Organic azide

An organic azide is an organic compound that contains an azide (–N₃) functional group. Because of the hazards associated with their use, few azides are used commercially although they exhibit interesting reactivity for researchers. Low molecular weight azides are considered especially hazardous and are avoided. In the research laboratory, azides are precursors to amines. They are also popular for their participation in the "click reaction" between an azide and an alkyne and in Staudinger ligation. These two reactions are generally quite reliable, lending themselves to combinatorial chemistry.

Phenyl azide ("diazoamidobenzol"), was prepared in 1864 by Peter Griess by the reaction of ammonia and phenyldiazonium. In the 1890s, Theodor Curtius, who had discovered hydrazoic acid (HN₃), described the rearrangement of acyl azides to isocyanates subsequently named the Curtius rearrangement. Rolf Huisgen described the eponymous 1,3-dipolar cycloaddition.

The interest in azides among organic chemists has been relatively modest due to the reported instability of these compounds. The situation has changed dramatically with the discovery by Sharpless et al. of Cu-catalysed (3+2)-cycloadditions between organic azides and terminal alkynes. 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" (perhaps, the only one known to a non-specialist), and the field of organic azides exploded.

Myriad methods exist, most often using preformed azide-containing reagent.

As a pseudohalide, azide generally displaces many leaving group, e.g. Br⁻, I⁻, TsO⁻, sulfonate, and others to give the azido compound. The azide source is most often sodium azide (NaN₃), although lithium azide (LiN₃) has been demonstrated.

Aliphatic alcohols give azides via a variant of the Mitsunobu reaction, with the use of hydrazoic acid. Hydrazines may also form azides by reaction with sodium nitrite: Alcohols can be converted into azides in one step using 2-azido-1,3-dimethylimidazolinium hexafluorophosphate (ADMP) or under Mitsunobu conditions with diphenylphosphoryl azide (DPPA).

Trimethylsilyl azide (CH₃)₃SiN₃, and tributyltin azide (CH₃CH₂CH₂CH₂)₃SnN₃, have all been used, including enantioselective modifications of the reaction are also known. Aminoazides are accessible by the epoxide and aziridine ring cleavage, respectively.

The azo transfer compounds, trifluoromethanesulfonyl azide and imidazole-1-sulfonyl azide, react with amines to give the corresponding azides. Diazo transfer onto amines using trifluoromethanesulfonyl azide (TfN₃) and Tosyl azide (TsN₃) has been reported.