CN105622501B - N-芳基-3-碘代喹啉衍生物及其制备方法 - Google Patents
N-芳基-3-碘代喹啉衍生物及其制备方法 Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- -1 substituted-phenyl Chemical group 0.000 claims abstract description 43
- 239000002904 solvent Substances 0.000 claims abstract description 26
- 239000012043 crude product Substances 0.000 claims abstract description 23
- 229910052740 iodine Chemical class 0.000 claims abstract description 23
- 239000011630 iodine Chemical class 0.000 claims abstract description 23
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical class [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 22
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical class OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 claims abstract description 19
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000000047 product Substances 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 238000010992 reflux Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 51
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 34
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 17
- 239000003208 petroleum Substances 0.000 claims description 17
- 238000004440 column chromatography Methods 0.000 claims description 16
- 239000012046 mixed solvent Substances 0.000 claims description 16
- 235000010290 biphenyl Nutrition 0.000 claims description 15
- 239000004305 biphenyl Substances 0.000 claims description 15
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 15
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims description 3
- VWRQCJRTHKUVNF-UHFFFAOYSA-N 1,1,3-triphenylprop-2-yn-1-ol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C#CC1=CC=CC=C1 VWRQCJRTHKUVNF-UHFFFAOYSA-N 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 238000010523 cascade reaction Methods 0.000 abstract description 2
- 241001597008 Nomeidae Species 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 25
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- 238000000926 separation method Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
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- 150000003254 radicals Chemical class 0.000 description 4
- UIGLAZDLBZDVBL-UHFFFAOYSA-N 1-phenylprop-2-yn-1-ol Chemical compound C#CC(O)C1=CC=CC=C1 UIGLAZDLBZDVBL-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000001340 2-chloroethyl group Chemical class [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 238000006890 Doebner-Miller synthesis reaction Methods 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
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- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
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- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
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- 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
- C07D215/16—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 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
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及N‑芳基‑3‑碘代喹啉衍生物及其制备方法,衍生物结构式为：或者
Description
技术领域
本发明涉及有机合成技术领域，具体涉及N-芳基-3-碘代喹啉衍生物及其制备方法。
背景技术
喹啉衍生物广泛存在于生物碱中，是一类重要的生物活性成分。喹啉的衍生物具有多样的药理作用，如有较强的抗疟疾(Larsen,R.D.；Corley,E.G.；King,A.O.；Carroll,J.D.；Davis,P.；Verhoeven,T.R.；Reider,P.J.；Labelle,M.；Gauthier,J.Y.；Xiang,Y.B.；Zamboni,R.J.,J.Org.Chem.1996,61,3398.)平喘(Dubé,D.；Blouin,M.；Brideau,C.；Chan,C.-C.；Desmarais,S.；Ethier,D.；Falgueyret,J.-P.；Friesen,R.W.；Girard,M.；Girard,Y.；Guay,J.；Riendeau,D.；Tagari,P.；Young,R.N.,Bioorg.Med.Chem.Lett.1998,8,1255.)，抗高血压(Ferrarini,P.L.；Mori,C.；Badawneh,M.；Calderone,V.；Greco,R.；Manera,C.；Martinelli,A.；Nieri,P.；Saccomanni,G.,Eur.J.Med.Chem.2000,35,815.)，抗细菌(Chen,Y.-L.；Fang,K.-C.；Sheu,J.-Y.；Hsu,S.-L.；Tzeng,C.-C.,J.Med.Chem.2001,44,2374.)，抗炎((a)Roma,G.；Di Braccio,M.；Grossi,G.；Mattioli,F.；Ghia,M.,Eur.J.Med.Chem.2000,35,1021-1035；(b)Kalluraya,B.；Sreenivasa,S.,IlFarmaco 1998,53,399.)等作用。因此，对喹啉类衍生物进行结构改造来开发喹啉衍生物药物是国内外的热点。喹啉的传统合成方法包括Skraup合成法，Combes合成法、Doebner-Miller合成法、合成法、Conrad-Limpach-Knorr合成法、Pfitzinger合成法以及陈超课题组最近发表的[2+2+2]喹啉合成法等((a)Marco-Contelles,J.；Pérez-Mayoral,E.；Samadi,A.；Carreiras,M.C.；Soriano,E.Chem.Rev.2009,109,2652.(b)Kouznetsov,V.V.；Mendez,L.Y.；Gomez,C.M.Curr.Org.Chem.2005,9,141.(c)Cheng,C.C.；Yan,S.J.Org.React.1982,28,37.(d)Reitsema,R.H.Chem.Rev.1948,43,43.(e)Bergstrom,F.W.Chem.Rev.1944,35,77.(f)Wang,Y.；Chen,C.；Peng,J.；Li,M.Angew.Chem.Int.Ed.2013,52,5323.)
