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with 2 affording the corresponding 1-(2-pyridinyl)- and 1-(3-
pyridinyl)-2-imidazolidinones, respectively, 3t and 3u, in 45%
and 46% yield (Table 3, entries 9 and 10).
A limitation of our method is that it does not work with aryl
bromides. For example, 4-bromotoluene was proved to be a poor
substrate under our reaction conditions. In fact, less than 15% of
1-(4-methylphenyl)-2-imidazolidinone was detected by HPLC in
the crude reaction mixture after 30 h at 100 °C. However, further
investigation is currently on going in our laboratories to set up
suitable reaction conditions for the mono N-arylation of 2-imi-
dazolidinone with aryl bromides.
In summary, we have developed a mild, practical, convenient
and general methodology for the mono N-arylation of unprotected
2-imidazolidinone. A variety of aryl- and heteroaryl-2-imidazolid-
inones were prepared in moderate to fairly good yields. Strong
electron-donating and free O–H and N–H groups on the aryl iodide
substrates were well tolerated. More importantly, n-butanol pro-
moted fast and clean reactions. Notably, its use in the copper-med-
iated synthesis of N-arylated 2-imidazolidinones is unprecedented.
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Acknowledgements
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We gratefully thank Dr. Francesco Tinazzi, Dr. Zadeo Cimarosti
and Dr. Pieter Westerduin (GlaxoSmithKline, Verona) for useful
discussion and valuable contributions.
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Supplementary data
Supplementary data (experimental procedures and character-
isation data for all substrates 3a–u) associated with this article
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