diazotransfer

Diazotransfer refers to a class of chemical reactions in which a diazo or azido group is transferred from a diazotransfer reagent to a substrate. The most widely used application is the conversion of primary amines into organic azides, providing a versatile handle for subsequent transformations.

Common diazotransfer reagents include tosyl azide (TsN3) and imidazole-1-sulfonyl azide hydrochloride (ISAZ). These reagents are typically used with a base in polar aprotic solvents and can operate under mild, room-temperature conditions. In some protocols, catalytic or additive systems may be employed to improve efficiency or selectivity. The general outcome is the replacement of the amine hydrogen with an azide group, producing an organic azide and a stoichiometric sulfonamide byproduct.

Mechanistically, the diazotransfer reagent serves as an azido group donor, delivering the N3 fragment to the substrate, while byproducts are released as non-azide species. The approach is valued for its operational simplicity and broad substrate tolerance, especially for primary amines, though reactivity with secondary amines can be limited and reagent safety must be managed.

Applications of diazotransfer products primarily center on azide chemistry. Organic azides are key intermediates in copper-catalyzed azide–alkyne cycloaddition (Click chemistry), enabling rapid assembly of triazoles for pharmaceuticals, bioconjugates, and materials. Diazotransfer thus provides a practical route to azide functionality without direct handling of reactive hydrazo or nitrene sources.

Safety and limitations: diazotransfer reagents and azides can be hazardous, with potential explosive or toxic risks. Reactions require appropriate safety precautions and waste management, and substrate scope can vary with reagent and conditions.