so that the physical, chemical and physiological properties of organic compounds or medicines are remarkably improved compared with those of parent molecules of the organic compounds or medicines.
Therefore, the selective introduction of fluorine or fluorinated groups in drug candidates has been considered as a powerful strategy in drug design and screening. Direct fluoroalkylation is a direct method for synthesizing organofluorine compounds and is widely concerned by people.
Transition metal catalyzed aromatic fluoroalkylation reactions have made significant progress over the past decade. The addition reaction of halofluoroalkanes with alkenes or alkynes via atom transfer radical addition strategies has become an attractive approach under the promotion of transition metal, light or radical initiators.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the arylformyl difluoromethyl olefin which has high efficiency, high yield, mild condition and environmental friendliness and a preparation method thereof.
The purpose of the invention can be realized by the following technical scheme:
an arylformyl difluoromethyl alkene having the formula:
wherein R is phenyl, substituted phenyl, heterocycle or alkyl substituent, R1Is phenyl, substituted phenyl or alkyl substituent, R2Is phenyl, substituted phenyl or alkyl substituent.
Further, when R is substituted phenyl, the substituent in the substituted phenyl is selected from phenyl, hydrogen, fluorine, bromine, chlorine, C1-C4One or more of alkyl, nitro, methoxy or trifluoromethyl;
further, when R is1When the substituted phenyl is substituted, the substituent in the substituted phenyl is selected from phenyl, hydrogen, fluorine, bromine, chlorine and C1-C4One or more of alkyl, nitro, methoxy or trifluoromethyl, R2Is phenyl or alkyl substituent.
A preparation method of the arylformyl difluoromethyl olefin comprises the following steps: mixing the compound 1, ruthenium catalyst, olefin 2, base and solvent in N2Under protection, stirring and reacting at normal temperature under the irradiation of visible light until the reaction is complete, and extracting and separating the obtained reaction liquid to obtain a compound 3 shown as the following formula, namely the arylformyl difluoromethyl olefin shown as the following formula:
further, the mol ratio of the compound 1, the olefin 2 and the alkali is (1.0-2.0): (1.0-2.0): (1.0-2.0), and the amount of the catalyst is 1mol percent of the compound 1.
Further, the catalyst comprises Ru (bpy)2Cl2·6H2O、RuCp*(PPh3)2Cl、[Ru(tpy)(MeCN)3]-(PF6)2、[Ru(tcmtpy)(MeCN)3]-(PF6)2、Ru(NCt-Bu)6][PF6]2、[RuCl2(p-cymene)]2、[Ru(dqp)2](PF6)2Or [ Ru (OAc)2(p-cymene)]One or more of them.
Further, the base includes Et3N、TMEDA、PMDETA、K2CO3、Et2NH、K2HPO4Or one or more of 2, 6-Lutidine.
Further, the solvent includes DME, DMF, DMSO, CH3CN, DCE、DMAc、MTBE、CHCl3Or one or more of NMP.
Further, the reaction time is 10-20 h.
Further, the extraction is carried out by adopting an extraction liquid, the extraction liquid comprises ethyl acetate and water with the volume ratio of (0.8-1) to 1, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4 times;
the separation is carried out by adopting eluent to separate and purify in a chromatographic column, wherein the eluent is n-hexane and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h.
The method has the advantages of easy availability of reagents and synthesis universality of halogenated fluoroolefin products, and can be used for cross coupling or functional group conversion.
Compared with the prior art, the method has the advantages of high efficiency, high yield, mild condition, environmental friendliness and the like. Has strong application potential in the fields of medicine and pesticide.
Detailed Description
The following examples are given for the detailed implementation and specific operation of the present invention, but the scope of the present invention is not limited to the following examples.
A preparation method of arylformyl difluoromethyl olefin comprises the following steps: mixing the compound 1, ruthenium catalyst, olefin 2, base and solvent in N2Protecting, stirring and reacting for 10-20h at normal temperature under the irradiation of visible light such as a blue LED lamp until the reaction is complete, extracting and separating the obtained reaction liquid to obtain a compound 3 shown as the following formula, namely the arylformyl difluoromethyl olefin shown as the following formula:
wherein R is phenyl, substituted phenyl, heterocycle or alkyl substituent, R1Is phenyl, substituted phenyl or alkyl substituent, R2Is phenyl, substituted phenyl or alkyl substituent.
When R is substituted phenyl, the substituent in the substituted phenyl is selected from phenyl, hydrogen, fluorine, bromine, chlorine and C1-C4One or more of alkyl, nitro, methoxy or trifluoromethyl;
when R is1When the substituted phenyl is substituted, the substituent in the substituted phenyl is selected from phenyl, hydrogen, fluorine, bromine, chlorine and C1-C4One or more of alkyl, nitro, methoxy or trifluoromethyl, R2Is phenyl or alkyl substituent.
