CN108794385A - 一种合成苯乙炔基吡啶衍生物的方法 - Google Patents

一种合成苯乙炔基吡啶衍生物的方法 Download PDF

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CN108794385A
CN108794385A CN201810814501.1A CN201810814501A CN108794385A CN 108794385 A CN108794385 A CN 108794385A CN 201810814501 A CN201810814501 A CN 201810814501A CN 108794385 A CN108794385 A CN 108794385A
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phenylethynylpyridin
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张国防
李莎莎
姜丽萍
许镭
邢芳芳
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Shaanxi Normal University
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Abstract

本发明公开了一种合成苯乙炔基吡啶衍生物的方法,该方法以醋酸钯为催化剂,以4,5‑双二苯基膦‑9,9‑二甲氧基杂蒽为配体,甲醇为溶剂,在碳酸铯碱性条件下,将2‑碘代吡啶与苯乙炔类化合物偶联制得苯乙炔基吡啶衍生物。本发明操作简单,反应高效、条件温和,底物适用性好,可广泛用于苯乙炔基吡啶衍生物的制备。

Description

一种合成苯乙炔基吡啶衍生物的方法
技术领域
本发明涉及一种以碘代吡啶和苯乙炔类化合物为底物,醋酸钯作为催化剂,4,5-双二苯基膦-9,9-二甲基氧杂蒽(Xantphos)为配体,在CsCO3碱性条件下合成苯乙炔基吡啶衍生物的方法。
背景技术
Sonogashira反应是一种由金属钯化合物催化的末端炔烃与sp2型碳的交叉耦联反应,这一反应为合成芳基炔烃衍生物提供了一种行之有效的反应路线。
苯乙炔基吡啶衍生物具有多种生理活性,是构筑杂环类结构的重要小分子,近来引起了研究者的关注,其在有机合成、分子电子学、天然产物活性分子、纳米结构、农药、染料、日用化学品合成、共聚物以及材料等领域有着广泛的用途,因此研究高效合成苯乙炔基吡啶衍生物的方法非常重要。
2010年Saisuree Prateeptongkum报道了利用K2PdCl4催化剂(0.5mol%),CuI(1mol%)做助催化剂,四甲基乙二胺(TMEDA)作溶剂,氩气保护下80℃下反应20h,可以高收率的合成多种苯乙炔基吡啶衍生物。2013年Rafique Ul Islam合成了用于Sonogashira偶联反应的钯-聚合物超分子催化剂,在无铜盐助催化剂和无配体条件下该催化反应转换频率(TOF)值较高。2014年Christopher W.D.Gallop提出了使用(N-杂环卡宾)-Cu和(N-杂环卡宾)-Pd配合物的100:1组合的Sonogashira反应催化剂体系。使用1mol%(NHC)-Cu和0.01mol%(NHC)-Pd的催化剂体系可以使芳基溴化物和芳基炔烃在空气和非无水溶剂中发生偶联,且收率较高。2016年Chizoba I.Ezugwu合成了非均相的N-杂环卡宾基MOF催化剂(1-Pd),它对于Sonogashira交叉偶联反应非常有效。2016年Monica Dell'Acqua以PdCl2(PPh3)2为催化剂,CuI做助催化剂,无水TEA作溶剂,在氮气保护下可以高收率的合成苯乙炔基吡啶衍生物。
目前,报道的这些反应虽然可以高产率的得到苯乙炔基吡啶衍生物,但是大部分反应中要加入铜盐助催化剂。而且这些反应要对溶剂进行严格的除水除氧,反应过程需要氮气或氩气保护,或者要先合成复杂的催化剂体系,这就造成合成苯乙炔基吡啶衍生物的方法和过程复杂,成本高,不利于苯乙炔基吡啶衍生物的放大合成。
发明内容
本发明所要解决的技术问题在于克服现有苯乙炔基吡啶衍生物制备方法对水、氧敏感需要氮气或氩气保护,溶剂需要严格的除水除氧,反应温度高,需要的有机碱含量高,且在Sonogashira反应中,需要加入铜盐作为助催化剂等缺点,提供一种操作简单、反应温和、反应速度快、高效安全的合成苯乙炔基吡啶衍生物的方法。
解决上述技术问题所采用的技术方案是:以甲醇为溶剂、醋酸钯为催化剂,Xantphos为配体,CsCO3提供碱性环境,将2-碘代吡啶和苯乙炔类化合物在50~60℃下反应,得到苯乙炔基吡啶衍生物,反应方程式如下所示:
式中R1代表H、NO2、卤素、C1~C4烷基、C1~C4烷氧基中任意一种。
上述合成方法中,所述2-碘代吡啶和苯乙炔类化合物的摩尔比为1:1.0~1.3,醋酸钯的加入量为2-碘代吡啶摩尔量的4%~8%,Xantphos的加入量为2-碘代吡啶摩尔量的8%~12%,CsCO3的加入量为2-碘代吡啶摩尔量的1~3倍。
上述Xantphos的结构式为
本发明以甲醇为溶剂、醋酸钯为催化剂,Xantphos为配体,碱性条件下,将2-碘代吡啶和苯乙炔类化合物进行Sonogashira偶联制得苯乙炔基吡啶衍生物。本发明操作简单,无需铜盐助催化剂,反应在空气中进行,所用得溶剂甲醇不用除水除氧,对设备要求低,反应高效、条件温和,底物适用性好,可广泛用于苯乙炔基吡啶衍生物的制备。
具体实施方式
下面结合实施例对本发明进一步详细说明,但本发明的保护范围不仅限于这些实施例。
实施例1
合成结构式如下的2-(2-苯基乙炔基)吡啶
称取0.0112g(0.05mmol)醋酸钯、0.0579g(0.10mmol)Xantphos、0.6516g(2.00mmol)碳酸铯于反应瓶中,并加入5mL甲醇、106.2μL(1.00mmol)2-碘吡啶、131.8μL(1.00mmol)苯乙炔,在55℃下反应6h,停止反应,自然降至室温,柱色谱分离,得到棕色液体2-(2-苯基乙炔基)吡啶,产率为96%,结构表征数据为:1H NMR(400MHz,CDCl3):δ8.63-8.62(d,1H),7.70-7.66(dt,1H),7.62-7.59(m,2H),7.52(d,1H),7.37-7.36(m,3H),7.24-7.23(m,1H);13C NMR(100MHz,CDCl3):δ150.05,143.44,136.17,132.04,128.99,128.40,127.16,122.76,122.26,89.23,88.64.
实施例2
合成结构式如下的2-((4-甲氧基苯基)乙炔基)吡啶
本实施例中,用等摩尔4-甲氧基苯乙炔替换实施例1中的苯乙炔,反应时间延长至10h,其他步骤与实施例1相同,得到棕红色液体2-((4-甲氧基苯基)乙炔基)吡啶,产率为96%,结构表征数据为:1H NMR(400MHz,CDCl3):δ8.60-8.59(d,1H),7.67-7.63(dt,1H),7.55-7.52(d,2H),7.50-7.48(d,1H),7.22-7.19(dq,1H),6.89-6.77(d,2H),3.83(s,3H);13C NMR(100MHz,CDCl3):δ160.26,149.73,143.78,136.20,133.59,126.95,122.47,114.30,114.01,89.32,87.41,55.16.
实施例3
合成结构式如下的2-((4-硝基苯基)乙炔基)吡啶
本实施例中,用等摩尔4-硝基苯乙炔替换实施例1中的苯乙炔,反应时间延长至10h,其他步骤与实施例1相同,得到微黄色固体2-((4-硝基苯基)乙炔基)吡啶,产率为90%,结构表征数据为:1H NMR(400MHz,CDCl3):δ8.68(d,1H),8.26(d,2H),7.76-7.72(dd,3H),7.59(d,1H),7.34(dt,1H);13C NMR(100MHz,CDCl3):δ151.79,148.94,143.89,137.78,134.20,130.55,128.95,125.09,125.02,94.59,88.15.
实施例4
合成结构式如下的2-(邻甲苯基乙炔基)吡啶
本实施例中,用等摩尔2-乙炔基甲苯替换实施例1中的苯乙炔,反应时间延长至10h,其他步骤与实施例1相同,得到棕色液体2-(邻甲苯基乙炔基)吡啶,产率为95%、结构表征数据为:1H NMR(400MHz,CDCl3):δ8.63-8.62(d,1H),7.70-7.66(dt,1H),7.58-7.56(d,1H),7.54-7.52(d,1H),7.29-7.16(m,4H),2.55(s,3H);13C NMR(100MHz,CDCl3):δ150.08,143.70,140.75,136.13,132.40,129.53,129.03,127.19,125.65,122.67,122.04,92.54,88.23,20.78.
实施例5
合成结构式如下的2-(邻氯苯基乙炔基)吡啶
本实施例中,用等摩尔1-氯-2-乙炔基苯替换实施例1中的苯乙炔,反应时间延长至10h,其他步骤与实施例1相同,得到棕色液体2-(邻氯苯基乙炔基)吡啶,产率为98%,结构表征数据为:1H NMR(400MHz,CDCl3):δ8.65-8.64(d,1H),7.72-7.68(t,1H),7.65-7.63(d,1H),7.59-7.57(d,1H),7.43-7.45(d,1H),7.31-7.24(m,3H);13C NMR(100MHz,CDCl3):δ150.15,143.14,136.33,136.18,133.73,130.01,129.35,127.53,126.55,123.08,122.29,93.42,85.80.

