Synlett 2024; 35(04): 474-478
DOI: 10.1055/s-0041-1738450
cluster
11th Singapore International Chemistry Conference (SICC-11)

Sequential Bromination/Dearomatization Reactions of 2-Methoxyphenols en route to Bromo-Substituted ortho-Quinonemonoacetals

Shunya Hayashi
,
Kiyosei Takasu
,
This work was financially supported by Grants-in-Aid from the Japan Society for the Promotion of Science (JSPS, 21H02068 and 21H05211), the Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS) from the Japan Agency for Medical Research and Development (AMED, 22ama121042j0001 and 22ama121034j0001), and the Tokyo Biochemical Research Foundation.


Abstract

A novel method involving the sequential dibromination and dearomatization of 2-methoxyphenols with N-bromosuccinimide (NBS) is described, providing rapid access to brominated ortho-quinone monoacetals (o-QMAs). Our method demonstrates two notable aspects: (1) the introduction of a bromo group(s) into the aromatic ring and its subsequent conversion into o-QMAs in a single operation, and (2) the use of NBS as a convenient oxidant in oxidative dearomatization reactions.

Supporting Information



Publication History

Received: 25 May 2023

Accepted after revision: 26 June 2023

Article published online:
11 August 2023

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  • References and Notes

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  • 7 The Experimental Procedure To a mixture of 2,3-dimethoxyphenol (55.3 mg, 0.359 mmol) in MeOH (3.6 mL) was added NBS (195 mg, 1.09 mmol) at 0 °C. After stirring for 10 min at this temperature, the mixture was diluted with EtOAc, which was extracted with EtOAc (3×). The combined organic layer was washed with H2O (2×) and brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, hexane/EtOAc = 15:1) to afford o-QMA 2a (98.7 mg, 81%) as a yellow amorphous solid. Spectral data of 2a matched the reported data in ref. 4.
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