发明内容
本发明的目的是提供N-芳基-3-碘代喹啉衍生物及其制备方法。
本发明采用的技术方案是：
N-芳基-3-碘代喹啉衍生物，其结构式为：
或者
式中，R1～R4为H、C1～C4直链或支链烃基、C1～C4直链或支链烷氧基；R5为苯基或取代苯基、C1～C4直链或支链烃基；R6、R7为苯基或取代苯基；
所述R5、R6、R7为取代苯基时，取代苯基上的取代基为C1～C4直链或支链烃基、C1～C4直链或支链烷氧基或卤素；所述的C1～C4直链烃基为甲基、乙基、丙基或丁基，支链烃基为异丙基、异丁基；
R1、R2、R3和R4可以相同或不同，R6和R7可以相同或不同；
优选的R1、R4为H，R2、R3为甲氧基。
一种N-芳基-3-碘代喹啉衍生物的制备方法，步骤包括：
A、将取代的芳香基叠氮、取代的炔丙醇与碘在有机溶剂中加热回流，反应12小时以上；
B、减压除去溶剂得到粗产物，将粗产物分离提纯得到产物即N-芳基-3-碘代喹啉衍生物。
所述步骤A中取代的芳香基叠氮、取代的炔丙醇、碘的物质的量比为1：0.8-1.2：2-6；
所述步骤A中有机溶剂选自甲苯、正己烷、四氢呋喃、二氯甲烷、二氯乙烷，1,2-二氯乙烷中的一种或几种，优选为1,2-二氯乙烷；
所述步骤A中加热回流温度为80-90℃；
所述步骤A中取代的芳香基叠氮为3,4-二甲氧基苯基叠氮；所述取代的炔丙醇为1,1,3-三苯基炔丙醇、1,1-二苯基-3-对甲苯基炔丙醇、1,1-二苯基-3-对甲氧基苯基炔丙醇、1,1-二苯基-3-邻氯苯基炔丙醇、1,1-二苯基-3-间氯苯基炔丙醇、1,1-二苯基-3-对氯苯基炔丙醇、1,1-二苯基-3-对氟苯基炔丙醇、1,1-二苯基-3-丁基炔丙醇、1,1-二(对甲苯基)-3-苯基炔丙醇、1,1-二(对甲氧基苯基)-3-苯基炔丙醇、1,1-二(对氯苯基)-3-苯基炔丙醇、1-苯基-1-对甲氧基苯基-3-苯基炔丙醇、1-(9-芴基)-3-苯基炔丙醇、1-(9-芴基)-3-对甲苯基炔丙醇或1-(9-芴基)-3-对氯苯基炔丙醇；
所述步骤B中分离提纯步骤具体为：以体积比为1:1:1的石油醚、乙酸乙酯、二氯甲烷的混合溶剂为展开剂，将粗产物通过柱层析分离得到产物。
本发明利用取代的芳香基叠氮、取代的炔丙醇与碘串联反应来制备N-芳基-3-碘代喹啉衍生物，具有反应步骤少，产率高的优点。
具体实施方式
下面结合实施例对本发明作详细的说明
实施例1
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1,3-三苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(347mg，产率：75％)。其结构式为：
表征数据为：M.p.229-230℃ 1H NMR(300MHz,CDCl3)δ7.71-7.55(m,7H),7.54-7.38(m,5H),7.37-7.28(m,3H),6.91(s,1H),6.53(s,1H),3.81(s,3H)；3.80(s,3H)；13C NMR(75MHz,CDCl3)δ161.55,157.94,156.37,152.52,140.22,139.29,138.86,137.25,130.95,130.26,130.19,129.97,129.54,129.15,128.53,128.23,127.92,125.83,106.89,100.07,98.49,57.13,56.63；IR(KBr)v 3047,2930,1614,1509,1397,1260,1220,1141,696,566。
实施例2
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-对甲苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(357mg，产率：76％)。其结构式为：
表征数据为：M.p.272-273℃；1H NMR(300MHz,DMSO-D6)δ7.65(d,J＝7.7Hz,2H),7.59-7.41(m,7H),7.41-7.22(m,5H),6.94(s,1H),6.43(s,1H),3.73(s,3H),3.65(s,3H),2.47(s,3H)；13C NMR(75MHz,DMSO-D6)δ161.07,157.76,156.82,151.87,140.00,139.89,138.28,137.57,131.17,130.28,129.73,128.62,128.55,128.08,124.67,106.37,100.82,100.06,56.95,56.73,21.65；IR(KBr)v 2930,2850,1618,1506,1404,1263,1224,703cm-1。
实施例3
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-对甲氧基苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色产物(382mg，产率：80％)。其结构式为：
