CN113121427A - 一种喹啉类衍生物及其制备方法和应用 - Google Patents
一种喹啉类衍生物及其制备方法和应用 Download PDFInfo
- Publication number
- CN113121427A CN113121427A CN202110295734.7A CN202110295734A CN113121427A CN 113121427 A CN113121427 A CN 113121427A CN 202110295734 A CN202110295734 A CN 202110295734A CN 113121427 A CN113121427 A CN 113121427A
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- China
- Prior art keywords
- reaction
- hydrogen
- group
- quinoline
- aryl
- Prior art date
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Links
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 70
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- -1 alkyne compound Chemical class 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 26
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 15
- 229910052751 metal Inorganic materials 0.000 claims abstract description 14
- 239000002184 metal Substances 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 239000003446 ligand Substances 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- GAURFLBIDLSLQU-UHFFFAOYSA-N diethoxy(methyl)silicon Chemical compound CCO[Si](C)OCC GAURFLBIDLSLQU-UHFFFAOYSA-N 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 238000006459 hydrosilylation reaction Methods 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
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 125000001174 sulfone group Chemical group 0.000 claims description 6
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 5
- 125000004185 ester group Chemical group 0.000 claims description 5
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 5
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 4
- MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 4
- 125000001033 ether group Chemical group 0.000 claims description 4
- 229940078494 nickel acetate Drugs 0.000 claims description 4
- BFSQJYRFLQUZKX-UHFFFAOYSA-L nickel(ii) iodide Chemical compound I[Ni]I BFSQJYRFLQUZKX-UHFFFAOYSA-L 0.000 claims description 4
- 229920001843 polymethylhydrosiloxane Polymers 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
- QQQSFSZALRVCSZ-UHFFFAOYSA-N triethoxysilane Chemical compound CCO[SiH](OCC)OCC QQQSFSZALRVCSZ-UHFFFAOYSA-N 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 3
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 3
- AKQNYQDSIDKVJZ-UHFFFAOYSA-N triphenylsilane Chemical compound C1=CC=CC=C1[SiH](C=1C=CC=CC=1)C1=CC=CC=C1 AKQNYQDSIDKVJZ-UHFFFAOYSA-N 0.000 claims description 3
- PTRATZCAGVBFIQ-UHFFFAOYSA-N Abametapir Chemical compound N1=CC(C)=CC=C1C1=CC=C(C)C=N1 PTRATZCAGVBFIQ-UHFFFAOYSA-N 0.000 claims description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- UQPSGBZICXWIAG-UHFFFAOYSA-L nickel(2+);dibromide;trihydrate Chemical compound O.O.O.Br[Ni]Br UQPSGBZICXWIAG-UHFFFAOYSA-L 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- KXFSUVJPEQYUGN-UHFFFAOYSA-N trimethyl(phenyl)silane Chemical compound C[Si](C)(C)C1=CC=CC=C1 KXFSUVJPEQYUGN-UHFFFAOYSA-N 0.000 claims description 2
- SRMJRXAKBYSQQO-UHFFFAOYSA-N (2-aminobenzoyl) 2-aminobenzoate Chemical class NC1=CC=CC=C1C(=O)OC(=O)C1=CC=CC=C1N SRMJRXAKBYSQQO-UHFFFAOYSA-N 0.000 abstract description 16
- 150000001345 alkine derivatives Chemical class 0.000 abstract description 14
