CN114805107B - 一种光催化实现的含氮杂环N-α位芳基化方法 - Google Patents
一种光催化实现的含氮杂环N-α位芳基化方法 Download PDFInfo
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
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Abstract
一种光催化实现的含氮杂环N‑α位芳基化方法,本发明涉及催化合成技术领域,具体涉及一种在无外加HAT试剂的条件下,光催化实现含氮杂环N‑α位芳基化的方法。方法:将溴代芳烃化合物、含氮化合物、Ir[dF(CF3)ppy]2(dtbbpy)PF6、氯化镍、4,4‑二叔丁基‑2,2‑联吡啶和碱加入到混合溶剂中,得到反应混合溶液,在室温、惰性气体氛围下,进行光源照射,得到含氮杂环N‑α位芳基类化合物。本发明通过无外加HAT试剂的情况下,完成C(sp3)‑C(sp2)的偶联,反应简便;使用廉价的溴代芳烃化合物以及光敏剂,体现了反应的经济环保特色。本发明的方法操作非常简单,原料商业可得,使用催化量的光氧化还原催化剂便能较高产率实现该反应,且原子经济性高,具有广泛的底物普适性。本发明应用于有机合成领域。
Description
技术领域
本发明涉及催化合成技术领域,具体涉及一种在无外加HAT试剂的条件下,光催化实现含氮杂环N-α位芳基化的方法。
背景技术
可见光光氧化还原催化已成为有机合成中的一项重要技术。这类催化利用过渡金属多吡啶基配合物,在可见光激发下,可与常见官能团进行单电子转移(SET),激活有机分子进行各种有价值的转化。在过去的一个世纪里,过渡金属催化的交叉偶联反应已发展成为有机合成中最常用的构建C-C、C-N和C-杂原子键的方法之一,尤其是许多途径通过镍催化来构建C-C键。
C-H键的官能团化是有机合成中重要的研究内容,即由C-H键构建C-C,C-N等。其中C-C键的形成是化学合成中的一个基本步骤,因此,研究者们致力于开发高效、有选择性和便捷的方法来实现C-C键的构建。目前为止,有许多基于过渡金属催化实现C-H键的功能化和烯烃复分解,可用于形成不同类型的C-C键。但在大多数情况下,需要对底物引入导向基团进行预活化或者添加化学计量添加剂来实现该类型的反应。对于直接的C(sp3)-H官能化仍然是一个具有挑战性的领域。因此,通过温和、高效、绿色的方法实现C(sp3)-H键的直接官能团化是极具意义又极具挑战性的研究课题之一,而对于它的的研究也随着有机化学的发展方兴未艾。
发明内容
本发明要解决目前无法直接的C(sp3)-H官能化的技术问题,而提供一种光催化实现的含氮杂环N-α位芳基化方法。
一种光催化实现的含氮杂环N-α位芳基化方法,包括如下步骤:
一、将溴代芳烃化合物、含氮杂环类化合物、Ir[dF(CF3)ppy]2(dtbbpy)PF6、氯化镍、4,4-二叔丁基-2,2-联吡啶(dtbbpy)和碱加入到混合溶剂中,得到混合溶液;
二、在惰性气氛、室温条件下,采用光源照射步骤一获得的混合溶液12-20h;
三、将步骤二处理的混合溶液进行旋蒸处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化合物,完成制备。
进一步的,步骤一所述溴代芳烃化合物为4-溴苯乙酮、对三氟甲基溴苯、对甲氧基溴苯、对溴苯甲醛、对溴苯乙腈、2-三氟甲基-4-溴吡啶或2-氟-4-溴吡啶。
进一步的,步骤一所述含氮杂环类化合物为N-Boc-吡咯烷、N-Piv-吡咯烷、N-Ac-吡咯烷、N-Cbz-吡咯烷、N-苯甲酰基吡咯烷、N-Boc-哌啶、N,N-二甲基丙酰胺、N-Boc-环庚胺或N-Boc-3-氟-吡咯烷。
进一步的,步骤一所述Ir[dF(CF3)ppy]2(dtbbpy)PF6为光氧化还原催化剂。
进一步的,步骤一金属催化剂为NiCl2、配体为dtbbpy。
进一步的,步骤一所述碱为碳酸钠。
进一步的,步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
进一步的,所述溴代芳烃化合物与混合溶剂的用量比为0.2~0.3mmol:2mL;所述含氮类化合物与混合溶剂的用量比为0.4~0.6mmol:2mL;Ir[dF(CF3)ppy]2(dtbbpy)PF6与混合溶剂的用量比为4~5mg:2mL;碱与混合溶剂的用量比值为0.4~0.6mmol:2mL。