The mol ratio of the compound 1, the olefin 2 and the alkali is (1.0-2.0): (1.0-2.0): 1.0-2.0), and the dosage of the catalyst is 1mol percent of the compound 1.
The catalyst comprises Ru (bpy)2Cl2·6H2O、RuCp*(PPh3)2Cl、[Ru(tpy)(MeCN)3]-(PF6)2、[Ru(tcmtpy)(MeCN)3]-(PF6)2、Ru(NCt-Bu)6][PF6]2、[RuCl2(p-cymene)]2、[Ru(dqp)2](PF6)2Or [ Ru (OAc)2(p-cymene)]One or more of them.
Bases include Et3N、TMEDA、PMDETA、K2CO3、Et2NH、K2HPO4Or one or more of 2, 6-Lutidine.
Solvents include DME, DMF, DMSO, CH3CN, DCE, DMAc, MTBE, CHCl3Or one or more of NMP.
The extraction is carried out by adopting an extraction liquid, the extraction liquid comprises ethyl acetate and water with the volume ratio of (0.8-1) to 1, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4 times;
separating, purifying with eluent of n-hexane and ethyl acetate at volume ratio of 10-100: 1 in chromatographic column for 1-2 hr.
Example 1
This example synthesized (E) -2, 2-difluoro-4- (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 231.26mg (yield 83%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3)δ＝8.13(d,J＝7.4Hz,2H),7.66-7.60(m,1H),7.50(t,J＝7.7Hz,2H),7.39(d,J＝8.5Hz,2H),7.05(dt,J＝16.3,2.7Hz,1H),6.88(d,J＝8.5Hz,2H),6.36(dt,J＝16.3,11.3Hz,1H),3.81(s,3H).
13C NMR(126MHz,CDCl3)δ＝189.17(t,J＝31.2Hz),160.86,136.65(t,J＝9.7Hz),134.34,132.30,130.27(t,J＝3.1Hz),128.98,128.78,127.03,117.31(t,J＝24.7Hz),116.58(t,J＝250.4Hz),114.29,55.40.
19F NMR(376MHz,CDCl3)δ＝-96.61(d,J＝11.3Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H14F2O2:311.0854；found:311.0853
Example 2
Synthesized in this example was (E) -2, 2-difluoro-1, 4-bis (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1- (4-methoxyphenyl) ethan-1-one (312.05mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 274.60mg (yield 88%) of a pale yellow oily liquid were obtained.
1H NMR(501MHz,CDCl3)δ＝8.03(d,J＝8.0Hz,2H),7.38(d,J＝8.8Hz,2H),7.29(d,J＝8.0Hz,2H),7.03(dt,J＝16.2,2.7Hz,1H),6.88(d,J＝8.8Hz,2H),6.34(dt,J＝16.2,11.3Hz,1H),3.81(s,3H),2.43(s,3H).
13C NMR(126MHz,CDCl3)δ＝188.71(t,J＝31.2Hz),160.80,145.52,136.47(t,J＝9.6Hz),130.40(t,J＝3.1Hz),129.73,129.49,128.94,127.07,117.52(t,J＝24.8Hz),116.62(t,J＝249.8Hz),114.25,55.37,21.83.
19F NMR(376MHz,CDCl3)δ＝-96.69(d,J＝12.8Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H16F2O3:341.0960；found:341.0962.
Example 3
Synthesized in this example is (E) -2, 2-difluoro-1- (3-methoxyphenyl) -4- (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1- (3-methoxyphenyl) ethan-1-one (312.05mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL dry solvent, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 265.24mg of a pale yellow oily liquid were obtained (yield 85%).
1H NMR(501MHz,CDCl3)δ＝7.72(d,J＝7.8Hz,1H),7.62(s,1H),7.43-7.36(m,3H),7.19-7.15(m,1H),7.03(dt,J＝16.2,2.7Hz,1H),6.88(d,J＝8.9Hz,2H),6.34(dt,J＝16.2,11.3Hz,1H),3.85(s,3H),3.81(s,3H).
13C NMR(126MHz,CDCl3)δ＝188.90(t,J＝31.3Hz),160.84,159.77,136.63(t,J＝9.6Hz),133.45,129.76,128.95,126.99,122.86(t,J＝3.7Hz),120.84,117.31(t,J＝24.9Hz),116.54(t,J＝250.1Hz),114.44,114.26,55.49,55.35.
19F NMR(376MHz,CDCl3)δ＝-96.67(d,J＝10.7Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H16F2O3:341.0960；found:341.0963.
