CN107400084B - 一种合成喹啉衍生物的方法 - Google Patents
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Abstract
本发明公开了一种合成喹啉衍生物的方法，其具体步骤为：在反应容器中，加入酮、邻氨基苯甲醇、铱络合物催化剂、碱和溶剂水，反应混合物在空气中回流反应，反应结束后冷却到室温；用乙酸乙酯萃取，旋转蒸发除去溶剂，然后通过柱分离，得到目标化合物。本发明不需要使用缚氢剂或者氧气，并使用环境友好的水作反应溶剂，在空气中回流12小时，该反应符合绿色化学的要求，具有广阔的应用前景。
Description
技术领域
本发明属有机合成化学技术领域，具体涉及一种喹啉衍生物的合成方法。
背景技术
喹啉衍生物是一类重要的含氮杂环化合物，广泛的存在于生物碱等天然产物中，并具有广泛的生理和药物活性(a)Michael,J.P.Nat.Prod.Rep.1997,14,605-618；b)Michael,J.P.Nat.Prod.Rep.2002,19,742-760)。例如，这类化合物被用作DNA-水解酶、DNA胞嘧啶脱氢酶抑制剂、阿尔茨海默病的多靶向配体、用于传送蛋白质的PET放射性配体等(a)J.D.Becherer,E.E.Boros,T.Y.Carpenter,D.J.Cowan,D.N.Deaton,C.D.Haffner,M.R.Jeune,I.W.Kaldor,J.C.Poole,F.Preugschat,T.R.Rheault,C.A.Schulte,B.G.Shearer,T.W.Shearer,L.M.Shewchuk,T.L.SmalleyJr.,E.L.Stewart,J.D.Stuart,J.C.Ulrich,J.Med.Chem.2015,58.7021-7056；b)M.E.Olson,D.Abate-Pella,A.L.Perkins,M Li,M.A.Carpenter,A.Rathore,R.S.Harris,D.A.Harki,J.Med.Chem.2015,58,7419-7430；c)Z.Wang,Y.Wang,B.Wang,W.Li,L.Huang,X.Li,J.Med.Chem.2015,58,8616-8637；d)C.Brouwer,K.Jenko,S.S.Zoghbi,R.B.Innis,V.W.Pike,J.Med.Chem.2014,57,6240-6251)
合成喹啉衍生物的经典方法已经发展起来，例如Skraup反应、Doebner-vonMiller反应、Conrad-Limpach反应、Pfitzinger反应和Friedlaeder反应。在这些方法中,Friedlaeder反应是最为简单的一种方法,即采用碱或酸催化邻氨基苯甲醛和酮反应环构制备喹啉衍生物(J.Marco-Contelles,E.Perez-Mayoral,A.Samadi,M.C.Carreiras,E.Soriano,Chem.Rev.2009,109,2652-2671)。但是邻氨基苯甲醛是非常不稳定的化合物,容易发生自聚,因而这种方法的潜力也受到严重的限制。
近些年，使用钌、铱以及其它的过渡金属催化剂催化由邻氨基苯甲醇和酮为原料来制备喹啉衍生物取得了一定的进展。然而，这些反应中需要加入过量的酮、不饱和烯烃或者氧气作为氢的受体，在反应过程中，通过氢转移实现邻氨基苯甲醇转化为邻氨基苯甲醛。而且，这些反应使用有机溶剂，容易造成环境污染。(a)C.S.Cho,B.T.Kim,T.J.Kim,S.C.Shim,Chem.Commun.2001,2576-2577；b)C.S.Cho,B.T.Kim,H.J.Choi,T.J.Kim,S.C.Shim,Tetrahedron 2003,59,7997-8002；c)K.Motokura,T.Mizugaki,K.Ebitani,K.Kaneda,Tetrahedron Lett.2004,45,6029-6032；d)a)K.Taguchi,S.Sakaguchi,Y.Ishii,Tetrahedron Lett.2005,46,4539-4542；e)R.Martinez,D.J.Ramon,M.Yus,Tetrahedron 2006,62,8982-8987；f)R.Martinez,D.J.Ramon,M.Yus,Tetrahedron 2006,62,8988-9001；g)R.Martinez,D.J.Ramon,M.Yus,Eur.J.Org.Chem.2007,1599-1605；h)H.V.Mierde,P.V.D.Voort,D.D.Vos,F.Verpoort,Eur.J.Org.Chem.2008,1625-1631).
