CN104744348B - 多取代吡啶衍生物及其制备方法 - Google Patents

多取代吡啶衍生物及其制备方法 Download PDF

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CN104744348B
CN104744348B CN201510078204.1A CN201510078204A CN104744348B CN 104744348 B CN104744348 B CN 104744348B CN 201510078204 A CN201510078204 A CN 201510078204A CN 104744348 B CN104744348 B CN 104744348B
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崔秀灵
沈金海
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Huaqiao University
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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

Abstract

本发明公开了一种多取代吡啶衍生物及其制备方法，该衍生物具有下式所示结构：其中R1、R2、R3、R4、R5、均选自氢原子、卤素原子、烷基、芳基、取代芳基、酰基、氨基、硝基、烷氧基中的任意一种；本发明还公开了其制备方法，采用炔酮和1‑芳基乙胺为原料，在适当碱的作用下，溶剂中加热反应完毕高收率地得到上式所示的多取代吡啶衍生物。该反应条件温和，反应时间短，底物范围广，反应专一性强，产率高，后处理简便。

Description

多取代吡啶衍生物及其制备方法
技术领域
本发明属于有机合成技术领域，特别是涉及多取代吡啶衍生物及其制备方法。
背景技术
多取代吡啶衍生物是一类用途比较广泛的有机合成中间体，在天然产物、医药生产、有机合成、材料科学中均具有重要的应用价值。因此，多取代吡啶的新合成方法研究具有重要的运用价值，受到相关领域科研工作者的关注。
传统合成吡啶衍生物方法包括胺类化合物与1，5-二羰基化合物的缩合反应，以及过渡金属催化的环化偶联反应。但是这些方法都存在诸多问题：1)以1，5-二羰基化合物作为原料，原料不易制备，且某些1，5-二羰基化合物难以获得；2)反应需要使用昂贵的过渡金属催化剂，容易造成产物中的金属残留，在医药工业中使用受限；3)难以合成多取代的吡啶衍生物，尤其是高选择性合成多取代不对称多取代吡啶衍生物。
发明内容
本发明的目的在于克服现有技术之不足，提供一种多取代2-吡啶衍生物及其制备方法。
本发明解决其技术问题所采用的技术方案是：多取代2-吡啶衍生物具有式I所示的结构：
式I中，R1、R2、R3、R4、R5、均选自氢原子、卤素原子、烷基、芳基、取代芳基、酰基、氨基、硝基、烷氧基中的任意一种。
制备上述多取代吡啶衍生物的方法，步骤为：于一溶剂中加入炔酮、1-芳基乙胺与碱；加热反应一段时间后冷却至室温，反应方程式为：
其中所述N-炔丙基烯胺酮中R1、R2、R3、R4、R5均选自氢原子、卤素原子、烷基、芳基、取代芳基、酰基、氨基、硝基或烷氧基中的任意一种；炔酮、胺、碱的投料物质的量比为1-10：1-10：2-20(优选为1-5:1-5:2-10，更优选为1：1:2)；反应时间为6-20h。
优选的，所述的碱为氢氧化钾、氢氧化钠、叔丁醇钠、叔丁醇钾、甲醇钠或碳酸铯中的至少一种。
优选的，所述溶剂为二甲亚砜，N，N－二甲基甲酰胺或N-甲基-2-吡咯烷酮中的至少一种。
优选的，所述炔酮、胺与所述溶剂的比值为每摩尔烯胺酮对应3～10L溶剂。
优选的，加热反应中添加水或氯化钠溶液进行淬灭。
优选的，所述加热反应采用油浴加热，油浴温度为80-120℃。
优选的，还包括稀释、洗涤、干燥、过滤、浓缩及柱层析纯化的步骤。
优选的，所述稀释是在反应停止后加入乙酸乙酯。
优选的，所述干燥是采用无水Na2SO4。
本发明的有益效果是，可合成其他方法不能合成的具有多种取代基的吡啶衍生物；所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强,后处理简便且绿色。
具体实施方式
实施例1
2,4,6-三苯基吡啶的制备
将1,3-二苯基-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol,氢氧化钾1mmol，二甲亚砜1.5mL加入10mL的反应管中，置于100℃的油浴中，反应12h。停止反应，冷却至室温。反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到106.7mg目标产物，收率为69％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.24–8.17(m,4H),7.87(s,2H),7.76–7.71(m,2H),7.53–7.40(m,9H)；13C NMR(100MHz,CDCl3)δ157.5,150.16(s),139.6,139.0 129.1,129.0,128.9,128.7,127.2,127.1,117.1.
