Acid-Mediated Halogen Exchange in Heterocyclic Arenes: A Highly Effective Iodination Method

Christian Wolf; Gilbert E. Tumambac; Cristina N. Villalobos

doi:10.1055/s-2003-41405

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Synlett 2003(12): 1801-1804
DOI: 10.1055/s-2003-41405

LETTER

Acid-Mediated Halogen Exchange in Heterocyclic Arenes: A Highly Effective Iodination Method

Christian Wolf*, Gilbert E. Tumambac, Cristina N. Villalobos
Department of Chemistry, Georgetown University, Washington, DC 20057, USA
e-Mail: cw27@georgetown.edu;

Further Information

Publication History

Received 30 July 2003
Publication Date:
28 August 2003 (online)

Abstract
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Abstract

Heterocyclic arenes including pyridyl, quinolyl, and isoquinolyl chlorides have been converted to their corresponding iodides in good to high yields via acid-mediated nucleophilic halogen exchange with sodium iodide. This procedure avoids the use of transition metals, harsh reaction conditions, and affords highly regioselective halide exchange. Chloride substituents in position 2 and 4 of pyridines and quinolines are readily substituted by iodide in 75-91% and conversion of 1-chloroisoquinoline to its iodide derivative was found to proceed with 90% yield. Positions that are not activated for nucleophilic aromatic substitution proved to be inert to halide exchange. Regioselective chloride/iodide exchange in 4,7-dichloroquinoline hydrochloride gave 7-chloro-4-iodoquinoline, an important precursor of anti-malaria drugs, in almost 90% yield.

Key words

chloride/iodide exchange - aryl iodides - nucleophilic aromatic substitution - cross-coupling reactions.

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Small amounts of starting materials were recovered in both cases.

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All known compounds show ¹H NMR and ¹³C NMR spectroscopy and mass spectrometry data consistent with the given structures.