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.

Fabrication of Nanofiber Filtration Membranes Using Polyethylene Terephthalate (PET): A Review

“…Some other narrative researches that have been performed with the help of VFD are involved bacteria and algal cells with graphene and magnetic polymer [78][79][80], protein folding [81], exfoliating single layered graphene and hexagonal Boron Nitride (h-BN) sheets from the bulk material [82], sol-gel synthesis of silica xero gel at room temperature and the incorporation of curcumin, [83] controlling the pore size and wall thickness of mesoporous silica [84,85], fabricating toroidal arrays of SWCNTs, [86] laterally 'slicing' CNTs, [87] accelerating enzymatic reaction, [88] probing the structure of self-organized systems [89,90], biodiesel catalysis [91] and many others. According to the extra capabilities of VFD as a various reaction media compared with Spinning Disc Processors (SDPs) or Rotating Tube Processors (RTPs), VFD will be more advantageous in reaction accomplishment [92]. It seems that it is also a good idea to apply VFD for better making of polymeric solution.…”

Rapid protein immobilization for thin film continuous flow biocatalysis

“…Some of the reactions in this manuscript were performed in continuous flow, further information on the reactor setup has been previously reported. 39 …”

“…39 This involves processing in a vortex fluidic device (VFD) which confines reagents to a ≈250 μM thin film. Here, micromixing, shear stress and mechanical vibrations 40,41 can operate upon reagents to increase reaction yields and efficiencies.…”

Organic oxidations promoted in vortex driven thin films under continuous flow

“…24 Reaction mixtures are rotated at high speeds (0-9k rpm), producing a large surface area as the liquid forms a thin film. The unique conditions found provide many benefits in organic, 25 biochemical 26,27 and materials chemistry. 28 Given the versatility of the VFD and its ease of use, we were motivated to explore the ways in which it could be integrated into oxidations that align with the tenets of green chemistry.…”

“…First, we posited that the thin film processing would improve gas exchange between the reaction medium and the atmosphere, perhaps improving the rate of aerobic oxidations and providing a simple and efficient method for deploying gaseous reagents in synthesis. Second, we suspected that the intense micro-mixing in the VFD that results from extremely rapid rotation of the inclined reaction tube, typically 45°for optimum processing, [25][26][27][28] would enable efficient mixing of immiscible materials such as non-polar organic substrates and oxidants in aqueous solution. The problem of immiscibility limits the use of these aqueous oxidants, even in conventional flow reactors, as evident by the use of phase transfer catalysis to promote such reactions.…”