表征数据为：M.p.253-254℃ 1H NMR(300MHz,DMSO-D6)δ7.63(d,J＝6.7Hz,2H),7.56-7.46(m,3H),7.45-7.38(m,4H),7.38-7.23(m,5H),6.98(s,1H),6.41(s,1H),3.89(s,3H),3.76(s,3H),3.65(s,3H)；13C NMR(75MHz,DMSO-D6)δ160.98,160.60,157.83,156.79,151.87,140.06,138.41,138.27,132.47,131.19,130.47,130.31,129.75,128.58,128.11,124.82,115.10,106.50,101.19,100.06,56.93,56.73,55.90；IR(KBr)v 2930,2850,1617,1508,1400,1263,1259,620cm-1。
实施例4
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-邻氯苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(288mg，产率：60％)。其结构式为：
表征数据为：M.p.225-226℃ 1H NMR(300MHz,CDCl3)δ7.96-7.86(m,1H),7.85-7.76(m,1H),7.72-7.60(m,4H),7.59-7.52(m,1H),7.52-7.44(m,2H),7.42-7.29(m,4H),7.25-7.14(m,1H),6.78(s,1H),6.56(s,1H),3.85(s,3H),3.81(s,3H).13C NMR(75MHz,CDCl3)δ159.00,158.29,156.56,153.06,139.22,138.94,138.71,136.86,131.60,131.08,130.75,130.66,130.35,130.18,129.90,129.80,128.95,128.90,128.76,128.28,128.22,127.00,125.72,105.90,100.32,98.16,57.19,56.77；IR(KBr)v 2930,1618,1508,1399,1253,1253,1220,618,597cm-1。
实施例5
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-间氯苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(350mg，产率：73％)。其结构式为：
表征数据为：M.p.124-125℃；1H NMR(300MHz,DMSO-D6)δ7.85-7.73(m,2H),7.66(d,J＝8.7Hz,1H),7.62-7.48(m,5H),7.48-7.29(m,6H),6.89(s,1H),6.45(s,1H),3.79(s,3H),3.69(s,3H)；13C NMR(75MHz,DMSO-D6)δ159.01,157.98,157.03,152.14,142.26,139.95,138.34,138.08,134.36,131.97,131.30,130.47,130.41,129.72,128.64,128.57,128.08,127.95,127.43,124.51,106.08,100.55,100.12,57.00,56.84；IR(KBr)v 2933,1625,1509,1260,1220,616cm-1。
实施例6
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-对氯苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(312mg，产率：65％)。其结构式为：
表征数据为：M.p.263-264℃；1H NMR(300MHz,DMSO-D6)δ7.81(d,J＝8.3Hz,2H),7.62(d,J＝7.4Hz,2H),7.56-7.45(m,5H),7.42(d,J＝7.6Hz,2H),7.39-7.24(m,3H),6.89(s,1H),6.43(s,1H),3.77(s,3H),3.66(s,3H)；13C NMR(75MHz,DMSO-D6)δ159.57,157.87,156.98,152.09,139.97,139.20,138.34,138.14,135.17,131.26,130.75,130.36,130.03,129.72,128.62,128.03,124.58,106.12,100.69,100.14,57.00,56.88；IR(KBr)v 2933,1621,1509,1260,1140,569cm-1。
实施例7
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-对氟苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(241mg，产率：51％)。其结构式为：
