Synthesis of unsymmetrical urea from aryl- or pyridyl carboxamides and aminopyridines using PhI(OAc)2via in situ formation of aryl- or pyridyl isocyanates

Abstract

A tandem synthesis of unsymmetrical ureas (N-aryl-N′-pyridylurea and N,N′-bipyridylurea) from aryl- or pyridyl carboxamides and aminopyridines via Hofmann rearrangement has been reported. In particular, benzamides, picolinamide, nicotinamide, and isonicotinamide generate reactive intermediate isocyanates, in situ, in the presence of PhI(OAc)₂, which upon further reaction with aminopyridines form urea derivatives. As the formation of pyridylisocyanates from their corresponding carboxamides via Hofmann rearrangement remained unexplored previously, attempts have been made to trap the isocyanates. While the three pyridylisocyanates were trapped as their corresponding carbamates, 3-pyridylisocyanate was isolated and characterized. Unlike closely related previous methods reported for urea synthesis, the current method avoids direct use of isocyanates or eliminates the use of toxic phosgene for the in situ generation of isocyanates.