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 229910052987 metal hydride Inorganic materials 0.000 abstract description 6
- 150000004681 metal hydrides Chemical class 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 5
- 238000005576 amination reaction Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 abstract description 3
- 239000007805 chemical reaction reactant Substances 0.000 abstract description 3
- 230000008878 coupling Effects 0.000 abstract description 3
- 238000010168 coupling process Methods 0.000 abstract description 3
- 238000005859 coupling reaction Methods 0.000 abstract description 3
- 238000009509 drug development Methods 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 238000006722 reduction reaction Methods 0.000 abstract description 3
- 229910052990 silicon hydride Inorganic materials 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 44
- 239000000047 product Substances 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- FSEXLNMNADBYJU-UHFFFAOYSA-N 2-phenylquinoline Chemical compound C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=N1 FSEXLNMNADBYJU-UHFFFAOYSA-N 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 238000001228 spectrum Methods 0.000 description 14
- GMTGCIAJHZEUNB-UHFFFAOYSA-N 2-Pentylquinoline Natural products C1=CC=CC2=NC(CCCCC)=CC=C21 GMTGCIAJHZEUNB-UHFFFAOYSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 239000012300 argon atmosphere Substances 0.000 description 12
- 239000007795 chemical reaction product Substances 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 238000001035 drying Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000002390 rotary evaporation Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- SAEVHZLHSHBXAD-UHFFFAOYSA-N 2,3-diphenylquinoline Chemical compound C1=CC=CC=C1C1=CC2=CC=CC=C2N=C1C1=CC=CC=C1 SAEVHZLHSHBXAD-UHFFFAOYSA-N 0.000 description 9
- ZOZGQRRDYNRSQF-UHFFFAOYSA-N 2,3-dipropylquinoline Chemical compound C1=CC=C2N=C(CCC)C(CCC)=CC2=C1 ZOZGQRRDYNRSQF-UHFFFAOYSA-N 0.000 description 9
- SEVBQRQACXXUJG-UHFFFAOYSA-N 2-(4-bromophenyl)quinoline Chemical compound C1=CC(Br)=CC=C1C1=CC=C(C=CC=C2)C2=N1 SEVBQRQACXXUJG-UHFFFAOYSA-N 0.000 description 9
- BUYMQKLWDAVPNE-UHFFFAOYSA-N 3-methyl-2-phenylquinoline Chemical compound CC1=CC2=CC=CC=C2N=C1C1=CC=CC=C1 BUYMQKLWDAVPNE-UHFFFAOYSA-N 0.000 description 9
- MRZFYCNMZOEKJX-UHFFFAOYSA-N 6,7-dimethoxy-2-phenylquinoline Chemical compound N1=C2C=C(OC)C(OC)=CC2=CC=C1C1=CC=CC=C1 MRZFYCNMZOEKJX-UHFFFAOYSA-N 0.000 description 8
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- VXTYWQBVPQPTIY-UHFFFAOYSA-N 2-phenylquinoline-3-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=CC=C2N=C1C1=CC=CC=C1 VXTYWQBVPQPTIY-UHFFFAOYSA-N 0.000 description 5
- WPLMYKCCCBUVKD-UHFFFAOYSA-N 6-chloro-2,3,4-triphenylquinoline Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C2N=C1C1=CC=CC=C1 WPLMYKCCCBUVKD-UHFFFAOYSA-N 0.000 description 5
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 5
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 4
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 description 4