Example 4
Synthesized in this example was (E) -2, 2-difluoro-4- (4-methoxyphenyl) -1- (p-tolyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1- (p-tolyl) ethan-1-one (296.06mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, which was then added a pre-weighed amount of Et3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 245.73mg (yield 83%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3)δ＝8.04(d,J＝7.9Hz,2H),7.38(d,J＝8.6Hz,2H),7.29(d,J＝8.0Hz,2H),7.04(dt,J＝16.2,2.7Hz,1H),6.88(d,J＝8.7Hz,2H),6.36(dt,J＝16.2,11.3Hz,1H),3.81(s,3H),2.42(s,3H).
13C NMR(126MHz,CDCl3):δ＝188.71(t,J＝31.0Hz),160.78,145.54,136.46(t,J＝9.8Hz),130.41(t,J＝2.8Hz),129.70,129.49,128.94,127.04,117.50(t,J＝24.8Hz),116.62(t,J＝249.9Hz),114.24,55.38,21.85.
19F NMR(376MHz,CDCl3)δ＝-103.34(d,J＝11.3Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H16F2O2:325.1010；found:325.1009.
Example 5
Synthesized in this example is (E) -2, 2-difluoro-4- (4-methoxyphenyl) -1- (naphthalen-2-yl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in 10mLIn a standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1- (naphthalen-2-yl) ethan-1-one (332.09mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed separately and added to a standard reaction tube, which was added with a pre-weighed Et3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 255.71mg of a pale yellow oily liquid was obtained (yield 77%).
1H NMR(501MHz,CDCl3)δ＝8.50(d,J＝8.5Hz,1H),8.14(d,J＝6.9Hz,1H),8.06(d,J＝8.2Hz,1H),7.90(d,J＝8.4Hz,1H),7.63(ddd,J＝8.5,6.9,1.5Hz,1H),7.61-7.50(m,2H),7.40(d,J＝8.5Hz,2H),7.12(dt,J＝16.3,2.7Hz,1H),6.89(d,J＝8.7Hz,2H),6.43(dt,J＝16.2,11.3Hz,1H),3.82(s,3H).k
13C NMR(126MHz,CDCl3):δ＝192.84(t,J＝31.5Hz),160.80,136.67(t,J＝9.5Hz),133.88,133.85,130.94,130.36,129.43(t,J＝4.9Hz),128.98,128.73,128.48,126.97,126.75,125.28,124.14,117.25(t,J＝25.1Hz),116.35(t,J＝251.7Hz),114.25,55.34.
19F NMR(376MHz,CDCl3)δ＝-96.99(d,J＝17.2Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C21H16F2O2:361.1010；found:361.1016.
Example 6
Synthesized in this example is (E) -2, 2-difluoro-1- (4-fluorophenyl) -4- (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-1- (4-fluorophenyl) -2-iodo-1-one (300.02mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 219.01mg (yield 73%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3)δ＝8.17(dd,J＝8.6,5.4Hz,2H),7.39(d,J＝8.7Hz,2H),7.17(t,J＝8.6Hz,2H),7.03(dt,J＝16.3,2.6Hz,1H),6.88(d,J＝8.6Hz,2H),6.33(dt,J＝16.0,11.4Hz,1H),3.81(s,3H).
13C NMR(126MHz,CDCl3)δ＝187.57(t,J＝31.8Hz),166.36(d,J＝257.5Hz),160.83,136.69(t,J＝9.6Hz),133.14(dt,J＝9.7,3.2Hz),128.96,128.52,126.81,116.87(t,J＝24.5Hz),116.52(t,J＝250.0Hz),116.05(d,J＝21.8Hz),114.23,55.32.
19F NMR(376MHz,CDCl3)δ＝-96.46(d,J＝10.9Hz),-102.16.
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H13F3O2:329.0760；found:329.0758.
Example 7
Synthesized in this example is (E) -1- (3-chlorophenyl) -2, 2-difluoro-4- (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 1- (3-chlorophenyl) -2, 2-difluoro-2-iodo-1-one (316.47mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 250.01mg (yield 79%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3)δ＝8.08(s,1H),8.00(d,J＝7.7Hz,1H),7.58(d,J＝8.0Hz,1H),7.43(t,J＝7.9Hz,1H),7.39(d,J＝8.5Hz,2H),7.04(dt,J＝16.2,2.8Hz,1H),6.88(d,J＝8.4Hz,2H),6.33(dt,J＝16.1,11.4Hz,1H),3.81(s,3H).
13C NMR(126MHz,CDCl3)δ＝187.89(t,J＝32.2Hz),160.90,136.94(t,J＝9.7Hz),135.00,134.18,133.67,130.03,130.00(t,J＝3.7Hz),128.96,128.26(t,J＝3.5Hz),126.76,116.56(t,J＝24.6Hz),116.41(t,J＝250.2Hz),114.24,55.25.
19F NMR(376MHz,CDCl3)δ＝-96.60(d,J＝11.5Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H13 35ClF2O2:345.0464；found:345.0467.
