Hofmann Rearrangement

Hofmann rearrangement converts an amide, with the loss of one carbon, into an amine. Beginning with the amide, strong base, and halogen, the strong base ionizes the amide to form an amide anion. Amide anions have certain characteristics in common with the enolate anions, and halogenation occurs in manner similar to the ?-halogenation of aldehydes and ketones. Halogenation enhances the acidity of the remaining hydrogen, which the base removes easily. To assist the task of retaining in memory the formidable Hofmann rearrangement mechanism, imagine the point of view of nitrogen atom at this point. In the bromoamide anion, nitrogen has one bond to a carbonyl carbon, which has the strong electronegative pull of oxygen working across it, and another bond to bromine, which also pulls tenaciously on electrons. From the point of view of nitrogen, these are two greedy neighbors. Intramolecular electron pair migrations occur to stabilize the entire system as an alkyl shift occurs from the carbonyl carbon onto nitrogen and the departure of halide ion. Isocyanate results, which contains a very electropositive carbon that draws the approach of a nucleophilic water molecule. This leads to N-alkylcarbamic acid, which is still unstable. Decarboxylization occurs as the last major step, releasing carbon dioxide to leave the final amine, with a new carbon-nitrogen bond.