- ATUPEWQJOFWXMI-UHFFFAOYSA-N ethyl 2-phenylquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CC2=CC=CC=C2N=C1C1=CC=CC=C1 ATUPEWQJOFWXMI-UHFFFAOYSA-N 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical group [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
- JRXXLCKWQFKACW-UHFFFAOYSA-N biphenylacetylene Chemical compound C1=CC=CC=C1C#CC1=CC=CC=C1 JRXXLCKWQFKACW-UHFFFAOYSA-N 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- GZTNBKQTTZSQNS-UHFFFAOYSA-N oct-4-yne Chemical compound CCCC#CCCC GZTNBKQTTZSQNS-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 3
- LTLVZQZDXQWLHU-UHFFFAOYSA-N 1-bromo-4-ethynylbenzene Chemical group BrC1=CC=C(C#C)C=C1 LTLVZQZDXQWLHU-UHFFFAOYSA-N 0.000 description 2
- WGUKMLPACNCLBY-UHFFFAOYSA-N NC(C(C(OC(C1=CC(Cl)=CC(C2=CC=CC=C2)=C1N)=O)=O)=CC(Cl)=C1)=C1C1=CC=CC=C1 Chemical compound NC(C(C(OC(C1=CC(Cl)=CC(C2=CC=CC=C2)=C1N)=O)=O)=CC(Cl)=C1)=C1C1=CC=CC=C1 WGUKMLPACNCLBY-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- YVXHZKKCZYLQOP-UHFFFAOYSA-N hept-1-yne Chemical compound CCCCCC#C YVXHZKKCZYLQOP-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- GHUURDQYRGVEHX-UHFFFAOYSA-N prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1 GHUURDQYRGVEHX-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
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- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical class [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
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- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
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- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
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- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
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- 125000006267 biphenyl group Chemical group 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
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- 150000001840 cholesterol esters Chemical class 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
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- 230000032050 esterification Effects 0.000 description 1
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- ACJOYTKWHPEIHW-UHFFFAOYSA-N ethyl 3-phenylprop-2-ynoate Chemical compound CCOC(=O)C#CC1=CC=CC=C1 ACJOYTKWHPEIHW-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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Abstract
本发明属于化学药物合成技术领域,具体涉及一种喹啉类衍生物及其制备方法和应用。本发明的反应体系中,首先金属催化剂、配体和硅氢试剂相互作用产生金属氢化物,与炔烃类化合物加成,和氨茴内酐类化合物发生亲电胺化反应,再经过分子内环化得到所述多取代喹啉类衍生物。该反应起始原料炔烃和氨茴内酐类化合物廉价易得,采用一步法就可以构建多种不同多取代的喹啉类衍生物,可以通过目标分子的氧化、还原、偶联等途径,快速转化成其他化合物,在药物开发和材料制备领域具有非常好的应用前景;并且本发明方法条件温和,绿色高效,操作简单,非常适用于大规模产业化生产。
Description
技术领域
本发明属于化学药物合成技术领域。更具体地,涉及一种喹啉类衍生物及其制备方法和应用。
背景技术
喹啉及其衍生物是一类重要的有机化合物,不仅广泛的存在于天然产物中,并且许多药物分子,如奎宁、氯喹、羟氯喹等都具有喹啉结构,同时喹啉分子还被广泛的应用于有机光电材料的开发。因此,喹啉及其衍生物是非常重要的化学原料,可以利用传统的人名反应如Skraup,Combes,Friedlander,Povarov等反应构建喹啉类化合物,但这些反应主要基于经典的缩合反应原理,通常原料较为复杂,反应条件较苛刻,且区域选择性差,具有一定的局限性。