进一步的,步骤二所述光源照射是采用波长为450±10nm LEDs照射,控制光照时间为12~20h。
本发明以含氮杂环N-α位芳基类化合物-1为例,反应机理如下:
光催化剂在光照条件下,受光激发达到激发态,随即与氯离子发生单电子转移(SET)过程,得到氯自由基和还原态的光催化剂,随后氯自由基能够选择性抽取N-Boc-吡咯烷的N-α位氢形成N-α位自由基中间体;配体dtbbpy与金属镍催化剂配位,随后与光催化剂发生SET过程得到零价的络合物,接着与溴代芳基化合物氧化加成,再与N-Boc-吡咯烷的N-α位自由基络合,最后经过氧化消除得到含氮杂环N-α位芳基类化合物-1。
本发明旨在探究一种溴代芳烃与N-Boc-吡咯烷在无外加HAT试剂的情况下,完成C(sp3)-C(sp2)的偶联。在光氧化还原和过渡金属协同催化的条件下,N-Boc-吡咯烷的N-α位形成自由基与卤代芳烃发生偶联,使反应更加简便、绿色、温和、高效。
本发明的有益效果是:
与现有技术相比,本发明通过一种便捷、绿色温和、高效率的方法来构筑含氮杂环N-α位芳基类化合物,主要具有以下优势:
(1)无外加HAT试剂的条件下,实现N-Boc-吡咯烷的N-α位的直接芳基化。
(2)反应在室温下通过光照便能实现含氮杂环N-α位芳基类化合物的合成,反应条件绿色温和。
(3)该反应体系用的溴代芳烃化合物、含氮类化合物、Ir[dF(CF3)ppy]2(dtbbpy)PF6、NiCl2、dtbbpy、Na2CO3以及混合溶剂都是廉价、易得的商用化学品,使得整个反应体系节约、效率高。
(4)该反应体系底物普适性好,适用于一些含敏感官能团的底物,且原子经济性高,通过反应条件的优化能够得到较高的产率。
(5)使用催化量的光敏剂便能实现该反应的转化,体现了反应的节约环保,并且具有潜在的药物合成应用价值。
本发明用于实现含氮杂环N-α位芳基化。
附图说明
图1为实施例三制备的含氮杂环N-α位芳基类化合物-3的1H NMR谱图;
图2为实施例三制备的含氮杂环N-α位芳基类化合物-3的13C NMR谱图
具体实施方式
本发明技术方案不局限于以下所列举的具体实施方式,还包括各具体实施方式之间的任意组合。
具体实施方式一:本实施方式一种光催化实现的含氮杂环N-α位芳基化方法,包括如下步骤:
一、将溴代芳烃化合物、含氮杂环类化合物、Ir[dF(CF3)ppy]2(dtbbpy)PF6、氯化镍、4,4-二叔丁基-2,2-联吡啶和碱加入到混合溶剂中,得到混合溶液;
二、在惰性气氛、室温条件下,采用光源照射步骤一获得的混合溶液12-20h;
三、将步骤二处理的混合溶液进行旋蒸处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化合物,完成制备。
具体实施方式二:本实施方式与具体实施方式一不同的是:步骤一所述溴代芳烃化合物为4-溴苯乙酮、对三氟甲基溴苯、对甲氧基溴苯、对溴苯甲醛、对溴苯乙腈、2-三氟甲基-4-溴吡啶或2-氟-4-溴吡啶。其它与具体实施方式一相同。
具体实施方式三:本实施方式与具体实施方式一或二不同的是:步骤一所述含氮杂环类化合物为N-Boc-吡咯烷、N-Piv-吡咯烷、N-Ac-吡咯烷、N-Cbz-吡咯烷、N-苯甲酰基吡咯烷、N-Boc-哌啶、N,N-二甲基丙酰胺、N-Boc-环庚胺或N-Boc-3-氟-吡咯烷。其它与具体实施方式一或二相同。
具体实施方式四:本实施方式与具体实施方式一至三之一不同的是:步骤一所述Ir[dF(CF3)ppy]2(dtbbpy)PF6为光氧化还原催化剂。其它与具体实施方式一至三之一相同。
具体实施方式五:本实施方式与具体实施方式一至四之一不同的是:步骤一所述碱为碳酸钠。其它与具体实施方式一至四之一相同。
具体实施方式六:本实施方式与具体实施方式一至五之一不同的是:步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。其它与具体实施方式一至五之一相同。
具体实施方式七:本实施方式与具体实施方式一至六之一不同的是:所述溴代芳烃化合物与混合溶剂的用量比为0.2~0.3mmol:2mL;所述含氮类化合物与混合溶剂的用量比为0.4~0.6mmol:2mL;Ir[dF(CF3)ppy]2(dtbbpy)PF6与混合溶剂的用量比为4~5mg:2mL;碱与混合溶剂的用量比值为0.4~0.6mmol:2mL。其它与具体实施方式一至六之一相同。