Example 8
Synthesized in this example is (E) -1- (2-bromophenyl) -2, 2-difluoro-4- (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in 10mL standard reaction tube, Ru (bpy)2Cl2·6H2O (1 mol%), 1- (2-bromophenyl) -2, 2-difluoro-2-iodoethane-1-one (360.92mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 292.35mg (yield 81%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3)δ＝7.65(d,J＝7.7Hz,1H),7.56(d,J＝7.5Hz,1H),7.42-7.30(m,4H),7.03(d,J＝16.1Hz,1H),6.90(d,J＝8.4Hz,2H),6.26(dt,J＝16.4,11.7Hz,1H),3.82(s,3H).
13C NMR(126MHz,CDCl3)δ＝192.54(t,J＝34.0Hz),160.88,137.29(t,J＝9.4Hz),136.27,133.83,132.43,129.01,128.85(t,J＝2.8Hz),127.00,126.86,120.13,115.81(t,J＝24.8Hz),115.56(t,J＝252.1Hz),114.27,55.32.
19F NMR(376MHz,CDCl3)δ＝-100.28(d,J＝11.6Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H13 81BrF2O2:388.9959；found:388.9957.
Example 9
Synthesized in this example is (E) -2, 2-difluoro-4- (4-methoxyphenyl) -1- (4- (trifluoromethyl) phenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1- (4- (trifluoromethyl) phenyl) ethan-1-one (350.03mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and a pre-weighed Et was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 248.52mg of a pale yellow oily liquid was obtained (yield 71%).
1H NMR(501MHz,CDCl3)δ＝8.22(d,J＝8.1Hz,2H),7.76(d,J＝8.2Hz,2H),7.40(d,J＝8.3Hz,2H),7.05(dt,J＝16.4,2.8Hz,1H),6.89(d,J＝8.4Hz,2H),6.33(dt,J＝16.3,11.4Hz,1H),3.82(s,3H).
13C NMR(126MHz,CDCl3)δ＝188.38(t,J＝32.7Hz),161.03,137.18(t,J＝9.6Hz),135.38(q,J＝32.9Hz),135.03,130.58,129.06,126.79,125.78(q,J＝4.0Hz),123.46(q,J＝272.8Hz),116.43(t,J＝24.4Hz),116.44(t,J＝250.0Hz),114.34,55.37.
19F NMR(376MHz,CDCl3)δ＝-63.43,-97.02(d,J＝11.4Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C13H13F5O2:379.0728；found:379.0726.
Example 10
Synthesized in this example is (E) -2, 2-difluoro-1- (furan-2-yl) -4- (4-methoxyphenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-1- (furan-2-yl) -2-iodo-1-one (271.99mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 233.91mg (yield 86%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3)δ＝7.73(s,1H),7.49(s,1H),7.36(d,J＝8.4Hz,2H),7.03(dt,J＝16.3,2.7Hz,1H),6.86(d,J＝8.4Hz,2H),6.60(dd,J＝3.7,1.7Hz,1H),6.25(dt,J＝16.2,11.6Hz,1H),3.78(s,3H).
13C NMR(126MHz,CDCl3)δ＝177.31(t,J＝33.3Hz),160.79,148.91,148.21,136.68(t,J＝9.5Hz),128.91,126.76,122.98(t,J＝5.2Hz),116.41(t,J＝25.0Hz),115.81(t,J＝249.9Hz),114.18,112.78,55.25.
19F NMR(376MHz,CDCl3)δ＝-100.44(d,J＝11.6Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C15H12F2O3:301.0647；found:301.0648.
Example 11
Synthesized in this example is (E) -2, 2-difluoro-4- (4-methoxyphenyl) -1- (thiophen-2-yl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 2-difluoro-2-iodo-1- (thien-2-yl) ethane were weighed out separately-1-ketone (288.05mg, 1.0mmol), 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were added to a standard reaction tube, and a pre-weighed amount of Et was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 253.48mg (yield 88%) of a pale yellow oily liquid were obtained.
1H NMR(501MHz,CDCl3)δ＝8.03(d,J＝3.9Hz,1H),7.78(d,J＝4.9Hz,1H),7.38(d,J＝8.4Hz,2H),7.19(t,J＝4.5Hz,1H),7.07(dt,J＝16.2,2.7Hz,1H),6.87(d,J＝8.4Hz,2H),6.29(dt,J＝16.2,11.5Hz,1H),3.80(s,3H).
13C NMR(126MHz,CDCl3)δ＝182.28(t,J＝33.0Hz),160.80,138.27,136.65(t,J＝9.6Hz),136.40,135.78(t,J＝5.0Hz),128.93,128.80,126.80,116.75(t,J＝24.9Hz),116.21(t,J＝250.5Hz),114.21,55.28.
19F NMR(376MHz,CDCl3)δ＝-98.30(d,J＝11.4Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C15H12F2O2:317.0418；found:317.0420.
