(656g) A Paradigm for Scale-up of Piperylene Sulfone as a Sustainable Pharmaceutical Solvent

Authors: 
Marus, G., Georgia Institute of Technology
Mestre, V. L., Georgia Institute of Technology
Vyhmeister, E., Georgia Institute of Technology


We report the path from laboratory scale to industrial scale for a potentially important new solvent for the pharmaceutical industry. Polar aprotic solvents, such as DMSO, offer many advantages, such dissolution of inorganic salts from organic reactions. However, solvent removal and further product purification are not trivial due to sizeable amounts of water that are needed for product isolation. Additionally, high boiling points prohibit efficient separation of these typical polar aprotic solvents. We have shown that piperylene sulfone has solvent properties very similar to DMSO, but is a fully recyclable dipolar aprotic solvent that undergoes a retro-cheletropic reaction at 110 degrees C, permitting facile solvent removal and recycle.

We made gram quantities in the laboratory, using a synthesis not appropriate for scale-up. When we showed the advantages of this solvent, a number of industrial firms asked for larger quantities, and one specialty chemical company offered to make kilogram or larger quantities if we could provide a method. What we report here is the route to developing a scaleable synthesis for larger quantities of piperylene sulfone. This quest has involved using readily available reagent, learning the reaction kinetics, and suppressing unwanted polymerization. This work is a blueprint for an industrial level scale-up of piperylene sulfone synthesis, and the methodology developed could be applied to many other novel chemical syntheses. In conclusion, we report a fully recyclable dipolar aprotic solvent capable of replacing traditional solvents, like DMSO, yet offering the advantages of benign separation and recycle in pharmaceutical processes.