CN114702400A - 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound and preparation method thereof - Google Patents
3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound and preparation method thereof Download PDFInfo
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- CN114702400A CN114702400A CN202210454569.XA CN202210454569A CN114702400A CN 114702400 A CN114702400 A CN 114702400A CN 202210454569 A CN202210454569 A CN 202210454569A CN 114702400 A CN114702400 A CN 114702400A
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- Prior art keywords
- phenylamino
- naphthoquinone
- alkenyl
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- naphthoquinone compound
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- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 57
- OPECBHGHSFBITB-UHFFFAOYSA-N PAN Natural products O=C1C2=CC=CC=C2C(=O)C=C1NC1=CC=CC=C1 OPECBHGHSFBITB-UHFFFAOYSA-N 0.000 claims abstract description 45
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 18
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000007800 oxidant agent Substances 0.000 claims abstract description 10
- 230000001590 oxidative effect Effects 0.000 claims abstract description 10
- 229910052742 iron Inorganic materials 0.000 claims abstract description 9
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 238000003760 magnetic stirring Methods 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical group O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 claims description 14
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical group [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 6
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 claims description 3
- CDVAIHNNWWJFJW-UHFFFAOYSA-N 3,5-diethoxycarbonyl-1,4-dihydrocollidine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C CDVAIHNNWWJFJW-UHFFFAOYSA-N 0.000 claims description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 3
- 229960002089 ferrous chloride Drugs 0.000 claims description 3
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 claims description 3
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 9
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 5
- 238000010276 construction Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 2
- 239000000575 pesticide Substances 0.000 abstract 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 abstract 1
- 239000013384 organic framework Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
- 238000001228 spectrum Methods 0.000 description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 14
- 238000004293 19F NMR spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 238000012512 characterization method Methods 0.000 description 11
- 239000011737 fluorine Substances 0.000 description 11
- 229910052731 fluorine Inorganic materials 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 239000003208 petroleum Substances 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- XGPOMXSYOKFBHS-UHFFFAOYSA-M sodium;trifluoromethanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C(F)(F)F XGPOMXSYOKFBHS-UHFFFAOYSA-M 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 10
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 9
- 239000011734 sodium Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 4
- 229910002651 NO3 Inorganic materials 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 2
- -1 2-phenylamino-1, 4-naphthoquinone compound Chemical class 0.000 description 2
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000007342 radical addition reaction Methods 0.000 description 2
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
- COXVPYKZDDKVRF-ULQDDVLXSA-N (4,4-difluorocyclohexyl)methyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)C=O)NC(=O)OCC2CCC(CC2)(F)F COXVPYKZDDKVRF-ULQDDVLXSA-N 0.000 description 1
- FOLCUFKJHSQMEL-BIXPGCQOSA-N (4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CCCCC1CCC(CC1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C=O FOLCUFKJHSQMEL-BIXPGCQOSA-N 0.000 description 1
- UXKLQDCALAWFIU-VKNDCNMPSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-tetradecoxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCCCC)C1=CC=CC=C1 UXKLQDCALAWFIU-VKNDCNMPSA-N 0.000 description 1
- VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 1
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- 125000000182 1,4-naphthoquinonyl group Chemical group C1(C(=CC(C2=CC=CC=C12)=O)*)=O 0.000 description 1
- RENYIDZOAFFNHC-UHFFFAOYSA-N 1-ethynyl-3-methylbenzene Chemical group CC1=CC=CC(C#C)=C1 RENYIDZOAFFNHC-UHFFFAOYSA-N 0.000 description 1
- JOUOQPWPDONKKS-UHFFFAOYSA-N 1-ethynyl-3-nitrobenzene Chemical group [O-][N+](=O)C1=CC=CC(C#C)=C1 JOUOQPWPDONKKS-UHFFFAOYSA-N 0.000 description 1
- XTKBMZQCDBHHKY-UHFFFAOYSA-N 1-ethynyl-4-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=C(C#C)C=C1 XTKBMZQCDBHHKY-UHFFFAOYSA-N 0.000 description 1
- QXSWHQGIEKUBAS-UHFFFAOYSA-N 1-ethynyl-4-fluorobenzene Chemical group FC1=CC=C(C#C)C=C1 QXSWHQGIEKUBAS-UHFFFAOYSA-N 0.000 description 1
