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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Scale-up of Sodium Persulfate Mediated, Nitroxide Catalyzed Oxidative Functionalization Reactions

Author(s): Katrina E. Doherty, Arturo L. Sandoval, Fabrizio Politano, Mason L. Witko, Chelsea M. Schroeder, William P. Brydon, Geoffrey P. Wadey, Kristiane K. Ohlhorst and Nicholas E. Leadbeater*

Volume 21, Issue 7, 2024

Published on: 05 October, 2023

Page: [941 - 946] Pages: 6

DOI: 10.2174/1570179421666230831105337

Price: $65

Abstract

Background: Oxidation is a valuable tool in preparative organic chemistry. Oxoammonium salts and nitroxides have proven valuable as reagents and catalysts in this endeavor.

Objective: The objective of this study is to scale up the oxidative amidation, ester formation, and nitrile formation using nitroxide as an organocatalyst.

Methods: Oxidative functionalization reactions were scaled from the 1 mmol to the 1 mole level. Sodium persulfate was used as the primary oxidant, and a nitroxide was employed as a catalyst. The products of the reactions were isolated in analytically pure form by extraction with no need for column chromatography.

Results: The oxidative amidation and esterification of aldehydes can be scaled up from 1 mmol to 1 mole effectively, with comparable product yields being obtained at each increment. This work shows that conditions developed on a small scale can be transferred to a larger scale without reoptimization. The oxidative functionalization of aldehydes to prepare nitriles is not amenable to direct scale-up due to the concomitant formation of significant quantities of the corresponding carboxylic acid, thereby compromising the product yield.

Conclusion: Two of the three oxidative transformations studied here can be scaled up successfully from the 1 mmol to the 1 mole level.

Keywords: Oxidative functionalization, scale-up, oxoammonium cations, amides, esters, and catalyst.

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