Curtius rearrangement

The Curtius rearrangement (or Curtius reaction or Curtius degradation), as first defined by Theodor Curtius, is a chemical reaction that involves the rearrangement of an acyl azide to an isocyanate. Several reviews have been published.



The isocyanate can be trapped by a variety of nucleophiles. Often water is added to hydrolyze the isocyanate to an amine. When done in the presence of tert-butanol, the reaction generates Boc-protected amines, useful intermediates in organic synthesis.

Carboxylic acids 1 can be easily converted to acyl azides 3 using diphenylphosphoryl azide 2.



Likewise, when the Curtius reaction is performed in the presence of benzyl alcohol, Cbz-protected amines are formed.

Reaction mechanism
The first step of the Curtius rearrangement is the loss of nitrogen gas forming an acyl nitrene (2). Once formed, acyl nitrenes very quickly rearrange by migration of R-group forming the desired isocyanate (3).



Scope
In one variation called the Darapasky Degradation (A. Darapsky, 1936) a Curtius rearrangement takes place as one of the steps from an α-cyanoester to an amino acid.