We are grateful to the Novartis-MIT Center for Continuous Manufacturing for financial support and to several colleagues at MIT (Stephen L. Buchwald, Klavs F. Jensen, and their co-workers) and Novartis (Gerhard Penn, Berthold Schenkel, Oljan Repic, Thierry Schlama, Mike Girgis, Lukas Padeste, and Felix Kollmer) for insightful discussions.
Safe and Efficient Tetrazole Synthesis in a Continuous-Flow Microreactor†
Article first published online: 8 MAR 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 50, Issue 15, pages 3525–3528, April 4, 2011
How to Cite
Palde, P. B. and Jamison, T. F. (2011), Safe and Efficient Tetrazole Synthesis in a Continuous-Flow Microreactor. Angew. Chem. Int. Ed., 50: 3525–3528. doi: 10.1002/anie.201006272
- Issue published online: 31 MAR 2011
- Article first published online: 8 MAR 2011
- Manuscript Revised: 9 FEB 2011
- Manuscript Received: 6 OCT 2010
- continuous-flow synthesis;
- synthetic methods;
Safer flow: 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.