具体实施方式八:本实施方式与具体实施方式一至七之一不同的是:步骤二所述光源照射是采用波长为450±10nm LEDs照射,控制光照时间为12~20h。其它与具体实施方式一至七之一相同。
具体实施方式九:本实施方式与具体实施方式一至八之一不同的是:步骤三所述薄层色谱法分离纯化所用溶剂为石油醚和乙酸乙酯的混合。其它与具体实施方式一至八之一相同。
具体实施方式十:本实施方式与具体实施方式一至九之一不同的是:所述石油醚和乙酸乙酯的体积比为10:1。其它与具体实施方式一至九之一相同。
采用以下实施例和对比实验验证本发明的有益效果:
实施例一:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)和0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Boc-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-1,其结构式为:
纯度99%,产率为85%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.91(d,J=8.2Hz,2H),7.27(d,J=8.1Hz,2H),4.90(d,J=61.8Hz,1H),3.64(d,J=6.4Hz,2H),2.60(s,3H),2.36(s,1H),1.89–1.76(m,3H),1.53–1.41(m,6H),1.18(s,3H).13C NMR(101MHz,CDCl3)δppm=197.73,154.43,150.82,135.71,128.45,125.65,79.52,61.17,47.15,35.91,28.36,28.34,26.52,23.26.
实施例二:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴二苯甲酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Boc-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-2,其结构式为:
纯度99%,产率为68%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.78(t,J=7.8Hz,4H),7.59(t,J=7.0Hz,1H),7.48(t,J=7.3Hz,2H),7.29(d,J=8.1Hz,2H),4.93(d,J=72.6Hz,1H),3.72–3.48(m,2H),2.35(d,J=17.8Hz,1H),1.90(d,J=6.0Hz,3H),1.47(s,4H),1.21(s,6H).13C NMR(101MHz,CDCl3)δppm=196.43,154.47,150.19,137.80,135.91,132.32,130.40–130.34,130.13(d,J=32.9Hz),128.25,125.40,79.56,60.93,60.57,60.00,47.92,47.44,47.29,35.93,34.78,31.43,30.18,28.36,28.34,23.45,23.26,22.56.
实施例三:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 2-甲基-4-溴苯腈、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Boc-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-3,其结构式为:
纯度99%,产率为73%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.54(d,J=7.9Hz,1H),7.12(s,1H),7.08(d,J=8.0Hz,1H),4.82(d,J=61.3Hz,1H),3.63(s,2H),2.53(s,3H),2.35(s,1H),1.86(dd,J=27.9,21.2Hz,3H),1.45(s,3H),1.18(s,6H).13C NMR(101MHz,CDCl3)δppm=154.33,150.63,149.68,141.97,132.65,127.32,123.43,118.31,110.78,79.69,60.90,47.35,35.86,34.80,28.47,28.16,23.76,23.51,20.53.
