CN109748809B - Method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivative - Google Patents
Method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivative Download PDFInfo
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- CN109748809B CN109748809B CN201910037112.7A CN201910037112A CN109748809B CN 109748809 B CN109748809 B CN 109748809B CN 201910037112 A CN201910037112 A CN 201910037112A CN 109748809 B CN109748809 B CN 109748809B
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- naphthoquinone
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- ethyl acetate
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- -1 2-substituted amino-1, 4-naphthoquinone Chemical class 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 10
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 132
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 35
- 150000002828 nitro derivatives Chemical class 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 12
- 229910052751 metal Inorganic materials 0.000 claims abstract description 10
- 239000002184 metal Substances 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 29
- 229960000583 acetic acid Drugs 0.000 claims description 19
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 17
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 13
- 239000011701 zinc Substances 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 229910007339 Zn(OAc)2 Inorganic materials 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- NYENCOMLZDQKNH-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)bismuthanyl trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F NYENCOMLZDQKNH-UHFFFAOYSA-K 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- DJWUNCQRNNEAKC-UHFFFAOYSA-L zinc acetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O DJWUNCQRNNEAKC-UHFFFAOYSA-L 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 125000000468 ketone group Chemical group 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 42
- 239000007787 solid Substances 0.000 abstract description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 abstract description 21
- 238000004440 column chromatography Methods 0.000 abstract description 21
- 239000000706 filtrate Substances 0.000 abstract description 21
- 239000012074 organic phase Substances 0.000 abstract description 21
- 239000003208 petroleum Substances 0.000 abstract description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 abstract description 21
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000001914 filtration Methods 0.000 abstract description 6
- 238000007259 addition reaction Methods 0.000 abstract description 5
- 238000001308 synthesis method Methods 0.000 abstract description 5
- 238000010790 dilution Methods 0.000 abstract 1
- 239000012895 dilution Substances 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 19
- 238000012512 characterization method Methods 0.000 description 19
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- 229940125904 compound 1 Drugs 0.000 description 15
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- RJKGJBPXVHTNJL-UHFFFAOYSA-N 1-nitronaphthalene Chemical compound C1=CC=C2C([N+](=O)[O-])=CC=CC2=C1 RJKGJBPXVHTNJL-UHFFFAOYSA-N 0.000 description 2
- CIWCIDRTACZSAZ-UHFFFAOYSA-N 2-anilino-3-chloronaphthalene-1,4-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C(Cl)=C1NC1=CC=CC=C1 CIWCIDRTACZSAZ-UHFFFAOYSA-N 0.000 description 2
- LLYXJBROWQDVMI-UHFFFAOYSA-N 2-chloro-4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1Cl LLYXJBROWQDVMI-UHFFFAOYSA-N 0.000 description 2
- KLGQWSOYKYFBTR-UHFFFAOYSA-N 2-nitrobenzamide Chemical compound NC(=O)C1=CC=CC=C1[N+]([O-])=O KLGQWSOYKYFBTR-UHFFFAOYSA-N 0.000 description 2
- SMHPLBXIVNQFBA-UHFFFAOYSA-N 6-nitroquinoline Chemical compound N1=CC=CC2=CC([N+](=O)[O-])=CC=C21 SMHPLBXIVNQFBA-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- OPECBHGHSFBITB-UHFFFAOYSA-N PAN Natural products O=C1C2=CC=CC=C2C(=O)C=C1NC1=CC=CC=C1 OPECBHGHSFBITB-UHFFFAOYSA-N 0.000 description 2
- 239000011968 lewis acid catalyst Substances 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000000191 1,4-naphthoquinones Chemical class 0.000 description 1
