Synlett 2003(12): 1801-1804  
DOI: 10.1055/s-2003-41405
LETTER
© Georg Thieme Verlag Stuttgart · New York

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: [email protected];
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Publikationsverlauf

Received 30 July 2003
Publikationsdatum:
28. August 2003 (online)

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.

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st-10

Only starting material was recovered after treatment of 3-chloropyridine hydrochloride with NaI.

st-12

Small amounts of starting materials were recovered in both cases.

st-13

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