Micelle-Enabled Hofmann Rearrangement in Water

An environmentally sustainable approach for the Hofmann rearrangement was developed. The presence of nanomicelles allows such a transformation to proceed smoothly in mild conditions with water as the sole reaction medium compared to traditional methods, which use significant amounts of organic solvents. A variety of amides containing functional groups have been constructed under these conditions, affording the compounding amine product in good to excellent yields (up to 99%). The process was scaled up and proven to be robust for its implementation in the synthesis of pharmaceutically relevant compounds.