- ORPVVAKYSXQCJI-UHFFFAOYSA-N 1-bromo-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1Br ORPVVAKYSXQCJI-UHFFFAOYSA-N 0.000 description 1
- KMAQZIILEGKYQZ-UHFFFAOYSA-N 1-chloro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1 KMAQZIILEGKYQZ-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- NEZGPRYOJVPJKL-UHFFFAOYSA-N 1-methylsulfanyl-4-nitrobenzene Chemical compound CSC1=CC=C([N+]([O-])=O)C=C1 NEZGPRYOJVPJKL-UHFFFAOYSA-N 0.000 description 1
- HCYIVAJBFNTKGZ-UHFFFAOYSA-N 1-nitro-2-prop-2-ynoxybenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC#C HCYIVAJBFNTKGZ-UHFFFAOYSA-N 0.000 description 1
- KLGHUFNKRIWCDQ-UHFFFAOYSA-N 1-nitrooctane Chemical compound CCCCCCCC[N+]([O-])=O KLGHUFNKRIWCDQ-UHFFFAOYSA-N 0.000 description 1
- NLOUGHWBUWXEAM-UHFFFAOYSA-N 2-(2-bromoanilino)naphthalene-1,4-dione Chemical compound BrC1=CC=CC=C1NC1=CC(=O)C2=CC=CC=C2C1=O NLOUGHWBUWXEAM-UHFFFAOYSA-N 0.000 description 1
- KYSBTGPZDQBHMH-UHFFFAOYSA-N 2-(2-hydroxyanilino)naphthalene-1,4-dione Chemical compound OC1=CC=CC=C1NC1=CC(=O)C2=CC=CC=C2C1=O KYSBTGPZDQBHMH-UHFFFAOYSA-N 0.000 description 1
- PEAIHGOMZYGGIZ-UHFFFAOYSA-N 2-(3-chloroanilino)naphthalene-1,4-dione Chemical compound ClC1=CC=CC(NC=2C(C3=CC=CC=C3C(=O)C=2)=O)=C1 PEAIHGOMZYGGIZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJEXYGNDMQLG-UHFFFAOYSA-N 2-(4-fluoroanilino)naphthalene-1,4-dione Chemical compound C1=CC(F)=CC=C1NC1=CC(=O)C2=CC=CC=C2C1=O ZOXJEXYGNDMQLG-UHFFFAOYSA-N 0.000 description 1
- BLXXUTVXRNZUQX-UHFFFAOYSA-N 2-(4-hydroxyanilino)naphthalene-1,4-dione Chemical compound C1=CC(O)=CC=C1NC1=CC(=O)C2=CC=CC=C2C1=O BLXXUTVXRNZUQX-UHFFFAOYSA-N 0.000 description 1
- VHJMLDQPIJTWAU-UHFFFAOYSA-N 2-(4-methoxyanilino)naphthalene-1,4-dione Chemical compound C1=CC(OC)=CC=C1NC1=CC(=O)C2=CC=CC=C2C1=O VHJMLDQPIJTWAU-UHFFFAOYSA-N 0.000 description 1
- DECIRKJAMAOVMR-UHFFFAOYSA-N 2-(4-methylanilino)naphthalene-1,4-dione Chemical compound C1=CC(C)=CC=C1NC1=CC(=O)C2=CC=CC=C2C1=O DECIRKJAMAOVMR-UHFFFAOYSA-N 0.000 description 1
- FEWFXZPGPSWQJK-UHFFFAOYSA-N 2-(methylamino)naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(NC)=CC(=O)C2=C1 FEWFXZPGPSWQJK-UHFFFAOYSA-N 0.000 description 1
- ROVUCMZIEJANNB-UHFFFAOYSA-N 2-(octylamino)naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(NCCCCCCCC)=CC(=O)C2=C1 ROVUCMZIEJANNB-UHFFFAOYSA-N 0.000 description 1
- KJOHPBJYGGFYBJ-UHFFFAOYSA-N 2-bromonaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(Br)=CC(=O)C2=C1 KJOHPBJYGGFYBJ-UHFFFAOYSA-N 0.000 description 1
- CCTJHVLTAJTPBV-UHFFFAOYSA-N 2-chloro-1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C(Cl)=CC(=O)C2=C1 CCTJHVLTAJTPBV-UHFFFAOYSA-N 0.000 description 1
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229910004664 Cerium(III) chloride Inorganic materials 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- BNUHAJGCKIQFGE-UHFFFAOYSA-N Nitroanisol Chemical compound COC1=CC=C([N+]([O-])=O)C=C1 BNUHAJGCKIQFGE-UHFFFAOYSA-N 0.000 description 1
- 229910007340 Zn(OAc)2.2H2O Inorganic materials 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- BEAZKUGSCHFXIQ-UHFFFAOYSA-L zinc;diacetate;dihydrate Chemical compound O.O.[Zn+2].CC([O-])=O.CC([O-])=O BEAZKUGSCHFXIQ-UHFFFAOYSA-L 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivatives, which comprises the steps of uniformly mixing a nitro compound, 2-substituted 1, 4-naphthoquinone, a catalyst, metal and a solvent at the temperature of 20-100 ℃, adding an H source, stirring for reacting for 1-24 hours, carrying out reduction-addition reaction on the nitro compound and the 2-substituted 1, 4-naphthoquinone, adding water for dilution after the reaction is finished, filtering, and extracting filtrate by ethyl acetate; the organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, filtration was performed, the solvent was removed by concentration under reduced pressure, and the solid was packed into a column and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain a red solid. Compared with the existing synthesis method, the synthesis method has the advantages of wide raw materials, easily obtained raw materials, better stability of the nitro compound compared with the amine compound, simple operation and mild reaction conditions.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a 2-substituted amino-1, 4-naphthoquinone derivative.
