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Updated: Apr 9, 2026

A Scalable Balz-Schiemann Reaction Protocol in a Continuous Flow Reactor
Published on: February 10, 2023
Temperature dependence of turnover in a Sc(OTf)3-catalyzed intramolecular Schmidt reaction
Charlie Fehl1, Erin E Hirt1, Sze-Wan Li1
1University of Kansas, Department of Medicinal Chemistry, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, United States.
Abstract:
The intramolecular Schmidt reaction of ketones and tethered azides is an efficient method for the generation of amides and lactams. This reaction is catalyzed by Lewis acids, which tightly bind the strongly basic amide product and result in product inhibition. We report herein conditions to achieve a catalytic Schmidt reaction using substoichiometric amounts of the heat-stable Lewis acid Sc(OTf)3. This species was shown to effectively release products of the Schmidt reaction in a temperature-dependent fashion. Thus, heat was able to promote catalyst turnover. A brief substrate scope was conducted using these conditions.
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