现有技术已公开一系列催化反应来构建喹啉化合物,其中过渡金属催化炔烃参与的环化反应在构建喹啉方面取得了一定的进展。如江焕峰公开了一种钯催化邻烯基苯胺和炔烃环化反应构建喹啉的方法(Zheng J,Li Z,Huang L,etal.Palladium-CatalyzedIntermolecular Aerobic Annulation of o-Alkenylanilinesand Alkynes forQuinoline Synthesis[J].Organic Letters,2016,18(15):3514.);周旺公开了一种钯催化邻氨基苯甲醛和炔烃环化反应构建喹啉的方法(Zhou W,Lei J.Palladium-catalyzedsynthesis of polysubstituted quinolines from 2-am ino aromatic ketones andalkynes[J].CHEMICAL COMMUNICATIONS-ROYA L SOCIETY OF CHEMISTRY,2014,50(42):5583.);张玉红公开了一种钴催化酰基导向的碳氢活化/炔烃环化反应构建喹啉的方法(Yan Q,Chen Z,Liu Z,et al.Cobalt-catalyzed synthesis of quinolines from theredox-neutral annul ation of anilides and alkynes[J].Organic ChemistryFrontiers,2016:10.1039.C6QO00059B.)。但是上述反应对炔烃的类型有一定的要求,仅有缺电子的内炔、二芳基乙炔等可以反应或反应效果较好,而对于更加广泛的末端炔、烷基炔以及杂芳基炔的兼容性较差,极大地限制了这些反应在有机合成和药物合成中的应用。
因此,迫切需要提供一种以廉价易得的化学试剂为起始原料,适用范围广,条件温和,绿色高效,操作简单的喹啉类衍生物的制备方法。
发明内容
本发明要解决的技术问题是克服现有喹啉类衍生物合成方法反应原料具有局限性,反应条件苛刻的缺陷和不足,提供一种以廉价易得的化学试剂为起始原料,适用范围广,条件温和,绿色高效,操作简单的喹啉类衍生物的制备方法。
本发明的目的是提供一种喹啉类衍生物的制备方法。
本发明另一目的是提供所述制备方法制备的喹啉类衍生物。
本发明另一目的是提供所述制备方法或所述喹啉类衍生物在制备具有喹啉结构化合物中的应用。
本发明上述目的通过以下技术方案实现:
一种喹啉类衍生物的制备方法,其特征在于,反应路线如下:
包括以下步骤:
将式(II)化合物和式(III)化合物溶于溶剂中,加入金属催化剂、配体和硅氢试剂反应,即得式(I)喹啉类衍生物;
其中,R1和R2各自独立地选自芳基、杂芳基、芳香稠环基、C1~10烷基、C3~10环烷基、酯基、酰基或氢;
R3选自氢、C1~10烷基、芳基或杂芳基;
R4选自氢、C1~10烷基、芳基、卤素、醚基、三氟甲基、乙酰基、酯基或砜基。
本发明的反应体系中,首先金属催化剂、配体和硅氢试剂相互作用产生金属氢化物,金属氢化物进一步的和式(II)炔烃类化合物进行加成得到烯基金属中间体;所得烯基金属中间体和式(III)化合物发生亲电胺化反应得到烯胺中间体,再经过分子内环化得到所述多取代喹啉类衍生物。其中,氨茴内酐是一种新型亲电胺化试剂,在特定金属催化剂的作用下,能够作为一种高效的伯芳胺类亲电试剂,并且在构建C-N键的同时产生醛/酮基,可以缩合成环。
本发明反应起始原料炔烃和氨茴内酐类化合物廉价易得,采用一步法就可以构建多种不同多取代的喹啉类衍生物,各取代基官能团包括卤素、羰基、酯基等易转化的官能团,可以通过目标分子的氧化、还原、偶联等途径,快速转化成其他化合物,在药物开发和材料制备领域具有非常好的应用前景。并且本发明方法条件温和,绿色高效,操作简单,非常适用于大规模产业化生产。
优选地,R1和R2各自独立地选自芳基、杂芳基、C1~10烷基、酯基或氢;
R3选自氢或芳基;
R4选自氢、卤素或醚基。
更优选地,R1选自H、苯基、甲基、-COOEt或-C3H7;
R2选自苯基、噻吩基、-C5H11或-C3H7;
R3选自氢或苯基;
R4选自氢、卤素或甲醚基。
更优选地,所述式(II)化合物为苯乙炔、4-溴苯乙炔、4-噻吩乙炔、1-庚炔、二苯乙炔、1-苯基-1-丙炔、苯基丙炔酸乙酯或4-辛炔或苯丙炔酸胆固醇酯。
更优选地,所述式(III)化合物为氨茴内酐3a、3-苯基-5-氯氨茴内酐3b或5,6-二甲氧基氨茴内酐3c。
进一步地,所述苯基上一个或多个氢被醚基、卤素、乙酰基、酯基、三氟甲基或砜基取代。
更进一步地,所述金属催化剂选自溴化镍、氯化镍、醋酸镍、碘化镍、醋酸铜、碘化铜、六水合四氟硼酸镍中的一种或多种溴化镍、氯化镍、醋酸镍、碘化镍、醋酸铜、碘化铜、六水合四氟硼酸镍中的一种或多种。
优选地,所述金属催化剂为溴化镍或六水合四氟硼酸镍。
进一步地,所述配体选自4,5-双二苯基膦-9,9-二甲基氧杂蒽、2,2-联吡啶、6,6'-二甲基-2,2'-联吡啶、5,5'-二甲基-2,2'-联吡啶中的一种或多种。
优选地,所述配体为2,2-联吡啶或6,6'-二甲基-2,2'-联吡啶。
更进一步地,所述硅氢试剂选自三苯基硅烷、三乙基硅烷、甲基二乙氧基硅烷、二苯基硅烷、苯基三甲基硅烷、三乙氧基硅烷、聚(甲基氢硅氧烷)中的一种或多种。
优选地,所述硅氢试剂为三苯基硅烷或甲基二乙氧基硅烷。
进一步地,所述溶剂选自N,N’-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮中的一种或多种。
优选地,所述溶剂为N,N’-二甲基甲酰胺或N,N-二甲基乙酰胺。
更进一步地,所述反应的温度为0~100℃。
优选地,所述反应的温度为40~80℃;更优选地,所述反应的温度为40℃。
更进一步地,所述反应的时间为2~24h。
优选地,所述反应的时间为6~18h。
进一步地,所述式(II)化合物和式(III)化合物的摩尔比为1:(1~4)。
优选地,所述式(II)化合物和式(III)化合物的摩尔比为1:(1~1.5)。
更进一步地,所述金属催化剂的添加量为式(II)化合物用量的1mol%~20mol%。优选地,金属催化剂的添加量为式(II)化合物用量的10mol%。
进一步地,所述配体的添加量为式(II)化合物用量的10mol%~50mol%。优选地,所述配体的添加量为式(II)化合物用量的20mol%。
更进一步地,所述硅氢试剂的添加量为式(II)化合物用量的100mol%~300mol%。优选地,所述硅氢试剂的添加量为式(II)化合物用量的200mol%。
进一步地,所述式(II)化合物在溶剂中的浓度为0.1mol/L~3.0mol/L。优选地,所述式(II)化合物在溶剂中的浓度为0.5mol/L。
另外的,本发明还提供了所述制备方法制备的喹啉类衍生物,所述喹啉类衍生物的结构如式(I)所示:
其中,R1和R2各自独立地选自芳基、杂芳基、芳香稠环基、C1~10烷基、C3~10环烷基、酯基、酰基或氢;
R3选自氢、C1~10烷基、芳基或杂芳基;
R4选自氢、C1~10烷基、芳基、卤素、醚基、三氟甲基、乙酰基、酯基或砜基。
优选地,所述喹啉类衍生物结构式选自以下任一结构式:
另外的,本发明还提供了所述制备方法或所述喹啉类衍生物在制备具有喹啉结构化合物中的应用。
本发明具有以下有益效果:
本发明的反应体系中,首先金属催化剂、配体和硅氢试剂相互作用产生金属氢化物,与炔烃类化合物加成,和氨茴内酐类化合物发生亲电胺化反应,再经过分子内环化得到所述多取代喹啉类衍生物。该反应起始原料炔烃和氨茴内酐类化合物廉价易得,采用一步法就可以构建多种不同多取代的喹啉类衍生物,可以通过目标分子的氧化、还原、偶联等途径,快速转化成其他化合物,在药物开发和材料制备领域具有非常好的应用前景;并且本发明方法条件温和,绿色高效,操作简单,非常适用于大规模产业化生产。
附图说明
图1为本发明一种喹啉类衍生物制备方法的合成路线图;
图2为本发明实施例1提供的2-苯基喹啉(1a)的核磁共振1H谱图;
图3为本发明实施例1提供的2-苯基喹啉(1a)的核磁共振13C谱图;
