CN111732516A - 一种n-芳基取代杂环化合物的制备方法 - Google Patents
一种n-芳基取代杂环化合物的制备方法 Download PDFInfo
- Publication number
- CN111732516A CN111732516A CN202010757079.8A CN202010757079A CN111732516A CN 111732516 A CN111732516 A CN 111732516A CN 202010757079 A CN202010757079 A CN 202010757079A CN 111732516 A CN111732516 A CN 111732516A
- Authority
- CN
- China
- Prior art keywords
- group
- aryl
- substituted heterocyclic
- preparation
- heterocyclic compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 238000004440 column chromatography Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- -1 amine compounds Chemical class 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000001412 amines Chemical class 0.000 claims abstract description 6
- 150000002828 nitro derivatives Chemical class 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical class 0.000 claims abstract description 3
- 238000010791 quenching Methods 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical compound O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 claims description 2
- OTYYBJNSLLBAGE-UHFFFAOYSA-N CN1C(CCC1)=O.[N] Chemical compound CN1C(CCC1)=O.[N] OTYYBJNSLLBAGE-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- AFTRVMGRCSLGAF-UHFFFAOYSA-N acetamide;n,n-dimethylformamide Chemical compound CC(N)=O.CN(C)C=O AFTRVMGRCSLGAF-UHFFFAOYSA-N 0.000 claims 1
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- SFDJOSRHYKHMOK-UHFFFAOYSA-N nitramide Chemical compound N[N+]([O-])=O SFDJOSRHYKHMOK-UHFFFAOYSA-N 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 30
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 abstract description 20
- 238000000034 method Methods 0.000 abstract description 14
- 239000003208 petroleum Substances 0.000 abstract description 10
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 abstract description 9
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052723 transition metal Inorganic materials 0.000 abstract description 4
- 150000003624 transition metals Chemical class 0.000 abstract description 4
- 239000006227 byproduct Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000005808 aromatic amination reaction Methods 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 238000005576 amination reaction Methods 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000005839 oxidative dehydrogenation reaction Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- JKZHCODDKJYEQX-UHFFFAOYSA-N 1-(4-nitrophenyl)-3,4-dihydro-2H-quinoline Chemical compound [O-][N+](=O)c1ccc(cc1)N1CCCc2ccccc12 JKZHCODDKJYEQX-UHFFFAOYSA-N 0.000 description 1
- HZONRRHNQILCNO-UHFFFAOYSA-N 1-methyl-2h-pyridine Chemical class CN1CC=CC=C1 HZONRRHNQILCNO-UHFFFAOYSA-N 0.000 description 1
- RJKGJBPXVHTNJL-UHFFFAOYSA-N 1-nitronaphthalene Chemical class C1=CC=C2C([N+](=O)[O-])=CC=CC2=C1 RJKGJBPXVHTNJL-UHFFFAOYSA-N 0.000 description 1