实施例四:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 2-氰基-5-溴吡啶、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Boc-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-4,其结构式为:
纯度99%,产率为60%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=8.58(s,1H),7.65(s,2H),4.90(d,J=53.6Hz,1H),3.61(s,2H),2.42(s,1H),1.99–1.78(m,3H),1.45(s,3H),1.20(s,6H).13C NMR(101MHz,CDCl3)δppm=154.17,149.36,144.88,143.92,134.11,132.25,128.31,117.47,80.40,59.26,58.95,47.50,36.03,34.75,28.57,28.34,23.79.
实施例五:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Piv-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-5,其结构式为:
纯度99%,产率为75%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.90(d,J=8.2Hz,2H),7.23(d,J=8.3Hz,2H),5.21(s,1H),3.88(s,2H),2.57(s,3H),2.12(ddd,J=198.2,45.5,37.5Hz,4H),1.28(s,9H).13C NMR(101MHz,CDCl3)δppm=197.80,176.53,150.18,135.65,128.76,125.35,62.71,48.97,39.21,33.21,27.08,26.63,26.02.
实施例六:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Ac-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-6,其结构式为:
纯度99%,产率为84%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.93(dd,J=21.4,8.2Hz,2H),7.31–7.26(m,1H),7.24(s,1H),5.10(dd,J=97.1,8.4Hz,1H),3.69(ddd,J=25.8,19.3,10.0Hz,2H),2.59(d,J=14.4Hz,3H),2.37(ddd,J=20.3,18.6,7.9Hz,1H),2.16(s,1H),2.07–1.80(m,5H).13C NMR(101MHz,CDCl3)δppm=197.79,197.56,170.19,169.43,148.63,136.35,135.76,129.00,128.63,125.68,62.09,60.27,48.52,47.01,36.19,34.09,26.65,23.88,22.72,21.96.
实施例七:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Cbz-吡咯烷,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-7,其结构式为:
纯度99%,产率为64%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=8.00–7.79(m,2H),7.54–7.10(m,6H),6.94–6.81(m,1H),5.05(dq,J=39.2,12.6Hz,2H),3.62(dt,J=70.9,6.7Hz,2H),2.58(d,J=9.2Hz,3H),2.35(s,1H),2.00–1.61(m,4H).13C NMR(101MHz,CDCl3)δppm=197.76,154.94,153.90,149.92,149.18,146.47,140.40,136.87,136.86,136.15,135.90,128.68,128.19,127.69,127.46,127.07,125.74,66.85,61.14,47.75,47.31,46.36,45.94,35.81,34.75,29.74,26.68,25.77,24.96,23.77,23.08.
实施例八:
本实施例一种光催化实现的氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol 1-Boc-哌啶,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-8,其结构式为:
纯度99%,产率为56%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.94(d,J=8.4Hz,2H),7.31(d,J=8.2Hz,2H),5.44(s,1H),4.08(d,J=13.4Hz,1H),2.82–2.71(m,1H),2.60(s,3H),2.31(d,J=13.9Hz,1H),1.99–1.86(m,1H),1.73–1.54(m,4H),1.46(s,9H).13C NMR(101MHz,CDCl3)δppm=197.81,155.55,146.49,135.45,128.66,126.69,53.44,40.34,28.33,26.62,25.24,19.37.
实施例九:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N-Boc-环庚胺,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-9,其结构式为:
纯度99%,产率为66%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.90(d,J=8.3Hz,2H),7.29(dd,J=16.6,8.3Hz,2H),5.21(dd,J=12.1,6.3Hz,1H),4.95(dd,J=12.2,5.7Hz,1H),4.19(d,J=10.9Hz,1H),3.93(d,J=14.6Hz,1H),3.08–2.83(m,1H),2.58(d,J=8.0Hz,3H),2.45–2.18(m,1H),2.01–1.23(m,17H).13C NMR(101MHz,CDCl3)δppm=197.74,155.97,155.62,150.53,149.48,135.53,128.54,125.80,125.59,79.60,60.55,58.59,43.49,43.18,36.19,35.41,29.85,29.66,29.15,28.43,28.22,26.53,25.70.