Example 12
This example synthesized (E) -4, 4-difluoro-6- (4-methoxyphenyl) -1-phenylhexyl-5-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), 1-difluoro-1-iodo-4-phenylbutan-2-one (310.08mg, 1.0mmol), 1-methoxy-4-vinylbenzene (268.36mg, 2.0mmol) were weighed out separately,added to a standard reaction tube and a pre-weighed amount of Et is added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 226.36mg (yield 73%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3):δ＝7.38(d,J＝8.3Hz,2H),7.33(t,J＝7.5Hz,2H),7.28-7.22(m,3H),6.99(dt,J＝16.2,2.7Hz,1H),6.93(d,J＝8.4Hz,2H),6.11(dt,J＝16.2,11.8Hz,1H),3.85(s,3H),3.10(t,J＝7.3Hz,2H),3.01(t,J＝7.3Hz,2H).
13C NMR(126MHz,CDCl3)δ＝199.36(t,J＝32.3Hz),160.79,140.13,136.66(t,J＝9.5Hz),128.90,128.55,128.33,126.78,126.35,115.50(t,J＝250.6Hz),115.48(t,J＝25.0Hz),114.18,55.25,38.13,28.77.
19F NMR(376MHz,CDCl3)δ＝-104.70(d,J＝11.7Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C19H18F2O2:339.1167；found:339.1170.
Example 13
Synthesized in this example was (E) -2, 2-difluoro-1-phenyl-4- (p-tolyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the raw materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1-methyl-4-vinylbenzene (236.36mg, 2.0mmol) were weighed respectively, added to a standard reaction tube, and the weighed materials were addedEt3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 228.44mg (yield 81%) of a pale yellow oily liquid was obtained.
1H NMR(501MHz,CDCl3):δ＝8.15(d,J＝7.7Hz,2H),7.65(t,J＝7.5Hz,1H),7.52(t,J＝7.7Hz,2H),7.36(d,J＝7.8Hz,2H),7.19(d,J＝7.7Hz,2H),7.10(dt,J＝16.4,2.8Hz,1H),6.47(dt,J＝16.3,11.3Hz,1H),2.37(s,3H).
13C NMR(126MHz,CDCl3):δ＝189.06(t,J＝31.4Hz),139.91,137.03(t,J＝9.4Hz),134.35,132.20,131.52,130.24(t,J＝2.8Hz),129.57,128.76,127.43,118.63(t,J＝23.9Hz),116.46(t,J＝250.2Hz),21.36.
19F NMR(376MHz,CDCl3)δ＝-96.94(d,J＝11.5Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H14F2O:295.0905；found:295.0909.
Example 14
Synthesized in this example was (E) -2, 2-difluoro-1-phenyl-4- (p-tolyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1- (tert-butyl) -4-vinylbenzene (320.52mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME at room temperature under 35W blue LED conditionsThe reaction was stirred until TLC monitored the starting material reaction to completion. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 239.73mg of a pale yellow oily liquid were obtained (yield 85%).
1H NMR(501MHz,CDCl3)δ＝8.16(d,J＝7.8Hz,2H),7.65(t,J＝7.4Hz,1H),7.52(t,J＝7.7Hz,2H),7.42(s,4H),7.13(dt,J＝16.3,2.6Hz,1H),6.51(dt,J＝16.1,11.3Hz,1H),1.35(s,9H).
13C NMR(126MHz,CDCl3)δ＝189.03(t,J＝31.2Hz),153.12,136.93(t,J＝9.5Hz),134.34,132.23,131.53,130.24(t,J＝3.5Hz),128.76,127.29,125.82,118.94(t,J＝24.8Hz),116.46(t,J＝250.2Hz),34.80,31.21.
19F NMR(376MHz,CDCl3)δ＝-96.96(d,J＝11.5Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H20F2O:337.1374；found:337.1372.
Example 15
This example synthesized (E) -4- (3, 4-dimethoxyphenyl) -2, 2-difluoro-1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1, 2-dimethoxy-4-vinylbenzene (328.4mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, and the extract and the reaction liquid are mixedThe volume ratio of (1) to (1-1.5) and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 267.93mg (yield 95%) of a pale yellow oily liquid were obtained.
1H NMR(501MHz,CDCl3)δ＝8.07(d,J＝7.8Hz,2H),7.53(t,J＝7.5Hz,1H),7.41(t,J＝7.7Hz,2H),7.00(dt,J＝16.3,2.7Hz,1H),6.93(d,J＝2.3Hz,2H),6.75(d,J＝8.6Hz,1H),6.35(dt,J＝16.0,11.2Hz,1H),3.81(s,3H),3.79(s,3H).
