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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