- KBIAVTUACPKPFJ-UHFFFAOYSA-N 1-ethynyl-4-methoxybenzene Chemical group COC1=CC=C(C#C)C=C1 KBIAVTUACPKPFJ-UHFFFAOYSA-N 0.000 description 1
- APGNXGIUUTWIRE-UHFFFAOYSA-N 4-Pentylphenylacetylene Chemical group CCCCCC1=CC=C(C#C)C=C1 APGNXGIUUTWIRE-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- HSWVJQBEXRKOBZ-QGZVFWFLSA-N FC1=C(OC2CCN(CC2)C=2N=C3C(=NC=2N[C@H]2COCC2)CN(CC3)C(C)=O)C=CC(=C1)F Chemical compound FC1=C(OC2CCN(CC2)C=2N=C3C(=NC=2N[C@H]2COCC2)CN(CC3)C(C)=O)C=CC(=C1)F HSWVJQBEXRKOBZ-QGZVFWFLSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- ZVDBUOGYYYNMQI-UHFFFAOYSA-N dodec-1-yne Chemical compound CCCCCCCCCCC#C ZVDBUOGYYYNMQI-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- DEGIOKWPYFOHGH-UHFFFAOYSA-N pent-1-ynylbenzene Chemical compound CCCC#CC1=CC=CC=C1 DEGIOKWPYFOHGH-UHFFFAOYSA-N 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- GHUURDQYRGVEHX-UHFFFAOYSA-N prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1 GHUURDQYRGVEHX-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- KAVUKAXLXGRUCD-UHFFFAOYSA-M sodium trifluoromethanesulfinate Chemical compound [Na+].[O-]S(=O)C(F)(F)F KAVUKAXLXGRUCD-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000006692 trifluoromethylation reaction Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/24—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings
- C07C225/26—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings
- C07C225/30—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings of condensed quinone ring systems formed by two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
1, 4-naphthoquinone and trifluoromethyl are important organic frameworks and have wide application in the fields of medicine and pesticides. The invention discloses a 3-trifluoromethyl alkenyl-2-phenylamino-1, 4-naphthoquinone compound and a preparation method thereof, and the preparation method specifically comprises the following steps: the alkyne of the structure (I), the 2-phenylamino-1, 4-naphthoquinone of the structure (II), the trifluoromethylating reagent of the structure (III), the persulfate oxidant and the iron catalyst are dispersed in a solvent and react for a certain time at a proper temperature under magnetic stirring to obtain the 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound of the structure (IV).
The method has the advantages of low price of used substrate, catalyst and oxidant, simple operation, mild reaction conditions, and effective construction of various 3-trisThe fluoromethyl alkenyl-2-phenylamino-1, 4-naphthoquinone compound has bright application prospect in the fields of medicine and pesticide.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to a 3-trifluoromethyl alkenyl-2-phenylamino-1, 4-naphthoquinone compound and a synthesis method thereof.
Background
1, 4-naphthoquinone is an important organic skeleton, and has wide application in various fields such as organic synthesis, functional materials, medicines and medicines. In addition, trifluoromethyl group-containing compounds generally have unique biological and chemical activities and are widely used in the synthesis of drugs at present. Therefore, the introduction of trifluoromethyl into the 1, 4-naphthoquinone skeleton is of great practical significance. The reported method of trifluoromethyl group on 1, 4-naphthoquinone so far is copper catalyzed direct trifluoromethylation of togni reagent with 1, 4-naphthoquinone (org. Lett.2013,15, 3730-. In addition, free radical coupling between silver-catalyzed togni reagent, olefin, and 2-phenylamino-1, 4-naphthoquinone also permits the construction of 3-trifluoromethyl alkylated 2-phenylamino-1, 4-naphthoquinones (J. org. chem.2019,84, 1006-reservoir 1014). Considering that the carbon-carbon double bond is an important functional group which can be converted again, the 3-trifluoromethyl alkenylated 2-phenylamino-1, 4-naphthoquinone compound has the characteristics of the skeleton compound, and simultaneously, a more proliferative molecule can be constructed through the conversion of the carbon-carbon double bond. However, through literature and patent search, this class of compounds has not been reported.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a method for constructing a 2-phenylamino-1, 4-naphthoquinone product (IV) containing trifluoromethylalkenyl through oxidation and deprotonation processes, wherein alkyne (I), 2-phenylamino-1, 4-naphthoquinone (II) and a trifluoromethylating reagent (III) are used as initial raw materials for reaction, persulfate is used as an oxidant, and under the action of an iron catalyst, persulfate can oxidize the trifluoromethylating reagent into trifluoromethyl free radicals through a free radical mechanism so as to generate free radical addition with alkyne, further generate free radical addition with 2-phenylamino-1, 4-naphthoquinone. The substrate, the catalyst and the oxidant used in the method have low price, simple operation and mild reaction conditions, and various 3-trifluoromethyl alkenyl-2-phenylamino-1, 4-naphthoquinone compounds can be effectively constructed.