表征数据为：M.p.231-232℃；1H NMR(300MHz,DMSO-D6)δ7.68-7.59(m,3H),7.59-7.48(m,6H),7.45(dd,J＝8.1,1.6Hz,2H),7.41-7.28(m,3H),6.90(s,1H),6.45(s,1H),3.78(s,3H),3.68(s,3H)；13C NMR(75MHz,DMSO-D6)δ164.77,161.49,159.93,157.88,156.93,152.04,139.99,138.31,138.20,136.78,136.73,131.30,131.24,131.19,130.35,129.72,128.61,128.05,124.78,117.18,116.88,106.21,100.93,100.11,56.98,56.81；IR(KBr)v 2932,1614,1509,1260,1224,844cm-1。
实施例8
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二苯基-3-丁基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(358mg，产率：79％)。其结构式为：
表征数据为：M.p.186-187℃；1H NMR(300MHz,DMSO-D6)δ7.80(s,1H),7.63-7.54(m,2H),7.54-7.44(m,3H),7.43-7.27(m,5H),6.37(s,1H),4.14(s,3H),3.77-3.58(m,5H),1.86-1.60(m,4H),1.08(t,J＝7.1Hz,3H)；13C NMR(75MHz,DMSO-D6)δ162.27,157.54,156.59,152.05,140.16,138.74,137.61,131.10,130.31,130.24,129.75,128.59,128.23,123.62,105.15,100.86,100.27,57.37,56.78,31.26,23.13,14.36；IR(KBr)v 2962,2861,1621,1513,1260,1216,1173,844,692cm-1。
实施例9
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二(对甲苯基)-3-苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(391mg，产率：82％)。其结构式为：
表征数据为：M.p.245-246℃；1H NMR(300MHz,DMSO-D6)δ7.80-7.63(m,3H),7.52(d,J＝8.3Hz,2H),7.49-7.42(m,2H),7.39-7.28(m,4H),7.19(d,J＝8.1Hz,2H),6.86(s,1H),6.45(s,1H),3.72(s,3H),3.68(s,3H),2.33(s,3H),2.25(s,3H)；13C NMR(75MHz,DMSO-D6)δ160.72,158.42,156.75,151.85,140.77,140.52,139.83,138.46,137.78,135.66,130.74,130.33,129.77,129.58,129.19,128.57,127.71,124.51,106.25,100.94,100.15,56.96,56.60,21.40,21.34；IR(KBr)v 2939,1618,1516,1260,1137,620cm-1。
实施例10
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二(对甲氧基苯基)-3-苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(458mg，产率：93％)。其结构式为：
表征数据为：M.p.253-254℃；1H NMR(300MHz,DMSO-D6)δ7.81-7.64(m,3H),7.57(d,J＝8.9Hz,2H),7.47(d,J＝7.6Hz,2H),7.37(d,J＝8.6Hz,2H),7.08(d,J＝8.9Hz,2H),6.95(d,J＝8.7Hz,2H),6.86(s,1H),6.50(s,1H),3.78(s,3H),3.72(d,J＝6.1Hz,9H)；13CNMR(75MHz,DMSO-D6)δ160.56,160.33,160.16,158.72,156.74,151.81,140.58,138.84,133.06,131.31,130.85,130.31,129.79,129.26,128.57,124.52,115.31,114.01,106.24,101.46,100.19,57.04,56.61,56.11,55.71；IR(KBr)v 2933,2839,1618,1513,1260,1173,1028,833cm-1。
