Tin can milling: low-tech mechanochemical synthesis of plant-based prepolymers incorporating perfluoropyridine

Perfluoropyridine (PFP) is a fluorinated small molecule heterocycle which can undergo a variety of substitutions in the 2-, 4-, and 6-position to afford rationally designed prepolymers. PFP is known to undergo mechanochemical substitutions, however ball mills have a large start-up cost and are bulky, creating a barrier of entry for researchers. We sought to provide a low tech, affordable, reproducible, and space-saving methodology towards general mechanochemistry while retaining the ability to work on gram scale. Herein we report the successful application of tin can milling (TCM) towards the gram scale synthesis of 4-tetrafluoropyridines (24 examples, up to ≥99% conversion) using a tomato paste can, aluminum beads, a rubber stopper, and agitation with a Burrell Wrist Action™ shaker unit. This approach eliminates problems of scalability with a mortar and pestle and provides a clean method to do benchtop-scale mechanochemistry without additional equipment. We further apply this technique towards making natural product-based prepolymers for polymerization by inverse vulcanization as a proof-of-concept for the use of TCM in monomer synthesis.