图4为本发明实施例2提供的2-(4-溴苯基)喹啉(1b)的核磁共振1H谱图;
图5为本发明实施例2提供的2-(4-溴苯基)喹啉(1b)的核磁共振13C谱图;
图6为本发明实施例3提供的2-(3-噻吩)喹啉(1c)的核磁共振1H谱图;
图7为本发明实施例3提供的2-(3-噻吩)喹啉(1c)的核磁共振13C谱图;
图8为本发明实施例4提供的2-(正戊基)喹啉(1d)的核磁共振1H谱图;
图9为本发明实施例4提供的2-(正戊基)喹啉(1d)的核磁共振13C谱图;
图10为本发明实施例5提供的2,3-二苯基喹啉(1e)的核磁共振1H谱图;
图11为本发明实施例5提供的2,3-二苯基喹啉(1e)的核磁共振13C谱图;
图12为本发明实施例6提供的3-甲基-2-苯基喹啉(1f)的核磁共振1H谱图;
图13为本发明实施例6提供的3-甲基-2-苯基喹啉(1f)的核磁共振13C谱图;
图14为本发明实施例7提供的2-苯基喹啉-3-羧酸乙酯(1g)的核磁共振1H谱图;
图15为本发明实施例7提供的2-苯基喹啉-3-羧酸乙酯(1g)的核磁共振13C谱图;
图16为本发明实施例8提供的2,3-二正丙基喹啉(1h)的核磁共振1H谱图;
图17为本发明实施例8提供的2,3-二正丙基喹啉(1h)的核磁共振13C谱图。
图18为本发明实施例9提供的6-氯-2,3,4-三苯基喹啉(1i)的核磁共振1H谱图。
图19为本发明实施例9提供的6-氯-2,3,4-三苯基喹啉(1i)的核磁共振13C谱图。
图20为本发明实施例10提供的6,7-二甲氧基-2-苯基喹啉(1j)的核磁共振1H谱图。
图21为本发明实施例10提供的6,7-二甲氧基-2-苯基喹啉(1j)的核磁共振13C谱图。
图22为本发明实施例11提供的2-苯基喹啉-3-羧酸胆固醇酯(1k)的核磁共振1H谱图。
图23为本发明实施例11提供的2-苯基喹啉-3-羧酸胆固醇酯(1k)的核磁共振13C谱图。
具体实施方式
以下结合说明书附图和具体实施例来进一步说明本发明,但实施例并不对本发明做任何形式的限定。除非特别说明,本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
其中,以下实施例所用原料均为市售或自制:下述的炔烃原料2a、2b、2c、2d、2e、2f、2g、2h化合物为商业可得,2i由相应的苯丙炔酸和胆固醇酯化制得;氨茴内酐3a,3b为商业可得,3c由相应的邻硝基苯甲醛一步获得(Jin,H.;Huang,L.;Xie,J.;Rudolph,M.;Rominger,F.;Hashmi,A.S.K.Angew.Chem.,Int.Ed.2016,55,794.)。
除非特别说明,以下实施例所用试剂和材料均为市购。
多取代喹啉衍生物的合成路线为:
具体制备方法包括以下步骤:
在氩气氛围下,在反应器中依次加入金属催化剂(5mol%)、配体(10mol%),密封反应器并用注射器加入溶剂(1.0mL),随后依次加入硅氢试剂(0.6mmol),式(Ⅱ)所示炔类化合物2(0.45mmol),式(III)所示氨茴内酐类化合物3(0.3mmol),40℃条件下反应16小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至1:1的石油醚与乙酸乙酯,得到多取代喹啉衍生物。
具体实施例如下:
实施例1化合物1a的制备
1a全称为2-苯基喹啉(1a),其反应式如下所示:
在氩气氛围下,在反应器中依次加入溴化镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基乙酰胺(DMA,1.0mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),苯乙炔2a(0.45mmol),氨茴内酐3a(0.3mmol),40℃条件下反应16小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2-苯基喹啉产物,产率为88%。
对2-苯基喹啉(1a)进行核磁共振检测,请参阅图2至图3,结果为:
1H NMR(400MHz,CDCl3)δ8.21(m,4H),7.86(d,J=8.6Hz,1H),7.81(d,J=8.1Hz,1H),7.75(t,J=7.6Hz,1H),7.53(m,4H).
13C NMR(100MHz,CDCl3)δ157.2,148.2,139.6,136.6,129.6,129.5,129.2,128.7,127.5,127.4,127.1,126.2,118.8.
本实施例可以通过简单易得的末端芳基乙炔和氨茴内酐为原料,经分子间[4+2]环加成得到2-芳基喹啉类衍生物。
实施例2化合物1b的制备
1b全称为2-(4-溴苯基)喹啉(1b),其反应式如下所示:
在氩气氛围下,在反应器中依次加入氯化镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基乙酰胺(DMA,1.0mL),随后依次加入三乙基硅烷(0.6mmol),4-溴苯乙炔2b(0.45mmol),氨茴内酐3a(0.36mmol),40℃条件下反应12小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2-(4-溴苯基)喹啉产物,产率为63%。
对2-(4-溴苯基)喹啉(1b)进行核磁共振检测,请参阅图4至图5,结果为:
1H NMR(400MHz,CDCl3)δ8.17(m,2H),8.04(d,J=8.4Hz,2H),7.80(m,2H),7.73(t,J=7.6Hz,1H),7.64(d,J=8.4Hz,2H),7.53(t,J=7.5Hz,1H)ppm.
13C NMR(100MHz,CDCl3)δ155.9,148.2,138.4,136.9,131.9,129.8,129.6,129.0,127.4,127.2,126.4,123.9,118.4ppm.
本实施例得到产物中含有溴原子,可以用于进一步的产物后期修饰,进一步丰富了产物类型。
实施例3化合物1c的制备
1c全称为2-(3-噻吩)喹啉(1c),其反应式如下所示:
在氩气氛围下,在反应器中依次加入六水合四氟硼酸镍(5mol%)、4,5-双(二苯基膦)-9,9-二甲基氧杂蒽Xantphos(10mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.0mL),随后依次加入聚(甲基氢硅氧烷)(PMHS,0.6mmol),4-噻吩乙炔2c(0.3mmol),氨茴内酐3a(0.3mmol),40℃条件下反应18小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2-(4-溴苯基)喹啉产物,产率为63%。
对2-(3-噻吩)喹啉(1c)进行核磁共振检测,请参阅图6至图7,结果为:
1H NMR(400MHz,CDCl3)δ8.16(d,J=8.6Hz,1H),8.12(d,J=8.5Hz,1H),8.05(d,J=1.9Hz,1H),7.89(m,1H),7.78(t,J=8.1Hz,2H),7.74–7.68(m,1H),7.50(t,J=7.4Hz,1H),7.45(m,1H)ppm.
13C NMR(100MHz,CDCl3)δ153.3,148.2,142.7,136.6,129.6,129.5,127.4,127.1,126.8,126.4,126.1,124.6,119.0ppm.
