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Synthesis 2011(6): 857-859  
DOI: 10.1055/s-0030-1258443
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© Georg Thieme Verlag Stuttgart ˙ New York

Practical One-Pot C-H Activation/Borylation/Oxidation: Preparation of 3-Bromo-5-methylphenol on a Multigram Scale

A. Monica Norberg, Milton R. Smith III*, Robert E. Maleczka Jr.*
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
Fax: +1(517)3531793; e-Mail: maleczka@chemistry.msu.edu;
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Publication History

Received 30 November 2010
Publication Date:
18 February 2011 (online)

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Abstract

A practical one-pot C-H activation/borylation/oxidation sequence for the generation of 3,5-disubstituted phenols is presented. Specifically, 3-bromo-5-methylphenol is prepared from 3-bromotoluene, without isolation of intermediates, on a multigram scale, and in high yield. The process proceeds under mild conditions and can be completed within one day.

Key words

phenol - C-H activation - borylation - oxidation - boronic ester

    References

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11

So as to establish a benchmark yield herein, the starting 3-bromotoluene was distilled over CaH2 under reduced pressure and degassed before use. In most cases the starting arene can be used as received, but yields are dependent on starting material quality, which can vary by vendor and batch. A use test prior to scale up is recommended.

14

WARNING: As with any oxidation of this type, one should be watchful for exotherms and control the rate of addition accordingly.