发明内容
本发明的目的在于提供一种合成喹啉衍生物的新方法。
本发明通过下述技术方案实现：一种合成喹啉衍生物(式Ⅰ)的新方法
其包含使酮(式II)
与化合物邻氨基苯甲醇(式III)反应
反应是在铱络合物催化剂存在下发生，其反应通式为
其中，R1选自C3-C4烷基、芳基、甲基苯基、乙基苯基、甲氧基苯基、三氟甲基苯基、卤代苯基、萘基；
R2选自氢、C2-C3烷基；
R3选自甲基、卤素。
发明通过下述技术方法实现：
在反应容器中，加入酮II、邻氨基苯甲醇III、铱络合物催化剂、碱和溶剂水，反应混合物在空气中回流反应数小时后，冷却到室温；用乙酸乙酯萃取，旋转蒸发除去溶剂，然后通过柱分离，得到目标化合物。
其中，铱络合物催化剂为铱络合物[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2
碱选自氢氧化钾；碱相对于酮的摩尔比为0.5-1.0equiv；催化剂用量相对于酮的摩尔比为1.0mol％；邻氨基苄醇相对于酮摩尔比为1.2equiv；反应时间为12小时以上。
与现有技术相比，本发明不需要使用缚氢剂或者氧气，并使用环境友好的水作反应溶剂，在空气中回流12小时，该反应符合绿色化学的要求，具有广阔的应用前景。
具体实施方式
展示一下实例来说明本发明的某些实施例，且不应解释为限制本发明的范围。对本发明公开的内容可以同时从材料，方法和反应条件上进行许多改进，变化和改变。所有这些改进，变化和改变均确定地落入本发明的精神和范围之内。
实施例1:2-苯基喹啉
2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。用乙酸乙酯萃取，反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：86％
1H NMR(500MHz,CDCl3)δ8.23(d,J＝8.6Hz,1H),8.19-8.16(m,3H),7.89(d,J＝8.6Hz,1H),7.84(d,J＝8.1Hz,1H),7.73(t,J＝7.0Hz,1H),7.53(t,J＝7.5Hz,3H),7.47(t,J＝7.3Hz,1H)；13C NMR(125MHz,CDCl3)δ157.4,148.3,139.7,136.8,129.8,129.6,129.3,128.8,127.6,127.5,127.2,126.3,119.0.
实施例2:2-(3-氟基苯基)喹啉
2-(3-fluorophenyl)quinoline
将间氟苯乙酮(166mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,0.1mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。用乙酸乙酯萃取，反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：80％
1H NMR(500MHz,CDCl3)δ8.23(d,J＝8.6Hz,1H),8.18(d,J＝8.5Hz,1H),7.93-7.91(m,2H),7.83(t,J＝6.9Hz,2H),7.75-7.72(m,1H),7.54(t,J＝7.5Hz,1H),7.49(q,J＝7.2Hz,1H),7.17-7.14(m,1H)；13C NMR(125MHz,CDCl3)δ164.3,162.4,155.8,148.2,141.9(d,JC-F＝7.4Hz),137.0,130.3(d,J＝8.1Hz),129.8(d,JC-F＝7.4Hz),127.5,127.3,126.6,123.1,118.7,116.2(d,JC-F＝21.2Hz),114.5(d,JC-F＝22.6Hz).