The purpose of the invention is realized as follows:
the alkyne of the structure (I), the 2-phenylamino-1, 4-naphthoquinone of the structure (II), the trifluoromethylating reagent of the structure (III), the persulfate oxidant and the iron catalyst are dispersed in a solvent and react for a certain time at a proper temperature under magnetic stirring to obtain the 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound with the structure (IV):
the specific structure of IV is as follows:
the persulfate oxidant is potassium persulfate, sodium persulfate or ammonium persulfate;
the iron catalyst is ferrous sulfate heptahydrate, ferric acetylacetonate, ferric chloride, ferric oxide, ferrous chloride or ferric nitrate;
the solvent is acetonitrile, toluene, 1, 2-dichloroethane, tetrahydrofuran or ethyl acetate;
the reaction temperature is 60 ℃ to 100 ℃;
the reaction time is 16-24 h.
Has the advantages that: compared with the related technology in the field of chemical synthesis, the invention realizes the construction of the 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound for the first time. The persulfate initiates generation of trifluoromethyl free radicals through a single electron process, and then generates free radical coupling with alkyne and 2-phenylamino-1, 4-naphthoquinone, so that the 2-phenylamino-1, 4-naphthoquinone compound containing trifluoromethyl alkenyl is constructed.
Drawings
FIGS. 1a, 1b and 1c are respectively a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum of a 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6a prepared according to example 1 of the present invention;
FIGS. 2a, 2b and 2c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of a 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6b prepared according to example 2 of the present invention;
FIGS. 3a, 3b and 3c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of a 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6c prepared according to example 3 of the present invention;
FIGS. 4a, 4b and 4c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6d according to example 4 of the present invention.
FIGS. 5a, 5b and 5c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6e prepared according to example 5 of the present invention.
FIGS. 6a, 6b and 6c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6f prepared according to example 6 of the present invention.
FIGS. 7a, 7b and 7c are nuclear magnetic resonance hydrogen spectra, fluorine spectra and carbon spectra, respectively, of 6g of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound prepared according to example 7 of the present invention.
FIGS. 8a, 8b and 8c are the hydrogen, fluorine and carbon nuclear magnetic resonance spectra, respectively, of a 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound prepared in example 8 according to the present invention for 6 h.
FIGS. 9a, 9b and 9c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6i prepared in example 9 according to the present invention.
FIGS. 10a, 10b and 10c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6j prepared in example 10 according to the present invention.
FIGS. 11a, 11b and 11c are a hydrogen nuclear magnetic resonance spectrum, a fluorine spectrum and a carbon spectrum, respectively, of 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound 6k prepared in example 11 according to the present invention.
Detailed Description
The invention is further described with reference to the following drawings and examples:
the 3-trifluoromethyl alkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof comprise the following steps:
the alkyne of the structure (I), the 2-phenylamino-1, 4-naphthoquinone of the structure (II), the trifluoromethylating reagent of the structure (III), the persulfate oxidant and the iron catalyst are dispersed in a solvent and react for a certain time at a proper temperature under magnetic stirring to obtain the 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound with the structure (IV):
the specific structure of IV is as follows:
the persulfate oxidant is potassium persulfate, sodium persulfate or ammonium persulfate;
the iron catalyst is ferrous sulfate heptahydrate, ferric acetylacetonate, ferric chloride, ferric oxide, ferrous chloride or ferric nitrate;
the solvent is acetonitrile, toluene, 1, 2-dichloroethane, tetrahydrofuran or ethyl acetate;
the reaction temperature is 60 ℃ to 100 ℃;
the reaction time is 16-24 h. 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone
Example 1
0.3mmol of phenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double rows and then placed into an oil bath kettle at 70 ℃ for heating reaction for 20 hours. After the reaction is finished, removing acetonitrile from the reaction mixture by a rotary evaporator, and separating the obtained residue by a silica gel column by using petroleum ether and ethyl acetate as eluting agents to obtain a target product which is a red solid. The characterization data are: E/Z3.77: 1;1H NMR(600MHz,CDCl3):δ[ppm]＝8.25-8.23(dd,J＝7.7,1.1Hz,0.18H), 8.21-8.20(dd,J＝7.7,1.1Hz,0.76H),8.17-8.16(dd,J＝7.7,1.1Hz, 0.26H),8.13-8.12(dd,J＝7.7,1.1Hz,0.76H),7.82-7.79(td,J＝7.7, 1.1Hz,1H),7.71-7.68(m,2H),7.28-7.25(t,J＝8.0Hz,1H),7.19-7.16 (m,2H),7.09-7.03(m,3H),6.82-6.81(d,J＝7.7Hz,1.62H),6.74-6.73 (d,J＝7.7Hz,0.49H),6.68-6.67(d,J＝7.7Hz,0.43H),6.64-6.62(d, J＝7.7Hz,1.69H),5.88-5.83(m,1H)；13C{1H}NMR(150MHz,CDCl3):δ[ppm] ＝182.6,182.2,181.0,180.8,142.5(q,J CF＝6.1Hz),142.0,137.8,137.6, 136.9,136.5,135.4,135.3,133.3,133.2,132.8,132.7,130.2,130.0, 128.7,128.6,128.5(q,J CF＝2.1Hz),128.4,128.2,127.5,127.3,126.6, 126.5,126.0,125.7,124.0,122.9(q,J CF＝33.9Hz),122.7(q,J CF＝ 274.4Hz),118.4(q,JCF＝33.5Hz),116.7,112.8；19F NMR(564MHz,CDCl3): δ[ppm]＝-56.1(d,J＝8.6Hz,2.32F),-60.8(d,J＝8.5Hz,0.58F)； HRMS(ESI-TOF):calcd.for C25H17F3NO2[M+H]+420.1211,found 420.1230.
