20.17 The Hofmann Rearrangement,The Hofmann Rearrangement,Treatment of amides with bromine in basic solution gives an amine with loss of the carbonyl carbon.,Br2,HO,RNH2,+,CO32,Examples,(94%),(CH3)3CCH2CNH2,Br2, NaOH,H2O,(CH3)3CCH2NH2,Br2, KOH,H2O,(87%),The Hofmann rearrangement involves 6 steps in 3 stages. 1. formation of an N-bromo amide (2 steps) 2. conversion of the N-bromo amide to an isocyanate (2 steps) 3. hydrolysis of the isocyanate (2 steps),Mechanism of the Hofmann Rearrangement,RNCO,RNH2,Step 1,Step 1,Step 2,Step 2,Step 3,Step 3,Step 4,Steps 5 and 6,H2O,HO,+,CO32,Stereochemistry,alkyl group migrates with retention of configuration,Br2, NaOH, H2O,Isocyanates are intermediates,NaOCH3 CH3OH,When the reaction is carried out in methanol instead of water, the product shown is isolated.,Br2,Isocyanates are intermediates,NaOCH3 CH3OH,When the reaction is carried out in methanol instead of water, the product shown is isolated.,Br2,