实施例3:2-(4-氟基苯基)喹啉
2-(4-fluorophenyl)quinoline
将对氟基苯乙酮(166mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：84％
1H NMR(500MHz,CDCl3)δ8.23(d,J＝8.6Hz,1H),8.18-8.14(m,3H),7.84(d,J＝8.7Hz,2H),7.73(t,J＝7.7Hz,1H),7.53(t,J＝7.5Hz,1H),7.21(t,J＝8.7Hz,2H)；13CNMR(125MHz,CDCl3)δ164.8(d,JC-F＝247.5Hz),156.2,148.2,136.9,135.8(JC-F＝1.8Hz),129.7,129.6,129.4(d,JC-F＝8.0Hz),127.4,127.0,126.3,118.6,115.8(d,JC-F＝21.3Hz).
实施例4:2-(4-氯苯基)喹啉
2-(4-chlorophenyl)quinoline
将对氯苯乙酮(186mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：80％
1H NMR(500MHz,CDCl3)δ8.11(d,J＝8.5Hz,1H),8.03(s,1H),7.80(d,J＝8.1Hz,1H),7.67(t,J＝7.3Hz,1H),7.56-7.52(m,3H),7.48-7.46(d,J＝8.4Hz,2H),2.47(s,3H)；13C NMR(125MHz,CDCl3)δ159.2,146.6,139.3,137.0,134.3,130.3,129.2,128.9,128.5,127.6,126.7,126.6,20.5.
实施例5:2-(2,4-二氯苯基)喹啉
2-(2,4-dichlorophenyl)quinoline
将2,4-二氯苯乙酮(227mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：84％
1H NMR(500MHz,CDCl3)δ8.24(d,J＝8.5Hz,1H),8.17(d,J＝8.5Hz,1H),7.89(d,J＝8.1Hz,1H),7.77-7.72(m,2H),7.68(d,J＝8.3Hz,1H),7.59(t,J＝7.5Hz,1H),7.54(d,J＝1.9Hz,1H),7.41(dd,J＝8.3and 1.9Hz,1H)；13C NMR(125MHz,CDCl3)δ156.3,148.1,138.2,135.8,135.2,133.1,132.6,129.9,129.8,129.7,127.6,127.5,127.2,127.0,122.5.
实施例6:2-(3-溴苯基)喹啉
2-(3-bromophenyl)quinoline
将对溴苯乙酮(239mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。用乙酸乙酯萃取，反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：82％
1H NMR(500MHz,CDCl3)δ8.36(m,1H),8.24(d,J＝8.6Hz,1H),8.18(d,J＝8.5Hz,1H),8.09(d,J＝7.8Hz,1H),7.85(d,J＝8.6Hz,2H),7.74(t,J＝7.7Hz,1H),7.60(d,J＝7.9Hz,1H),7.55(t,J＝7.5Hz,1H),7.39(t,J＝7.9Hz,1H)；13C NMR(125MHz,CDCl3)δ155.6,148.2,141.7,137.0,132.2,130.6,130.3,129.9,129.8,127.5,127.4,126.6,126.0,123.1,118.7.
实施例7:2-(4-溴苯基)喹啉
2-(4-bromophenyl)quinoline
将对溴苯乙酮(239mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。用乙酸乙酯萃取，反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：86％
1H NMR(500MHz,CDCl3)δ8.24(d,J＝8.6Hz,1H),8.16(d,J＝8.5Hz,1H),8.07(d,J＝8.5Hz,2H),7.84(t,J＝7.0Hz,2H),7.74(t,J＝7.2Hz,1H),7.66(d,J＝8.5Hz,2H),7.54(t,J＝7.5Hz,1H)；13C NMR(125MHz,CDCl3)δ156.0,148.2,138.5,137.0,132.0,129.8,129.7,129.1,127.5,127.2,126.5,123.9,118.5,
实施例8:2-(4-三氟甲基苯基)喹啉
2-(4-(trifluoromethyl)phenyl)quinoline
将对三氟苯乙酮(226mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：87％
1H NMR(500MHz,CDCl3)δ8.28(t,J＝8.2Hz,3H),8.20(d,J＝8.5Hz,1H),7.91(d,J＝8.6Hz,1H),7.87(d,J＝8.2Hz,1H),7.79-7.75(m,3H),7.57(t,J＝7.5Hz,1H)；13CNMR(125MHz,CDCl3)δ155.6,148.3,142.9,137.1,131.2(q,JC-F＝32.2Hz),130.0,129.9,127.8,127.5,127.4,126.8,125.7,125.3(q,JC-F＝270.6Hz),118.7.
