Dielectrically Monitored Flow Synthesis of Functional Vaccine Adjuvant Mixtures via Microwave-Assisted Catalytic Chain Transfer Processing

A novel flow process to produce low-molecular-weight (Mwt) methacrylate oligomer mixtures that have potential as vaccine adjuvants and chain transfer agents (CTAs) is reported. The chemistry and process were designed to significantly reduce the number of stages required to manufacture methyl methacrylate oligomer-in-monomer mixtures with an oligomer Mwt range of dimers to pentamers and >50% conversion. Combining rapid in-flow, in situ catalytic chain transfer polymerization catalyst synthesis and volumetric microwave heating of the reaction medium resulted in catalyst flow synthesis being completed in <4 min, removing the need to pre-synthesize it. The steady-state operation was then successfully maintained with very low levels of external energy, as the process utilized the reaction exotherm. The microwave process outperformed a comparative conventionally heated system by delivering a 20% increase in process throughput with no change in final product quality or conversion. Additionally, combining flow and in situ catalyst processing enabled the use of a more oxidatively unstable catalyst. This allowed for in situ catalyst deactivation post-generation of the oligomers, such that residual catalyst did not need to be removed prior to preparing subsequent vaccine adjuvant or CTA screening formulations. Finally, dielectric property measurements were able to monitor the onset of reaction and steady-state operation.