实施例11
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1,1-二(对氯苯基)-3-苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(229mg，产率：46％)。
其结构式为：
表征数据为：M.p.247-248℃；1H NMR(300MHz,DMSO-D6)δ7.82-7.62(m,7H),7.58-7.43(m,6H),6.90(s,1H),6.49(s,1H),3.77(s,3H),3.75(s,3H)；13C NMR(75MHz,DMSO-D6)δ161.01,157.23,156.78,152.10,140.22,138.66,138.35,137.03,135.94,135.33,131.76,130.71,130.48,129.95,129.86,129.05,128.56,124.70,106.28,100.49,99.96,57.32,56.71；IR(KBr)v 2935,2836,1618,1513,1437,1397,1260,1220,1014,830,703,591cm-1。
实施例12
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1-苯基-1-对甲氧基苯基-3-苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(382mg，产率：80％)。其结构式为：
表征数据为：M.p.240-241℃；1H NMR(300MHz,DMSO-D6)δ7.83-7.63(m,3H),7.57(d,J＝8.8Hz,2H),7.52-7.28(m,7H),7.05(d,J＝8.8Hz,2H),6.87(s,1H),6.52(s,1H),3.75(s,3H),3.73(s,3H),3.71(s,3H)；13C NMR(75MHz,DMSO-D6)δ160.73,160.39,158.45,156.86,151.90,140.47,138.82,138.48,132.79,130.35,130.27,129.80,129.63,129.36,128.63,128.58,124.64,115.24,106.24,100.40,100.14,57.09,56.64,56.10；IR(KBr)v2939,1643,1506,1401,1253,1220,1112,701cm-1。
实施例13
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1-(9-芴基)-3-苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(282mg，产率：61％)。其结构式为：
表征数据为：M.p.155-156℃；1H NMR(300MHz,DMSO-D6)δ9.32(d,J＝8.4Hz,1H),8.80(d,J＝7.2Hz,1H),8.74(d,J＝8.1Hz,1H),8.62(d,J＝8.6Hz,1H),8.07(s,1H),8.01(t,J＝7.7Hz,1H),7.88(t,J＝7.6Hz,1H),7.84-7.64(m,4H),7.59(s,2H),7.23(s,1H),6.65(s,1H),3.89(s,3H),3.60(s,3H)；13C NMR(75MHz,DMSO-D6)δ159.12,154.39,151.35,150.59,141.56,135.40,135.06,133.44,130.77,130.56,130.48,130.33,130.22,129.64,128.62,128.27,127.64,125.60,125.44,124.44,123.96,123.81,106.89,105.45,89.10,57.39,56.48；IR(KBr)v 2935,1639,1618,1506,1253,757,616cm-1。
实施例14
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1-(9-芴基)-3-对甲苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(277mg，产率：59％)。
其结构式为：
表征数据为：M.p.236-237℃；1H NMR(300MHz,DMSO-D6)δ9.39(d,J＝8.1Hz,1H),8.88(d,J＝7.2Hz,1H),8.82(d,J＝8.1Hz,1H),8.69(d,J＝8.4Hz,1H),8.20-8.04(m,2H),8.02-7.81(m,3H),7.75(d,1H),7.65-7.41(m,2H),7.21(s,1H),6.79(s,1H),5.23(s,1H),3.97(s,3H),3.70(s,3H),2.50(s,3H)；13C NMR(75MHz,DMSO-D6)δ159.36,154.36,151.33,150.63,139.87,138.73,135.37,135.05,133.41,130.71,130.61,130.45,130.19,128.64,128.24,127.68,125.56,125.42,124.37,123.93,123.81,107.03,105.39,89.22,57.35,56.54,21.71；IR(KBr)v 2933,1618,1509,1263,1213,1213,761,616cm-1。
