Curtius rearrangement

[10][11] It was believed that the Curtius rearrangement was a two-step processes, with the loss of nitrogen gas forming an acyl nitrene, followed by migration of the R-group to give the isocyanate.

However, recent research has indicated that the thermal decomposition is a concerted process,[12] with both steps happening together, due to the absence of any nitrene insertion or addition byproducts observed or isolated in the reaction.

Research has shown that the Curtius rearrangement is catalyzed by both Brønsted[15] and Lewis acids, via the protonation of, or coordination to the acyl oxygen atom respectively.

[17] However, photochemical rearrangement is not concerted and instead occurs by a nitrene intermediate, formed by the cleavage of the weak N–N bond and the loss of nitrogen gas.

Hydrazine is used to convert the ester to an acylhydrazine, which is reacted with nitrous acid to give the acyl azide.

[27] In their synthesis of the antiviral drug oseltamivir, also known as Tamiflu, Ishikawa et al. used the Curtius rearrangement in one of the key steps in converting the acyl azide to the amide group in the target molecule.

An important benefit of the Curtius reaction highlighted by the authors was that it could be carried out at room temperature, minimizing the hazard from heating.

The scheme overall was highly efficient, requiring only three “one-pot” operations to produce this important and valuable drug used for the treatment of avian influenza.