the nmr spectrum of the product prepared in this example is shown in fig. 1a, the nmr spectrum is shown in fig. 1b, and the nmr spectrum is shown in fig. 1 c. From the map, it was confirmed that the obtained product was the objective compound 6 a.
Example 2
In a clean and dry 100.3mmol of 3-methylphenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a mL Schlenk pressure-resistant reaction tube, then 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double tubes, and then the reaction tube is placed in an oil bath kettle at 70 ℃ for heating reaction for 20 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z is 1.89: 1;1H NMR(600MHz,CDCl3):δ[ppm]＝8.25-8.24(dd,J＝7.6,1.1 Hz,0.33H),8.22-8.21(dd,J＝7.7,1.1Hz,0.69H),8.17-8.15(dd,J＝ 7.7,1.1Hz,0.37H),8.13-8.12(dd,J＝7.7,1.1Hz,0.69H),7.82-7.79 (td,J＝7.7,1.1Hz,1H),7.72-7.69(qd,J＝7.7,1.1Hz,1H),7.67(s, 0.63H),7.61(s,0.34H),7.28-7.17(m,2H),7.16-7.08(m,1H),7.01-6.92 (m,2H),6.82-6.80(d,J＝7.7Hz,1.39H),6.69-6.67(d,J＝7.7Hz,0.72H), 6.58-6.56(d,J＝7.7Hz,0.37H),6.45-6.44(d,J＝7.7Hz,0.65H),6.40 (s,0.38H),6.32(s,0.65H),5.87-5.80(m,1H),2.16(s,1.10H),2.13 (s,1.96H)；；13C{1H}NMR(150MHz,CDCl3):δ[ppm]＝182.7,182.3,181.0, 180.8,142.6(q,JCF＝6.1Hz),142.0,141.9,141.8(q,JCF＝5.8Hz), 138.0,137.9,137.6,136.9,136.5,135.4,135.3,133.3,133.2,132.8, 132.7,130.1,130.00,129.99,129.4,129.2(q,J CF＝2.4Hz),128.6,128.2, 127.38,127.37,127.3,127.2,126.54,126.49,126.1,126.0,125.5,125.4 (q,JCF＝2.2Hz),123.9,122.8(q,J CF＝33.6Hz),122.6(q,J CF＝273.6 Hz),118.3(q,JCF＝33.4Hz),116.7,113.0；19F NMR(564MHz,CDCl3):δ [ppm]＝-56.0(d,J＝8.6Hz,1.96F),-60.8(d,J＝8.6Hz,1.02F)；HRMS (ESI-TOF):calcd.for C26H19F3NO2[M+H]+434.1368,found 434.1361；HRMS (ESI-TOF):calcd.for C26H18F3NO2Na[M+Na]+456.1187,found 456.1154.
the nmr spectrum of the product prepared in this example is shown in fig. 2a, the nmr spectrum is shown in fig. 2b, and the nmr spectrum is shown in fig. 2 c. From the map, it was confirmed that the obtained product was the objective compound 6 b.
Example 3
0.3mmol of 4-pentylphenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double tubes, and then the reaction tube is placed in an oil bath kettle at 80 ℃ for heating reaction for 20 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z> 20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.21-8.19(dd,J＝7.7,1.1Hz, 1H),8.13-8.12(dd,J＝7.7,1.1Hz,1H),7.82-7.79(td,J＝7.7,1.1 Hz,1H),7.71-7.68(td,J＝7.7,1.1Hz,1H),7.66(s,1H),7.25-7.22 (t,J＝7.9Hz,2H),7.18-7.15(t,J＝7.9Hz,1H),6.85-6.83(d,J＝ 7.8Hz,2H),6.79-6.78(d,J＝7.7Hz,2H),6.54-6.53(d,J＝7.7Hz, 2H),5.82-5.78(q,J＝8.6Hz,1H),2.51-2.49(t,J＝7.7Hz,2H),1.57-1.52 (m,2H),1.35-1.30(m,2H),1.29-1.25(m,2H),0.89-0.87(t,J＝7.6Hz, 3H)；13C{1H}NMR(150MHz,CDCl3):δ[ppm]＝182.7,181.1,143.6,142.5 (q,JCF＝5.9Hz),141.9,137.5,135.4,133.6,133.3,132.7,130.0,128.6, 128.4,127.6,127.3,126.5,125.6,124.0,123.7,122.8(q,JCF＝274.6 Hz),122.2(q,JCF＝33.8Hz),116.7,35.7,31.5,30.9,22.6,14.2；19F NMR(564MHz,CDCl3):δ[ppm]＝-57.2(d,J＝8.6Hz,3F)；HRMS(ESI-TOF): calcd.for C30H27F3NO2[M+H]+490.1994,found 490.1970；HRMS(ESI-TOF): calcd.for C30H26F3NO2Na[M+Na]+512.1813,found 512.1823.