实施例15
在两口烧瓶中依次加入3,4-二甲氧基苯基叠氮(0.5mmol)，1-(9-芴基)-3-对氯苯基炔丙醇(0.5mmol),碘(1.5mmol),ClCH2CH2Cl(3mL)，然后加热至84℃，搅拌15小时(TLC监测)。减压除去溶剂得到粗产品，以石油醚：乙酸乙酯：二氯甲烷＝1:1:1的混合溶剂为展开剂，通过柱层析分离得到棕色固体产物(278mg，产率：58％)。其结构式为：
表征数据为：M.p.261-262℃；1H NMR(300MHz,DMSO-D6)δ9.41(d,J＝8.3Hz,1H),8.93(d,J＝7.5Hz,1H),8.87(d,J＝8.1Hz,1H),8.72(d,J＝8.5Hz,1H),8.24-8.07(m,2H),8.08-7.82(m,5H),7.78(d,J＝7.6Hz,1H),7.36(d,J＝7.5Hz,1H),6.78(s,1H),3.99(s,3H),3.77(s,3H)；13C NMR(75MHz,DMSO-D6)δ157.94,154.56,151.60,150.61,140.48,135.57,135.20,135.16,133.56,132.75,130.92,130.78,130.60,130.34,129.92,128.40,127.69,125.70,125.54,124.54,124.07,123.76,106.78,105.63,89.41,57.47,56.76；IR(KBr)v 2935,1618,1513,1477,1260,1166,1014,761,573cm-1。
Claims (7)
1.一种N-芳基-3-碘代喹啉衍生物的制备方法，步骤包括：
A、将取代的芳香基叠氮、取代的炔丙醇与碘在有机溶剂中加热回流，反应12小时以上；
B、减压除去溶剂得到粗产物，将粗产物分离提纯得到产物即N-芳基-3-碘代喹啉衍生物；
所述步骤A中取代的芳香基叠氮为3,4-二甲氧基苯基叠氮；所述取代的炔丙醇为1,1,3-三苯基炔丙醇、1,1-二苯基-3-对甲苯基炔丙醇、1,1-二苯基-3-对甲氧基苯基炔丙醇、1,1-二苯基-3-邻氯苯基炔丙醇、1,1-二苯基-3-间氯苯基炔丙醇、1,1-二苯基-3-对氯苯基炔丙醇、1,1-二苯基-3-对氟苯基炔丙醇、1,1-二苯基-3-丁基炔丙醇、1,1-二(对甲苯基)-3-苯基炔丙醇、1,1-二(对甲氧基苯基)-3-苯基炔丙醇、1,1-二(对氯苯基)-3-苯基炔丙醇、1-苯基-1-对甲氧基苯基-3-苯基炔丙醇、1-(9-芴基)-3-苯基炔丙醇、1-(9-芴基)-3-对甲苯基炔丙醇或1-(9-芴基)-3-对氯苯基炔丙醇；
所述N-芳基-3-碘代喹啉衍生物，其结构式为：
式中，R1～R4为H、C1～C4直链或支链烃基、C1～C4直链或支链烷氧基；R5为苯基或取代苯基、C1～C4直链或支链烃基；R6、R7为苯基或取代苯基；
所述R5、R6、R7为取代苯基时，取代苯基上的取代基为C1～C4直链或支链烃基、C1～C4直链或支链烷氧基或卤素；所述的C1～C4直链烃基为甲基、乙基、丙基或丁基，支链烃基为异丙基、异丁基。
2.如权利要求1所述的制备方法，其特征在于：所述R1、R4为H，R2、R3为甲氧基。
3.如权利要求1所述的制备方法，其特征在于：所述步骤A中取代的芳香基叠氮、取代的炔丙醇、碘的物质的量比为1：0.8-1.2：2-6。
4.如权利要求1所述的制备方法，其特征在于：所述步骤A中有机溶剂选自甲苯、正己烷、四氢呋喃、二氯甲烷、二氯乙烷，1,2-二氯乙烷中的一种或几种。
5.如权利要求4所述的制备方法，其特征在于：所述步骤A中有机溶剂为1,2-二氯乙烷。
6.如权利要求1所述的制备方法，其特征在于：所述步骤A中加热回流温度为80-90℃。
7.如权利要求1所述的制备方法，其特征在于：所述步骤B中分离提纯步骤具体为：以体积比为1:1:1的石油醚、乙酸乙酯、二氯甲烷的混合溶剂为展开剂，将粗产物通过柱层析分离得到产物。
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| Synthesis of Substituted Quinolines by the Electrophilic Cyclization of N-(2-Alkynyl)anilines;Xiaoxia Zhang，et al.;《Tetrahedron》;20101231;第66卷(第6期);第1177页 |
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