Decarboxylative Bromination of Heteroarenes: Initial Mechanistic Insights

Pritesh R. Patel; Scott H. Henderson; Mark S. Roe; Mark A. Honey

doi:10.1055/s-0040-1707901

Synlett, Table of Contents

Synlett 2020; 31(16): 1603-1607
DOI: 10.1055/s-0040-1707901

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Decarboxylative Bromination of Heteroarenes: Initial Mechanistic Insights

Pritesh R. Patel

^aSchool of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, UK

,

Scott H. Henderson

^bSussex Drug Discovery Centre, University of Sussex, Brighton, BN1 9RH, UK

,

Mark S. Roe

^cSchool of Life Sciences, University of Sussex, Brighton, BN1 9RH, UK

,

Mark A. Honey ∗

^dSchool of Science, Faculty of Engineering and Science, University of Greenwich, Chatham, Kent, ME4 4TB, UK Email: m.a.honey@gre.ac.uk

› Author Affiliations

Abstract

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Abstract

After an initial report from our laboratory describing metal-free decarboxylative halogenation of various azaheteroarenes, we set out to investigate the possible mechanism by which this chemistry occurs. Evidence from this mechanistic investigation suggests that this chemistry occurs via a radical pathway, with ¹H NMR studies suggesting that the acidic substrates activate NBS.

Key words

decarboxylation - halogenation - reaction mechanism - bromosuccinimide - azahetarenes

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References

References and Notes
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15 Bromination of Azahetarenecarboxylic Acids; General Procedure The appropriate carboxylic acid (0.280 mmol) was dissolved in the solvent (1.5 mL) and NBS (0.280 mmol) was added. The vessel was sealed and the mixture was stirred at rt for 16 h. H₂O (10 mL) was added and the organic material was extracted with EtOAc (2 × 4 mL). The organic layers were combined, dried (MgSO₄), filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography (silica gel, EtOAc–PE or CH₂Cl₂–MeOH).
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