Curtius Rearrangement

In 1885, German chemist Theodor Curtius reported the thermal decomposition of an acyl azide to an isocyanate, with the loss of nitrogen. This reaction subsequently became known as the Curtius rearrangement. Compared with the uncatalyzed reaction, acid catalysis through the use of either protic or Lewis acids significantly lowers the required reaction temperature, allowing for the use of more delicate substrates.

The acyl azide precursors can be made through several methods, including reacting acid chlorides or mixed anhydrides with alkali azide or trimethylsilyl azide, treating acylhydrazones with nitrous acid or nitrosonium tetrafluoroborate, or treating carboxylic acids with diphenyl phosphoryl azide (DPPA). If the reaction is carried out in the presence of water, amines, or alcohols, then the corresponding amines, ureas, and carbamates are formed.

It is possible to induce the Curtius rearrangement through the use of photochemical conditions—this is known as the Harger reaction.

The Curtius rearrangement has been successfully employed in several total synthesis campaigns including that of the antitumor and antibacterial streptonigrone, as well as pancratistatin, another compound with potent antitumor and antiviral activities.