Claims (6)

1.一种合成苯乙炔基吡啶衍生物的方法,其特征在于:以甲醇为溶剂、醋酸钯为催化剂,4,5-双二苯基膦-9,9-二甲基氧杂蒽为配体,碳酸铯提供碱性环境,将2-碘代吡啶和苯乙炔类化合物在50~60℃下反应,得到苯乙炔基吡啶衍生物。
2.根据权利要求1所述的合成苯乙炔基吡啶衍生物的方法,其特征在于:所述苯乙炔类化合物为苯乙炔、硝基取代苯乙炔、卤代苯乙炔、C1~C4烷基取代苯乙炔、C1~C4烷氧基取代苯乙炔中任意一种。
3.根据权利要求1或2所述的合成苯乙炔基吡啶衍生物的方法,其特征在于:所述2-碘代吡啶和苯乙炔类化合物的摩尔比为1:1.0~1.3。
4.根据权利要求1或2所述的合成苯乙炔基吡啶衍生物的方法,其特征在于:所述醋酸钯的加入量为2-碘代吡啶摩尔量的4%~8%。
5.根据权利要求1或2所述的合成苯乙炔基吡啶衍生物的方法,其特征在于:所述4,5-双二苯基膦-9,9-二甲基氧杂蒽的加入量为2-碘代吡啶摩尔量的8%~12%。
6.根据权利要求1或2所述的合成苯乙炔基吡啶衍生物的方法,其特征在于:所述碳酸铯的加入量为2-碘代吡啶摩尔量的1~3倍。
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CN114950569A (zh) * 2022-06-30 2022-08-30 齐鲁工业大学 一种催化芳基卤化物与末端炔烃反应的催化剂及反应方法

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