Organic Azides in Process Chemistry: Reactivity, Hazards, and Safe Handling

Organic azides are commonly exploited as precursors to a variety of key functional groups that are increasingly relevant in the manufacturing of active pharmaceutical ingredients . Azides allow access to complex nitrogen‐rich heterocyclic structures that are responsible for the bioactive properties of numerous substances. However, organic azide intermediates and the reagents used to synthesize them are associated with relevant safety risks, due to their potential explosivity and toxicity. These problematic features can be tamed with thorough evaluation prior to scale‐up and by establishing the appropriate safety measures. This review provides an overview of the synthetic relevance of azides as reagents and intermediates, with a summary of reagents used in azide formation. The second part of the review provides some general rules for their handling at various stages, from process development to subsequent industrialization. These include dos and don’ts in terms of chemical compatibility, equipment selection and refinement both at lab and plant scale, strategies for azide quenching, and waste handling. The last section is devoted to recent developments in azide chemistry handling in continuous mode.