实施例2
2,6-二苯基-4-(4-甲苯基)吡啶的制备
将3-苯基-1-(4-甲苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜5mL加入10mL的反应管中，置于80℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到125.2mg目标产物，收率为78％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.19(d,J＝7.5Hz,4H),7.85(s,2H),7.62(d,J＝8.0Hz,2H),7.50(t,J＝7.5Hz,4H),7.43(d,J＝7.3Hz,2H),7.30(d,J＝7.9Hz,2H),2.41(s,3H)；13C NMR(100MHz,CDCl3)δ157.4,150.0,139.6,139.0,136.0,129.8,128.9,128.6,127.1,126.9,116.8,21.2.
实施例3
2,6-二苯基-4-(2-甲苯基)吡啶的制备
将3-苯基-1-(2-甲苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜3mL加入10mL的反应管中，置于120℃的油浴中，反应12h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到115.6mg目标产物，收率为72％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.18(d,J＝7.3Hz,4H),7.66(s,2H),7.49(t,J＝7.5Hz,4H),7.42(t,J＝7.2Hz,2H),7.32(d,J＝5.3Hz,4H),2.35(s,3H)；13C NMR(100MHz,CDCl3)δ156.8,151.3,139.8,139.5,135.1,130.7,129.2,129.0,128.7,128.3,127.1,126.1,119.3,20.4.
实施例4
2,6-二苯基-4-(4-甲氧基苯基)吡啶的制备
将3-苯基-1-(4-甲氧基苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，KOH1mmol，N,N-二甲基甲酰胺5mL加入10mL的反应管中，置于120℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到94.4mg目标产物，收率为56％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.24–8.15(m,4H),7.84(s,2H),7.69(d,J＝8.8Hz,2H),7.53–7.46(m,4H),7.44(d,J＝7.2Hz,2H),7.04(d,J＝8.8Hz,2H),3.86(s,3H)；13C NMR(100MHz,CDCl3)δ160.5,157.4,149.6,139.7,131.3,128.9,128.6,128.3,127.1,116.6,114.5,55.4.
实施例5
2,6-二苯基-4-(2-甲氧基苯基)吡啶的制备
将3-苯基-1-(2-甲氧基苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，碳酸铯1mmol，N-甲基-2-吡咯烷酮4mL加入10mL的反应管中，置于120℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到80.1mg目标产物，收率为48％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.17(d,J＝7.5Hz,4H),7.85(s,2H),7.49(t,J＝7.5Hz,4H),7.41(dt,J＝12.5,6.2Hz,4H),7.11–7.01(m,2H),3.84(s,3H)；13C NMR(100MHz,CDCl3)δ156.7,156.6,147.9,139.8,130.5,130.0,128.8,128.6,128.4,127.1,121.0,119.7,111.4,55.6
实施例6
2,6-二苯基-4-(4-氟苯基)吡啶的制备
将3-苯基-1-(4-氟苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜3mL加入10mL的反应管中，置于100℃的油浴中，反应10h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到80.5mg目标产物，收率为52％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.19(d,J＝7.5Hz,4H),7.82(s,2H),7.71(dd,J＝8.5,5.4Hz,2H),7.51(t,J＝7.5Hz,4H),7.44(t,J＝7.1Hz,2H),7.22(dd,J＝15.0,6.5Hz,2H)；13C NMR(100MHz,CDCl3)δ163.4(d,J＝249.1Hz),157.6,149.2,139.5,135.2(d,J＝3.2Hz),129.2,129.0,128.9,128.8,127.2,116.9,116.1(d,J＝21.7Hz).