- RUKISNQKOIKZGT-UHFFFAOYSA-N 2-nitrodiphenylamine Chemical compound [O-][N+](=O)C1=CC=CC=C1NC1=CC=CC=C1 RUKISNQKOIKZGT-UHFFFAOYSA-N 0.000 description 1
- OJDLVTDZALFNGV-UHFFFAOYSA-N 3-methyl-N-(4-nitrophenyl)-N-phenylaniline Chemical compound CC1=CC=CC(N(C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 OJDLVTDZALFNGV-UHFFFAOYSA-N 0.000 description 1
- LMPVRWVQOMNVKC-UHFFFAOYSA-N 3-methyl-n-(4-nitrophenyl)aniline Chemical compound CC1=CC=CC(NC=2C=CC(=CC=2)[N+]([O-])=O)=C1 LMPVRWVQOMNVKC-UHFFFAOYSA-N 0.000 description 1
- UQOKZDUUBVGFAK-UHFFFAOYSA-N 4-nitro-n,n-diphenylaniline Chemical compound C1=CC([N+](=O)[O-])=CC=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 UQOKZDUUBVGFAK-UHFFFAOYSA-N 0.000 description 1
- XXYMSQQCBUKFHE-UHFFFAOYSA-N 4-nitro-n-phenylaniline Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC1=CC=CC=C1 XXYMSQQCBUKFHE-UHFFFAOYSA-N 0.000 description 1
- YVVDXLGQZPTNEZ-UHFFFAOYSA-N 6-methyl-1-(4-nitrophenyl)-3,4-dihydro-2H-quinoline Chemical compound CC1=CC2=C(C=C1)N(CCC2)C3=CC=C(C=C3)[N+](=O)[O-] YVVDXLGQZPTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 1
- DAGBDYNZYXKKRR-UHFFFAOYSA-N CC(C=C(C=C1)[N+]([O-])=O)=C1N(C)C1=CC=CC=C1 Chemical compound CC(C=C(C=C1)[N+]([O-])=O)=C1N(C)C1=CC=CC=C1 DAGBDYNZYXKKRR-UHFFFAOYSA-N 0.000 description 1
- XLNKESOXYDUVTE-UHFFFAOYSA-N CCN(C1=CC=C(C)C=C1)C(C=C1)=CC=C1[N+]([O-])=O Chemical compound CCN(C1=CC=C(C)C=C1)C(C=C1)=CC=C1[N+]([O-])=O XLNKESOXYDUVTE-UHFFFAOYSA-N 0.000 description 1
- GLYZGBIYLJHQJQ-UHFFFAOYSA-N CN(C(C=C1)=CC=C1[N+]([O-])=O)C(C=CC=C1)=C1F Chemical compound CN(C(C=C1)=CC=C1[N+]([O-])=O)C(C=CC=C1)=C1F GLYZGBIYLJHQJQ-UHFFFAOYSA-N 0.000 description 1
- QRIIFPSJMHNFID-UHFFFAOYSA-N CN(C(C=C1)=CC=C1[N+]([O-])=O)C1=CC(Br)=CC=C1 Chemical compound CN(C(C=C1)=CC=C1[N+]([O-])=O)C1=CC(Br)=CC=C1 QRIIFPSJMHNFID-UHFFFAOYSA-N 0.000 description 1
- QYONTRMWYPIOFR-UHFFFAOYSA-N CN(C(C=C1)=CC=C1[N+]([O-])=O)C1=CC(Cl)=CC=C1 Chemical compound CN(C(C=C1)=CC=C1[N+]([O-])=O)C1=CC(Cl)=CC=C1 QYONTRMWYPIOFR-UHFFFAOYSA-N 0.000 description 1
- ARSHTOVNACGQEG-UHFFFAOYSA-N CN(C1=CC=CC=C1)C(C=C1)=CC(Cl)=C1[N+]([O-])=O Chemical compound CN(C1=CC=CC=C1)C(C=C1)=CC(Cl)=C1[N+]([O-])=O ARSHTOVNACGQEG-UHFFFAOYSA-N 0.000 description 1
- PLWQMOLJWPSHFD-UHFFFAOYSA-N COC1=CC=CC(N(C)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 Chemical compound COC1=CC=CC(N(C)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 PLWQMOLJWPSHFD-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- SBBCVKIPRFRFON-UHFFFAOYSA-N N,4-dimethyl-N-(4-nitrophenyl)aniline Chemical compound C=1C=C([N+]([O-])=O)C=CC=1N(C)C1=CC=C(C)C=C1 SBBCVKIPRFRFON-UHFFFAOYSA-N 0.000 description 1