实施例十:
本实施例一种光催化实现的含氮杂环N-α位芳基化方法,该方法包括如下步骤:
一、将0.2mmol 4-溴苯乙酮、氯化镍(10mmol%)、dtbbpy(10mmol%)、0.4mmol碳酸钠加入到2mL混合溶剂中,然后加入4-5mg(2mmol%)光催化剂Ir[dF(CF3)ppy]2(dtbbpy)PF6,再加入0.5mmol N,N-二甲基丙酰胺,得到混合溶液;
二、通入氩气5min,然后在室温条件下,采用10W波长为450±10nm LEDs作为光源照射步骤一获得的混合溶液18h,同时进行磁力搅拌,采用TLC监测反应进度;
三、将步骤二处理的混合溶液进行减压蒸馏处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化产物,完成制备。
步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
步骤三分离纯化采用的溶剂为石油醚和乙酸乙酯按体积比为10:1的混合。
本实施例制备的含氮杂环N-α位芳基化产物通过核磁氢谱、碳谱、以及高分辨质谱鉴定为含氮杂环N-α位芳基类化合物-10,其结构式为:
纯度99%,产率为75%;其核磁数据分析为:1H NMR(400MHz,CDCl3)δppm=7.94(dd,J=18.8,8.2Hz,2H),7.30(dd,J=18.0,6.3Hz,2H),4.63(d,J=20.6Hz,2H),2.96(d,J=10.7Hz,3H),2.60(d,J=6.7Hz,3H),2.41(dt,J=22.4,7.4Hz,2H),1.26–1.11(m,3H).13CNMR(101MHz,CDCl3)δppm=197.80,197.56,174.18,143.15,142.31,136.57,136.25,129.05,128.73,128.27,128.00,126.40,53.09,50.73,34.97,34.17,26.70,26.35,9.57,9.33.
Claims (6)
1.一种光催化实现的含氮杂环N-α位芳基化方法,其特征在于该方法包括如下步骤:
一、将溴代化合物、含氮类化合物、Ir[dF(CF3)ppy]2(dtbbpy)PF6、氯化镍、4,4-二叔丁基-2,2-联吡啶和碱加入到混合溶剂中,得到混合溶液;
二、在惰性气氛、室温条件下,采用光源照射步骤一获得的混合溶液12-20h;
三、将步骤二处理的混合溶液进行旋蒸处理去除溶剂,然后采用薄层色谱法分离纯化,所得产物即为含氮杂环N-α位芳基化合物,完成制备;所述含氮杂环N-α位芳基化合物为
步骤一所述溴代化合物为4-溴苯乙酮、4-溴二苯甲酮或2-甲基-4-溴苯腈;
步骤一所述含氮类化合物为N-Boc-吡咯烷、N-Piv-吡咯烷、N-Ac-吡咯烷、N-Cbz-吡咯烷或N-Boc-哌啶;
步骤一所述Ir[dF(CF3)ppy]2(dtbbpy)PF6为光氧化还原催化剂;
步骤一所述碱为碳酸钠。
2.根据权利要求1所述一种光催化实现的含氮杂环N-α位芳基化方法,其特征在于,步骤一所述混合溶剂为丙酮和乙酸乙酯按体积比1:2的混合。
3.根据权利要求1所述一种光催化实现的含氮杂环N-α位芳基化方法,其特征在于,所述溴代化合物与混合溶剂的用量比为0.2~0.3mmol:2mL;所述含氮类化合物与混合溶剂的用量比为0.4~0.6mmol:2mL;Ir[dF(CF3)ppy]2(dtbbpy)PF6与混合溶剂的用量比为4~5mg:2mL;碱与混合溶剂的用量比值为0.4~0.6mmol:2mL。
4.根据权利要求1所述一种光催化实现的含氮杂环N-α位芳基化方法,其特征在于,步骤二所述光源照射是采用波长为450±10nm LEDs照射,控制光照时间为12~20h。
5.根据权利要求1所述一种光催化实现的含氮杂环N-α位芳基化方法,其特征在于,步骤三所述薄层色谱法分离纯化所用溶剂为石油醚和乙酸乙酯的混合。
6.根据权利要求5所述一种光催化实现的含氮杂环N-α位芳基化方法,其特征在于,所述石油醚和乙酸乙酯的体积比为10:1。
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