Background
2-substituted amino-1, 4-naphthoquinone derivatives are important molecules, widely exist in medicines, natural products and bacterial metabolites, have unique physicochemical properties and various biological activities such as tuberculosis resistance, malaria resistance, bacteria resistance and tumor resistance, and are frequently used in the aspects of pesticides, herbicides, bactericides and the like. In addition, 2-substituted amino-1, 4-naphthoquinone derivatives are intermediates for synthesizing other important compounds. For example, the 2-substituted amino-1, 4-naphthoquinone can be used to synthesize important compound CBI, thereby obtaining natural product CC-1065, which is a potential antitumor antibiotic.
At present, the synthesis of 2-substituted amino-1, 4 has been already performedThe method of preparing the naphthoquinone compound comprises the addition reaction of 1, 4-naphthoquinone and amine under the action of a catalyst. E.g. using Lewis acids CeCl3·7H2O(J.Fluorine Chem.2011,132,94–101)，FeCl3(J.chem.2015,180, 152-160) or iodine (J.chem.Res.2013,37, 34-37). In addition, 2-substituted amino-1, 4-naphthoquinone can also be obtained by nucleophilic addition reaction of 2-position halogen atom substituted 1, 4-naphthoquinone with amine (Tetrahedron1991,47, 8043-9965), or 2-substituted amino-1, 4-naphthoquinone can be obtained by metal-catalyzed cross-coupling reaction (Synthesis2007,7, 989-998). It is known that the conventional synthesis methods all use amine as a nitrogen source and are limited in terms of the source of raw materials. Therefore, the exploration of raw materials for replacing amine and a new method for synthesizing the 2-substituted amino-1, 4-naphthoquinone compound have important practical significance.
Disclosure of Invention
The invention aims to: in the method, a nitro compound and 2-substituted 1, 4-naphthoquinone are used as raw materials, and the 2-substituted amino-1, 4-naphthoquinone compound is formed through nitro reduction-addition reaction in the presence of a Lewis acid catalyst and a metal/hydrogen source system.
In order to achieve the purpose, the invention adopts the technical scheme that: a method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivative, under 20 duC-100 duC, nitro compound, 2-substituted 1, 4-naphthoquinone, catalyst, metal and solvent are mixed, then add H source, stir and react for 1-24H, nitro compound and 2-substituted 1, 4-naphthoquinone produce reduction-addition reaction, after the reaction is over, add water to dilute in the reaction system, filter, filtrate is extracted with ethyl acetate; the organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, filtration was performed, the solvent was removed by concentration under reduced pressure, and the solid was packed into a column and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain a red solid.
Further, the catalyst is Lewis acid and is Cu (OAc)2·H2O、Cu(OTf)2、FeCl3、Zn(OAc)2·2H2O、Zn(OTf)2、ZnCl2、Pd(OAc)2、La(OTf)3、Bi(OTf)3、Co(OAc)2·4H2And O, a mixture of one or more of them.
Further, the metal is one of zinc powder, iron powder and magnesium powder.
Further, the hydrogen source is one of glacial acetic acid, trifluoroacetic acid and formic acid.
Further, the solvent is one of methanol, ethanol, isopropanol, hexafluoroisopropanol, water, tetrahydrofuran, dioxane, acetonitrile, ethyl acetate and dichloromethane.
Further, the molecular formula of the nitro compound is as follows,
the reaction formula is as follows,
wherein R is2Is H, alkyl, alkoxy, hydroxyl, halogen atom, alkylthio, aldehyde, ketone, ester or amide, R1Is H or a halogen atom. More preferably, R1H, Cl or Br. R2The substitution position(s) of (b) is the 2-, 3-, or 4-position of the phenyl ring. More preferably, R2Is H, 4-methyl (the substitution position of methyl on the benzene ring is 4), 4-methoxy, 2-hydroxy, 4-F, 3-Cl, 2-Br, 4-thiomethyl, 2-allyloxy, 2-propargyl, 2-CO2NH2；
Further, the nitro compound may be R3NO2，
The reaction formula is as follows:
wherein R is3Is C1～C8Alkyl of (2), preferably R3Is methyl or n-octyl, R1Is H or a halogen atom. More preferably, R1H, Cl or Br.
Further, the nitro compound may also be a nitro-substituted heterocyclic compound or a polysubstituted nitrobenzene. More preferably, the nitro compound is 1-nitronaphthalene, 6-nitroquinoline or 2-chloro-4-nitrotoluene.
Further, the molecular formula of the 2-substituted-1, 4-naphthoquinone is shown as
R1Is H or a halogen atom. Preferred R1 is H, Cl or Br.
