8.3 Rearrangement to Electron Deficient Nitrogen
8.3.1 Hofmann Rearrangement
This rearrangement provides an effective method for the synthesis of primary aliphatic and aromatic amines from primary amides (Scheme 1).
Scheme 1
Mechanism
Treatment of amide with sodium hypobromite gives N -bromo-amide which reacts with base to afford a conjugate base within which rearrangement takes place to give isocyanate. The formed isocyanate may be isolated in anhydrous conditions or it can be converted into amine by aqueous workup (Scheme 2).
Scheme 2
The workup can also be with alcohol or amine to give urethane or urea, respectively (Scheme 3).
Scheme 3
Latter, it has been observed that PhI(OAc)2 ( L.-H. Zhang, G. S. Kauffman, J. A. Pesti, J. Yin, J . Org. Chem. 1997 , 62 , 6918. ) and PhI(CF3 CO2)2 ( R. H. Boutin, G.M. Loudon, J. Org. Chem. 1984 , 49 , 4211. ) are much better reagents for the reaction. The following mechanism has been proposed for the formation of isocyante using PhI(CF3 CO2 )2 :
