Organic azides engage in useful organic reactions. The terminal nitrogen is mildly nucleophilic. Generally, nucleophiles attack the azide at the terminal nitrogen N, while electrophiles react at the internal atom N. Azides easily extrude diatomic nitrogen, a tendency that is exploited in many reactions such as the Staudinger ligation or the Curtius rearrangement.
Azides may be reduced to amines by hydrogenolysis or with a phosphine (e.g., triphenylphosphine) in the Staudinger reaction. This reaction allows azides to serve as protected -NH synthons, as illustrated by the synthesis of 1,1,1-tris(aminomethyl)ethane:
In the azide alkyne Huisgen cycloaddition, organic azides react as 1,3-dipoles, reacting with alkynes to give substituted 1,2,3-triazoles.
Some azide reactions are shown in the following scheme. Probably the most famous is the reaction with phosphines, which leads to iminophosphoranes 22; these can be hydrolysed into primary amines 23 (the Staudinger reaction), react with carbonyl compounds to give imines 24 (the aza-Wittig reaction), or undergo other transformations. Thermal decomposition of azides gives nitrenes, which participate in a variety of reactions; vinyl azides 19 decompose into 2H-azirines 20. Alkyl azides with low nitrogen-content ((nC + nO) / nN ≥ 3) are relatively stable and decompose only above ca. 175 °C.
Direct photochemical decomposition of alkyl azides leads almost exclusively to imines (e.g. 25 and 26). 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 presence of triplet sensitisers, however, may change the reaction mechanism and result in the formation of triplet nitrenes. The latter were observed directly by ESR spectroscopy at −269 °C as well as inferred in some photolyses. Triplet methyl nitrene is 31 kJ/mol more stable than its singlet form, and thus is most likely the ground state.
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. The uncatalysed reaction is a concerted pericyclic process, in which the configuration of the alkene component is transferred to the triazoline product. The Woodward–Hoffmann denomination is [π4s+π2s] and the reaction is symmetry-allowed. 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. The reaction is generally free from significant solvent effects because both the reactants and the transition state (TS) are non-polar.
Another azide regular is tosyl azide here in reaction with norbornadiene in a nitrogen insertion reaction: