Continuous Flow Microwave-Assisted Reaction Optimization and Scale-Up Using Fluorous Spacer Technology

Abstract

Microwave-assisted organic synthesis in a laboratory-scale monomodal microwave reactor is investigated for continuous flow applications using fluorous spacer technology. The benchtop continuous flow microwave described allows sequential processing of multiple plugs using small amounts of reagents for reaction optimization, scale-up and array synthesis. The system features online monitoring of temperature, pressure and microwave power. Several different reactions have been scaled up, including a Suzuki-Miyaura cross-coupling reaction and nucleophilic substitutions. In all cases it was possible to optimize the reaction conditions on a small scale (∼300 µL processing volume), and achieve similar conversions on an intermediate scale (∼30 mL), offering the potential for further scale-up without modifying the optimized conditions (direct scalability) producing similar isolated yields in the C-C bond formation reaction.

Microdroplets in Microfluidics: An Evolving Platform for Discoveries in Chemistry and Biology

“…These principles were demonstrated with α‐diazo‐β‐keto ester synthesis and a nucleophilic aromatic substitution reaction, albeit with far larger droplet volumes (>100 μL) than used in non‐industrial applications of droplet‐based synthesis 186. Using perfluoromethyldecalin (PFMD), a low‐microwave absorber, as a carrier phase, the group also showed that microwave technology can be applied to Suzuki–Miyaura cross‐coupling and nucleophilic substitution reactions in droplets 187…”

Concepts and Optimization Strategies of Experimental Design in Continuous-Flow Processing

“…d K represents the combination of k variables varied 2 or 3 at a time while the remaining (k−2) or (k−3) is kept at the 0 level. [14]. The work showed the advantages of using an immiscible fluorinated spacer (perfluromethyldecalin, PFMD) for the formation of discrete reaction plugs in the system.…”

Camera-enabled techniques for organic synthesis

“…Many devices are highly portable, being hand-held or even smaller in size, allowing rapid reconfiguration and minimising the impact on an experimental setup. Specialist devices can operate beyond the normal visible regions, providing for instance near-IR imagery for low-light situations or IR thermal imagery for monitoring exothermic events and microwave chemistries [39–41]. Such equipment usually comes at a significantly increased cost.…”