13C NMR(126MHz,CDCl3)δ＝188.77(t,J＝31.3Hz),150.31,148.98,136.68(t,J＝9.6Hz),134.06,131.93,129.91(t,J＝2.9Hz),128.48,126.94,121.22,117.15(t,J＝24.6Hz).116.37(t,J＝250.1Hz),110.86,109.25,55.59,55.55.
19F NMR(376MHz,CDCl3)δ＝-96.38(d,J＝11.1Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H16F2O3:341.0960；found:341.0958.
Example 16
Synthesized in this example is (E) -4- (2-chlorophenyl) -2, 2-difluoro-1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1-chloro-2-vinylbenzene (277.18mg, 2.0mmol) were weighed separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, an eluent is adopted for chromatography columnThe eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 200.24mg of a pale yellow oily liquid was obtained (yield 71%).
1H NMR(501MHz,CDCl3)δ＝8.15(d,J＝7.9Hz,2H),7.65(t,J＝7.5Hz,1H),7.59-7.48(m,4H),7.41-7.34(m,1H),7.31-7.23(m,2H),6.50(dt,J＝16.3,11.3Hz,1H).
13C NMR(126MHz,CDCl3)δ＝188.77(t,J＝31.3Hz),134.49,134.27,133.26(t,J＝9.8Hz),132.66,132.04,130.55,130.27(t,J＝3.4Hz),130.03,128.82,127.49,127.14,122.47(t,J＝24.6Hz),115.98(t,J＝251.3Hz).
19F NMR(376MHz,CDCl3)δ＝-97.62(d,J＝11.3Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C16H11 35ClF2O:315.0359；found:315.0360.
Example 17
Synthesized in this example is (E) -4- (3-bromophenyl) -2, 2-difluoro-1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1-bromo-3-vinylbenzene (366.10mg, 2.0mmol) were weighed separately and added to a standard reaction tube, and a pre-weighed amount of Et was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally obtaining the bland208.70mg of a yellow oily liquid (yield 74%).
1H NMR(501MHz,CDCl3)δ＝8.12(d,J＝7.7Hz,2H),7.65(t,J＝7.5Hz,1H),7.60(s,1H),7.57-7.48(m,2H),7.47(d,J＝8.0Hz,1H),7.37(d,J＝7.9Hz,1H),7.24(qd,J＝7.9,7.1,2.1Hz,1H),7.03(dt,J＝16.4,2.7Hz,1H),6.50(dt,J＝16.3,11.4Hz,1H).
13C NMR(126MHz,CDCl3)δ＝188.76(t,J＝31.5Hz),136.45(t,J＝9.1Hz),135.49(t),134.52,132.51,132.08,130.40,130.29,130.26(t,J＝3.1Hz),128.86,126.19,123.05,121.36(t,J＝24.8Hz),116.02(t,J＝251.1Hz).
19F NMR(376MHz,CDCl3)δ＝-97.50(d,J＝11.6Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C16H11BrF2O:337.0034；found:337.0037.
Example 18
Synthesized in this example is (E) -4- (4-fluorophenyl) -2, 2-difluoro-1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1-fluoro-4-vinylbenzene (244.28mg, 2.0mmol) were weighed separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally, 188.96mg of a pale yellow oily liquid was obtained (yield 67%).
1H NMR(501MHz,CDCl3)δ＝8.14(d,J＝7.8Hz,2H),7.64(t,J＝7.4Hz,1H),7.51(t,J＝7.6Hz,2H),7.43(dd,J＝8.6,5.4Hz,2H),7.12-7.01(m,3H),6.44(dt,J＝16.3,11.3Hz,1H).
13C NMR(126MHz,CDCl3)δ＝188.88(t,J＝31.4Hz),163.48(d,J＝250.0Hz),135.77(t,J＝9.8Hz),134.45,132.07,130.50,130.22(t,J＝3.2Hz),129.28(d,J＝8.5Hz),128.80,119.47(t,J＝24.7Hz),115.91(d,J＝21.9Hz),116.24(t,J＝250.7Hz).
19F NMR(376MHz,CDCl3)δ＝-97.10(d,J＝11.4Hz),-110.80(p,J＝8.0,6.9Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C16H11F3O:299.0654；found:29.0656.
Example 19
Synthesized in this example was (E) -2, 2-difluoro-1-phenyl-4- (4- (trifluoromethyl) phenyl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1- (trifluoromethyl) -4-vinylbenzene (344.30mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 174.86mg of a pale yellow oily liquid were obtained (yield 62%).
1H NMR(501MHz,CDCl3):δ＝8.14(d,J＝7.8Hz,2H),7.68-7.59(m,3H),7.59-7.49(m,4H),7.15(d,J＝16.1Hz,1H),6.60(dt,J＝16.2,11.1Hz,1H).
