CN103804286B - 一种由3-氮杂-1,5-烯炔制备吡啶衍生物的方法 - Google Patents

一种由3-氮杂-1,5-烯炔制备吡啶衍生物的方法 Download PDF

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CN103804286B
CN103804286B CN201210437566.1A CN201210437566A CN103804286B CN 103804286 B CN103804286 B CN 103804286B CN 201210437566 A CN201210437566 A CN 201210437566A CN 103804286 B CN103804286 B CN 103804286B
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CN103804286A (zh
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万伯顺
信晓义
吴凡
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Dalian Institute of Chemical Physics of CAS
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    • 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
    • C07D213/60—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 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/803—Processes of preparation
    • 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
    • C07D213/60—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 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3

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  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

本发明涉及一种由3-氮杂-1,5-烯炔衍生物制备吡啶衍生物的方法，具体地说是由3-氮杂-1,5-烯炔经两步反应脱掉亚磺酸分子制备吡啶衍生物的新方法。本发明不使用过渡金属催化剂，经简单的操作步骤就得到多取代的吡啶衍生物。

Description

一种由3-氮杂-1,5-烯炔制备吡啶衍生物的方法
技术领域
本发明涉及一种由3-氮杂-1,5-烯炔衍生物制备吡啶衍生物的方法，具体地说是由3-氮杂-1,5-烯炔经两步反应脱掉亚磺酸分子制备吡啶衍生物的新方法。
背景技术
吡啶是最重要的杂环之一，广泛存在于天然产物、医药和功能材料中（文献1：a)Jones,G.ComprehensiveHeterocyclicChemistryII，Vol.5(Eds.:Katritzky,A.R.;Rees,C.W.;Scriven,E.F.V.;McKillop,A.),Pergamon,Oxford,1996,pp.167-243;b)Henry,G.D.Tetrahedron2004,60,6043;c)Joule,J.A.;Mills,K.HeterocyclicChemistry，4thed,BlackwellScience,Cambridge,2000,p.63–120;d)Michael,J.P.Nat.Prod.Rep.2005,22,627）。常用的合成方法是将六元环分解成不同的片段再加以组合，如[4+2]、[3+3]、[2+2+2]等环加成和其它的合成方法（文献2：构建吡啶环的综述:a)Henry，G.D.Tetrahedron2004,60,6043;b)Hill,M.D.Chem.Eur.J.2010,16，12052）。我们发展了由3-氮杂-1,5-烯炔衍生物制备吡啶衍生物的新方法。该方法不使用过渡金属催化剂，经简单的操作步骤就能高收率的得到吡啶衍生物产物。该方法操作简单，原料廉价易得。
发明内容
本发明的目的在于提供一种合成吡啶衍生物的新方法。
式1.由3-氮杂-1,5-烯炔合成吡啶衍生物
具体操作步骤如下（式1）：
于反应器中进行反应，反应器抽真空后通氩气置换三次。加入3-氮杂-1,5-烯炔I。步骤A：加入醇类溶剂（兼做催化剂），或在其它有机溶剂中加入醇、酚或其它质子酸做催化剂，室温-100℃反应直到原料I消失。然后用旋转蒸发仪抽调溶剂。步骤B：加入适量的高沸点溶剂，在80–150℃反应。反应结束后，用真空泵抽掉溶剂，固体溶于二氯甲烷上样进行硅胶柱层析，得到吡啶衍生物II。
本发明有以下优点：
1．反应物3-氮杂-1,5-烯炔由廉价易得的原料醛、磺酰胺和端炔经简单反应步骤得到。
2．生成的1,2-二氢吡啶的反应操作简单；不使用过渡金属催化剂，环境友好。
具体实施方式
为了更好地理解本发明，通过以下实例进行说明。
实施例1
