A mechanistic investigation of the N-hydroxyphthalimide catalyzed benzylic oxidation mediated by sodium chlorite

Grunshaw, Thomas and Wood, Susanna H. and Sproules, Stephen and Parrott, Andrew and Nordon, Alison and Shapland, Peter D. P. and Wheelhouse, Katherine M. P. and Tomkinson, Nicholas C. O. (2024) A mechanistic investigation of the N-hydroxyphthalimide catalyzed benzylic oxidation mediated by sodium chlorite. Journal of Organic Chemistry, 89 (11). pp. 7933-7945. ISSN 0022-3263 (https://doi.org/10.1021/acs.joc.4c00583)

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Abstract

A detailed investigation into the mechanistic course of N-hydroxyphthalimide catalyzed oxidation of benzylic centers using sodium chlorite as the stoichiometric oxidant is reported. Through a combination of experimental, spectroscopic, and computational techniques, the transformation is interrogated, providing improved reaction conditions and an enhanced understanding of the mechanism. Performing the transformation in the presence of acetic acid or a pH 4.5 buffer leads to extended reaction times but improves the catalyst lifetime, leading to the complete consumption of the starting material. Chlorine dioxide is identified as the active oxidant that is able to oxidize the N-hydroxyphthalimide anion to the phthalimide-N-oxyl radical, the proposed catalytically active species, which is able to abstract a hydrogen atom from the substrate. A second molecule of chlorine dioxide reacts with the resultant radical and, after loss of hypochlorous acid, leads to the observed product. Through a broad variety of techniques including UV/vis, EPR and Raman spectroscopy, isotopic labeling, and the use of radical traps, evidence for the mechanism is presented that is supported through electronic structural calculations.

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