实施例9:2-(2-甲基苯基)喹啉
2-(2-methylphenyl)quinoline
将对甲基苯乙酮(160mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：82％
1H NMR(500MHz,CDCl3)δ8.22(d,J＝8.4Hz,1H),8.17(d,J＝8.5Hz,1H),7.87(d,J＝7.7Hz,1H),7.74(t,J＝7.0Hz,1H),7.58-7.53(m,2H),7.51-7.49(m,1H),7.36-7.30(m,3H),2.4(s,3H)；13C NMR(125MHz,CDCl3)δ160.3,147.9,140.7,136.0,136.0,130.8,129.7,129.6,129.6,128.5,127.5,126.7,126.4,126.0,122.3,20.3.
实施例10:2-(4-甲基苯基)喹啉
2-(4-methylphenyl)quinoline
将对甲基苯乙酮(160mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：78％
1H NMR(500MHz,CDCl3)δ8.21(d,J＝8.6Hz,1H),8.17(d,J＝8.6Hz,1H),8.08(d,J＝8.1Hz,2H),7.87(d,J＝8.6Hz,1H),7.82(d,J＝7.6Hz,1H),7.73-7.70(m,1H),7.53-7.50(m,1H),7.34(d,J＝7.9Hz,2H),2.44(s,3H)；13C NMR(125MHz,CDCl3)δ157.3,148.3,139.4,136.9,136.6,129.6,129.5,127.4,127.1,126.0,118.8,21,3.
实施例11:2-(4-乙基苯基)喹啉
2-(4-ethylphenyl)quinoline
将对乙基苯乙酮(178mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：81％
1H NMR(500MHz,CDCl3)δ8.20(d,J＝8.6Hz,1H),8.17(d,J＝8.5Hz,1H),8.10(d,J＝8.2Hz,2H),7.87(d,J＝8.6Hz,1H),7.82(d,J＝8.0Hz,1H),7.71(t,J＝7.1Hz,1H),7.51(t,J＝7.5Hz,1H),7.37(d,J＝8.1Hz,2H),2.74(q,J＝7.6Hz,2H),1.29(t,J＝7.6Hz,3H)；13C NMR(125MHz,CDCl3)δ152.6,143.5,141.0,132.4,131.9,124.9,124.8,123.6,122.8,122.7,122.3,121.3,114.1,24.0,10.8.
实施例12:2-(4-甲氧基苯基)喹啉
2-(4-methoxyphenyl)quinoline
将对甲氧基苯乙酮(180mg,1.0mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：81％
1H NMR(500MHz,CDCl3)δ8.19(d,J＝8.6Hz,1H),8.15-8.13(m,3H),7.85(d,J＝8.6Hz,1H),7.82(d,J＝8.1Hz,1H),7.71(t,J＝7.7Hz,1H),7.50(t,J＝7.5Hz,1H),7.06(d,J＝8.7Hz,2H),3.89(s,3H)；13C NMR(125MHz,CDCl3)δ160.8,156.9,148.3,136.6,132.2,129.5,129.5,128.9,127.4,126.9,125.9,118.5,114.2,55.4.
实施例13:2-(2-吡啶基)喹啉
2-(pyridin-2-yl)quinoline
将2-乙酰基吡啶(145mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：81％
1H NMR(500MHz,CDCl3)δ8.74(d,J＝4.6Hz,1H),8.65(d,J＝7.9Hz,1H),8.56(d,J＝8.6Hz,1H),8.28(d,J＝8.6Hz,1H),8.18(d,J＝8.5Hz,1H),7.86(m,2H),7.73(t,J＝7.6Hz,1H),7.55(t,J＝3.6Hz,1H),7.36-7.34(m,1H)；.13C NMR(125MHz,CDCl3)δ156.2,156.7,149.1,147.8,136.8,136.7,129.7,129.4,128.8,127.5,126.6,123.9,121.7,118.8.
