842
R. Hosseinzadeh et al. / Tetrahedron Letters 49 (2008) 840–843
Table 1 (continued)
Entry
Aryl halide
Producta
Time (h)
6
Yieldb (%)
67
I
O
9
N
N
H
H
OCH2CH3
O
10
4
70
H3CH2CO
I
N
N
H
H
a
Reactions were carried out with 1 mmol of aryl iodide, 1 mmol of phenylurea, 15 mol % of CuI, 15 mol % of N,N0-dibenzylethylenediamine, and
5 mmol of KF/Al2O3 in THF at 65–70 °C.
b
Isolated yields; products were characterized by 1H NMR and mp.16
heated phenylurea in the absence of aryl halide and catalyst
system in refluxing toluene or in the presence of 2 equiv of
aniline and N,N0-diphenylurea was formed as sole product
in both reactions.
Thus, the optimized reaction conditions utilized
15 mol % of CuI, 15 mol % of N,N0-dibenzylethylenedi-
amine as ligand, and 5 equiv KF/Al2O3 as base in refluxing
THF under argon.
These optimized reaction conditions were applied to the
coupling of various aryl iodides and phenylurea (Table 1).15
As shown in Table 1, the reaction between phenylurea and
iodobenzene gave an excellent yield of N,N0-diphenylurea
after 3 h (entry 1).
No significant electronic effects were observed for substi-
tuted aryl iodides based on the yields of reactions and
reaction times. Substrates possessing electron withdrawing
substituents such as CF3, in the meta-position (entry 7),
bromine and nitro in the para-position (entries 6 and 8)
and electron-releasing substituents such as OEt (entry 10)
in the para-position, OMe (entries 2 and 3) and Me (entries
4 and 5) in the ortho and para-positions of the aromatic
rings also gave good to excellent yields of the corresponding
diarylureas. Reaction of the bulky aryl halides 1-iodonaph-
thalene with phenylurea gave N-(1-naphthyl)-N0-phenyl-
urea in a good yield (entry 9). Unfortunately, attempts to
perform the analogous coupling reaction using aryl
bromides and phenylurea in this catalytic system were
unsuccessful.
In summary, we have developed an efficient and inex-
pensive catalytic system for the synthesis of symmetrical
and unsymmetrical N,N0-diarylureas via the reaction of
various aryl iodides with phenylurea using N,N0-dibenzyl-
ethylenediamine as ligand and KF/Al2O3 as base. We
believe that this protocol is an excellent complement to
palladium-catalyzed methods.
References and notes
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atmosphere were added CuI (28.5 mg, 15 mol %) and N,N0-dibenzyl-
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780 mg). The reaction was carried out with stirring at 65–70 °C for the
Acknowledgment
Financial support of this work from the Research Council
of Mazandaran University is gratefully acknowledged.