- ZBIUDUGTFMNNDR-UHFFFAOYSA-N N-(4-fluorophenyl)-N-methyl-4-nitroaniline Chemical compound CN(c1ccc(F)cc1)c1ccc(cc1)[N+]([O-])=O ZBIUDUGTFMNNDR-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- JBKYEFPEDCZWGQ-UHFFFAOYSA-N n-ethyl-4-nitro-n-phenylaniline Chemical compound C=1C=C([N+]([O-])=O)C=CC=1N(CC)C1=CC=CC=C1 JBKYEFPEDCZWGQ-UHFFFAOYSA-N 0.000 description 1
- GRJOQWGGWXHXQQ-UHFFFAOYSA-N n-methyl-2,4-dinitro-n-phenylaniline Chemical compound C=1C=C([N+]([O-])=O)C=C([N+]([O-])=O)C=1N(C)C1=CC=CC=C1 GRJOQWGGWXHXQQ-UHFFFAOYSA-N 0.000 description 1
- FVFQVUSECGNYPG-UHFFFAOYSA-N n-methyl-4-nitro-n-phenylaniline Chemical compound C=1C=C([N+]([O-])=O)C=CC=1N(C)C1=CC=CC=C1 FVFQVUSECGNYPG-UHFFFAOYSA-N 0.000 description 1
- DUBLUHJLPAQLQK-UHFFFAOYSA-N n-methyl-n-(4-nitrophenyl)pyridin-2-amine Chemical compound C=1C=CC=NC=1N(C)C1=CC=C([N+]([O-])=O)C=C1 DUBLUHJLPAQLQK-UHFFFAOYSA-N 0.000 description 1
- SPDMXSGGASSBLX-UHFFFAOYSA-N n-methyl-n-(4-nitrophenyl)pyridin-4-amine Chemical compound C=1C=C([N+]([O-])=O)C=CC=1N(C)C1=CC=NC=C1 SPDMXSGGASSBLX-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/02—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of hydrogen atoms by amino groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及有机化学合成技术领域，具体涉及一种N‑芳基取代杂环化合物的制备方法，是以碱为促进剂，有机溶剂条件下，胺类化合物和硝基类衍生物，以1:1~1:3的摩尔比，在常温常压下反应30‑60分钟；反应结束后加水淬灭，有机溶剂萃取，柱层析分离(V石油醚:V乙酸乙酯=40:1~20:1)，得到N‑芳基取代杂环衍生物。本发明利用硝基苯作为Ar‑H来源，N‑甲基苯胺、N‑乙基苯胺、N‑甲基杂环、四氢喹啉等都可以作为胺源，在t‑BuONa/DMSO/O2体系下，实现芳环的直接芳胺化反应。这种方法有以下优点：方法简单，高的原子经济性，避免使用了昂贵的过渡金属，温和的反应条件，产生的是环境友好的副产物。
Description
技术领域
本发明属于有机化学合成技术领域，涉及一种N-芳基取代杂环化合物的制备方法。
背景技术
N-芳基取代杂环化合物是很多天然产物和药物的重要结构单元(Hili R, YudinA K. Nat. Chem. Boil.2006, 2(6): 284-287)，另外，这些化合物可以用来制备配体，人工染料，电子材料和光学材料(Lawrence, S. A. Cambridge University Press,Cambridge, 2004; pp 265-305)。因此，发展了很多种合成N-芳基取代杂环化合物的方法。在这些方法中，最经典的方法是Ullmann偶联(Ullmann F. Ueber eine neueBildungsweise von Diphenylaminderivaten[J]. Ber. Deut. Chem. Ges.1903, 36(2):2382-2384) 和Buchwald-Hartwig 偶联(Guram A S, Buchwald S L. J. Am. Chem. Soc.1994, 116(17): 7901-7902; Paul F, Patt J, Hartwig J. F. J. Am. Chem. Soc.1994, 116(13): 5969-5970; Shekhar S, Ryberg P, Hartwig J F, et al. J. Am. Chem. Soc. 2006, 128(11): 3584-3591)。这些方法的缺点是需要预制备芳基卤化物或者芳基硼酸酯，同时会产生卤化氢或者硼酸副产物，不利于原子经济性。而CDC偶联胺化反应可以很好的解决这一问题，CDC偶联胺化反应是Ar-H键和N-H键直接偶联，不需要预官能团化。在过去的几十年中，直接Ar-Ｈ胺化构建N-芳基化合物的研究主要集中在铱，钯，铁，铜，钴，银，锰等过渡金属催化( Park Y, Kim Y, Chang S. Chem. Rev. 2017,117, 9247-9301; Cho S H, Kim J Y, Kwak J, Chang S. Chem. Soc. Rev. 2011,40, 5068; YuanJ, Liu C, Lei A. Chem. Commun. 2015,51, 1394-1409; Kim H, Chang S. ACS Catal. 2016,6, 2341-2351)。这种方法是过渡金属在导向基的辅助下插入Ar-H键形成稳定的环状金属络合中间体，接着和胺源反应生成含Ｃ-Ｎ键的目标产物。
尽管过渡金属催化的Ar-H直接胺基化反应广泛应用，但是也存在一系列的缺点，例如：1) 需要用到昂贵的配体和催化剂，有时需要一些添加剂；2）需要较苛刻的条件（高温或者是长时间反应）；3）产生重金属污染，尤其是在合成对重金属含量要求较高的化合物时；4）反应底物中导向基团的去除是较大的难题。通过文献调研我们发现，无金属催化的Ar-H 和N-H 直接偶联的CDC反应研究较少，仍然存在很大的挑战性和研究价值。
发明内容
本发明的目的在于提供一种非金属条件下直接氧化脱氢偶联（CDC）制备N-芳基取代杂环化合物的制备方法，利用硝基苯作为Ar-H来源，N-甲基苯胺、N-乙基苯胺、N-甲基杂环、四氢喹啉等都可以作为胺源，在t-BuONa/DMSO/O2体系下，实现芳环的直接芳胺化反应。这种方法有以下优点：方法简单，高的原子经济性，避免使用了昂贵的过渡金属，温和的反应条件，产生的是环境友好的副产物。
