azidation

Azidation is a class of chemical reactions in which an azide group (−N3) is introduced into a substrate, generating an organic azide or an azido-containing intermediate. The azide moiety is a versatile functional group used as a synthetic handle for further transformations, most notably in click chemistry to produce 1,4-disubstituted-1,2,3-triazoles. Azidation encompasses a range of reaction types that apply to diverse substrates, including alkenes, alkynes, alcohols, amines, and carboxylic acids.

Common approaches to azidation vary by substrate. Radical azidation of alkenes or alkynes adds azidyl radicals across multiple bonds to give alkyl or vinyl azides, which can be further converted. Nucleophilic or SN2-type azidation converts leaving-group-bearing substrates (for example, alcohol derivatives such as tosylates or halides) into azides using sodium azide or related azidating salts. Diazotransfer methods convert primary amines into azides using reagents such as imidazole-1-sulfonyl azide hydrochloride (ISAZ) or diphenylphosphoryl azide (DPPA). DPPA is also used to form acyl azides from carboxylic acids, enabling subsequent Curtius rearrangements. Electrophilic azidation strategies, including metal-catalyzed or photoredox-catalyzed processes, also provide azide installation under mild conditions.

Azides are widely exploited in chemical biology, materials science, and pharmaceutical synthesis, particularly as precursors to triazole compounds via 1,3-dipolar cycloaddition. They are subject to safety considerations because many azides are toxic and can be shock-sensitive or explosive when concentrated; proper handling, storage, and waste disposal are essential.