CN113698343A - 一种含2位取代的多取代喹啉的合成方法 - Google Patents

一种含2位取代的多取代喹啉的合成方法 Download PDF

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CN113698343A
CN113698343A CN202110992053.6A CN202110992053A CN113698343A CN 113698343 A CN113698343 A CN 113698343A CN 202110992053 A CN202110992053 A CN 202110992053A CN 113698343 A CN113698343 A CN 113698343A
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polysubstituted quinoline
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polysubstituted
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aryl
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郭灿城
杨统林
郭欣
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Changsha Material Technology Co ltd
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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
    • C07D215/04—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
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Abstract

本发明公开了一种含2位取代的多取代喹啉的合成方法，该方法是在含氧气氛下，1‑邻胺基芳基醇、芳基甲醛和亚砜在含碱的甲苯溶液体系中进行一锅反应，合成得到2位取代的多取代喹啉化合物；该方法制得的2位取代的多取代喹啉化合物中，吡啶环上2位碳原子及2位上的取代基由芳基甲醛提供，3位碳原子及3位上的芳基由亚砜提供，吡啶环上其它原子以及4位碳原子上的取代基都由1‑邻氨基苯基醇提供。该合成含2位取代的多取代喹啉的方法反应条件温和，原料来源广泛易得，绿色环保，价格低廉，操作简单，有利于工业化生产。

Description

一种含2位取代的多取代喹啉的合成方法
技术领域
本发明涉及一种含2位取代的多取代喹啉的合成方法，特别涉及一种以1-邻氨基苯基醇、二苄基亚砜和芳香醛在氢氧化钾作用下一锅反应合成含2位取代的多取代喹啉的方法，属于有机合成领域。
背景技术
喹啉是一种具有重要生理活性和广泛合成用途的化学结构。喹啉环存在不同位置，它们可以连接不同的取代基，而在不同位置连接不同取代基所形成的喹啉化合物，其生理活性和合成用途也不同。含2-位取代的多取代喹啉化合物存在于很多天然产物中，一些药物分子中也存在这种结构。含2-位取代的多取代喹啉可以由3-取代苯胺与甘油通过Skraup反应得到，而复杂的3含2-位取代的多取代喹啉则需要用到特殊的合成方法。文献(S.B.Wakade,D.K.Tiwari,P. S.K.P.Ganesh,M.Phanindrudu,P.R.Likhar,D.K.Tiwari,Org.Lett.2017,19, 4948-4951)报道了过二硫酸钾存在下由芳基甲基酮、取代的苯并异恶唑与 DMSO反应合成含2-位取代的多取代喹啉的方法：
Figure BDA0003232663080000011
该合成含2-位取代的多取代喹啉的方法需要用到难得到的取代的苯并异恶唑原料，并且3位只能是芳甲酰基，2-位上的碳和取代基来自亚砜。
发明内容
针对现有含2-位取代的多取代喹啉合成方法中存在的使用难得到原料以及喹啉的3-位碳上只能是酰基的缺陷，本发明的目的是在于提供一种在含氧气氛下，由易得原料1-邻氨基苯基醇和芳基甲醛得到含2-位取代的多取代喹啉化合物的方法，该方法原料来源广泛易得，绿色环保，价格低廉，操作简单，有利于工业化生产。
为了实现上述技术目的，本发明提供了一种在含氧气氛下，1-邻氨基苯基醇和芳基甲醛，在含碱的亚砜溶液体系中进行一锅反应得到含2-位取代的多取代喹啉化合物的方法；
所述1-邻氨基芳基醇具有式1结构：
Figure BDA0003232663080000021
所述芳基醛具有式2结构：
Figure BDA0003232663080000022
所述亚砜结构为：
Figure BDA0003232663080000023
所述含2位取代的多取代喹啉化合物具有式4结构：
Figure BDA0003232663080000024
其中，
式1中R1可以是氢、苯基、联苯基、萘；
式2中Ar选自苯、萘、联苯、呋喃或它们的取代物，取代基至少是氢、甲基、甲氧基、三氟甲基、氟、氯中的一种，取代基的位置可以是芳环的任意位置；
式3中的取代基R2可以是苯、萘、联苯、噻吩。
本发明的合成反应需要有机碱和无机碱的存在。具体包括苯甲酸钠、苯甲酸钾、乙酸钠、乙醇钾、甲醇钠、甲醇钾、叔丁醇钠、叔丁醇钾、碳酸钠、碳酸锶、氢氧化钠、氢氧化钾中至少一种。优选的碱是氢氧化钾。
本发明中，亚砜既是溶剂，又是反应原料；当反应体系中反应物为固体时，可以加入惰性的甲苯作为辅助溶剂。
优选的方案，1-邻氨基苯基醇与碱化合物的摩尔比为1:1～3。最优选为 1:1.5～2。
优选的方案，所述反应的条件为：在空气或氧气气氛下，于100-140℃温度下，反应5-10小时。较优选的方案，所述反应的条件为：在空气或氧气气氛下，于120℃温度下，反应8小时。
本发明的含氧气氛可以为空气，也可以是纯氧气氛，最好是纯氧气氛。
本发明使用的亚砜是良性反应溶剂，同时也是2-位取代的多取代喹啉合成过程中的碳源之一，是其他溶剂无法替换的。当亚砜为固体状态时，反应体系中可以加入甲苯等有机溶剂，但反应效果明显比采用单一的亚砜溶剂效果要差。
本发明的2-位取代的多取代喹啉合成过程中，1-邻氨基苯基醇和芳基甲醛按等摩尔比反应，而亚砜作为溶剂和反应底物，需要大量过量。
优选的方案，反应结束后采用柱层析法分离提纯产物；所述柱层析采用的洗脱液为石油醚和乙酸乙酯的混合溶剂，其中石油醚和乙酸乙酯之间的体积比为(20～40):1。
本发明提出的合成2-位取代的多取代喹啉的方法，反应方程式如下：
Figure BDA0003232663080000031
该方法制得的2-位取代的多取代喹啉化合物的吡啶环的6个原子中，原料 1-邻氨基苯基醇提供了氮原子以及与之相连的3个碳原子，芳基甲醛提供了另一个与氮原子相连的2号位碳原子及2位上的芳基，亚砜提供了3号位碳原子及3位上的取代基。上述反应的原理可以通过1-邻氨基苯甲醇与苯甲醛在在二苄基亚砜溶液体系中进行一锅反应得到2,3-二苯基喹啉的过程进行说明：
Figure BDA0003232663080000041
首先，原料1-邻氨基苯甲醇被氧化成邻氨基苯甲醛A和它的互变异构B，原料苯甲醛与二苄基亚砜反应生成苄基亚磺酰取代1,2-二苯乙烯C，苄基亚磺酰取代1,2-二苯乙烯C被空气氧化成苄基磺酰取代1,2-二苯乙烯D；然后，邻氨基苯甲醛异构体B与苄基磺酰取代1,2-二苯乙烯D发生[4+2]环加成反应形成不稳定加成产物E，不稳定加成产物E迅速脱水形成环状化中间体F，最后在加热条件下，环化中间体脱出一分子苯甲基亚磺酸得到3,4-二苯基喹啉产物。反应中间体A、C、D和F都能通过气质联用仪器捕捉到它们的存在。
实验发现，如果用脂肪醛代替芳香醛无法得到相应的目标产物；如果用酮代替醛也无法得到相应的目标产物；如果用二甲基亚砜代替二苄基亚砜所得到的目标产物也不是所期望的目标产物。
相对于现有的合成方法和技术，本发明具有以下优点和效果：
1)本发明首次实现了1-邻氨基苯基醇和芳基甲醛在取代亚砜中直接环化合成含2-位取代的多取代喹啉；
2)本发明使用易得到的原料，不需要使用难得到的或者昂贵的原料，原料来源广，成本低；
3)本发明采用常见的有机碱或者无机碱，避免了使用昂贵的金属配合物作为催化剂，符合绿色环保、经济节约等要求；
4)本发明的反应过程在含氧气氛和较低温度下进行反应，反应条件温和；
5)本发明合成的含2-位取代的多取代喹啉化合物的收率较高；
6)本发明的合成过程通过一锅法反应，反应步骤少，操作简单。
具体实施方式
以下结合具体实施例对本发明作进一步地具体详尽的描述，但本发明的实施方式不限于此，对于未特别注明的工艺参数，可参照常规技术进行。
除另有说明外，所有反应均在Schlenk试管中进行。
所有反应原料溶剂从商业来源获得，并且不经进一步纯化而使用。
产品分离采用硅胶色谱柱，硅胶(粒度300目～400目)。
1H NMR(400MHz)和13C NMR(100MHz)检测采用Bruker ADVANCE III光谱仪，以CDCl3为溶剂，以TMS为内标，化学位移以百万分率(ppm)计，以四甲基硅烷的0.0ppm为参考位移。使用以下缩写(或其组合)来解释多重性： s＝单峰，d＝双峰，t＝三重峰，q＝四重峰，m＝多重峰，br＝宽峰。偶合常数J的单位为赫兹(Hz)。化学位移以ppm表示，参考氘代氯仿在77.0ppm三重态的中心线或参考氘代DMSO在39.52ppm七重态的中心线。
1、实施过程
在反应试管中加入0.5毫摩尔1-邻氨基苯基醇，0.5毫摩尔芳基甲醛，2毫摩尔氢氧化钾，2毫升取代亚砜溶剂(取代亚砜为固体时，加入等量甲苯)，氧气气氛下，120℃加热磁力搅拌，反应8小时，冷却至室温，浓缩后经柱层析分离提纯，得到目标产物，所用柱层析洗脱液为石油醚和乙酸乙酯的混合溶剂。
2、实施效果
以下实施例均是按上述实施过程进行：
Figure BDA0003232663080000061
3、部分实施产物的氢谱和碳谱数据
2,3,4-Triphenylquinoline(1):
Figure BDA0003232663080000062
黄色固体。1H NMR(400MHz,CDCl3)δ8.34(d,J＝8.4Hz,1H),7.77(t,J＝7.5Hz,1H),7.65(d, J＝8.3Hz,1H),7.53–7.42(m,3H),7.32(d,J＝6.6Hz,3H),7.29–7.24(m,3H),7.20(d,J＝6.8Hz, 2H),7.05(d,J＝2.7Hz,3H),6.97(d,J＝2.9Hz,2H)；13C NMR(101MHz,CDCl3)δ158.90,147.59, 147.26,141.10,138.28,136.88,132.88,131.29,130.22,129.85,129.62,129.27,127.70,127.57, 127.50,127.25,127.19,126.58,126.52,126.49,126.23.
2-(naphthalen-2-yl)-3,4-diphenylquinoline(2):
Figure BDA0003232663080000071
黄色固体。1H NMR(400MHz,CDCl3)δ8.32(d,J＝8.3Hz,1H),8.00(s,1H),7.83–7.69(m, 3H),7.66–7.58(m,2H),7.52–7.39(m,4H),7.35–7.27(m,3H),7.17(d,J＝6.4Hz,2H),7.07– 6.88(m,5H)；13C NMR(101MHz,CDCl3)δ158.68,147.97,147.32,138.51,138.26,136.92,133.13, 133.04,132.69,131.43,130.33,129.83,129.62,129.51,128.54,127.83,127.48,127.34,126.99, 126.74,126.69,126.43,126.23,125.83.HRMS(EI):calcd for C31H21N:407.1674,found:407.1676.
2-(Naphthalen-2-yl)-3,4-diphenylquinoline(3).
Figure BDA0003232663080000072
黄色固体。1H NMR(400MHz,CDCl3)δ8.30(d,J＝8.4Hz,1H),7.80–7.72(m, 1H),7.64–7.55(m,3H),7.53–7.45(m,5H),7.42(t,J＝7.5Hz,2H),7.36–7.27(m, 4H),7.21–7.14(m,2H),7.08–7.01(m,3H),7.00–6.93(m,2H).13C NMR(101 MHz,CDCl3)δ158.46,147.77,147.32,140.70,140.22,140.04,138.30,136.91, 132.90,131.37,130.39,130.28,129.63,129.38,128.66,127.77,127.43,127.25, 127.01,126.65,126.60,126.57,126.37.HRMS(EI):calcd for C33H23N:433.1830, found:433.1833.
2,3-Diphenylquinoline(4)]:
Figure BDA0003232663080000073
黄色固体。1H NMR(400MHz,CDCl3)δ8.26(d,J＝8.5Hz,1H),8.21(s,1H),7.90(d,J＝8.1 Hz,1H),7.77(t,J＝7.6Hz,1H),7.60(t,J＝7.5Hz,1H),7.53–7.46(m,2H),7.37–7.26(m,8H)；13C NMR(101MHz,CDCl3)δ158.34,147.24,140.37,139.93,137.53,134.50,129.98,129.71,129.56, 129.37,128.18,127.96,127.88,127.42,127.18,127.13,126.70.
2-(furan-2-yl)-3-phenylquinoline(5):
Figure BDA0003232663080000081
白色固体。1H NMR(400MHz,CDCl3)δ8.26(d,J＝8.5Hz,1H),8.04(s,1H),7.80(d,J＝ 8.1Hz,1H),7.77–7.70(m,1H),7.58–7.51(m,2H),7.49–7.44(m,3H),7.42–7.36(m,2H),6.34–6.28(m,1H),5.95(d,J＝3.4Hz,1H)；13C NMR(101MHz,CDCl3)δ152.14,147.49,147.06, 143.74,139.93,137.78,133.36,129.87,129.29,129.26,128.52,127.89,127.34,126.81,126.64, 113.76,111.37.
2-(naphthalen-2-yl)-3-phenylquinoline(6):
Figure BDA0003232663080000082
黄色固体。1H NMR(400MHz,CDCl3)δ8.31(d,J＝8.4Hz,1H),8.25(s,1H),8.13(s,1H),7.93 (d,J＝8.0Hz,1H),7.81(dd,J＝15.1,7.7Hz,3H),7.74(d,J＝8.4Hz,1H),7.62(t,J＝7.4Hz,1H), 7.57–7.45(m,3H),7.37–7.27(m,5H)；13C NMR(101MHz,CDCl3)δ158.09,147.35,139.90, 137.87,137.65,134.65,133.13,132.89,129.73,129.63,129.38,128.52,128.28,127.57,127.50, 127.46,127.20,126.76,126.29,125.88,77.32,77.00,76.68.HRMS(EI):calcd for C25H17N:331.1361, found:331.1364.
3-(Naphthalen-2-yl)-2-phenylquinoline(7).
Figure BDA0003232663080000083
黄色固体。1H NMR(400MHz,CDCl3)δ8.30(d,J＝8.9Hz,2H),7.96–7.91(m, 2H),7.89–7.83(m,2H),7.82–7.77(m,1H),7.71(d,J＝8.5Hz,1H),7.65–7.59 (m,1H),7.57–7.48(m,4H),7.32–7.22(m,4H)；13C NMR(101MHz,CDCl3)δ 158.32,147.21,140.19,138.06,137.61,134.40,133.36,132.29,130.04,129.72, 129.33,128.39,128.11,128.00,127.98,127.89,127.65,127.48,127.47,127.26, 126.81,126.25,126.17.
3-([1,1'-Biphenyl]-4-yl)-2-phenylquinoline(8)
Figure BDA0003232663080000091
黄色固体。1H NMR(400MHz,CDCl3)δ8.24(d,J＝7.3Hz,2H),7.92–7.87(m, 1H),7.79–7.72(m,1H),7.64–7.53(m,5H),7.53–7.48(m,2H),7.48–7.42(m, 2H),7.38–7.29(m,6H).13C NMR(101MHz,CDCl3)δ158.38,147.26,140.43, 140.35,139.91,138.92,137.65,134.16,130.18,130.08,129.71,129.41,128.82, 128.12,128.05,127.50,127.46,127.28,127.00,126.90,126.83.HRMS(EI):calcd for C27H19N:357.1517,found:357.1519.
2-Phenyl-3-(thiophen-3-yl)quinoline(9).
Figure BDA0003232663080000092
黄色固体。1H NMR(400MHz,CDCl3)δ8.29–8.18(m,2H),7.86(d,J＝8.0Hz, 1H),7.73(t,J＝7.4Hz,1H),7.57(t,J＝7.4Hz,1H),7.53–7.44(m,2H),7.34(d,J ＝4.1Hz,3H),7.24–7.19(m,1H),7.17(s,1H),6.82(d,J＝4.9Hz,1H)；13C NMR (101MHz,CDCl3)δ158.35,146.98,140.33,140.18,137.10,129.68,129.65,129.40, 129.27,128.84,128.29,128.05,127.36,127.22,126.85,125.33,123.75.
2-(3-fluorophenyl)-3,4-diphenylquinoline(10):
Figure BDA0003232663080000093
白色固体。1H NMR(400MHz,CDCl3)δ8.27(d,J＝8.3Hz,1H),7.75(t,J＝7.3Hz,1H),7.60(d, J＝8.4Hz,1H),7.48(t,J＝7.3Hz,1H),7.35–7.26(m,3H),7.20–7.09(m,5H),7.07–6.99(m,3H), 6.96–6.85(m,3H)；13C NMR(101MHz,CDCl3)δ162.29(d,J＝245.3Hz),157.50,148.06,147.18, 143.28,137.93,136.73,132.83,131.24,130.26,129.63(d,J＝4.4Hz),129.15,129.07,127.85,127.52, 127.41,126.91,126.81,126.64(d,J＝6.3Hz),125.77(d,J＝2.9Hz),117.01(d,J＝22.5Hz),114.63 (d,J＝21.0Hz).HRMS(EI):calcdfor C27H18FN:375.1423,found:375.1420.
2-(4-chlorophenyl)-3,4-diphenylquinoline(11):
Figure BDA0003232663080000101
白色固体。1H NMR(400MHz,CDCl3)δ8.27(d,J＝8.4Hz,1H),7.75(t,J＝7.6Hz,1H),7.59(d, J＝8.1Hz,1H),7.47(t,J＝7.3Hz,1H),7.36–7.26(m,5H),7.19(d,J＝8.4Hz,2H),7.16–7.10(m, 2H),7.07–7.00(m,3H),6.92–6.85(m,2H)；13C NMR(101MHz,CDCl3)δ157.53,148.07,147.16, 139.43,137.98,136.71,133.85,132.76,131.33,131.27,130.21,129.57,129.53,127.89,127.81, 127.55,127.36,126.81,126.71,126.64,126.56.HRMS(EI):calcd for C27H18ClN:391.1128,found: 391.1126.
3,4-diphenyl-2-(4-(trifluoromethyl)phenyl)quinoline(12):
Figure BDA0003232663080000102
白色固体。1H NMR(400MHz,CDCl3)δ8.31(d,J＝8.2Hz,1H),7.79(t,J＝7.4Hz,1H),7.64(d, J＝8.3Hz,1H),7.60–7.47(m,5H),7.38–7.29(m,3H),7.22–7.14(m,2H),7.12–7.01(m,3H), 6.91(d,J＝5.9Hz,2H)；13C NMR(101MHz,CDCl3)δ157.31,137.72,136.59,132.79,131.29, 130.30,130.24,129.76,129.61,127.88,127.62,127.49,127.11,126.87,126.74,124.66(q,J＝7.4,3.7 Hz).HRMS(EI):calcd for C28H18F3N:425.1391,found:425.1390.