实施例14:2-(2-萘基)喹啉
2-(naphthalen-2-yl)quinoline
将对2-萘基乙酮(204mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：83％
1H NMR(500MHz,CDCl3)δ8.62(s,1H),8.37(dd,J＝8.6and 1.7Hz,1H),8.26(d,J＝8.6Hz,1H),8.22(d,J＝8.5Hz,1H),8.18(d,J＝8.5Hz,1H),8.04(d,J＝8.6Hz,1H),8.0(d,J＝8.0Hz,1H),7.91(m,1H),7.84(d,J＝8.0Hz,1H),7.76-7.73(m,1H),7.76-7.73(m,3H)；.13C NMR(125MHz,CDCl3)δ157.1,148.4,136.9,126.7,133.8,133.5,129.7,129.6,128.8,128.5,127.7,127.4,127.2,127.1,126.7,126.3,125.0,119.1.
实施例15:3-甲基-(2-苯基)喹啉
3-methyl-2-phenylquinoline
将苯丙酮(161mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：86％
1H NMR(500MHz,CDCl3)δ8.14(d,J＝8.5Hz,1H),8.04(s,1H),7.81(d,J＝8.1Hz,1H),7.68-7.64(m,1H),7.56-7.50(m,3H),7.49-7.46(m,2H),7.44-7.42(m,1H),2.80(q,J＝7.5Hz,2H),1.19(t,J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3)δ160.6,146.3,140.9,135.3,134.9,129.3,128.8,128.7,128.3,128.0,127.7,126.9,126.3,26.0,14.7.
实施例16:2-(4-氯苯基)-3-甲基喹啉
2-(4-chlorophenyl)-3-methylquinoline
将对氯苯丙酮(203mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：78％
1H NMR(500MHz,CDCl3)δ8.11(d,J＝8.5Hz,1H),8.03(s,1H),7.80(d,J＝8.1Hz,1H),7.67(t,J＝7.3Hz,1H),7.56-7.52(m,3H),7.48-7.46(d,J＝8.4Hz,2H),2.47(s,3H)；13C NMR(125MHz,CDCl3)δ159.2,146.6,139.3,137.0,134.3,130.3,129.2,128.9,128.5,127.6,126.7,126.6,20.5.
实施例17:2-(4-溴苯基)-3-甲基喹啉
2-(4-bromophenyl)-3-methylquinoline
将对溴苯丙酮(256mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：79％
1H NMR(500MHz,CDCl3)δ8.10(d,J＝8.5Hz,1H),8.02(s,1H),7.78(d,J＝8.1Hz,1H),7.69-7.65(m,1H),7.63(d,J＝8.4Hz,2H),7.55-7.52(m,1H),7.51-7.47(m,2H),2.46(s,3H)；13C NMR(125MHz,CDCl3)δ159.2,146.6,139.7,136.9,131.4,130.6,129.2,128.9,128.8,127.6,126.7,126.6,122.5,20.5.
实施例18:3-乙基-(2-苯基)喹啉
3-ethyl-2-phenylquinoline
将苯丁酮(178mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：85％
1H NMR(500MHz,CDCl3)δ8.14(d,J＝8.5Hz,1H),8.04(s,1H),7.81(d,J＝8.1Hz,1H),7.68-7.64(m,1H),7.56-7.50(m,3H),7.49-7.46(m,2H),7.44-7.42(m,1H),2.80(q,J＝7.5Hz,2H),1.19(t,J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3)δ160.6,146.3,140.9,135.3,134.9,129.3,128.8,128.7,128.3,128.0,127.7,126.9,126.3,26.0,14.7.
