Elemental Sulfur-Mediated Aromatic Halogenation
Junpei Matsuoka, Yuna Yano, Yuuka Hirose, Koushi Mashiba, Nanako Sawada, Akira Nakamura, Tomohiro Maegawa*
*School of Pharmaceutical Sciences, Kindai University, Higashi-Osaka, Osaka 577-8502, Japan,
Email: maegawa
phar.kindai.ac.jp
J. Matsuoka, Y. Yano, Y. Hirose, K. Mashiba, N. Sawada, A. Nakamura, T. Maegawa, J. Org. Chem., 2024, 89, 770-777.
DOI: 10.1021/acs.joc.3c02259
Abstract
Elemental sulfur (S8) mediates aromatic halogenations using N-halosuccinimides for bromination and chlorination or 1,3-diiodo-5,5-dimethylhydantoin for iodination. The reaction effectively halogenated also less-reactive aromatic compounds, such as ester-, cyano-, and nitro-substituted anisole derivatives.
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proposed mechanism
Details
The document discusses a novel method for aromatic halogenation using elemental sulfur (S8) and N-halosuccinimides (NBS and NCS). This method effectively halogenates less-reactive aromatic compounds, such as ester-, cyano-, and nitro-substituted anisole derivatives, which do not react with N-halosuccinimides alone. The use of S8 as a catalyst is highlighted for its cost-effectiveness, odorlessness, and solid-state, making it a practical alternative to other sulfur compounds. The study demonstrates successful bromination, chlorination, and iodination of various substrates, achieving high yields. The reaction mechanism involves the formation of an S8−Y species, which facilitates halogenation. The method's simplicity and efficiency make it suitable for synthesizing building blocks and pharmaceutical intermediates in organic and medicinal chemistry. The research, supported by JSPS KAKENHI grants, aims to further elucidate the reaction mechanism and expand the substrate scope. The findings are published in the Journal of Organic Chemistry, with detailed experimental procedures and characterization data available in the supporting information.
Key Words
bromination, chlorination, iodination, NBS, NCS, DIH
ID: J42-Y2024