13C NMR(126MHz,CDCl3)δ＝188.72(t,J＝31.3Hz),137.80,135.42(t,J＝9.6Hz),134.58,132.06,131.37(q,J＝32.1,31.5Hz),130.26(t,J＝3.5Hz),128.88,127.73,120.72,125.86(q,J＝3.9Hz),123.96(q,J＝272.3Hz),115.97(t,J＝251.5Hz).
19F NMR(376MHz,CDCl3)δ＝-62.76,-97.64(d,J＝11.4Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H11F5O:349.0622；found:349.0624.
Example 20
This example synthesizes 2, 2-difluoro-1, 4-diphenylpent-4-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and prop-1-en-2-ylbenzene (236.36mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 203.06mg of a pale yellow oily liquid were obtained (yield 72%).
1H NMR(501MHz,CDCl3):δ＝8.06(d,J＝7.8Hz,2H),7.62(t,J＝7.3Hz,1H),7.47(t,J＝7.4Hz,2H),7.41(d,J＝6.8Hz,2H),7.38-7.26(m,3H),5.46(d,J＝112.5Hz,2H),3.47(t,J＝17.6Hz,2H).
13C NMR(126MHz,CDCl3)δ＝189.44(t,J＝30.5Hz),140.88,139.22(t,J＝3.2Hz),134.20,132.26,130.13(t,J＝3.6Hz),128.63(t,J＝12.4Hz),128.33,127.75,126.35,119.29,118.64(t,J＝255.0Hz),39.35(t,J＝23.1Hz).
19F NMR(376MHz,CDCl3)δ＝-97.96(t,J＝17.5Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C17H14F2O:295.0905；found:295.0904.
Example 21
This example synthesized (E) -2, 2-difluoro-4- (naphthalen-2-yl) -1-phenylbut-3-en-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 2-vinylnaphthalene (304.82mg, 2.0mmol) were weighed out separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 211.52mg of a pale yellow oily liquid were obtained (yield 75%).
1H NMR(501MHz,CDCl3)δ＝8.19(d,J＝7.8Hz,2H),7.82(d,J＝7.7Hz,4H),7.69-7.59(m,2H),7.56-7.47(m,4H),7.29(dt,J＝16.3,2.7Hz,1H),6.63(dt,J＝16.3,11.3Hz,1H).
13C NMR(126MHz,CDCl3)δ＝189.01(t,J＝31.4Hz),137.15(t,J＝9.6Hz),134.42,133.88,133.30,132.20,131.71,130.28(t,J＝3.2Hz),128.81,128.67,128.40,127.79,126.99,126.71,123.30,119.88(t,J＝24.6Hz),116.43(t,J＝250.5Hz).
19F NMR(376MHz,CDCl3)δ＝-97.09(d,J＝12.0Hz).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C20H14F2O:331.0905；found:331.0908.
Example 22
This example synthesized 2- (3, 4-dihydronaphthalen-2-yl) -2, 2-difluoro-1-phenyleth-1-one
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 2, 2-difluoro-2-iodo-1-phenylethane-1-one (282.03mg, 1.0mmol) and 1, 2-dihydronaphthalene (260.38mg, 2.0mmol) were weighed separately and added to a standard reaction tube, and a pre-weighed Et was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 199.12mg (yield 70%) of a pale yellow oily liquid were obtained.
1H NMR(501MHz,CDCl3)δ＝8.11(d,J＝7.9Hz,2H),7.62(t,J＝7.5Hz,1H),7.49(t,J＝7.6Hz,2H),7.24-7.09(m,4H),6.89(s,1H),2.89(t,J＝8.2Hz,2H),2.47(t,J＝8.4Hz,2H).
13C NMR(126MHz,CDCl3)δ＝189.14(t,J＝31.3Hz),135.67,134.33,132.62,132.01,131.78(t,J＝23.2Hz),130.25(t,J＝2.8Hz),129.14(t,J＝9.1Hz),129.01,128.75,127.80,127.70,126.88,117.17(t,J＝251.6Hz),27.45,21.53.
19F NMR(376MHz,CDCl3)δ＝-101.81(s).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C18H14F2O:307.0905；found:307.0907.
Example 23
This example synthesized ethyl (E) -2, 2-difluoro-4- (4-methoxyphenyl) but-3-enoate
The preparation method comprises the following steps:
in a 10mL standard reaction tube, Ru (bpy) was added2Cl2·6H2O (1 mol%), the starting materials 1, 1-difluoro-1-iodo-3-methoxypropan-2-one (249.98mg, 1.0mmol) and 1-methoxy-4-vinylbenzene (268.38mg, 2.0mmol) were weighed separately and added to a standard reaction tube, and Et weighed in advance was added3N (1.1mmol), dissolved in 4mL DME, was stirred at room temperature under 35W blue LED until the starting material reaction was complete as monitored by TLC. After the reaction is finished, ethyl acetate and water of (0.8-1):1 are used for extraction, the volume ratio of the extraction liquid to the reaction liquid is 1 (1-1.5), and the extraction times are 3-4. Further, separating and purifying in a chromatographic column by using an eluent, wherein the eluent is petroleum ether and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h. Finally 179.38mg (yield 70%) of a pale yellow oily liquid were obtained.