实施例7
2,6-二苯基-4-(4-氯苯基)吡啶的制备
将3-苯基-1-(4-氯苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，NaOH1mmol，N-甲基-2-吡咯烷酮5mL加入10mL的反应管中，置于80℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到121.1mg目标产物，收率为71％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.24–8.14(m,4H),7.81(s,2H),7.65(dd,J＝8.8,2.1Hz,2H),7.55–7.40(m,8H)；13C NMR(100MHz,CDCl3)δ157.6,148.9,139.4,137.5,135.2,129.3,129.1,128.7,128.4,127.1,116.8.
实施例7
2,6-二苯基-4-(4-叔丁基苯基)吡啶的制备
将3-苯基-1-(4-叔丁基苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，甲醇钠1mmol，二甲亚砜3mL加入10mL的反应管中，置于100℃的油浴中，反应18h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到96.2mg目标产物，收率为53％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.20(d,J＝8.0Hz,4H),7.88(s,2H),7.69(d,J＝8.2Hz,2H),7.49(ddd,J＝29.6,13.0,7.7Hz,9H),1.38(s,9H)；13C NMR(100MHz,CDCl3)δ157.4,152.3,150.0,139.7,136.1,129.0,128.7,127.1,126.8,126.1,117.0,34.7,31.3.
实施例8
2,6-二苯基-4-(4-三氟甲基苯基)吡啶的制备
将3-苯基-1-(4-三氟甲基苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜3mL加入10mL的反应管中，置于100℃的油浴中，反应14h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到135.0mg目标产物，收率为72％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.20(d,J＝7.6Hz,4H),7.85(dd,J＝12.2,5.9Hz,4H),7.78(d,J＝8.3Hz,2H),7.49(dt,J＝26.3,7.4Hz,6H)；13C NMR(100MHz,CDCl3)δ157.8,148.8,139.2,129.3,128.8,128.7,127.6,127.1,126.1(dd,J＝7.0,3.4Hz),117.0.
实施例9
2,4-二苯基-6-(4-甲基苯基)吡啶的制备
将1-苯基-3-(4-甲基苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，KOH1mmol，二甲亚砜5mL加入10mL的反应管中，置于90℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,柱层析纯化得到58.1mg目标产物，收率为45％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.20(dd,J＝5.3,3.3Hz,2H),8.11(d,J＝8.2Hz,2H),7.86(s,2H),7.75(dd,J＝5.2,3.2Hz,2H),7.55–7.41(m,6H),7.32(d,J＝8.0Hz,2H),2.43(s,3H)；13C NMR(100MHz,CDCl3)δ157.5,157.4,150.1,139.7,139.2,139.0,136.8,129.4,129.1,129.0,128.9,128.7,127.2,127.1,127.0),116.8,116.8,21.3.
实施例10
2,4-二苯基-6-(4-甲氧基苯基)吡啶的制备
将1-苯基-3-(4-甲氧基苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钠1mmol，二甲亚砜5mL加入10mL的反应管中，置于110℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到99.8mg目标产物，收率为75％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.23–8.14(m,4H),7.82(dd,J＝3.3,1.3Hz,2H),7.76–7.70(m,2H),7.55–7.40(m,6H),7.07–7.00(m,2H),3.87(s,3H)；13C NMR(100MHz,CDCl3)δ160.6,157.3,157.1,150.1,139.7,139.2,132.2,129.1,128.9,128.9,128.7,128.4,127.2,127.1,116.5,116.3,114.1,55.4.