于反应器中进行反应，反应器抽真空后通氩气置换三次后，加入0.2mmol（100.7mg）的3-氮杂-1,5-烯炔Ia和2mL乙醇，70℃下搅拌反应16小时。反应结束后，用旋转蒸发仪抽掉溶剂。然后加入1mLDMF（N,N-二甲基甲酰胺），140℃下搅拌反应4小时。用真空泵抽掉溶剂，然后把样品溶于二氯甲烷上样进行硅胶柱层析，洗脱剂为石油醚：乙酸乙酯=20:1的混合溶剂，得到68.7mg的吡啶IIa。分离收率为99%。
化合物Ia的表征数据如下：
1HNMR(400MHz,CDCl3)δ7.92(d,J=8.3Hz,2H),7.64(d,J=7.7Hz,2H),7.40–7.27(m,8H),7.16(dd,J=8.1,1.4Hz,2H),6.54(s,1H),6.10(s,1H),3.76(s,3H),3.60(s,3H),2.31(s,3H);
13CNMR(100MHz,CDCl3)δ164.9,164.2,144.9,139.7,135.3,133.9,131.7,129.8,129.1,128.8,128.7,128.5,128.4,128.0,121.7,117.4,89.7,82.8,55.0,53.0,52.0,21.7;
HRMSCalculatedforC28H25NO6NaS[M+Na]+526.1300,found526.1300。
化合物IIa的表征数如下：
1HNMR(500MHz,CDCl3)δ8.07(m,2H),7.87(s,1H),7.47(m,8H),4.02(s,3H),3.73(s,3H);
13CNMR(126MHz,CDCl3)δ167.9,165.8,158.0,150.1,146.5,137.8,137.5,130.1,129.2,129.1,128.8,128.8,128.2,127.5,123.8,53.3,52.7;
HRSCalculatedforC21H17NO4Na[M+Na]+370.1055,found370.1057.
实施例2
于反应器中进行反应，反应器抽真空后通氩气置换三次后，加入0.2mmol（104.3mg）的3-氮杂-1,5-烯炔Ib和2mL乙醇，70℃下搅拌反应16小时。反应结束后，用旋转蒸发仪抽掉溶剂。然后加入1mLDMF（N,N-二甲基甲酰胺），140°C下搅拌反应4小时。用真空泵抽掉溶剂，然后把样品溶于二氯甲烷上样进行硅胶柱层析，洗脱剂为石油醚：乙酸乙酯=20:1的混合溶剂，得到69.4mg的吡啶IIb。分离收率为95%。
化合物Ib的表征数据如下：
1HNMR(400MHz,CDCl3)δ7.91(d,J=7.8Hz,2H),7.63(m,2H),7.32(m,5H),7.15(d,J=7.4Hz,2H),7.06(t,J=8.2Hz,2H),6.50(s,1H),6.12(s,1H),3.77(s,3H),3.63(s,3H),2.32(s,3H);
13CNMR(100MHz,CDCl3)δ164.8,164.2,162.9(d,J=244.7Hz),145.0,139.5,135.2,131.7,130.0,129.9,129.8,129.2,128.5,128.4,121.5,118.1,115.7(d,J=21.9Hz),89.8,82.7,54.4,53.1,52.2,21.7;
HRMSCalculatedforC28H24NO6FNaS[M+Na]+544.1206,found544.1205.
化合物IIb的表征数如下：
1HNMR(400MHz,CDCl3)δ8.07(dd,J=8.5,5.5Hz,2H),7.82(s,1H),7.44(m,5H),7.17(t,J=8.6Hz,2H),4.01(s,3H),3.73(s,3H);
13CNMR(100MHz,CDCl3)δ167.8,165.7,164.2(d，J=250.3Hz),156.9,150.2,146.4,137.3,133.9(d,J=3.1Hz),129.5,129.4,129.2,128.8,128.1,123.4,116.0(d,J=21.8Hz),53.3,52.8;
HRMSCalculatedforC21H16NO4FNa[M+Na]+388.0961,found388.0965。

Claims (3)

1.一种由3-氮杂-1,5-烯炔衍生物制备吡啶衍生物的方法，其特征在于：
以下式所示的3-氮杂-1,5-烯炔衍生物(I)为原料通过A和B两个步骤生成吡啶衍生物(II)，反应式如下：
其中R1、R2、R3为苯基、或取代的苯基，苯基上的取代基为F、Cl、Br、I、NO2中的一种、或二种、或三种；R4、R5为C1-C4酯基；
步骤A：以C1–C10的一元醇溶剂，室温–100℃反应；
步骤B：在N,N-二甲基甲酰胺溶剂中进行加热反应,N,N-二甲基甲酰胺溶剂的用量为每毫摩尔反应物I用溶剂5–20毫升。
2.按照权利要求1所述的方法，其特征在于：
在步骤A中，溶剂为C1–C10的一元醇,溶剂的用量为每毫摩尔反应物I用溶剂5–20毫升。
3.按照权利要求1所述的方法，其特征在于：
在步骤B中，反应温度为80–150℃。
CN201210437566.1A 2012-11-06 2012-11-06 一种由3-氮杂-1,5-烯炔制备吡啶衍生物的方法 Expired - Fee Related CN103804286B (zh)

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