Curtius and Hofmann rearrangements

Curtius and Hofmann rearrangements are two important reactions which have as common intermediate a particular species, called nitrene (nitrogen analogue of carbene).

Curtius rearrangement

Curtius rearrangement is a useful reaction which allows to obtain a primary amine starting from an acyl azide. The resulting amine has a carbon less, because the last step of the reaction involves the loss of a molecule of CO2 . Although this is the most useful application of the reaction, changing the final step it is possible to obtain different products, such as carbamates or urea derivatives (in this case CO2 is not lost).

Transposition of Curtius overall reaction

  • Reaction mechanism

Transposition of Curtius reaction mechanism

As anticipated, the starting substrate for the Curtius rearrangement is an acyl azide. We can obtain an acyl azide simply treating an acyl chloride with sodium azide, NaN3  (the nucleophilic species is N3 - ). For heating the acyl azide decomposes (it loses nitrogen, N2 ) to give an intermediate very special called nitrene. The nitrene has a nitrogen atom with atypical configuration; it is neutral, since surrounded by 5 electrons, but still presents an important electronic gap, since it is not in octect configuration. We could represent the situation of its orbit as follows:

orbital nitrenes

Three orbital sp2 are completely filled and the orbital is empty. This configuration makes this particularly nitrogen atom really electrophilic , so that the molecule rearranges, with a carbon - carbon bond transposition to give a new carbon - nitrogen bond.

The result is an isocyanate, a neutral molecule in which all atoms reached the octect.

At this point adding water the isocyanate reacts rapidly to give carbamic acid that spontaneously decomposes losing a molecule of CO2 .

Thinking about our starting substrate, we got a primary amine with a skeleton of carbon which corresponds to the group -R the initial molecule. It 'was lost, (in the case has been used H2O  to hydrolyze the isocyanate) the acyl carbon atom.

Hofmann rearrangement

Transposition Hofmann

Hofmann rearrangement (also called Hofmann degradation) allows to obtain the same products of Curtius rearrangement, with the difference that starts from an amide rather than by a acyl azide or an acyl chloride.

Since you are working with an amide (stable to hydrolysis reactions unlike an acyl azide), the reaction can be performed directly in an aqueous solvent.

  • Mechanism of reaction

Hofmann transposition of reazion mechanism