本实施例芳杂环乙炔可以参与反应得到相应的2-位芳杂环取代喹啉产物,进一步丰富了产物类型。
实施例4化合物1d的制备
1d全称为2-(正戊基)喹啉(1d),其反应式如下所示:
在氩气氛围下,在反应器中依次加入碘化镍(5mol%)、6,6'-二甲基-2,2'-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.5mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),1-庚炔2d(0.3mmol),氨茴内酐3a(0.3mmol),40℃条件下反应10小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2-(正戊基)喹啉产物,产率为46%。
对2-(正戊基)喹啉(1d)进行核磁共振检测,请参阅图8至图9,结果为:
1H NMR(400MHz,CDCl3)δ8.05(d,J=8.4Hz,2H),7.76(d,J=7.9Hz,1H),7.67(t,J=7.7Hz,1H),7.47(t,J=7.5Hz,1H),7.29(d,J=8.4Hz,1H),3.00–2.93(m,2H),1.82(m,2H),1.46–1.35(m,4H),0.90(t,J=6.9Hz,3H)ppm.
13C NMR(100MHz,CDCl3)δ163.1,147.9,136.1,129.3,128.8,127.4,126.7,125.6,121.3,39.3,31.7,29.7,22.5,14.0ppm.
本实施例,烷基乙炔可以参与反应得到相应的2-位烷基取代喹啉产物,进一步丰富了产物类型。
实施例5化合物1e的制备
1e全称为2,3-二苯基喹啉(1e),其反应式如下所示:
在氩气氛围下,在反应器中依次加入氯化镍(5mol%)、5,5'-二甲基-2,2'-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.2mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),二苯乙炔2e(0.3mmol),氨茴内酐3a(0.3mmol),40℃条件下反应18小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2,3-二苯基喹啉产物,产率为52%。
对2,3-二苯基喹啉(1e)进行核磁共振检测,请参阅图10至图11,结果为:
1H NMR(400MHz,CDCl3)δ8.20(d,J=8.5Hz,1H),8.16(s,1H),7.85(d,J=8.1Hz,1H),7.72(m,J=7.7Hz,1H),7.55(m,J=7.5Hz,1H),7.45(m,J=6.2,2.5Hz,2H),7.31–7.21(m,8H)ppm.
13C NMR(100MHz,CDCl3)δ158.4,147.3,140.4,140.0,137.5,134.5,130.0,129.7,129.6,129.4,128.2,128.0,127.9,127.4,127.2,127.1,126.7ppm.
本实施例,二芳基乙炔可以参与反应得到相应的2,3-位双取代喹啉产物,进一步丰富了产物类型。
实施例6化合物1f的制备
1f全称为3-甲基-2-苯基喹啉(1f),其反应式如下所示:
在氩气氛围下,在反应器中依次加入六水合四氟硼酸镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.0mL),随后依次加入三乙氧基硅烷(0.6mmol),1-苯基-1-丙炔2f(0.3mmol),氨茴内酐3a(0.3mmol),40℃条件下反应18小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到3-甲基-2-苯基喹啉产物,产率为75%。
对3-甲基-2-苯基喹啉(1f)进行核磁共振检测,请参阅图12至图13,结果为:
1H NMR(400MHz,CDCl3)δ8.13(d,J=8.5Hz,1H),8.02(s,1H),7.78(d,J=8.1Hz,1H),7.69–7.64(m,1H),7.62–7.58(m,2H),7.54–7.42(m,4H),2.47(s,3H)ppm.
13C NMR(100MHz,CDCl3)δ160.5,146.6,140.8,136.7,129.3,129.2,128.8,128.7,128.3,128.1,127.6,126.7,126.4,20.6ppm.
本实施例,不对称内炔乙炔可以参与反应高区域选择性的得到相应的2,3-位双取代喹啉产物,进一步丰富了产物类型。
实施例7化合物1g的制备
1g全称为对2-苯基喹啉-3-羧酸乙酯(1g),其反应式如下所示:
在氩气氛围下,在反应器中依次加入醋酸镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.0mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),苯基丙炔酸乙酯2g(0.3mmol),氨茴内酐3a(0.3mmol),40℃条件下反应12小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2-苯基喹啉-3-羧酸乙酯产物,产率为80%。
对2-苯基喹啉-3-羧酸乙酯(1g)进行核磁共振检测,请参阅图14至图15,结果为:
1H NMR(400MHz,CDCl3)δ8.65(s,1H),8.19(d,J=8.5Hz,1H),7.92(d,J=8.1Hz,1H),7.84–7.79(m,1H),7.65–7.57(m,3H),7.50–7.43(m,3H),4.19(q,J=7.1Hz,2H),1.08(t,J=7.1Hz,3H).
13C NMR(100MHz,CDCl3)δ168.0,158.1,148.3,140.8,139.0,131.5,129.5,128.6,128.5,128.2,128.2,127.2,125.8,125.5,61.5,13.6.