本发明所述的N-芳基取代杂环化合物的制备方法，是以碱为促进剂，有机溶剂条件下，胺类化合物和硝基类化合物，以1:1~1:3的摩尔比，在常温常压下反应30-60分钟；反应结束后加水淬灭，有机溶剂萃取，柱层析分离(V石油醚:V乙酸乙酯 = 40:1~20:1)，得到N-芳基取代杂环衍生物。
进一步地，所述胺类化合物为N-烷基或N-芳基苯胺衍生物、1,2,3,4-四氢喹啉衍生物、吲哚啉衍生物、苯胺衍生物或N-甲基吡啶衍生物，结构式为：
其中，X = C（碳）或N（氮）；
R1、R2、R3、R4、R5和R6为氢、C1～C40的脂肪基团（如甲基、乙基、丙基、异丙基、丁基、苄基）、C4～C60内的芳香基团（吡啶衍生物基、苯基、取代苯基、1-萘基、2-萘基）、烷氧基、羟基、硝基、胺基或者卤素（氟、氯、溴，碘）。
进一步地，所述硝基类化合物的结构式为：
R7和R8为氢、C1～C40的脂肪基团（如甲基、乙基、丙基、异丙基、丁基、苄基）、C4～C60内的芳香基团（吡啶衍生物基、苯基、取代苯基、1-萘基、2-萘基）、烷氧基、羟基、硝基、胺基或者卤素（氟、氯、溴，碘）。
进一步地，所述的促进剂碱为t-BuONa、t-BuOK、KOH、NaOH或K2CO3，促进剂的用量为胺类衍生物摩尔量的1-3倍。
进一步地，所述的有机溶剂可采用DMF(N,N-二甲基甲酰胺)、DMA(N,N-二甲基乙酰胺)、DMSO(二甲基亚砜)、NMP(氮甲基吡咯烷酮)、CH2Cl2(二氯甲烷)、CHCl3(氯仿)、CCl4(四氯化碳)、1,2-二氯乙烷、1,4-二氧六环、乙腈、乙醚、DME(乙二醇二甲醚)或THF(四氢呋喃)等。
本发明N-芳基取代杂环化合物的合成通式为：
本发明相对于现有技术具有以下优点：
1、本发明在碱为促进剂的促进下，由胺类衍生物与硝基苯或硝基萘类衍生物进行反应，通过直接氧化脱氢偶联（CDC）的方法，一步即可高效得N-芳基取代杂环化合物，该反应原料及促进剂廉价易得，合成工艺简单。
2、反应条件温和，室温及空气条件下就能反应，产率优良（可达83%）；
3、反应迅速，30-60分钟类反应完毕。
4、反应能实现克级制备。
具体实施方式
下面通过具体实施例对本发明作进一步说明。
实施例1： 3a-3h制备。
将N-甲基苯胺类化合物1a-1h (0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯2a (184.5 mg, 1.5 mmol)，加入2.0 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 = 20/1），得到纯品N-甲基二苯基衍生物3a-3h。
其合成路线如下：
N-methyl-4-nitro-N-phenylaniline：3a
黄色固体，产率为83%； 1H NMR (400 MHz, CDCl3) δ 7.98 -7.92 (m, 2H), 7.36(t, J = 7.8 Hz, 2H), 7.21 (t, J = 7.4 Hz, 1H), 7.16 -7.11 (m, 2H), 6.57 (dd,J = 7.3, 5.3 Hz, 2H), 3.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.7, 146.3,138.0, 130.2, 126.7, 126.6, 125.7, 112.3, 40.5.
4-fluoro-N-methyl-N-(4-nitrophenyl) aniline: 3b
黄色固体，产率为75%；1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 9.3 Hz, 2H),7.31 - 7.10 (m,4H), 6.62 (d, J = 9.3 Hz, 2H), 3.38 (s, 1H). 13C NMR (100 MHz,CDCl3) δ 160.6 (d, J = 245.7Hz), 153.4, 142.0, 137.9, 128.22 (d, J = 8.4 Hz),125.3, 116.6(d, J = 22.6 Hz), 111.8, 40.1.
N,4-dimethyl-N-(4-nitrophenyl) aniline: 3c
黄色固体，68%；1H NMR (400 MHz, CDCl3) δ 8.14 (dd, J = 7.3, 2.1 Hz, 2H),7.40-7.32 (m, 2H), 7.25-7.17 (m, 2H), 6.73 (dd, J = 7.4, 2.0 Hz, 2H), 3.47(s, 3H), 2.49 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 154.0, 143.8, 138.0, 136.8,130.8, 126.6, 125.8, 112.2, 40.5, 21.1.
3-chloro-N-methyl-N-(4-nitrophenyl)aniline：3d
黄色固体，白色固体，产率为73%；1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 9.3Hz, 2H), 7.38 (t, J = 8.0 Hz, 1H), 7.30-7.22 (m, 2H), 7.15 (dd, J = 8.0, 0.9Hz, 1H), 6.72 (d, J = 9.3 Hz, 2H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ153.3, 147.7, 138.8, 135.5, 131.2, 126.7, 126.6, 125.8, 124.6, 113.3, 40.5.
3-bromo-N-methyl-N-(4-nitrophenyl) aniline: 3e
黄色固体，产率为76%；1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 9.3 Hz, 2H),7.40 (m, 2H), 7.31 (t, J = 7.9 Hz, 1H), 7.18 (dd, J = 8.0, 0.8 Hz, 1H), 6.72(d, J = 9.3 Hz, 2H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 152.8, 147.3,138.5, 130.9, 129.1, 129.0, 125.3, 124.5, 122.9, 112.8, 40.0.