Further, the molar ratio of the 2-substituted-1, 4-naphthoquinone to the nitro compound is 1: 1-2, more preferably, the molar ratio of 2-substituted-1, 4-naphthoquinone to the nitro compound is 1: 1.2;
the molar ratio of the metal to the nitro compound is 1-20: 1, more preferably, the molar ratio of metal to said nitro compound is 5: 1;
the molar ratio of the hydrogen source to the nitro compound is 1-20: 1; more preferably, the molar ratio of hydrogen source to nitro compound is 15: 1;
the molar ratio of the catalyst to the nitro compound is 1:2-20, and preferably, the molar ratio of the catalyst to the nitro compound is 1: 5.
Due to the adoption of the technical scheme, the invention has the beneficial effects that:
the invention takes nitro compound and 2-substituted-1, 4-naphthoquinone as raw materials, and forms the 2-substituted amino-1, 4-naphthoquinone compound through nitro reduction-addition reaction in the presence of Lewis acid catalyst and metal/hydrogen source system. Compared with the existing synthesis method, the synthesis method has the advantages of wide raw materials, easily obtained raw materials, better stability of the nitro compound compared with the amine compound, simple operation and mild reaction conditions.
Detailed Description
Example 1:
in order to explain the technical solutions of the present invention in more detail, the present invention is further described below by way of related examples. The following examples are given by way of illustration and example only and are not intended to limit the scope of the present invention.
Example 1: the synthesis of 2-phenylamino-1, 4-naphthoquinone has the following reaction formula,
compound 1, 4-naphthoquinone (0.3mmol,47.4mg), nitrobenzene (0.36mmol,44.3mg), zinc powder (1.5mmol,98mg), Zn (OAc) 2.2H 2O (0.06mmol,13.1mg) and water (0.6mL) were mixed in this order, acetic acid (4.5mmol,0.26mL) was added thereto, and the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 69.5mg of a red solid with a yield of 93%.
Characterization data: melting point 184-,
1H NMR(400MHz,CDCl3)δ8.21–8.03(m,2H),7.84–7.70(m,1H),7.73–7.61(m,1H),7.57(s,1H),7.43(t,J＝7.9Hz,2H),7.26(t,J＝7.4Hz,3H),7.21(d,J＝7.3Hz,1H),6.42(s,1H).
13C NMR(101MHz,CDCl3)δ183.92,182.05,144.69,137.41,134.91,133.18,132.34,130.34,129.68,126.51,126.14,125.60,122.58,103.36.
in this embodiment, the reaction temperature may be 50 ℃ or 100 ℃.
Example 2: synthesis of 2- (4-methylphenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), p-nitrotoluene (0.36mmol,49.3mg), iron powder (1.5mmol), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with water (0.6mL), and after adding acetic acid (4.5mmol,0.26mL), the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 64.7mg of a red solid with a yield of 82%.
Characterization data: melting point 201-,
1H NMR(400MHz,CDCl3)δ8.09(d,J＝7.6Hz,2H),7.73(t,J＝7.5Hz,1H),7.64(m,1H),7.50(s,1H),7.17(q,J＝8.4Hz,4H),6.33(s,1H),2.34(s,3H).
13C NMR(101MHz,CDCl3)δ184.20,182.50,145.40,136.00,135.24,135.12,133.69,132.61,130.77,130.59,130.34,126.84,126.51,123.09,103.39,21.35.
example 3: synthesis of 2- (4-methoxyphenyl amino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), p-methoxynitrobenzene (0.36mmol,55.1mg), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with water (0.6mL), and after adding acetic acid (4.5mmol,0.26mL), the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain a red solid 61.1mg, yield 93%.
Characterization data: melting point 155-,
1H NMR(400MHz,CDCl3)δ8.09(m,2H),7.74(m,1H),7.64(m,1H),7.45(s,1H),7.18(m,2H),6.94(m,2H),6.21(s,1H),3.82(s,3H).
13C NMR(101MHz,CDCl3)δ183.79,182.21,157.69,145.70,134.94,133.43,132.26,130.46,130.07,126.49,126.19,124.89,114.94,102.56,55.63.
example 4: synthesis of 2- (2-hydroxyphenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), o-nitrophenol (0.3mmol), zinc powder (1.5mmol,98mg), Co (OAc)24H2O (0.06mmol) was mixed with ethanol (0.6mL), to which was added acetic acid (4.5mmol,0.26mL), followed by stirring at room temperature for 5H. After completion of the reaction, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 1) to obtain 46.9mg of a red solid with a yield of 89%.