1H NMR(501MHz,CDCl3)δ7.38(d,J＝8.4Hz,2H),7.02(dt,J＝16.4,2.4Hz,1H),6.90(d,J＝8.4Hz,2H),6.15(dt,J＝16.4,11.2Hz,1H),4.34(q,J＝7.6Hz,2H),3.81(s,3H),1.35(t,J＝7.6Hz,3H)；
13C NMR(126MHz,CDCl3)δ164.1(t,J＝35.3Hz),160.8,136.3(t,J＝9.5Hz),128.8,126.8,116.3(t,J＝25.0Hz),114.2,113.0(t,J＝248.2Hz),63.0,55.3,13.9.
19F NMR(376MHz,CDCl3)δ-102.7(d,J＝10.8Hz,2F).
HRMS(ESI-TOF):m/z[M+Na]+calcd for C13H14O3F2:279.0803；found279.0805.
The foregoing is directed to preferred embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (10)
1. An arylformyl difluoromethyl olefin, wherein the compound has the formula:
wherein R is phenyl, substituted phenyl, heterocycle or alkyl substituent, R1Is phenyl, substituted phenyl or alkyl substituent, R2Is phenyl, substituted phenyl or alkyl substituent.
2. The aroyl difluoromethyl olefin of claim 1, wherein when R is substituted phenyl, said substituent on said substituted phenyl is selected from phenyl, hydrogen, fluoro, bromo, chloro, C1-C4One or more of alkyl, nitro, methoxy or trifluoromethyl.
3. The aroyl difluoromethyl olefin of claim 1, wherein R is1When the substituted phenyl is substituted, the substituent in the substituted phenyl is selected from phenyl, hydrogen, fluorine, bromine, chlorine and C1-C4One or more of alkyl, nitro, methoxy or trifluoromethyl, R2Is phenyl or alkyl substituent.
4. A process for the preparation of an arylformyldifluoromethylolefin as claimed in any of claims 1 to 3, wherein the process is: mixing compound 1, catalyst, olefin 2, base and solvent in N2Under protection, the reaction is carried out under the irradiation of visible light until the reaction is complete, and the obtained reaction liquid is extracted and separated to obtain a compound 3 shown as the following formula, namely the arylformyl difluoromethyl olefin shown as the following formula:
5. the process of claim 4 wherein the molar ratio of compound 1, olefin 2 and base is (1.0-2.0): (1.0-2.0): 1.0-2.0), and the amount of catalyst is 1 mol% of compound 1.
6. The process of claim 4 wherein the catalyst comprises Ru (bpy)2Cl2·6H2O、RuCp*(PPh3)2Cl、[Ru(tpy)(MeCN)3]-(PF6)2、[Ru(tcmtpy)(MeCN)3]-(PF6)2、Ru(NCt-Bu)6][PF6]2、[RuCl2(p-cymene)]2、[Ru(dqp)2](PF6)2Or [ Ru (OAc)2(p-cymene)]One or more of them.
7. The process of claim 4 wherein the base comprises Et3N、TMEDA、PMDETA、K2CO3、Et2NH、K2HPO4Or one or more of 2, 6-Lutidine.
8. The method of claim 4, wherein the solvent comprises DME, DMF, DMSO, CH3CN, DCE, DMAc, MTBE, CHCl3Or one or more of NMP.
9. The process of claim 4, wherein the reaction time is 10-20 h.
10. The method for preparing arylformyl difluoromethyl olefin according to claim 4, wherein the extraction is performed by using an extraction liquid, the extraction liquid comprises ethyl acetate and water in a volume ratio of (0.8-1):1, the volume ratio of the extraction liquid to the reaction liquid is 1: (1-1.5), and the extraction times are 3-4 times;
the separation is carried out by adopting eluent to separate and purify in a chromatographic column, wherein the eluent is n-hexane and ethyl acetate with the volume ratio of (10-100):1, and the elution time is 1-2 h.
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| CN108276267A (en) * | 2018-01-19 | 2018-07-13 | 上海应用技术大学 | A kind of fluorine-containing 1,1- diphenyl ethylene derivatives, preparation method and applications |
Non-Patent Citations (2)
| Title |
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| KANGKUI LI ET AL: "Blue Light Induced Difluoroalkylation of Alkynes and Alkenes", 《ORGANIC LETTERS》 * |
| TANMAY CHATTERJEE ET AL: "Controlled Fluoroalkylation Reactions by Visible-Light Photoredox Catalysis", 《ACCOUNTS OF CHEMICAL RESEACH》 * |
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