本实施例,苯基丙炔酸乙酯类贫电子炔烃可以参与反应高区域选择性的得到相应的2,3-位双取代喹啉产物,进一步拓展了该方法的适用范围,丰富了产物类型。
实施例8化合物1h的制备
1h全称为2,3-二正丙基喹啉(1h),其反应式如下所示:
在氩气氛围下,在反应器中依次加入六水合四氟硼酸镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N-甲基吡咯烷酮(NMP,1.0mL),随后依次加入三乙氧基硅烷(0.6mmol),4-辛炔2h(0.3mmol),氨茴内酐3a(0.3mmol),室温条件下反应12小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2,3-二正丙基喹啉产物,产率为79%。
对2,3-二正丙基喹啉(1h)进行核磁共振检测,请参阅图16至图17,结果为:
1H NMR(400MHz,CDCl3)δ8.01(d,J=8.5Hz,1H),7.83(s,1H),7.70(d,J=8.1Hz,1H),7.60(ddd,J=8.4,6.9,1.4Hz,1H),7.47–7.40(m,1H),2.99–2.92(m,2H),2.80–2.73(m,2H),1.88–1.80(m,2H),1.71(dt,J=14.9,7.4Hz,2H),1.05(dt,J=10.7,7.3Hz,6H)ppm.
13C NMR(100MHz,CDCl3)δ162.1,146.4,134.8,133.9,128.4,128.9,127.2,126.8,125.5,37.78,34.4,23.5,23.0,14.3,14.0ppm.
本实施例,4-辛炔类双烷基取代内炔烃可以参与反应得到相应的2,3-位双烷基取代喹啉产物,进一步拓展了该方法的适用范围,丰富了产物类型。
实施例9化合物1i的制备
1i全称为6-氯-2,3,4-三苯基喹啉(1i),其反应式如下所示:
在氩气氛围下,在反应器中依次加入六水合四氟硼酸镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.0mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),二苯乙炔2e(0.3mmol),3-苯基-5-氯氨茴内酐3b(0.3mmol),40℃条件下反应18小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到6-氯-2,3,4-三苯基喹啉产物,产率为74%。
对6-氯-2,3,4-三苯基喹啉(1i)进行核磁共振检测,请参阅图18至图19,结果为:
1H NMR(400MHz,CDCl3)δ8.21(d,J=8.9Hz,1H),7.67(m,J=8.9,2.3Hz,1H),7.59(d,J=2.1Hz,1H),7.40(m,J=6.6,2.9Hz,2H),7.33–7.28(m,3H),7.25–7.20(m,3H),7.16–7.11(m,2H),7.05–6.99(m,3H),6.91(m,J=6.5,3.0Hz,2H)ppm.
13C NMR(100MHz,CDCl3)δ159.2,146.9,145.6,140.7,137.9,136.2,133.7,132.4,131.3,131.2,130.2,130.1,129.8,127.9,127.7,127.6,127.5,127.4,126.5,125.3ppm.
本实施例得到多取代喹啉产物,进一步拓展了该方法的适用范围,丰富了产物类型。
实施例10化合物1j的制备
1j全称为6,7-二甲氧基-2-苯基喹啉(1j),其反应式如下所示:
在氩气氛围下,在反应器中依次加入溴化镍(5mol%)、2,2-联吡啶(10mol%),密封反应器并用注射器加入N,N-二甲基甲酰胺(DMF,1.0mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),苯乙炔2a(0.3mmol),5,6-二甲氧基氨茴内酐3c(0.3mmol),40℃条件下反应18小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到6,7-二甲氧基-2-苯基喹啉产物,产率为68%。
对6,7-二甲氧基-2-苯基喹啉(1j)进行核磁共振检测,请参阅图20至图21,结果为:
1H NMR(400MHz,CDCl3)δ8.11(d,J=7.3Hz,2H),8.03(d,J=8.5Hz,1H),7.72(d,J=8.5Hz,1H),7.51(t,J=7.5Hz,3H),7.43(t,J=7.3Hz,1H),7.05(s,1H),4.06(s,3H),4.01(s,3H)ppm.
13C NMR(100MHz,CDCl3)δ155.3,152.5,149.6,145.2,139.9,134.8,128.8,128.7,127.2,122.6,117.2,108.3,104.9,56.1,56.0ppm.
本实施例得到多取代喹啉产物,进一步拓展了该方法的适用范围,丰富了产物类型。
实施例11化合物1k的制备
1k全称为2-苯基喹啉-3-羧酸胆固醇酯(1k),其反应式如下所示:
在氩气氛围下,在反应器中依次加入溴化镍(5mol%)、2,2-联吡啶(5mol%),密封反应器并用注射器加入N,N-二甲基乙酰胺(1.5mL),随后依次加入甲基二乙氧基硅烷(0.6mmol),苯丙炔酸胆固醇酯2i(0.3mmol),氨茴内酐3a(0.3mmol),80℃条件下反应10小时。经薄层色谱分析确定反应结束,将反应液经饱和氯化钠水溶液水洗,乙酸乙酯萃取,干燥、过滤后用400目硅胶经旋蒸浓缩制成干粉,再采用柱层析分离反应产物,400目硅胶10g,展开剂为体积比为50:1至5:1的石油醚与乙酸乙酯,得到2,3-二正丙基喹啉产物,产率为53%。
对2-苯基喹啉-3-羧酸胆固醇酯(1k)进行核磁共振检测,请参阅图22至图23,结果为:
1H NMR(400MHz,CDCl3)δ8.64(s,1H),8.18(d,J=8.5Hz,1H),7.92(d,J=8.1Hz,1H),7.83–7.77(m,1H),7.66–7.60(m,2H),7.59(t,J=7.5Hz,1H),7.47(q,J=5.4Hz,3H),5.38–5.29(m,1H),4.76–4.61(m,1H),2.21–2.14(m,1H),2.09–1.93(m,3H),1.87–1.78(m,2H),1.72(d,J=12.2Hz,1H),1.59–1.25(m,12H),1.18–1.00(m,8H),0.92(d,J=8.4Hz,7H),0.88(d,J=1.6Hz,3H),0.86(d,J=1.6Hz,3H),0.67(s,3H)ppm.
