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A rapid and efficient route to benzazole heterocycles

Nature Protocols volume 5, pages 1731–1736 (2010)Cite this article

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Abstract

This protocol describes a rapid, high-yielding, microwave-mediated route that affords benzazole heterocycles in high crude purity and represents a significant advancement toward an environmentally friendly reaction. The reaction of aryl isothiocyanates with o-nucleophilic anilines produces thiourea intermediates that, in the presence of a carbodiimide-functionalized resin, cyclize to benzazoles with the safe removal of one equivalent of hydrogen sulfide. This procedure takes ∼8.5 h to complete: 1–3 h for setup, 4.5 h for benzazole formation and 2 h for workup and purification.

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Figure 4: Disposable 1-ml syringe with the plunger removed (top) and a disposable 1-ml syringe with the plunger removed and the end cut off at approximately the 0.8-ml mark (bottom).
Figure 5: Example of a nitrogen flush setup.

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Acknowledgements

This research is dedicated to the memory of our former colleague A.D. Mills. We thank the National Cancer Institute (U19CA113298), the National Science Foundation (CHE-0910870) and the National Institute for General Medical Sciences (GM089153) for their generous financial support. R.D.C. thanks the American Chemical Society's Division of Medicinal Chemistry for Predoctoral Fellowship support (sponsored by Sanofi-Aventis); the Howard Hughes Medical Institute for the Med into Grad Fellowship; and The University of California, Davis for the R.B. Miller Graduate Fellowship and for the Outstanding Dissertation Award. NMR spectrometers were in part funded by the National Science Foundation (CHE-0443516 and CHE-9808183).

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  1. Richard D Carpenter

    Present address: Present address: Department of Biomedical Engineering, University of California, Davis, California, USA.,

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  1. Department of Chemistry, University of California, Davis, California, USA

    Richard D Carpenter & Mark J Kurth

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R.D.C. codesigned and carried out the experiments, wrote the paper and is the corresponding author. M.J.K. co-designed the experiments and provided senior authorship.

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Correspondence to Richard D Carpenter.

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Carpenter, R., Kurth, M. A rapid and efficient route to benzazole heterocycles. Nat Protoc 5, 1731–1736 (2010). https://doi.org/10.1038/nprot.2010.132

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