实施例19:2-环丙基喹啉
2-cyclopropylquinoline
将环丙基甲酮(101mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：70％
1H NMR(500MHz,CDCl3)δ7.97(d,J＝8.4Hz,2H),7.71(d,J＝8.3Hz,1H),7.62(t,J＝7.0Hz,1H),7.40(t,J＝7.5Hz,1H),7.14(d,J＝8.5Hz,1H),2.25-2.20(m,1H),1.17-1.14(m,2H),1.11-1.06(m,2H)；13C NMR(125MHz,CDCl3)δ163.4,148.0,135.7,129.2,128.7,127.4,126.7,125.1,119.3,18.1,10.2.
实施例20:2-叔丁基喹啉
2-(tert-butyl)quinoline
将嚬哪酮(120mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、邻氨基苄醇(123mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：61％
1H NMR(500MHz,CDCl3)δ8.07(d,J＝8.5Hz,2H),7.76(d,J＝8.2Hz,1H),7.66(t,J＝7.0Hz,1H),7.52(d,J＝8.7Hz,1H),7.46(t,J＝7.5Hz,1H),1.47(s,9H)；13C NMR(125MHz,CDCl3)δ169.2,147.4,135.9,129.4,129.0,127.2,126.4,125.6,118.2,38.1,30.1.
实施例21:6-氟-(2-苯基)喹啉
6-fluoro-2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、2-氨基-5-氟苄醇(141mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：93％
1H NMR(500MHz,CDCl3)δ8.18-8.14(m,4H),7.90(d,J＝8.7Hz,1H),7.55-7.43(m,5H).13C NMR(125MHz,CDCl3)δ161.3,159.3(d,JC-F＝325.4Hz),145.4,139.3,136.1(d,JC-F＝5.0Hz),132.2(d,JC-F＝9.1Hz),129.4,128.9,127.7(d,JC-F＝10.0Hz),127.4,119.9(d,JC-F＝26.2Hz),119.7,110.5(d,JC-F＝22.0Hz).
实施例22:6-氯-(2-苯基)喹啉
6-chloro-2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、2-氨基-5-氯苄醇(157mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：83％
1H NMR(500MHz,CDCl3)δ8.12(m,4H),7.90(d,J＝8.6Hz,1H),7.81(d,J＝2.3Hz,1H),7.67-7.64(dd,J＝8.9Hz,J＝2.3Hz,1H),7.53(t,J＝7.4Hz,2H),7.47(t,J＝7.3Hz,1H).13C NMR(125MHz,CDCl3)δ157.5,146.6,139.2,135.8,131.9,131.3,130.5,129.5,128.8,127.7,127.5,126.1,119.8.
实施例23:7-氯-(2-苯基)喹啉
7-chloro-2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、2-氨基-5-氯苄醇(157mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：84％
1H NMR(500MHz,CDCl3)δ8.21(d,J＝8.7Hz,1H),8.18-8.15(m,3H),7.90(d,J＝8.6Hz,1H),7.78(d,J＝8.7Hz,1H),7.56-7.52(m,2H),7.50-7.47(m,2H)；13C NMR(125MHz,CDCl3)δ158.2,148.6,139.2,136.5,135.5,129.6,128.9,128.7,128.6,127.6,127.3,125.5,119.1.
实施例24:7-溴-(2-苯基)喹啉
7-bromo-2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、2-氨基-4-溴苄醇(201mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：94％
1H NMR(500MHz,CDCl3)δ8.36(d,J＝1.8Hz,1H),8.16(m,3H),7.87(d,J＝8.6Hz,1H),7.67(d,J＝8.6Hz,1H),7.60-7.58(dd,J＝8.6Hz,J＝1.9Hz,1H),7.53(m,2H),7.53(m,2H),7.48(m,1H)；13C NMR(125MHz,CDCl3)δ158.1,148.8,139.1,136.6,132.0,129.7,129.6,128.8,128.6,127.5,125.7,123.6,119.2
实施例25:6-甲基-(2-苯基)喹啉
6-methyl-2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、2-氨基-5-甲基苄醇(137mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：85％
1H NMR(500MHz,CDCl3)δ8.14(d,J＝7.5Hz,2H),8.10(d,J＝8.6Hz,1H),8.07(d,J＝8.5Hz,1H),7.82(d,J＝8.9Hz,1H),7.58-7.5(m,4H),7.45(t,J＝7.3Hz,1H),2.55(s,3H)；.13C NMR(125MHz,CDCl3)δ156.4,146.8,139.7,136.07,136.02,131.87,129.3,129.0,128.7,127.4,127.1,126.2,118.9,21.5.