The nmr spectrum of the product prepared in this example is shown in fig. 3a, the nmr spectrum is shown in fig. 3b, and the nmr spectrum is shown in fig. 3 c. From the map, it was confirmed that the obtained product was the objective compound 6 c.
Example 4
0.3mmol of 4-methoxy phenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double rows and then placed into an oil bath kettle at 70 ℃ for heating reaction for 20 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z>20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.23-8.22(dd,J＝7.7, 1.1Hz,1H),8.16-8.15(dd,J＝7.7,1.1Hz,1H),7.81-7.78(td,J＝7.7, 1.1Hz,1H),7.72-7.69(td,J＝7.7,1.1Hz,1H),7.61(s,1H),7.12-7.06 (m,3H),6.70-6.68(m,4H),6.62-6.59(m,2H),5.76-5.72(q,J＝8.6Hz, 1H),3.75(s,3H)；13C{1H}NMR(150MHz,CDCl3):δ[ppm]＝182.3,180.9, 160.6,142.1,141.1(q,JCF＝5.9Hz),136.9,135.3,133.2,132.7,130.14, 130.13,128.2,128.0,127.3,126.5,126.3,126.1,125.9,123.3(q,J CF＝273.5Hz),116.5(q,JCF＝34.1Hz),113.7,112.8,55.4；19F NMR(564 MHz,CDCl3):δ[ppm]＝-56.3(d,J＝8.6Hz,3F)；HRMS(ESI-TOF):calcd. for C26H19F3NO3[M+H]+450.1317,found 450.1311；HRMS(ESI-TOF):calcd.for C26H18F3NO3Na[M+Na]+472.1136,found 472.1154.
The nmr spectrum of the product prepared in this example is shown in fig. 4a, the nmr spectrum is shown in fig. 4b, and the nmr spectrum is shown in fig. 4 c. From the map, it was confirmed that the obtained product was the objective compound 6 d.
Example 5
0.3mmol of 4-ethoxy was added to a clean and dry 10mL Schlenk pressure-resistant reaction tubePhenyl acetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate, 0.5mmol of potassium persulfate, and 2mL of acetonitrile as a solvent are added, and the reaction tube is replaced by nitrogen through double rows and then placed in an oil bath kettle at 70 ℃ for heating reaction for 16 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z>20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.23-8.22(dd,J＝7.7, 1.1Hz,1H),8.16-8.15(dd,J＝7.7,1.1Hz,1H),7.81-7.78(td,J＝7.7, 1.1Hz,1H),7.72-7.69(td,J＝7.7,1.1Hz,1H),7.61(s,1H),7.12-7.06 (m,3H),6.70-6.67(m,4H),6.61-6.58(m,2H),5.76-5.72(q,J＝8.6Hz, 1H),3.98-3.95(q,J＝7.1Hz,2H),1.39-1.37(t,J＝7.1Hz,3H)；13C{1H} NMR(150MHz,CDCl3):δ[ppm]＝182.3,180.9,160.0,142.1,141.2(q, J CF＝5.9Hz),136.9,135.2,133.2,132.7,130.1,130.0,128.2,128.0, 127.3,126.5,126.2,126.1,126.0,123.3(q,J CF＝273.8Hz),116.4(q, J CF＝33.8Hz),114.2,112.8,63.6,14.8；19F NMR(564MHz,CDCl3):δ[ppm] ＝-56.1(d,J＝8.6Hz,3F)；HRMS(ESI-TOF):calcd.for C27H21F3NO3[M+H]+ 464.1474,found 464.1488.
The nmr spectrum of the product prepared in this example is shown in fig. 5a, the nmr spectrum is shown in fig. 5b, and the nmr spectrum is shown in fig. 5 c. From the map, it was confirmed that the obtained product was the objective compound 6 e.
