TY - JOUR
T1 - Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine
AU - Britton, Joshua
AU - Chalker, Justin
AU - Raston, Colin
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - acylations
KW - amides
KW - amino acids
KW - flow chemistry
KW - synthetic methods
UR - http://onlinelibrary.wiley.com/doi/10.1002/chem.201501785/abstract;jsessionid=44A001DFA273315899B93475FB2D6C21.f02t04
UR - http://www.scopus.com/inward/record.url?scp=84936998069&partnerID=8YFLogxK
U2 - 10.1002/chem.201501785
DO - 10.1002/chem.201501785
M3 - Article
SN - 0947-6539
VL - 21
SP - 10660
EP - 10665
JO - Chemistry-A European Journal
JF - Chemistry-A European Journal
IS - 30
ER -