Characterization data: melting point 190-193 ℃,
1H NMR(400MHz,DMSO-d6)δ9.32(s,1H),8.03(d,J＝7.4Hz,1H),7.97–7.83(m,4H),7.83(t,J＝7.2Hz,1H),7.76(t,J＝7.3Hz,1H),7.44(d,J＝8.4Hz,2H),7.32(s,1H),6.24(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.88,181.46,167.24,145.39,141.00,134.94,132.82,132.44,130.43,130.27,128.72,126.22,125.33,122.34,103.37.
example 5: synthesis of 2- (4-hydroxyphenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), p-nitrophenol (0.36mmol,50.0mg), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with water (0.6mL), and after adding acetic acid (4.5mmol,0.26mL), the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 1) to obtain 58.8mg of a red solid in a yield of 74%.
Characterization data: melting point 240-,
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.06(s,1H),8.03(dd,J＝7.7,1.1Hz,1H),7.92(dd,J＝7.6,1.2Hz,1H),7.83(td,J＝7.5,1.4Hz,1H),7.75(td,J＝7.4,1.4Hz,1H),7.15(d,J＝8.7Hz,2H),6.91–6.73(m,2H),5.86(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.53,182.14,155.75,147.48,135.30,133.25,132.85,130.86,129.37,126.46,126.22,125.67,116.22,101.16.
example 6: synthesis of 2- (4-fluorophenylamino) -1, 4-naphthoquinone
Sequentially mixing 1, 4-naphthoquinone (0.3mmol,47.4mg), p-nitrofluorobenzene (0.36mmol,50.7mg), magnesium powder (1.5mmol), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with water (0.6mL), and after trifluoroacetic acid (4.5mmol) was added thereto, the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 44.0mg of a red solid in yieldThe content was 85%.
Characterization data: melting point 243-245 c,
1H NMR(400MHz,DMSO-d6)δ9.24(s,1H),8.05(d,J＝7.5Hz,1H),7.93(d,J＝7.5Hz,1H),7.82(m,1H),7.77(m,1H),7.41(m,2H),7.28(t,J＝8.8Hz,2H),5.98(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.78,181.74,158.42,146.82,135.16,134.59,132.89,132.81,130.65,126.36,126.32,126.23,125.53,116.45,116.22,101.97.
example 7: synthesis of 2- (3-chlorophenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), m-nitrochlorobenzene (0.6mmol), zinc powder (1.5mmol,98mg) and FeCl were sequentially added3(0.06mmol) was mixed with water (0.6mL), to which was added acetic acid (7.2 mmol), followed by stirring at room temperature for 5 h. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 62.9mg of a red solid with a yield of 74%.
Characterization data: melting point 155-,
1H NMR(400MHz,DMSO-d6)δ9.25(s,1H),8.00(d,J＝7.6Hz,1H),7.89(d,J＝7.6Hz,1H),7.76(m,2H),7.3(m,2H),7.20(m,1H),7.20(m,1H),6.10(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.90,181.41,145.79,139.90,135.00,133.57,132.88,132.45,130.97,130.44,126.25,125.38,124.88,123.21,121.92,103.13.
example 8: synthesis of 2- (2-bromophenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), o-nitrobromobenzene (0.36mmol,72.7mg), zinc powder (3.6mmol), Bi (OTf)3(0.06mmol) was mixed with water (0.6mL), and acetic acid (4.5mmol,0.26mL) was added thereto, followed by stirring at room temperature for 5 h. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 36.4mg of a red solid with a yield of 87%.
Characterization data: the melting point is 135-138 ℃,
1H NMR(400MHz,DMSO-d6)δ9.06(s,1H),8.05(d,J＝7.5Hz,1H),7.92(d,J＝7.5Hz,1H),7.84(t,J＝7.4Hz,1H),7.81–7.69(m,2H),7.56–7.38(m,2H),7.28(t,J＝7.4Hz,1H),5.41(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.47,181.30,146.80,136.39,135.17,133.58,132.93,132.63,130.39,129.15,128.85,128.35,126.26,125.54,120.67,102.97.HRMS(ESI)m/z calcd for C16H11BrNO2 +(M+H)+327.9968,found 327.9964.
example 9: synthesis of 2- (3-chloro-4-methylphenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), 2-chloro-4-nitrotoluene (0.6mmol), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with methylene chloride (0.6mL), and after adding acetic acid (4.5mmol,0.26mL), the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Then, filtering, concentrating under reduced pressure, and introducingSeparation was performed by column chromatography (petroleum ether: ethyl acetate 1:1) to give 33.9mg of a red solid, with a yield of 88%.