Example 6
0.3mmol of 4-fluorophenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double tubes, and then the reaction tube is placed in an oil bath kettle at 100 ℃ for heating reaction for 20 hours. After the reaction is finished, removing the ethyl by directly passing the reaction mixture through a rotary evaporatorNitrile, and separating the obtained residue through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain the target product as a red solid. The characterization data are: E/Z> 20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.21-8.19(dd,J＝7.7,1.1Hz, 1H),8.15-8.13(dd,J＝7.7,1.1Hz,1H),7.83-7.80(td,J＝7.7,1.1 Hz,1H),7.73-7.70(m,2H),7.28-7.25(m,2H),7.20-7.17(m,1H), 6.82-6.80(d,J＝8.2Hz,2H),6.74-6.71(t,J＝8.2Hz,2H),6.59-6.56 (m,2H),5.88-5.84(q,J＝8.6Hz,1H)；13C{1H}NMR(150MHz,CDCl3):δ [ppm]＝182.5,180.9,162.8(d,JCF＝247.3Hz),142.0,137.4,135.5, 133.2,132.9,132.4(d,JCF＝3.5Hz),130.4(d,J CF＝1.9Hz),129.9, 128.7,127.3,126.6,125.8,124.0,122.6(q,J CF＝273.6Hz),123.0(q, J CF＝34.6Hz),116.1,114.5(d,JCF＝21.5Hz)；19F NMR(564MHz,CDCl3): δ[ppm]＝-56.2(d,J＝8.6Hz,3F),-112.4(s,1F)；HRMS(ESI-TOF): calcd.for C25H16F4NO2[M+H]+438.1117,found 438.1142.
The nmr spectrum of the product prepared in this example is shown in fig. 6a, the nmr spectrum is shown in fig. 6b, and the nmr spectrum is shown in fig. 6 c. From the map, it was confirmed that the obtained product was the objective compound 6 f.
Example 7
0.3mmol of 4-trifluoromethylphenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double rows and then placed into an oil bath kettle at 70 ℃ for heating reaction for 16 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z>20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.21-8.19(dd,J＝7.7, 1.1Hz,1H),8.14-8.13(dd,J＝7.7,1.1Hz,1H),7.83-7.80(td,J＝7.7, 1.1Hz,1H),7.74-7.70(m,2H),7.31-7.27(m,4H),7.22-7.20(t,J＝8.1 Hz,1H),6.82-6.81(d,J＝8.4Hz,2H),6.74-6.72(d,J＝8.4Hz,2H), 5.97-5.92(q,J＝8.6Hz,1H)；13C{1H}NMR(150MHz,CDCl3):δ[ppm]＝182.3, 180.9,142.2,141.1(q,J CF＝5.9Hz),140.2,137.4,135.6,133.1,133.0, 130.4(q,J CF＝32.3Hz),129.9,128.89,128.87,127.3,126.6,126.0, 124.8(q,JCF＝33.5Hz),124.5(q,J CF＝3.8Hz),124.1,123.9(q,J CF＝275.4Hz),122.4(q,JCF＝272.8Hz),115.6；19F NMR(564MHz,CDCl3): δ[ppm]＝-56.1(d,J＝8.6Hz,3F),-62.6(s,3F)；HRMS(ESI-TOF):calcd. for C26H16F6NO2[M+H]+488.1085,found 488.1100.
The nmr spectrum of the product prepared in this example is shown in fig. 7a, the nmr spectrum is shown in fig. 7b, and the nmr spectrum is shown in fig. 7 c. From the graph, it was confirmed that 6g of the objective compound was obtained as a product.
Example 8
0.3mmol of 3-nitrophenylacetylene, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethylsulfinate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of ammonium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added to be used as a solvent, the reaction tube is replaced by double-line nitrogen and then is placed into an oil bath kettle at 90 ℃ for heating reaction for 20 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z> 20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.20-8.18(dd,J＝7.7,1.1Hz, 1H),8.14-8.13(d,J＝7.7Hz,1H),8.06-8.03(dq,J＝7.7,1.0Hz,1H), 7.84-7.81(td,J＝8.0,1.2Hz,1H),7.79(s,1H),7.73-7.71(td,J＝ 8.0,1.1Hz,1H),7.41-7.40(t,J＝1.2Hz,1H),7.29-7.22(m,4H), 7.01-6.99(d,J＝8.1Hz,1H),6.82-6.81(d,J＝8.2Hz,2H),6.03-5.98 (q,J＝8.6Hz,1H)；13C{1H}NMR(150MHz,CDCl3):δ[ppm]＝182.2,180.9, 147.6,142.4,140.1(q,JCF＝5.8Hz),138.3,137.1,135.7,134.6(q, J CF＝1.9Hz),133.1,129.8,129.0,128.6,127.4,126.7,126.5,124.9 (q,JCF＝33.5Hz),124.1,123.6(q,J CF＝2.3Hz),123.5,122.3(q,J CF＝275.4Hz),114.8；19F NMR(564MHz,CDCl3):δ[ppm]＝-56.1(d,J＝ 8.6Hz,3F)；HRMS(ESI-TOF):calcd.for C25H16F3N2O4[M+H]+465.1062,found 465.1047.
The nmr spectrum of the product prepared in this example is shown in fig. 8a, the nmr spectrum is shown in fig. 8b, and the nmr spectrum is shown in fig. 8 c. From the graph, it was confirmed that the obtained product was the objective compound 6 h.