实施例26:8-甲基-(2-苯基)喹啉
8-methyl-2-phenylquinoline
将苯乙酮(144mg,1.2mmol)、[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2(8.3mg,0.01mmol,1mol％)、氢氧化钾(56mg,1.0mmol,1.0equiv.)、2-氨基-3-甲基苄醇(137mg,1.0mmol)和水(1mL)依次加入到5mL圆底烧瓶中。反应混合物在空气中回流反应12小时后，冷却到室温。用乙酸乙酯萃取，旋转蒸发除掉溶剂，然后通过柱层析(展开剂：石油醚/乙酸乙酯)得到纯净的目标化合物，产率：83％
1H NMR(500MHz,CDCl3)δ8.26(d,J＝7.4Hz,2H),8.17(d,J＝8.6Hz,1H),7.89(d,J＝8.6Hz,1H),7.65(d,J＝8.1Hz,1H),7.57(d,J＝8.1Hz,1H),7.53(t,J＝7.7Hz,2H),7.45(t,J＝6.9Hz,1H),7.40(t,J＝7.5Hz,1H),2.91(s,3H)；13C NMR(125MHz,CDCl3)δ155.5,147.2,139.8,137.7,136.9,129.7,129.2,128.8,127.5,127.1,126.0,125.4,118.2,17.9。
Claims (6)
1.一种合成喹啉衍生物Ⅰ的方法，其特征在于，
其包含使酮II
与化合物邻氨基苯甲醇Ⅲ反应
反应是在铱络合物催化剂存在下发生，
其中，R1选自C3-C4烷基、甲基苯基、乙基苯基、甲氧基苯基、三氟甲基苯基、卤代苯基、萘基；
R2选自氢、C2-C3烷基；
R3选自甲基、卤素；
其具体步骤如下：
在反应容器中，加入酮II、邻氨基苯甲醇Ⅲ、铱络合物催化剂、碱和溶剂水，反应混合物在空气中回流反应，反应结束后冷却到室温；用乙酸乙酯萃取，旋转蒸发除去溶剂，然后通过柱分离，得到目标化合物；
其中，铱络合物催化剂为[Cp*Ir(6,6’-(OH)2bpy)(H2O)][OTf]2，其结构式如下：
2.如权利要求1所述的合成喹啉衍生物的方法，其特征在于，催化剂用量相对于酮的摩尔比为1.0mol％。
3.如权利要求1所述的合成喹啉衍生物的方法，其特征在于，碱选自氢氧化钾。
4.如权利要求1或3所述的合成喹啉衍生物的方法，其特征在于，碱相对于酮的摩尔比为0.5-1.0。
5.如权利要求1所述的合成喹啉衍生物的方法，其特征在于，邻氨基苄醇相对于酮摩尔比为1.2。
6.如权利要求1所述的合成喹啉衍生物的方法，其特征在于，反应时间为12小时以上。
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| "Dehydrogenative oxidation of alcohols in aqueous media using water-soluble and reusable Cp* Ir catalysts bearing a functional bipyridine ligand";Kawahara, Ryoko, et al.,;《Journal of the American Chemical Society》;20120216;第134卷(第8期);第3643-3646页 * |
| "Synthesis of quinolines from amino alcohol and ketones catalyzed by [IrCl (cod)] 2 or IrCl3 under solvent-free conditions";Taguchi, K., et al.;《Tetrahedron letters》;20050523;第46卷(第27期);第4539-4542页 * |
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