Stereospecific synthesis of resorcin[4]arenes and pyrogallol[4]arenes in dynamic thin films

Abstract

Acid catalysed condensation of resorcinol and pyrogallol with aromatic aldehydes using a microfluidic vortex fluidic device (VFD) under continuous flow conditions results in the selective formation of resorcin[4]arenes and pyrogallol[4]arenes as predominantly their C(4v) isomers. Notably C(2v) isomers and C(2h) isomers can be also prepared with the latter being converted to the C(4v) isomer when the VFD operates in confined mode.

Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine

“…250 mm thin film in the VFD results in controlled heat transfer for the highlye xothermic acylation reactions, which was observed by real-time IR imaging, with such flow chemistry improving the safety metricso fa mide synthesis. [11] We also demonstrate that an ew assembly line approach to molecular synthesis can be achieved by using aVFD.…”

“…The centerpiece of this strategy involves the use of at hin film vortex fluidic device (VFD). [11] The VFD is at hin film flow-chemistry platform that has emerged as effective technology in organic synthesis. [11][12][13][14][15][16] The VFD can operate under continuous flow,i nw hich reagents are introduced through jet feeds into the hemisphere of an inclined rapidlyr otatingt ube.…”

“…[11] The VFD is at hin film flow-chemistry platform that has emerged as effective technology in organic synthesis. [11][12][13][14][15][16] The VFD can operate under continuous flow,i nw hich reagents are introduced through jet feeds into the hemisphere of an inclined rapidlyr otatingt ube. The reagents experience high shear forces and intensem icromixing, with mechanoenergy delivered to the dynamic thin film in the rapidly rotatingg lass tube, dramatically accelerating organic reactions.…”

“…[27] Thisd ebenzylation lends further credencet hat VFD flow chemistry can lead to unexpected types of reactivity. [11] Given that reactions in the VFD under continuous-flow mode generallyt ake only 20 minutesf or gram-scale quantities, we anticipate that new and interesting reactivity can be identified on ashort time scale without significant labor and expense. VFD processing is high throughput, with the ability to rapidly scan flow space and field effects, [15] in defining new possibilities in organic synthesis under shear.…”

Vortex Fluidic Chemical Transformations

“…Kinetic control was possible in the synthesis of macrocyclic resorcin[4]arenes and pyrogallo[4]arenes (Figure 2C). [20] Condensation using both the VFD, and non-VFD conditions produced the thermodynamically favored isomers, with the exception of the condensation of vanillin and pyrogallol. In the latter reaction, the thermodynamic and kinetic isomers were produced in a 3:4 ratio respectively.…”