title: Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine.
abstract: 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 ≤80 seconds 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.
authors.affiliation: Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Bedford Park, South Australia, 5042 (Australia).
authors.forename: Joshua
authors.initials: J
authors.lastname: Britton
authors.affiliation: Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Bedford Park, South Australia, 5042 (Australia).
authors.forename: Justin M
authors.initials: JM
authors.lastname: Chalker
authors.affiliation: Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Bedford Park, South Australia, 5042 (Australia). Colin.Raston@flinders.edu.au.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Raston
mesh_terms: D000215:Acylation; D000577:Amides / Q000138:chemical synthesis*; D000779:Anesthetics, Local / Q000138:chemical synthesis*; D060326:Chemistry Techniques, Synthetic / Q000191:economics / Q000295:instrumentation*; D004867:Equipment Design; D008012:Lidocaine / Q000138:chemical synthesis*; D013997:Time Factors
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D008012:Lidocaine
keywords: acylations; amides; amino acids; flow chemistry; synthetic methods