Elsevier

Tetrahedron Letters

Volume 53, Issue 48, 28 November 2012, Pages 6475-6478
Tetrahedron Letters

Acid and base catalyzed Davis–Beirut reaction: experimental and theoretical mechanistic studies and synthesis of novel 3-amino-2H-indazoles

https://doi.org/10.1016/j.tetlet.2012.09.026Get rights and content

Abstract

The Davis–Beirut reaction, which provides an efficient synthesis of 2H-indazoles and, subsequently, indazolones, is shown to proceed rapidly from o-nitrosobenzaldehyde and primary amines under both acid and base catalysis. Experimental and theoretical evidence in support of a reaction mechanism is provided in which o-nitrosobenzylidine imine is a pivotal intermediate in this N,N-bond forming heterocyclization reaction. The Davis–Beirut reaction is also shown to effectively synthesize a number of novel 3-amino-2H-indazole derivatives.

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Acknowledgments

Financial support was provided by the National Science Foundation (CHE-0910870) and the National Institutes of Health (GM089153). We also acknowledge the National Science Foundation’s Partnership for Advanced Computational Infrastructure (Pittsburgh Supercomputer Center). J.G.H. thanks the United States Department of Education for a GAANN Fellowship and B.A. thanks the Bristol–Myers Squibb Graduate Chemist Fellowship and Alfred P. Sloan Minority Ph.D. Program for fellowship support.

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