3-methoxy-N-methyl-N-(4-nitrophenyl) aniline: 3f
黄色固体，产率为71%；1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 9.2 Hz, 2H),7.36 (t, J = 8.1 Hz, 1H), 6.83 (m, 2H), 6.76 (s, 1H), 6.69 (d, J = 9.2 Hz,2H), 3.82 (s, 3H), 3.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 160.6, 153.2,147.1, 137.8, 130.4, 125.3, 118.2, 112.1, 111.9, 111.8, 55.0, 40.0.
3-methyl-N-(4-nitrophenyl)aniline: 3g
黄色固体， 产率为72%；1H NMR (400 MHz, CDCl3) δ 8.11- 8.00 (m, 2H), 7.35(t, J = 7.7 Hz, 1H), 7.10 (m, 3H), 6.74-6.62 (m, 2H), 3.40 (s, 3H), 2.40 (s,3H). 13C NMR (100 MHz, CDCl3) δ 154.0, 146.4, 140.4, 138.0, 130.1, 127.8,127.4, 125.9, 123.8, 112.4, 40.6, 21.5.
2-fluoro-N-methyl-N-(4-nitrophenyl) aniline: 3h
黄色固体，产率为42%；1H NMR (400 MHz, CDCl3) δ 8.04 (t, J = 6.3 Hz, 2H),7.40-7.07 (m, 4H), 6.58 (d, J = 9.3 Hz, 2H), 3.34 (s, 3H). 13C NMR (100 MHz,CDCl3) δ 158.5 (d, J = 249.5 Hz), 153.3, 138.6, 133.21 (d, J = 12.1 Hz),129.5, 128.9 (d, J = 7.8 Hz), 125.7, 125.4 (d, J = 3.4 Hz), 117.4 (d, J =19.9 Hz), 111.8, 39.8.
实施例2： 3i, 3j的制备。
将N-乙基苯胺类化合物1i、1j (0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯2a (184.5 mg, 1.5 mmol)，加入2.0 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 = 20/1），得到纯品N-甲基二苯基衍生物3i, 3j。
其合成路线如下：
N-ethyl-4-nitro-N-phenylaniline: 3i
N-ethyl-4-methyl-N-(4-nitrophenyl)aniline: 3j
实施例3： 3k, 3l制备。
将N, N-二苯基胺类化合物1k, 1l (0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯2a (184.5 mg, 1.5 mmol)，加入2.0 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 =20/1），得到纯品N-甲基二苯基衍生物3k, 3l.
其合成路线如下：
4-nitro-N,N-diphenylaniline: 3k
黄色固体，产率为67%；1H NMR (400 MHz, CDCl3) δ 8.05 (t, J = 6.3 Hz, 2H),7.39 (t, J = 7.8 Hz, 4H), 7.28 -7.18 (m, 6H), 6.94 (t, J = 6.3 Hz, 2H). 13CNMR (100 MHz, CDCl3) δ 153.6, 145.8, 140.3, 130.1, 126.7, 125.9, 125.6,118.3.
3-methyl-N-(4-nitrophenyl)-N-phenylaniline: 3l
黄色固体，产率为42%；1H NMR (400 MHz, CDCl3) δ 8.03 (t, J = 6.2 Hz, 2H),7.37 (t, J = 7.8 Hz, 2H), 7.29-7.16 (m, 4H), 7.01 (m, 3H), 6.91 (d, J = 9.3Hz, 2H), 2.32 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.1,145.2, 145.1, 139.5,129.4, 129.2, 126.7, 126.2, 126.0, 125.2, 124.9, 123.3, 117.5, 20.85.
实施例4：3o, 3p的制备。
将1,2,3,4-四氢喹啉类化合物1o, 1p (0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯2a (184.5 mg, 1.5 mmol)，加入2.0 mL二甲亚砜中（DMSO），室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯=20/1），得到纯品N-甲基二苯基衍生物3o, 3p.
其合成路线如下：
1-(4-nitrophenyl)-1,2,3,4-tetrahydroquinoline: 3o
黄色固体，产率为63%；1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 9.2 Hz, 2H),7.23 (d, J = 8.1 Hz, 1H), 7.18 (d, J = 9.4 Hz, 3H), 7.11 (t, J = 7.6 Hz, 1H),6.99 (t, J = 7.4 Hz, 1H), 3.71 (t, J = 6.3 Hz, 2H), 2.77 (t, J = 6.3 Hz, 2H),2.05 (dd, J = 12.6, 6.3 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 153.4, 140.6,134.0, 131.0, 129.3, 126.5, 125.5, 123.0, 120.6，117.3, 48.8, 27.2, 24.1.
6-methyl-1-(4-nitrophenyl)-1,2,3,4-tetrahydroquinoline: 3p
黄色固体，产率为66%；1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 9.3 Hz, 2H),7.21-7.12 (m, 3H), 7.01 (s, 1H), 6.96 (d, J = 8.2 Hz, 1H), 3.71 (t, J = 6.3Hz, 2H), 2.74 (t, J = 6.3 Hz, 2H), 2.34 (s, 3H), 2.05 (dd, J = 12.6, 6.3 Hz,2H). 13C NMR (100 MHz, CDCl3) δ 153.5, 139.6, 137.9, 132.8, 131.3, 129.7,127.1, 125.5, 120.9, 116.7, 48.7, 27.1, 24.2, 20.8.
