LETTER
Synthesis of N-Substituted Pyrroles in Water
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Scheme 4. Primary aromatic amide with electron-rich
functionality as well as electron-poor functionality under-
go condensation with 2,5-dimethoxytetrahydrofuran
equally well to afford the corresponding acylpyrroles in
excellent isolated yields. In all cases, a mixture of amide
and 2,5-dimethoxytetrahydrofuran was vigorously stirred
in water at 60 °C in the presence of iron(III) chloride until
completion of the reaction.17 The probable pathway for
this transformation involves hydrolysis of FeCl3 in water
and in situ generation of HCl as active catalyst.
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FeCl3⋅7H2O (2 mol%)
ArCONH2
+
OMe
MeO
N
O
H2O, 60 °C, 4h
COAr
4
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No
Ar
4a
4b
4c
4d
4e
C6H5 4-MeC6H4 4-ClC6H4 4-BrC6H4 4-MeOC6H4
Yield (%)
82 85 76 74 80
Scheme 4 Synthesis of N-acylpyrroles in water. Reagents and
conditions: arylamide (5 mmol), 2,5-dimethoxytetrahydrofuran
(6 mmol), H2O (4 mL).
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In summary, we described a single step, environmentally
friendly, and simple procedure for the synthesis of N-aryl,
alkyl, sulfonyl, and acyl pyrroles in the presence of
iron(III) chloride catalyst. Exploitation of this strategy for
the generation of novel multicyclic structures and their
biological evaluation is currently under way.
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Supporting Information for this article is available online at
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Acknowledgment
Financial support of this work by Chemistry and Chemical Re-
search Center of Iran is gratefully appreciated
References and Notes
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Synlett 2009, No. 14, 2245–2248 © Thieme Stuttgart · New York