Characterization data: the melting point is 195-197 ℃,
1H NMR(400MHz,DMSO-d6)δ9.22(s,1H),8.01(dd,J＝7.6,1.0Hz,1H),7.90(dd,J＝7.6,1.1Hz,1H),7.78(m,2H),7.38(dd,J＝13.4,5.3Hz,2H),7.24(dd,J＝8.2,2.2Hz,1H),6.04(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.71,181.44,146.04,137.34,134.97,133.54,132.78,132.52,132.24,131.71,130.43,126.20,125.34,123.81,122.24,102.58,19.14.HRMS(ESI)m/z calcd for C17H13ClNO2 +(M+H)+298.0629,found 298.0633.
example 10: synthesis of 2- (4-methylthiophenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), methyl (4-nitrophenyl) sulfide (0.36mmol,60.9mg), zinc powder (1.5mmol,98mg), Cu (OAc)2H2O (0.06mmol) was mixed with water (0.6mL), to which was added acetic acid (3.6mmol,0.26mL), followed by stirring at room temperature for 5H. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 71.7mg of a red solid with a yield of 81%.
Characterization data: melting point 162-165 deg.c,
1H NMR(400MHz,CDCl3)δ8.96(d,J＝7.7Hz,2H),8.61(t,J＝7.6Hz,1H),8.52(t,J＝7.5Hz,1H),8.41(s,1H),8.16(d,J＝8.4Hz,2H),8.06(d,J＝8.5Hz,2H),7.22(s,1H),3.36(s,3H).
13C NMR(101MHz,CDCl3)δ183.87,182.08,144.75,135.92,135.03,134.74,133.32,132.44,130.43,127.98,126.62,126.26,123.22,103.47,16.29.HRMS(ESI)m/z calcd for C17H14NO2S+(M+H)+296.0740,found 296.0741.
example 11: synthesis of 2- (2-allyloxyphenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), o-allyloxynitrobenzene (0.36mmol,64.5mg), zinc powder (1.5mmol,98mg), La (OTf)3(0.06mmol) was mixed with hexafluoroisopropanol ((0.6mL), acetic acid (4.5mmol,0.26mL) was added thereto, and after stirring at room temperature for 5 hours, water was added to the reaction system to dilute it, followed by filtration, the filtrate was extracted with ethyl acetate (3 × 10mL), the organic phases were combined, washed with saturated brine in this order, dried over anhydrous sodium sulfate, followed by filtration, concentration under reduced pressure, and separation by column chromatography (petroleum ether: ethyl acetate: 5:1) gave 70.5mg of a red solid with a yield of 77%.
Characterization data: the melting point is between 83 and 85 ℃,
1H NMR(400MHz,DMSO-d6)δ8.71(s,1H),8.04(d,J＝7.5Hz,1H),7.93(d,J＝7.5Hz,1H),7.84(t,J＝7.4Hz,1H),7.77(t,J＝7.4Hz,1H),7.37(d,J＝7.7Hz,1H),7.22(t,J＝7.7Hz,1H),7.15(d,J＝8.1Hz,1H),7.03(t,J＝7.5Hz,1H),6.07–5.90(m,1H),5.82(s,1H),5.38(d,J＝17.2Hz,1H),5.22(d,J＝10.5Hz,1H),4.64(d,J＝4.6Hz,2H).
13C NMR(101MHz,DMSO-d6)δ182.18,181.39,150.86,145.11,134.89,133.13,132.54,130.10,126.53,126.30,126.04,125.24,123.92,120.97,117.07,113.22,102.67,68.48.HRMS(ESI)m/z calcd for C19H16NO3 +(M+H)+306.1125,found 306.1121.
example 12: synthesis of 2- (2-propargyloxyphenylamino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), o-propargyloxynitrobenzene (0.12mmol), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with tetrahydrofuran (0.6mL), and after adding acetic acid (4.5mmol,0.26mL), the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 62.7mg of a red solid with a yield of 69%.
Characterization data: the melting point is 82-86 ℃,
1H NMR(400MHz,CDCl3)δ8.12(t,J＝7.7Hz,2H),7.95(s,1H),7.75(t,J＝7.5Hz,1H),7.67(t,J＝7.5Hz,1H),7.45(dd,J＝7.9,1.4Hz,1H),7.21–6.97(m,3H),6.48(s,1H),4.81(d,J＝2.4Hz,2H),2.56(t,J＝2.4Hz,1H).
13C NMR(101MHz,CDCl3)δ184.30,182.31,149.49,144.30,135.10,133.52,132.63,130.78,127.82,126.85,126.41,125.66,122.26,121.84,113.41,104.03,56.86.HRMS(ESI)m/z calcd for C19H14NO3 +(M+H)+304.0968,found 304.0963.
example 13: reaction of 1, 4-naphthoquinone with o-nitrobenzamide
Compound 1, 4-naphthoquinone (0.3mmol,47.4mg), o-nitrobenzamide (0.36mmol,59.8mg), iron powder (7.2), Pd (OAc)2(0.06mmol) and water (0.6mL) were mixed in this order, acetic acid (0.36mmol) was added thereto, and the mixture was stirred at room temperature for 5 hours. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 1) to obtain 53.4mg of a red solid with a yield of 91%.
