Integrated micro flow synthesis based on sequential Br-Li exchange reactions of p-, m-, and o-dibromobenzenes.
Integrated micro flow synthesis based on sequential Br-Li exchange reactions of p-, m-, and o-dibromobenzenes.
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DOI：
10.1002/asia.200700231
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发表时间：
2007-12
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影响因子：
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通讯作者：
A. Nagaki;Yutaka Tomida;H. Usutani;Heejin Kim;Naofumi Takabayashi;T. Nokami;Hideho Okamoto;J. Yoshida-J.-Yo
中科院分区：
文献类型：
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作者：
A. Nagaki;Yutaka Tomida;H. Usutani;Heejin Kim;Naofumi Takabayashi;T. Nokami;Hideho Okamoto;J. Yoshida-J.-Yo
由微混合器和微管反应器组成的微流系统为对、间和邻二溴苯上引入两种亲电试剂提供了一种有效的方法。对二溴苯与nBuLi的Br-Li交换反应可以通过微流系统在20℃下进行，但批量反应需要更低的温度（< -48℃）。得到的对溴苯基锂在20℃的微流体系中与一种亲电试剂反应，得到的对取代溴苯在20℃的微流体系中进行第二次Br-Li交换反应，然后与另一种亲电试剂在一次流动中反应。用微流系统可以对间二溴苯进行类似的转化。而邻二溴苯的Br-Li交换反应，在与亲电试剂反应后，应在-78℃下进行，以避免生成苯。第二次Br-Li交换反应与亲电试剂的反应可以在0℃下进行，使用本方法可以在比常规间歇反应更高的温度下一次合成多种对、间和邻二取代苯。
A micro flow system consisting of micromixers and microtube reactors provides an effective method for the introduction of two electrophiles onto p-, m-, and o-dibromobenzenes. The Br-Li exchange reaction of p-dibromobenzene with nBuLi can be conducted by using the micro flow system at 20 degrees C, although much lower temperatures (< -48 degrees C) are needed for a batch reaction. The resulting p-bromophenyllithium was allowed to react with an electrophile in the micro flow system at 20 degrees C. The p-substituted bromobenzene thus obtained was subjected to a second Br-Li exchange reaction followed by reaction with a second electrophile at 20 degrees C in one flow. A similar transformation can be carried out with m-dibromobenzene by using the micro flow system. However, the Br-Li exchange reaction of o-dibromobenzene followed by reaction with an electrophile should be conducted at -78 degrees C to avoid benzyne formation. The second Br-Li exchange reaction followed by reaction with an electrophile can be carried out at 0 degrees C. By using the present method, a variety of p-, m-, and o-disubstituted benzenes were synthesized in one flow at much higher temperatures than are required for conventional batch reactions.