Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine
Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine
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DOI：
10.1002/chem.201501785
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发表时间：
2015-07-20
影响因子：
4.3
通讯作者：
Raston, Colin L.
中科院分区：
文献类型：
--
作者：
Britton, Joshua;Chalker, Justin M.;Raston, Colin L.
使用涡旋流控装置(VFD)的薄膜流动化学在剪切作用下的胺的可伸缩酰化反应中是有效的，与传统的间歇工艺相比，酰胺的产率显著提高。优化的单相流动条件在室温下在80秒内有效，使人们能够在多克尺度上获得结构多样化的酰胺、官能化氨基酸和取代脲。流动条件下的酰胺合成也扩展到局部麻醉剂利多卡因的全合成，在两个串联的VFD单元中进行顺序反应。合成也可以在单一的VFD中进行，其中串联反应包括沿着快速旋转的管的不同位置的试剂输送和原位溶剂替换，作为分子流水线过程。这进一步突出了VFD在有机合成中的多功能性，以及对甲氧基苄基胺非常有效的脱苄基的发现。
Thin film flow chemistry using a vortex fluidic device (VFD) is effective in the scalable acylation of amines under shear, with the yields of the amides dramatically enhanced relative to traditional batch techniques. The optimized monophasic flow conditions are effective in 80seconds at room temperature, enabling access to structurally diverse amides, functionalized amino acids and substituted ureas on multigram scales. Amide synthesis under flow was also extended to a total synthesis of local anesthetic lidocaine, with sequential reactions carried out in two serially linked VFD units. The synthesis could also be executed in a single VFD, in which the tandem reactions involve reagent delivery at different positions along the rapidly rotating tube with in situ solvent replacement, as a molecular assembly line process. This further highlights the versatility of the VFD in organic synthesis, as does the finding of a remarkably efficient debenzylation of p-methoxybenzyl amines.