Characterization data: melting point 166-,
1H NMR(400MHz,DMSO-d6)δ9.32(s,1H),8.04(d,J＝7.5Hz,1H),7.98–7.85(m,4H),7.84(t,J＝7.4Hz,1H),7.76(t,J＝7.4Hz,1H),7.44(d,J＝8.3Hz,2H),7.32(s,1H),6.24(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.98,181.55,167.32,145.49,141.08,135.04,132.92,132.54,130.52,130.36,128.80,126.31,125.42,122.43,103.47.HRMS(ESI)m/z calcd for C17H13ClNO2 +(M+H)+293.0921,found 293.0912.
example 14: synthesis of 2- (naphthalene-1-amino) -1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), 1-nitronaphthalene (0.36mmol,62.3mg), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with isopropanol (0.6mL), to which was added acetic acid (4.5mmol,0.26mL), followed by stirring at room temperature for 5 h. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 1) to obtain 28.7mg of a red solid with a yield of 82%.
Characterization data: melting point 155-,
1H NMR(400MHz,CDCl3)δ8.18(dd,J＝7.7,1.2Hz,1H),8.10(dd,J＝7.5,1.1Hz,1H),8.00–7.87(m,2H),7.85–7.72(m,3H),7.69(td,J＝7.5,1.4Hz,1H),7.62–7.44(m,4H),6.01(s,1H).
13C NMR(101MHz,CDCl3)δ183.80,182.17,146.48,134.92,134.52,133.32,132.85,132.33,130.46,128.74,127.39,126.98,126.74,126.48,126.20,125.58,122.42,121.74.
example 15: synthesis of 2- (quinoline-6-amino) -1, 4-naphthoquinone
The compounds 1, 4-naphthoquinone (0.3mmol,47.4mg), 6-nitroquinoline (0.36mmol,62.6mg), magnesium powder (1.5mmol,98mg), FeCl were sequentially added3(0.06mmol,13.1mg) was mixed with water (0.6mL), and after formic acid (4.5mmol) was added thereto, the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 1) to obtain 45.9mg of a red solid with a yield of 81%.
Characterization data: the melting point is 190 ℃ and 192 ℃,
1H NMR(400MHz,DMSO-d6)δ11.99(s,1H),9.49(s,1H),8.85(dd,J＝4.1,1.2Hz,1H),8.40(d,J＝8.3Hz,1H),8.12–8.01(m,2H),7.99–7.90(m,2H),7.90–7.72(m,3H),7.53(dd,J＝8.3,4.2Hz,1H),6.39(s,1H).
13C NMR(101MHz,DMSO-d6)δ182.94,181.50,149.97,145.61,145.21,138.74,136.32,135.74,134.95,132.80,132.51,130.45,130.02,128.34,126.55,126.23,125.35,122.01,119.57,102.96.HRMS(ESI)m/z calcd for C19H13N2O2 +(M+H)+301.0972,found 301.0979.
example 16: synthesis of 2-methylamino-1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), nitromethane (0.36mmol,21.9mg), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with isopropanol (0.6mL), and after adding acetic acid (4.5mmol,0.26mL), the mixture was stirred at room temperature for 5 h. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 26.3mg of a yellow solid with a yield of 87%.
Characterization data: melting point 225-,
1H NMR(400MHz,DMSO-d6)δ7.94(dd,J＝11.9,7.8Hz,2H),7.80(t,J＝7.4Hz,1H),7.75–7.56(m,2H),5.57(s,1H),2.77(d,J＝5.0Hz,3H).
13C NMR(101MHz,DMSO-d6)δ181.34,180.99,149.40,134.69,133.19,131.98,130.27,125.74,125.26,99.08,28.80.
example 17: synthesis of 2-n-octylamino-1, 4-naphthoquinone
The compound 1, 4-naphthoquinone (0.3mmol,47.4mg), 1-nitro-n-octane (0.36mmol,57.3mg), zinc powder (0.36mmol), Zn (OTf)2(0.06mmol) was mixed with water (0.6mL), to which was added acetic acid (4.5mmol,0.26mL), followed by stirring at room temperature for 5 h. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 35.1mg of a yellow solid in a yield of 91%.
Characterization data: melting point of 100-,
1H NMR(400MHz,CDCl3)δ8.08(dd,J＝7.7,0.5Hz,1H),8.01(d,J＝7.7Hz,1H),7.70(dd,J＝11.0,4.1Hz,1H),7.62–7.51(m,1H),5.92(s,1H),5.71(s,1H),3.15(dd,J＝13.2,6.8Hz,2H),1.75–1.58(m,2H),1.42–1.11(m,11H),0.86(t,J＝6.8Hz,3H).
