Hoffmann Bromamide Degradation Reaction

The Hoffmann bromamide degradation reaction converts an amide directly into a

primary amine that has ONE FEWER carbon than the starting amide -- the only method in

this chapter that shortens the chain rather than preserving or extending it:

The mechanism proceeds through a sequence of intermediates: bromine first brominates the

acidic amide nitrogen to give an $N$-bromoamide; base then removes the remaining

$N-\text{H}$ proton and the resulting anion undergoes a concerted 1,2-shift in which the

$\text{R}$ group migrates from carbon to nitrogen AS the bromide ion leaves, forming a

highly reactive isocyanate ($\text{R}-\text{N}=\text{C}=\text{O}$) -- the step that

actually expels the original carbonyl carbon from the $\text{R}$ group's chain. The

isocyanate is then hydrolysed by the aqueous base to a carbamic acid, which

spontaneously loses $\text{CO}_2$ to give the final primary amine.

Because $\text{R}$ MIGRATES with retention of its own configuration in this rearrangement,

the Hoffmann degradation is also valued in stereochemistry problems as one of the classic

migratory reactions that proceeds without racemisation at the migrating carbon.

Contrast with $\text{LiAlH}_4$ reduction of the same amide (Section 25.5.1): reducing

$\text{R}-\text{CONH}_2$ with $\text{LiAlH}_4$ keeps the carbonyl carbon and simply …