Safe and Efficient Tetrazole Synthesis in a Continuous-Flow Microreactor

Angewandte Chemie 50(15), 3525-3528, DOI: 10.1002/anie.201006272

The synthesis of 5-substituted tetrazoles in flow (see scheme) is safe, efficient, scalable, requires no metal promoter, and uses a near-equimolar amount of NaN3, yet nonetheless displays a broad substrate scope. The hazards associated with HN3 are essentially eliminated, shock-sensitive metal azides such as Zn(N3)2 are avoided, and residual NaN3 is quenched in-line with NaNO2.