2-(3,5-bis(trifluoromethyl)phenyl)-3,4-diphenylquinoline(13):
Figure BDA0003232663080000103
白色固体。1H NMR(400MHz,CDCl3)δ8.29(d,J＝8.4Hz,1H),7.89(s,2H),7.80(t,J＝7.4Hz, 1H),7.73(s,1H),7.64(d,J＝8.4Hz,1H),7.53(t,J＝7.5Hz,1H),7.35–7.28(m,3H),7.20–7.13(m, 2H),7.13–7.04(m,3H),6.90(d,J＝5.3Hz,2H)；13C NMR(101MHz,CDCl3)δ155.31,148.56, 147.36,142.79,137.29,136.33,132.69,131.15,131.05,130.72,130.39,130.19,129.97,129.73, 127.95,127.63,127.49,127.11,127.01,126.77,124.56,121.85,121.30(q,J＝7.2,3.6Hz). HRMS(EI):calcd for C29H17F6N:493.1265,found:493.1262.
2-(4-chlorophenyl)-3-phenylquinoline(14):
Figure BDA0003232663080000104
白色固体。1H NMR(400MHz,CDCl3)δ8.26(d,J＝8.5Hz,1H),8.24(s,1H),7.93(d,J＝8.1Hz, 1H),7.80(t,J＝7.3Hz,1H),7.63(t,J＝7.5Hz,1H),7.46(d,J＝8.4Hz,2H),7.39–7.35(m,3H), 7.32–7.28(m,4H)；13C NMR(101MHz,CDCl3)δ156.94,147.11,139.59,138.64,137.89,134.38, 134.30,131.42,129.86,129.69,129.25,128.42,128.16,127.48,127.41,127.26,127.01.HRMS(EI): calcd for C21H14ClN:315.0815,found:315.0814.
3-phenyl-2-(4-(trifluoromethyl)phenyl)quinoline(15):
Figure BDA0003232663080000111
无色油状液体。1H NMR(400MHz,CDCl3)δ8.26(d,J＝6.3Hz,2H),7.93(d,J＝8.0Hz,1H), 7.80(t,J＝7.5Hz,1H),7.70–7.51(m,5H),7.40–7.33(m,3H),7.30–7.24(m,2H)；13CNMR(101 MHz,CDCl3)δ156.67,147.15,143.82,139.29,137.94,134.40,130.38,129.98,129.72,129.37, 128.47,127.54,127.52,127.39,127.27,124.89(q,J＝3.7Hz),122.78.
2-(4-methoxyphenyl)-3-phenylquinoline(16):
Figure BDA0003232663080000112
无色油状液体。1H NMR(400MHz,CDCl3)δ8.28(d,J＝7.6Hz,1H),8.21(s,1H),7.91(d,J＝ 8.0Hz,1H),7.78(t,J＝7.7Hz,1H),7.60(t,J＝7.4Hz,1H),7.46(d,J＝8.7Hz,2H),7.41–7.31(m, 5H),6.86(d,J＝8.8Hz,2H),3.85(s,3H)；13C NMR(101MHz,CDCl3)δ159.69,157.82,140.16, 137.83,134.46,131.50,129.69,129.07,128.30,127.41,127.17,127.06,126.58,113.42,55.24.
4-phenyl-2-(p-tolyl)quinoline(17):
Figure BDA0003232663080000113
无色油状液体。1H NMR(400MHz,CDCl3)δ8.25(d,J＝8.4Hz,1H),8.18(s,1H),7.88(d, J＝8.0Hz,1H),7.75(dd,J＝11.2,4.1Hz,1H),7.57(t,J＝7.4Hz,1H),7.37(d,J＝8.0Hz,2H), 7.34–7.29(m,3H),7.29–7.26(m,2H),7.10(d,J＝7.9Hz,2H),2.34(s,3H)；13CNMR(101MHz, CDCl3)δ158.27,147.03,140.07,137.98,137.77,134.54,129.98,129.71,129.65,129.16,128.64, 128.23,127.41,127.15,126.66,21.25.