13C NMR(101MHz,CDCl3)δ182.96,182.01,148.02,134.81,133.75,131.96,130.55,126.30,126.22,100.72,42.67,31.83,29.30,29.25,28.30,27.12,22.71,14.18.
example 18: synthesis of 2-chloro-3-phenylamino-1, 4-naphthoquinone
The compound 2-chloro-1, 4-naphthoquinone (0.3mmol,57.7mg), nitrobenzene ((1.2mmol), zinc powder (1.5mmol,98mg), Zn (OAc)2·2H2O (0.06mmol,13.1mg) was mixed with dioxane (0.6mL), and acetic acid (4.5mmol,0.26mL) was added thereto, followed by stirring at room temperature for 5 h. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 74.0mg of a red solid with a yield of 87%.
Characterization data: melting point 213-215 ℃,
1H NMR(400MHz,CDCl3)δ8.19(d,J＝7.5Hz,1H),8.12(d,J＝7.5Hz,1H),7.84–7.72(m,1H),7.69(t,J＝7.0Hz,2H),7.36(t,J＝7.8Hz,2H),7.22(t,J＝7.4Hz,1H),7.09(d,J＝7.8Hz,2H).
13C NMR(101MHz,CDCl3)δ180.70,137.55,135.19,133.12,132.75,130.02,128.57,127.22,125.79,124.42,77.48,77.16,76.84.
example 19: synthesis of 2-chloro-3-phenylamino-1, 4-naphthoquinone
The compound 2-bromo-1, 4-naphthoquinone (0.3mmol,71.1mg), nitrobenzene (0.36mmol,44.3mg), zinc powder (1.5mmol,98mg), Cu (OAc)2H2O (0.06mmol) was mixed with acetonitrile (0.6mL), to which was added acetic acid (4.5mmol,0.26mL), followed by stirring at room temperature for 5H. After completion, the reaction mixture was diluted with water, filtered, and the filtrate was extracted with ethyl acetate (3X 10 mL). The organic phases were combined, washed successively with saturated brine and dried over anhydrous sodium sulfate. Subsequently, the mixture was filtered, concentrated under reduced pressure, and separated by column chromatography (petroleum ether: ethyl acetate: 5:1) to obtain 87.6mg of a red solid, which was 89% in yield.
Characterization data: melting point 160-,
1H NMR(400MHz,DMSO-d6)δ9.25(s,1H),8.00(d,J＝7.6Hz,2H),7.89–7.70(m,2H),7.28(t,J＝7.8Hz,2H),7.10(t,J＝8.0Hz,3H).
13C NMR(101MHz,DMSO-d6)δ179.85,176.83,145.82,138.98,134.85,133.28,131.84,130.34,128.12,126.73,126.48,124.55,124.33,107.69.
Claims (2)
1. a method for synthesizing 2-substituted amino-1, 4-naphthoquinone derivatives is characterized in that: uniformly mixing a nitro compound, a compound I, a catalyst, metal and a solvent at the temperature of 20-100 ℃, adding a hydrogen source, stirring for reacting for 1-24h, and separating and purifying;
the structural formula of the compound I is as follows:
the structural formula of the nitro compound is as follows:
The reaction formula is as follows:
the catalyst is Cu (OAc)2•H2O、FeCl3、Zn(OAc)2•2H2O、Zn(OTf)2、Pd(OAc)2、La(OTf)3、Bi(OTf)3、Co(OAc)2•4H2A mixture of one or more of O;
the metal is one of zinc powder, iron powder and magnesium powder;
the hydrogen source is one of glacial acetic acid, trifluoroacetic acid and formic acid;
the solvent is one of methanol, ethanol, isopropanol, hexafluoroisopropanol, water, tetrahydrofuran, dioxane, acetonitrile, ethyl acetate and dichloromethane.
2. The method for synthesizing a 2-substituted amino-1, 4-naphthoquinone derivative according to claim 1, wherein: the molar ratio of the compound I to the nitro compound is 1: 1-2, the molar ratio of the metal to the nitro compound is 1-20: 1, the molar ratio of the hydrogen source to the nitro compound is 1-20: 1, the molar ratio of the catalyst to the nitro compound is 1: 2-20.
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| Intramolecular Michael-type addition of azadienes to 1,4-naphthoquinones instead of Aza-Diels–Alder cycloaddition:a synthesis of ascididemin;Antonio M. Echavarren等;《J. Chem. Soc., Perkin Trans.1》;20021231;第1360-1365页 * |
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