实施例11
2,4-二苯基-6-(4-氟苯基)吡啶的制备
将1-苯基-3-(4-氟苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，甲醇钠1mmol，N-甲基吡咯烷酮1.5mL加入10mL的反应管中，置于100℃的油浴中，反应18h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到74.5mg目标产物，收率为56％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.23–8.16(m,4H),7.88(d,J＝1.3Hz,1H),7.83(d,J＝1.3Hz,1H),7.74(dd,J＝5.2,3.2Hz,2H),7.56–7.44(m,6H),7.24–7.14(m,2H)；13C NMR(100MHz,CDCl3)δ163.6(d,J＝248.4Hz),157.6,156.5,150.3,139.5,139.0,135.7(d,J＝3.1Hz),129.1,129.1,129.0,128.9(d,J＝8.3Hz),128.7,127.8,127.1,117.1,116.8,115.59(d,J＝21.6Hz).
实施例12
2,4-二苯基-6-(4-氯苯基)吡啶的制备
将1-苯基-3-(4-氯苯基)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜4mL加入10mL的反应管中，置于80℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到121.1mg目标产物，收率为71％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.28–8.13(m,2H),7.88(s,1H),7.73(d,J＝7.2Hz,1H),7.60–7.34(m,5H)；13C NMR(101MHz,CDCl3)δ157.5,150.2,139.6,139.0,129.1,129.0,128.9,128.8,128.7,128.4,127.2,127.1,117.1.
实施例14
2,4-二苯基-6-(噻吩-3-)吡啶的制备
将1-苯基-3-(噻吩-3-)-丙-2-炔-1-酮0.5mmol，1-苯基乙胺0.5mmol，叔丁醇钠1mmol，二甲亚砜2.5mL加入10mL的反应管中，置于120℃的油浴中，反应20h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,硅胶柱层析纯化得到81.4mg目标产物，收率为52％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.24–8.12(m,2H),7.82–7.68(m,5H),7.56–7.39(m,7H),7.18–7.09(m,1H)；13C NMR(100MHz,CDCl3)δ157.3,152.7,150.2,145.4,139.0,138.8,129.1,129.1,129.0,128.7,127.9,127.7,127.1,127.0,124.6,116.8,115.3.
实施例15
2-(2-萘基)-4,6-二苯基吡啶的制备
将1,3-二苯基-丙-2-炔-1-酮0.5mmol，1-(2-萘基)乙胺0.5mmol，KOH 1mmol，二甲亚砜3.5mL加入10mL的反应管中，置于120℃的油浴中，反应12h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,柱层析纯化得到160.6mg目标产物，收率为90％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.70(s,1H),8.42(dd,J＝8.6,1.8Hz,1H),8.29(dd,J＝5.2,3.4Hz,2H),8.06(d,J＝1.3Hz,1H),8.02(dd,J＝8.9,5.9Hz,2H),7.93(dd,J＝8.9,2.8Hz,2H),7.85–7.77(m,2H),7.62–7.48(m,8H)；13C NMR(101MHz,CDCl3)δ157.7,157.4,150.3,139.7,139.1,137.0,133.8,133.6,129.2,129.1,129.1,128.8,128.4,127.8,127.3,127.3,126.5,126.5,126.3,125.0,117.4,117.2.
实施例16
2-(噻吩-2-)-4,6-二苯基吡啶的制备
将1,3-二苯基-丙-2-炔-1-酮0.5mmol，1-(噻吩-2-)乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜3.5mL加入10mL的反应管中，置于100℃的油浴中，反应12h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,柱层析纯化得到142.4mg目标产物，收率为91％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.24–8.12(m,2H),7.82–7.68(m,5H),7.56–7.39(m,7H),7.18–7.09(m,1H)；13C NMR(100MHz,CDCl3)δ157.3,152.7,150.2,145.4,139.0,138.8,129.1,129.1,129.0,128.7,127.9,127.7,127.1,127.0,124.6,116.8,115.3.
