Organic azide

[7] The situation has changed dramatically with the discovery by Sharpless et al. of Cu-catalysed (3+2)-cycloadditions between organic azides and terminal alkynes.

[8][9] The azido- and the alkyne groups are "bioorthogonal", which means they do not interact with living systems, and at the same time they undergo an impressively fast and selective coupling.

This type of formal 1,3-dipolar cycloaddition became the most famous example of so-called "click chemistry"[10][11] (perhaps, the only one known to a non-specialist), and the field of organic azides exploded.

Generally, nucleophiles attack the azide at the terminal nitrogen Nγ, while electrophiles react at the internal atom Nα.

[28] Azides easily extrude diatomic nitrogen, a tendency that is exploited in many reactions such as the Staudinger ligation or the Curtius rearrangement.

[28] It is proposed that the azide group is promoted to the singlet excited state and then undergoes concerted rearrangement without the intermediacy of nitrenes.

The (3+2)-cycloaddition of azides to double or triple bonds is one of the most utilised cycloadditions in organic chemistry and affords triazolines (e.g. 17) or triazoles, respectively.

[40][41][42] The uncatalysed reaction is a concerted pericyclic process, in which the configuration of the alkene component is transferred to the triazoline product.

According to Sustmann, this is a Type II cycloaddition, which means the two HOMOs and the two LUMOs have comparable energies, and thus both electron-withdrawing and electron-donating substituents may lead to an increase in the reaction rate.

[43][44] The reaction is generally free from significant solvent effects because both the reactants and the transition state (TS) are non-polar.