Example 9
0.3mmol of 1-dodecyne, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double calandria, and then the reaction tube is placed into an oil bath kettle at 70 ℃ for heating reaction for 16 hours. After the reaction is finished, removing acetonitrile from the reaction mixture by a rotary evaporator, and separating the obtained residue by a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: E/Z>20:1； 1H NMR(600MHz,CDCl3):δ[ppm]＝8.15-8.12(m,2H),7.79-7.76(td,J ＝7.7,1.2Hz,1H),7.71(s,1H),7.70-7.67(td,J＝7.7,1.1Hz,1H), 7.30-7.27(t,J＝8.2Hz,2H),7.19-7.17(t,J＝8.0Hz,1H),7.02-7.01 (d,J＝7.8Hz,2H),5.54-5.49(q,J＝8.6Hz,1H),1.83(s,2H),1.16-1.10 (m,16H),0.85-0.82(t,J＝7.3Hz,3H)；13C{1H}NMR(150MHz,CDCl3):δ [ppm]＝182.5,180.9,145.8(q,JCF＝5.6Hz),141.3,137.4,135.2,133.1, 132.7,130.0,128.7,127.1,126.4,126.0,125.1,122.8(q,J CF＝33.7 Hz),122.5(q,JCF＝271.2Hz),116.8,31.9,31.6,29.8,29.6,29.5,29.4, 29.3,28.3,22.7,14.2；19F NMR(564MHz,CDCl3):δ[ppm]＝-57.8(d,J ＝8.6Hz,3F)；HRMS(ESI-TOF):calcd.for C29H33F3NO2[M+H]+484.2463,found 484.2446.
The nmr spectrum of the product prepared in this example is shown in fig. 9a, the nmr spectrum is shown in fig. 9b, and the nmr spectrum is shown in fig. 9 c. From the map, it was confirmed that the obtained product was the target compound 6 i.
Example 10
0.3mmol of 1-phenyl propyne, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double tubes, and then the reaction tube is placed in an oil bath kettle at 80 ℃ for heating reaction for 20 hours. After the reaction is finished, the reaction mixture is directly subjected to a rotary evaporator to remove acetonitrile, and the obtained residue is separated by a silica gel column by using petroleum ether and ethyl acetate as eluents to obtain a target product which is a red solid. The characterization data are: Z/E> 20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.21-8.20(d,J＝7.8Hz,1H), 8.11-8.10(d,J＝7.8Hz,1H),7.81-7.79(td,J＝7.7,1.2Hz,1H), 7.70-7.67(td,J＝7.7,1.2Hz,1H),7.64(s,1H),7.33-7.30(t,J＝8.2 Hz,2H),7.24-7.21(t,J＝8.0Hz,1H),7.14-7.11(m,1H),7.02-6.99(t, J＝8.2Hz,2H),6.85-6.84(d,J＝7.8Hz,2H),6.45-6.44(d,J＝7.8 Hz,2H),1.98(s,3H)；13C{1H}NMR(150MHz,CDCl3):δ[ppm]＝182.7,179.9, 141.9,138.5,138.2,137.3(q,JCF＝3.6Hz),135.3,133.2,132.7,130.1, 128.7(q,JCF＝2.1Hz),128.5,128.2(q,J CF＝28.9Hz),127.8,127.24, 127.21,126.5,125.7,123.8(q,J CF＝274.3Hz),123.7,117.6,18.5(q, JCF＝2.4Hz)；19F NMR(564MHz,CDCl3):δ[ppm]＝-59.2(s,3F)；HRMS (ESI-TOF):calcd.for C26H19F3NO2[M+H]+434.1368,found 434.1361；HRMS (ESI-TOF):calcd.for C26H18F3NO2Na[M+Na]+456.1187,found 456.1154.
The nmr spectrum of the product prepared in this example is shown in fig. 10a, the nmr spectrum is shown in fig. 10b, and the nmr spectrum is shown in fig. 10 c. From the map, it was confirmed that the obtained product was the target compound 6 j.