实施例5：3q, 3r的制备。
将N-甲基吡啶类化合物1q, 1r(0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯2a (184.5 mg, 1.5 mmol)，加入2.0 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 = 20/1），得到纯品N-甲基二苯基衍生物3q, 3r.
其合成路线如下：
N-methyl-N-(4-nitrophenyl)pyridin-2-amine: 3q
黄色固体，产率为85%；1H NMR (400 MHz, CDCl3) δ 8.41 (dd, J = 4.8, 1.1 Hz,1H), 8.19 -8.12 (m, 2H), 7.63 (td, J = 8.4, 1.9 Hz, 1H), 7.26-7.16 (m, 2H),7.11 (d, J = 8.3 Hz, 1H), 6.98 (dd, J = 7.0, 5.2 Hz, 1H), 3.59 (s, 3H). 13CNMR (100 MHz, CDCl3) δ 157.7, 152.6, 149.0, 141.4, 138.0, 125.5, 119.0,118.4, 115.0 , 38.3.
N-methyl-N-(4-nitrophenyl)pyridin-4-amine: 3r
黄色固体，产率为71%；1H NMR (400 MHz, CDCl3) δ 8.43 (m, 2H), 8.20 (d, J =9.1 Hz, 2H), 7.23 (d, J = 9.1 Hz, 2H), 6.93 (d, J = 4.8 Hz, 2H), 3.45 (s,3H). 13C NMR (100 MHz, CDCl3) δ 152.9, 152.0, 150.8, 142.7, 125.5, 121.2,113.6, 39.5.
实施例6：3s, 3s′的制备。
将苯胺1s (0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯2a (184.5 mg, 1.5mmol)，加入2.0 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 = 20/1），得到纯品N, N二苯基衍生物3s, 3s′.
其合成路线如下：
4-nitro-N-phenylaniline: 3s
黄色固体，产率为36%；1H NMR (400 MHz, DMSO) δ 9.47 (s, 1H), 8.17 (d, J =8.6 Hz, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.33 (t, J = 7.8 Hz, 1H), 7.27-7.17(m, 4H), 6.79-6.70 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 143.1, 138.8, 135.6,129.7, 126.7, 125.7, 124.4, 117.5, 116.1.
2-nitro-N-phenylaniline: 3s′
黄色固体，产率为10%；1H NMR (400 MHz, CDCl3) δ 8.17-8.09 (m, 2H), 7.45-7.36(m, 2H), 7.22-7.16 (m, 3H), 7.00-6.91 (m, 2H), 6.35 (s, 1H). 13C NMR (100 MHz,CDCl3) δ 150.2, 139.8, 139.5, 129.8, 126.2, 124.7, 122.0, 113.7.
实施例7：3t-3v的制备。
将N-甲基苯胺1a (53.5 mg, 0.5 mmol)、t-BuONa(294 mg，1.5 mmol)，硝基苯类化合物2b-2d (1.5 mmol)，加入2.0 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 = 20/1），得到纯品N-甲基二苯基衍生物3t-3v.
其合成路线如下：
3-chloro-N-methyl-4-nitro-N-phenylaniline: 3t
黄色固体，产率为38%；1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 9.3 Hz, 1H),7.47 (t, J = 7.7 Hz, 2H), 7.33 (t, J = 7.3 Hz, 1H), 7.21 (d, J = 8.1 Hz, 2H),6.71 (d, J = 2.6 Hz, 1H), 6.55 (dd, J = 9.3, 2.6 Hz, 1H), 3.38 (s, 3H). 13CNMR (100 MHz, CDCl3) δ 152.8, 145.9, 136.7, 130.4, 130.2, 128.3, 127.2,126.7, 115.1, 111.2, 40.5.
N-methyl-2,4-dinitro-N-phenylaniline: 3u
黄色固体，产率为18%；1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 8.27 (d, J =9.3 Hz, 1H), 7.36 (t, J = 7.4 Hz, 2H), 7.21 (m, 2H), 7.10 (d, J = 8.0 Hz,2H), 3.47 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.3, 146.2, 139.2, 138.8,130.1, 127.8, 126.2, 123.3, 123.1, 121.2, 42.5.
N,2-dimethyl-4-nitro-N-phenylaniline: 3v
黄色固体，产率为25%；1H NMR (400 MHz, CDCl3) δ 8.14-8.06 (m, 2H), 7.29-7.21(m, 3H), 6.90 (t, J = 7.3 Hz, 1H), 6.72 (d, J = 8.2 Hz, 2H), 3.33 (s, 3H),2.12 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 153.6, 148.3, 144.1, 135.8, 129.3,126.9, 125.7, 122.9, 120.3, 116.8, 40.4, 19.0.