实施例17
2,3,4,6-四苯基吡啶的制备
将1,3-二苯基-丙-2-炔-1-酮0.5mmol，1,2-二苯基乙胺0.5mmol，叔丁醇钾1mmol，二甲亚砜5mL加入10mL的反应管中，置于100℃的油浴中，反应12h。停止反应，冷却至室温。反应液乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩,柱层析纯化得到109.2mg目标产物，收率为57％。该化合物的核磁表征如下：1H NMR(400MHz,CDCl3)δ8.19(d,J＝7.4Hz,2H),7.80(s,1H),7.50(t,J＝7.6Hz,2H),7.46–7.38(m,3H),7.26–7.20(m,6H),7.18–7.05(m,5H),6.94(d,J＝6.3Hz,2H)；13C NMR(100MHz,CDCl3)δ158.0,155.6,150.6,141.0,139.8,139.1,137.9,132.8,131.4,130.2,129.3,129,0,128.7,127.9,127.7,127.5,127.3,127.3,127.0,126.6,120.
上述实施例仅用来进一步说明本发明的一种多取代吡啶衍生物及其制备方法，但本发明并不局限于实施例，凡是依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰，均落入本发明技术方案的保护范围内。

Claims (7)

1.一种多取代吡啶衍生物的制备方法，为如下步骤：
于一溶剂中加入炔酮、1-芳基乙胺与碱；
加热反应一段时间后冷却至室温，反应方程式为：
其中，R1、R2、R3、R4、R5均选自氢原子、卤素原子、烷基、芳基、取代芳基、酰基、氨基、硝基、烷氧基中的任意一种；
其中炔酮、胺、碱的投料物质的量比为1-10：1-10：2-20；反应时间为6-20h；所述的多取代吡啶衍生物为：2,4,6-三苯基吡啶、2,6-二苯基-4-（4-甲苯基）吡啶、2,6-二苯基-4-（2-甲苯基）吡啶、2,6-二苯基-4-（4-甲氧基苯基）吡啶、2,6-二苯基-4-（2-甲氧基苯基）吡啶、2,6-二苯基-4-（4-氟苯基）吡啶、2,6-二苯基-4-（4-氯苯基）吡啶、2,6-二苯基-4-（4-叔丁基苯基）吡啶、2,6-二苯基-4-（4-三氟甲基苯基）吡啶、2,4-二苯基-6-（4-甲基苯基）吡啶、2,4-二苯基-6-（4-甲氧基苯基）吡啶、2,4-二苯基-6-（4-氟苯基）吡啶、2,4-二苯基-6-（4-氯苯基）吡啶、2,4-二苯基-6-（噻吩-3-）吡啶、2-（2-萘基）-4,6-二苯基吡啶、2-（噻吩-2-）-4,6-二苯基吡啶、2,3,4,6-四苯基吡啶中的一种；
所述加热反应采用油浴加热，油浴温度为80-120℃。
2.根据权利要求1所述的多取代衍生物的制备方法，其特征在于，所述的碱为氢氧化钾、氢氧化钠、叔丁醇钠、叔丁醇钾、甲醇钠或碳酸铯中的至少一种。
3.根据权利要求1所述的多取代衍生物的制备方法，其特征在于，所述溶剂为二甲亚砜、N，N－二甲基甲酰胺、或N-甲基-2-吡咯烷酮中的至少一种。
4.根据权利要求1所述的多取代吡啶衍生物的制备方法，其特征在于，加热反应中添加水或氯化钠溶液进行淬灭。
5.根据权利要求1所述的多取代吡啶衍生物的制备方法，其特征在于，还包括稀释、洗涤、干燥、过滤、浓缩及柱层析纯化的步骤。
6.根据权利要求5所述的多取代吡啶衍生物的制备方法，其特征在于，所述稀释是在反应停止后加入乙酸乙酯。
7.根据权利要求5所述的多取代吡啶衍生物的制备方法，其特征在于，所述干燥采用无水Na2SO4。
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