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

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.

Key words

bromination - oxidation - dearomatization - phenols - quinone monoacetals

Publikationsverlauf

Eingereicht: 25. Mai 2023

Angenommen nach Revision: 26. Juni 2023

Artikel online veröffentlicht:
11. August 2023

• 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.
• 8 While the precise intricacies of the reaction mechanism for the oxidative dearomatization remain to be elucidated, we propose plausible pathways which may involve the intermediacy of aryl hypobromite G or dienones H, I, and J (Figure 2).
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• 10 It should be noted that the corresponding p-QMAs 11 and 12 could be involved as well as the o-QMAs as intermediates in these reactions: upon treatment of 4-methoxyphenol with NBS (1.05 equiv) in MeOH (0 °C, 40 min), oxidative dearomatization proceeded to afford the corresponding p-QMA in 61% yield (Scheme 5). Note that no aromatic bromination occurred in this reaction, although the reason is not clear.
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