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.
1521-3773/asset/2002_left.gif?v=1&s=ac6b0d94a94d7ce7a210002b8096b42feffc0bcf)
1521-3773/asset/2002_right.gif?v=1&s=451042aa3415ae3ad0729984d26dee1866aca82e)
Communication
Safe and Efficient Tetrazole Synthesis in a Continuous-Flow Microreactor†
Article first published online: 8 MAR 2011
DOI: 10.1002/anie.201006272
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
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
- †
Publication History
- Issue published online: 31 MAR 2011
- Article first published online: 8 MAR 2011
- Manuscript Revised: 9 FEB 2011
- Manuscript Received: 6 OCT 2010
Keywords:
- azides;
- continuous-flow synthesis;
- microreactors;
- synthetic methods;
- tetrazoles
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.