13C NMR(100MHz,CDCl3)δ167.3,158.1,148.2,140.9,139.4,138.9,131.4,129.5,128.6,128.4,128.1,127.1,125.9,125.8,122.7,75.4,56.6,56.1,49.9,42.2,39.6,39.4,37.4,36.8,36.5,36.1,35.7,31.8,31.8,28.2,27.9,27.1,24.2,23.8,22.8,22.5,20.9,19.1,18.7,11.8ppm.
本实施例对复杂的天然产物分子如胆固醇等进行后期修饰,进一步证明该方法的应用价值。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (10)
2.根据权利要求1所述制备方法,其特征在于,R1和R2各自独立地选自芳基、杂芳基、C1~10烷基、酯基或氢;
R3选自氢或芳基;
R4选自氢、卤素或醚基。
3.根据权利要求2所述制备方法,其特征在于,R1选自H、苯基、甲基、-COOEt或-C3H7;
R2选自苯基、噻吩基、-C5H11或-C3H7;
R3选自氢或苯基;
R4选自氢、卤素或甲醚基。
4.根据权利要求3所述制备方法,其特征在于,所述苯基上一个或多个氢被醚基、卤素、乙酰基、酯基、三氟甲基或砜基取代。
5.根据权利要求1~4任一所述制备方法,其特征在于,所述金属催化剂选自溴化镍、氯化镍、醋酸镍、碘化镍、醋酸铜、碘化铜、六水合四氟硼酸镍中的一种或多种。
6.根据权利要求1~4任一所述制备方法,其特征在于,所述配体选自4,5-双二苯基膦-9,9-二甲基氧杂蒽、2,2-联吡啶、6,6'-二甲基-2,2'-联吡啶、5,5'-二甲基-2,2'-联吡啶中的一种或多种。
7.根据权利要求1~4任一所述制备方法,其特征在于,所述硅氢试剂选自三苯基硅烷、三乙基硅烷、甲基二乙氧基硅烷、二苯基硅烷、苯基三甲基硅烷、三乙氧基硅烷、聚(甲基氢硅氧烷)中的一种或多种。
8.根据权利要求1~4任一所述制备方法,其特征在于,所述反应的温度为0~100℃。
10.权利要求1~8任一所述制备方法或权利要求9所述喹啉类衍生物在制备具有喹啉结构化合物中的应用。
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CN114989082A (zh) * | 2022-06-30 | 2022-09-02 | 华东理工大学 | 基于i价铜化物和三取代膦协同催化的羟氯喹的高效制备方法 |
CN115504932A (zh) * | 2022-08-12 | 2022-12-23 | 河南师范大学 | 一种3-取代喹啉类化合物的合成方法 |
CN115724794A (zh) * | 2022-10-24 | 2023-03-03 | 广东工业大学 | 一种2-胺基喹啉衍生物的制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1060285A (zh) * | 1990-09-28 | 1992-04-15 | 美国辉瑞有限公司 | 含氮非芳香杂环的稠环类似物 |
CN1468852A (zh) * | 2003-05-30 | 2004-01-21 | 中国科学院大连化学物理研究所 | 对映选择性铱催化氢化取代芳香吡啶环和吡嗪环的方法 |
US20040242615A1 (en) * | 2001-09-14 | 2004-12-02 | Teruo Yamamori | Utilities of olefin derivatives |
CN1589307A (zh) * | 2001-10-17 | 2005-03-02 | 通用显示公司 | 磷光化合物及包括该磷光化合物的元件 |
-
2021
- 2021-03-19 CN CN202110295734.7A patent/CN113121427B/zh not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1060285A (zh) * | 1990-09-28 | 1992-04-15 | 美国辉瑞有限公司 | 含氮非芳香杂环的稠环类似物 |
US20040242615A1 (en) * | 2001-09-14 | 2004-12-02 | Teruo Yamamori | Utilities of olefin derivatives |
CN1589307A (zh) * | 2001-10-17 | 2005-03-02 | 通用显示公司 | 磷光化合物及包括该磷光化合物的元件 |
CN1468852A (zh) * | 2003-05-30 | 2004-01-21 | 中国科学院大连化学物理研究所 | 对映选择性铱催化氢化取代芳香吡啶环和吡嗪环的方法 |
Non-Patent Citations (5)
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114989082A (zh) * | 2022-06-30 | 2022-09-02 | 华东理工大学 | 基于i价铜化物和三取代膦协同催化的羟氯喹的高效制备方法 |
CN115504932A (zh) * | 2022-08-12 | 2022-12-23 | 河南师范大学 | 一种3-取代喹啉类化合物的合成方法 |
CN115504932B (zh) * | 2022-08-12 | 2024-01-26 | 河南师范大学 | 一种3-取代喹啉类化合物的合成方法 |
CN115724794A (zh) * | 2022-10-24 | 2023-03-03 | 广东工业大学 | 一种2-胺基喹啉衍生物的制备方法 |
CN115724794B (zh) * | 2022-10-24 | 2024-05-10 | 广东工业大学 | 一种2-胺基喹啉衍生物的制备方法 |
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