实施例8：克级反应制备3a
将N-甲基苯胺1a (1.07 g, 10 mmol)、t-BuONa(5.88 g，30 mmol)，硝基苯2a (3.69g, 30 mmol)，加入40 mL二甲基亚砜（DMSO）中，室温下反应60 分钟后停止反应，用水淬灭，二氯甲烷萃取，柱层析分离（采用硅胶柱；洗脱剂：石油醚/乙酸乙酯 = 20/1），得到纯品N-甲基二苯基衍生物3a，白色固体，产率78%。
其合成路线如下：
尽管已经对本发明的技术方案做了较为详细的阐述和列举，应当理解，对于本领域技术人员来说，对上述实施例做出修改或者采用等同的替代方案，这对本领域的技术人员而言是显而易见，在不偏离本发明精神的基础上所做的这些修改或改进，均属于本发明要求保护的范围。
Claims (7)
1.一种N-芳基取代杂环化合物的制备方法，其特征在于，以碱为促进剂，在有机溶剂条件下，胺类化合物和硝基类化合物，以1:1~1:3的摩尔比，在常温常压下反应30-60分钟；反应结束后加水淬灭，有机溶剂萃取，柱层析分离，得到N-芳基取代杂环衍生物。
2.根据权利要求1所述的一种N-芳基取代杂环化合物的制备方法，其特征在于，所述胺类化合物为N-烷基或N-芳基苯胺衍生物、1,2,3,4-四氢喹啉衍生物、吲哚啉衍生物、苯胺衍生物或N-甲基吡啶衍生物，结构式为：
其中，X = C或N；
R1、R2、R3、R4、R5和R6为氢、C1～C40的脂肪基团、C4～C60内的芳香基团、烷氧基、羟基、硝基、胺基或者卤素。
3.根据权利要求2所述的一种N-芳基取代杂环化合物的制备方法，其特征在于，所述C1～C40的脂肪基团为甲基、乙基、丙基、异丙基、丁基或苄基，C4～C60内的芳香基团为吡啶衍生物基、苯基、取代苯基、1-萘基或2-萘基，卤素为氟、氯、溴或碘。
4.根据权利要求1所述的一种N-芳基取代杂环化合物的制备方法，其特征在于，所述硝基类化合物的结构式为：
R7和R8为氢、C1～C40的脂肪基团、C4～C60内的芳香基团、烷氧基、羟基、硝基、胺基或者卤素。
5.根据权利要求4所述的一种N-芳基取代杂环化合物的制备方法，其特征在于，所述C1～C40的脂肪基团为甲基、乙基、丙基、异丙基、丁基或苄基，C4～C60内的芳香基团为吡啶衍生物基、苯基、取代苯基、1-萘基或2-萘基，卤素为氟、氯、溴或碘。
6.根据权利要求1所述的一种N-芳基取代杂环化合物的制备方法，其特征在于，所述的促进剂碱为t-BuONa、t-BuOK、KOH、NaOH或K2CO3，促进剂的用量为胺类衍生物摩尔量的1-3倍。
7.根据权利要求1所述的一种N-芳基取代杂环化合物的制备方法，其特征在于，所述的有机溶剂采用N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、氮甲基吡咯烷酮、二氯甲烷、氯仿、四氯化碳、1,2-二氯乙烷、1,4-二氧六环、乙腈、乙醚、乙二醇二甲醚或四氢呋喃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010757079.8A CN111732516B (zh) | 2020-07-31 | 2020-07-31 | 一种n-芳基取代杂环化合物的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010757079.8A CN111732516B (zh) | 2020-07-31 | 2020-07-31 | 一种n-芳基取代杂环化合物的制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111732516A true CN111732516A (zh) | 2020-10-02 |
| CN111732516B CN111732516B (zh) | 2021-01-05 |
Family
ID=72943820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010757079.8A Active CN111732516B (zh) | 2020-07-31 | 2020-07-31 | 一种n-芳基取代杂环化合物的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111732516B (zh) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115521193A (zh) * | 2022-09-30 | 2022-12-27 | 陕西蒲城海泰新材料产业有限责任公司 | 一种3,3′,6,6′-四甲氧基-2,2′-联萘的工业化制备方法 |
| CN116063302A (zh) * | 2023-02-24 | 2023-05-05 | 南昌大学 | 一种α-咔啉及其衍生物的制备方法 |
| CN117304051A (zh) * | 2023-09-22 | 2023-12-29 | 南昌大学 | 一种苯茴香胺类化合物的制备方法 |
| CN118439966A (zh) * | 2024-07-05 | 2024-08-06 | 南昌大学 | 一种对硝基苯胺类化合物的合成方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5612483A (en) * | 1994-09-13 | 1997-03-18 | Bayer Aktiengesellschaft | Process for the preparation of nitro-substituted arylamines |
| CN103180294A (zh) * | 2010-08-31 | 2013-06-26 | 日产化学工业株式会社 | 二胺、聚酰亚胺前体、聚酰亚胺、液晶取向剂、液晶取向膜及液晶显示元件 |