4-(naphthalen-2-yl)-2,3-diphenylquinoline(18)
Figure BDA0003232663080000114
黄色固体。1H NMR(400MHz,CDCl3)δ8.36(d,J＝8.4Hz,1H),7.88–7.84(m,1H),7.82 –7.75(m,3H),7.73(s,1H),7.64(d,J＝8.4Hz,1H),7.56–7.43(m,5H),7.35–7.25(m,4H),6.99 (s,5H).13C NMR(101MHz,CDCl3)δ158.99,147.44,147.30,141.08,138.18,134.42,133.09, 132.67,132.25,131.28,131.23,129.89,129.69,129.54,129.34,128.09,127.94,127.66,127.63, 127.57,127.36,126.75,126.60,126.59,126.32,126.18,126.16.
4-([1,1'-biphenyl]-4-yl)-2,3-diphenylquinoline(19)
Figure BDA0003232663080000121
.黄色固体。1H NMR(400MHz,CDCl3)δ8.30(d,J＝8.3Hz,1H),7.79–7.72(m,1H),7.71 –7.67(m,1H),7.65–7.59(m,2H),7.57–7.52(m,2H),7.51–7.33(m,6H),7.25–7.17(m,5H), 7.06–6.99(m,3H),6.97–6.90(m,2H).13C NMR(101MHz,CDCl3)δ159.00,147.41,147.27, 141.07,140.41,139.85,138.27,135.90,133.00,131.37,130.78,129.91,129.68,129.40,128.77, 127.65,127.60,127.42,127.40,126.95,126.66,126.62,126.60,126.37.HRMS(EI):calcd for C33H23N:433.1830,found:433.1833。

Claims (4)

1.一种含2位取代的多取代喹啉的合成方法，其特征在于：1-邻胺基芳基醇、芳基甲醛和亚砜在含碱的甲苯溶液体系中进行一锅反应，合成得到2位取代的多取代喹啉化合物；该方法制得的2位取代的多取代喹啉化合物中，吡啶环上2位碳原子及2位上的取代基由芳基甲醛提供，3位碳原子及3位上的芳基由亚砜提供，吡啶环上其它原子以及4位碳原子上的取代基都由1-邻氨基苯基醇提供。
所述1-邻氨基芳基醇具有式1结构：
Figure FDA0003232663070000011
所述芳基醛具有式2结构：
Figure FDA0003232663070000012
所述亚砜具有式3结构：
Figure FDA0003232663070000013
所述含2位取代的多取代喹啉化合物具有式4结构：
Figure FDA0003232663070000014
其中，
式1中R1可以是氢、苯基、联苯基、萘；
式2中Ar选自苯、萘、联苯、呋喃或它们的取代物，取代基至少是氢、甲基、甲氧基、三氟甲基、氟、氯中的一种，取代基的位置可以是芳环的任意位置；
式3中的取代基R2可以是苯、萘、联苯、噻吩。
2.根据权利要求1所述的一种含2位取代的多取代喹啉的合成方法，其特征在于：
所述碱为包含包括苯甲酸钠、苯甲酸钾、乙酸钠、乙醇钾、甲醇钠、甲醇钾、叔丁醇钠、叔丁醇钾、碳酸钠、碳酸锶、氢氧化钠、氢氧化钾中至少一种。优选的碱是氢氧化钾。
3.根据权利要求1所述的一种含2位取代的多取代喹啉的合成方法，其特征在于：DMSO即是溶剂，又是反应原料。
4.根据权利要求1所述的一种含2位取代的多取代喹啉的合成方法，其特征在于：所述反应的条件为：在空气或氧气气氛下，于100-140℃温度下，反应5-10小时。
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