Example 11
0.3mmol of 1-phenyl pentyne, 0.2mmol of 2-phenylamino-1, 4-naphthoquinone, 0.4mmol of sodium trifluoromethanesulfonate, 0.02mmol of ferrous sulfate heptahydrate and 0.5mmol of potassium persulfate are sequentially added into a clean and dry 10mL Schlenk pressure-resistant reaction tube, 2mL of acetonitrile is added as a solvent, the reaction tube is replaced by nitrogen through double tubes, and then the reaction tube is placed in an oil bath kettle at 70 ℃ for heating reaction for 16 hours. After the reaction is finished, the reaction mixture is directly removed of acetonitrile through a rotary evaporator, and the obtained residue is separated through a silica gel column by using petroleum ether and ethyl acetate as eluent to obtain a target product which is a red solid. The characterization data are: Z/E> 20:1；1H NMR(600MHz,CDCl3):δ[ppm]＝8.21-8.20(d,J＝7.8Hz,1H), 8.14-8.13(dd,J＝7.8,1.1Hz,1H),8.09-8.08(dd,J＝7.7,1.1Hz,1H), 7.78-7.75(td,J＝7.7,1.2Hz,1H),7.69-7.66(td,J＝7.7,1.2Hz,1H), 7.55(s,1H),7.30-7.27(t,J＝8.0Hz,2H),7.22-7.20(t,J＝8.1Hz, 1H),7.16-7.13(tt,J＝7.8,1.1Hz,1H),7.09-7.05(m,2H),6.94-6.93 (d,J＝7.8Hz,2H),3.75-6.73(d,J＝7.9Hz,2H),2.35-2.30(m,1H), 2.20-2.15(m,1H),1.69-1.61(m,2H),0.94-0.91(t,J＝7.3Hz,3H)；13C{1H} NMR(150MHz,CDCl3):δ[ppm]＝182.5,180.7,141.8,138.9,138.4,138.2 (q,J CF＝3.8Hz),135.1,133.1,132.7,132.5(q,J CF＝27.2Hz),130.3, 128.7,128.6(q,JCF＝2.1Hz),127.8,127.4,127.1,126.5,126.0,124.2, 123.9(q,JCF＝275.6Hz),118.6,35.6(q,J CF＝1.6Hz),21.0,14.9； 19F NMR(564MHz,CDCl3):δ[ppm]＝-55.3(s,3F)；HRMS(ESI-TOF):calcd. for C28H23F3NO2[M+H]+462.1681,found 462.1697.
The nmr spectrum of the product prepared in this example is shown in fig. 11a, the nmr spectrum is shown in fig. 11b, and the nmr spectrum is shown in fig. 11 c. From the map, it was confirmed that the obtained product was the target compound 6 k.
In one embodiment, the 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof disclosed by the invention are characterized in that under the catalysis of an iron catalysis test and the oxidation effect of persulfate, sodium trifluoromethanesulfonate is initiated to generate trifluoromethyl free radicals through a single electron process, then the trifluoromethyl free radicals are oxidized by persulfate after the free radical relay addition is carried out on the trifluoromethyl free radicals and alkyne and 2-phenylamino-1, 4-naphthoquinone respectively, and then the 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound is constructed through the deprotonation effect.
The foregoing is illustrative of the preferred embodiments of the invention to enable any person skilled in the art to make or use the invention, and some modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the scope or spirit of the invention. Accordingly, the scope of the invention is not limited by the specific embodiments described above.
Claims (6)
1. A3-trifluoromethyl alkenyl-2-phenylamino-1, 4-naphthoquinone compound and a preparation method thereof are characterized by comprising the following steps:
the alkyne of the structure (I), the 2-phenylamino-1, 4-naphthoquinone of the structure (II), the trifluoromethylating reagent of the structure (III), the persulfate oxidant and the iron catalyst are dispersed in a solvent and react for a certain time at a proper temperature under magnetic stirring to obtain the 3-trifluoromethylalkenyl-2-phenylamino-1, 4-naphthoquinone compound with the structure (IV):
the specific structure of IV is as follows:
2. the 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof according to claim 1, wherein: the persulfate oxidant is potassium persulfate, sodium persulfate or ammonium persulfate.
3. The 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof according to claim 1, wherein: the iron catalyst is ferrous sulfate heptahydrate, ferric acetylacetonate, ferric chloride, ferric oxide, ferrous chloride or ferric nitrate.
4. The 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof according to claim 1, wherein: the solvent is acetonitrile, toluene, 1, 2-dichloroethane, tetrahydrofuran or ethyl acetate.
5. The 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof according to claim 1, wherein: the reaction temperature is 60 ℃ to 100 ℃.
6. The 3-trifluoromethylated alkenyl-2-phenylamino-1, 4-naphthoquinone compound and the preparation method thereof according to claim 1, wherein: the reaction time is 16-24 h.
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| CN109748811A (en) * | 2019-01-24 | 2019-05-14 | 中国农业大学 | A kind of method for the naphthoquinone derivatives that synthesis of alkyl carboxylate replaces |
| CN114702399A (en) * | 2022-05-05 | 2022-07-05 | 信阳师范学院 | 2-trifluoroalkyl-1, 4-naphthoquinone compound and synthetic method thereof |
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| CN109748811A (en) * | 2019-01-24 | 2019-05-14 | 中国农业大学 | A kind of method for the naphthoquinone derivatives that synthesis of alkyl carboxylate replaces |
| CN114702399A (en) * | 2022-05-05 | 2022-07-05 | 信阳师范学院 | 2-trifluoroalkyl-1, 4-naphthoquinone compound and synthetic method thereof |
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