-
2020
- 2020-07-31 CN CN202010757079.8A patent/CN111732516B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5612483A (en) * | 1994-09-13 | 1997-03-18 | Bayer Aktiengesellschaft | Process for the preparation of nitro-substituted arylamines |
| CN103180294A (zh) * | 2010-08-31 | 2013-06-26 | 日产化学工业株式会社 | 二胺、聚酰亚胺前体、聚酰亚胺、液晶取向剂、液晶取向膜及液晶显示元件 |
Non-Patent Citations (2)
| Title |
|---|
| HIROFUMI UEDA ET AL.: "Acetic Acid Promoted Metal-Free Aerobic Carbon−Carbon Bond Forming Reactions at α‑Position of Tertiary Amines", 《ORGANIC LETTERS》 * |
| SHAILESH KUMAR ET AL: "KOtBu-Mediated Aerobic Transition-Metal-Free Regioselective β-Arylation of Indoles: Synthesis of β‑(2-/4-Nitroaryl)-indoles", 《ORGANIC LETTERS》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115521193A (zh) * | 2022-09-30 | 2022-12-27 | 陕西蒲城海泰新材料产业有限责任公司 | 一种3,3′,6,6′-四甲氧基-2,2′-联萘的工业化制备方法 |
| CN116063302A (zh) * | 2023-02-24 | 2023-05-05 | 南昌大学 | 一种α-咔啉及其衍生物的制备方法 |
| CN116063302B (zh) * | 2023-02-24 | 2025-07-04 | 南昌大学 | 一种α-咔啉及其衍生物的制备方法 |
| CN117304051A (zh) * | 2023-09-22 | 2023-12-29 | 南昌大学 | 一种苯茴香胺类化合物的制备方法 |
| CN118439966A (zh) * | 2024-07-05 | 2024-08-06 | 南昌大学 | 一种对硝基苯胺类化合物的合成方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111732516B (zh) | 2021-01-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111732516A (zh) | 一种n-芳基取代杂环化合物的制备方法 | |
| CN108017613B (zh) | 钌催化杂环芳酮与二苯乙炔反应制备多芳取代萘衍生物的方法 | |
| CN110183341A (zh) | 1,2-二羰基类化合物及其合成方法 | |
| KR102708701B1 (ko) | 벤즈이미다졸 유도체의 제조방법 | |
| CN106187890B (zh) | 一种利用钯-铜共催化合成吖啶酮衍生物的方法 | |
| CN111393384B (zh) | 一种含邻位碳硼烷席夫碱配体的亚铜配合物的应用 | |
| CN112979529B (zh) | 一种芳香胺吲哚萘醌衍生物及其制备方法 | |
| CN118598813B (zh) | L-苹果酸萨米多芬及其制备方法 | |
| CN103787839B (zh) | 合成2,3,4,5,6-五氟苯酚的方法 | |
| CN108689957B (zh) | 一种2r/2s-三氟甲基吗啉及其盐酸盐的制备方法和应用 | |
| CN110396094B (zh) | 一种喹啉酮并杂芳环类化合物及其衍生物和合成方法 | |
| CN102127038B (zh) | 一种合成单硫醚类化合物的方法 | |
| CN105646327A (zh) | 2-全氟烷基吲哚衍生物及其合成方法 | |
| CN113416162B (zh) | 一种双手性联萘o-n-n三齿配体及其制备方法 | |
| CN110878099A (zh) | 一种吡咯[1,2,α]吲哚生物碱衍生物的制备方法 | |
| CN104860881A (zh) | 8-(硝基甲基)喹啉类化合物和8-甲氨基四氢喹啉类化合物的合成方法 | |
| CN104829518A (zh) | 一种甘氨酸类衍生物的制备方法 | |
| CN111732528B (zh) | 一种n-芳基吲哚啉衍生物的制备方法 | |
| CN118103355A (zh) | 用于制备作为荧光示踪剂的吡嗪羧酸类衍生物的氢化合成方法 | |
| CN117304149B (zh) | 4-苯乙炔苯酐的合成方法 | |
| CN111848491B (zh) | 1-甲酰基咔唑的制备方法 | |
| CN106543040B (zh) | 一种医药中间体氨基甲酸酯化合物的合成方法 | |
| CN100528863C (zh) | 舍吲哚的制备方法 | |
| CN121085721A (zh) | 一种烯丙基偕二氟化合物的制备方法 | |
| CN118005468A (zh) | 氮碳材料催化醇类和腈类合成n-烷基化酰胺类化合物的方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |