Solvent-free synthesis of N,N'-diarylureas using microwave technology

Article abstract of DOI:10.1002/jccs.200300065

A simple and rapid solvent-free synthesis of N,N'-diarylureas in a microwave oven has been reported for the first time. Nine compounds were synthesized. The reaction time is short (2-5 min) and gives excellent yield (80-95%).

Full text of DOI:10.1002/jccs.200300065

Journal of the Chinese Chemical Society, 2003, 50, 425-427
425
Solvent-free Synthesis of N,N¢-Diarylureas Using Microwave Technology
Ting Sun (
), Jing Li (
) and Yu-Lu Wang* (
)
College of Chemistry and Environmental Science, Henan Normal University,
The Key Laboratory of Environmental Science and Technology of Higher Education of Henan Province,
Xinxiang, 453002, Henan, P. R . China
A simple and rapid solvent-free synthesis of N,N¢-diarylureas in a microwave oven has been reported for
the first time. Nine compounds were synthesized. The reaction time is short (2~5 min) and gives excellent
yield (80-95%).
Keywords: Solvent-free synthesis; Microwave technology; N,N¢-diarylureas.
Scheme I
INTRODUCTION
NO2
N
NO2
NHC NH Ar
O
The N,N¢-diarylurea derivatives are very interesting re-
agents due to their useful properties and important medical1-3
and biological applications.4,5 It has been reported that N,N¢-
diarylurea derivatives can be synthesized from correspond-
ing isocyanate with aromatic amine in organic solvent.6,7 But
most of the cases mentioned above suffer from drawbacks
such as extended reaction time, tedious purification and toxic
solution. Consequently, a simple, rapid, convenient and envi-
ronmentally benign method for synthesis of N,N¢-diarylureas
is required.
Microwave
solid-state
C
O
Ar
NH2
+
1
2
Ar:
a) 4-methylphenyl
b) 4-methoxyphenyl
c) 3,4-dimethylphenyl
d) 4-chlorophenyl
e) 4-bromophenyl
f) 4-iodophenyl
g) 2-nitrophenyl
h) 3-nitrophenyl
i) 4-nitrophenyl
donating substituents needed lower power or shorter time
than those with electron-attracting substituents. Among the
three nitroanilines, the reaction of 3-nitroaniline has the
rapidest reaction rate and needs the lowest microwave power.
The reaction of 4-iodoaniline is easier to complete than that
of 4-bromoaniline and 4-chloroaniline.
Recently, the microwave technique assisted organic re-
action has gained considerable attention. This method has a
number of advantages such as short reaction time, high yield
and simple experimental procedure. Most of the reactions un-
der microwave irradiation using solvent were practically lim-
ited because high vapour pressure sometimes leads to explo-
sions. Solvent-free organic synthesis under microwave irra-
diation has great applied value and expansive prospects be-
cause of energy saving, high efficiency and environment ac-
ceptability. It has been applied to several organic reactions.8,9
The solvent-free synthesis N,N¢-diarylureas using micro-
waves has not been reported so far.
The structure of the products were confirmed by IR, El-
emental analysis, 1H NMR, and MS spectroscopy.
EXPERIMENTAL SECTION
Melting points were determined with a Kolfer micro
melting point apparatus and were uncorrected. The reactions
were carried out in a Galanz Cambi-Grill microwave oven
(the power output 750 W). IR spectra were recorded on a
Bio-Rad Win-IR spectrophotometer in KBr. 1H NMR spectra
were measured on a Mercury 300 spectrophotometer using
TMS as internal standard and d6-DMSO as solvent. Elemen-
tal analyses were performed on a Elementar Vario EL. Mass
spectra were recorded on a KYKY QP-1000A.
RESULTS AND DISCUSSION
Nine N,N¢-diarylureas were prepared from 2-nitrophen-
ylisocyanate with corresponding aromatic amine in satisfy-
ing yields (80-95%) (Scheme I). The results are summarized
in Table 1.
It was found that the aromatic amines with electron-

426 J. Chin. Chem. Soc., Vol. 50, No. 3A, 2003
Sun et al.
Table 1. The Solvent-free Synthesis of N,N¢-diarylureas under Microwave Irradiation
Entry
Ar
Reaction time/min
Microwave Power/w
Yields/%
2a
2b
2c
2d
2e
2f
2g
2h
2i
4-MeC6H4
4-MeOC6H4
3,4-(Me)2C6H3
4-ClC6H4
4-BrC6H4
4-IC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2.5
2.5
2
3
3
2.5
5
5
80%
80%
80%
80%
100%
80%
100%
80%
100%
93
90
95
89
86
90
80
88
90
5
General Procedure for the Preparation of N,N¢-
diarylureas (2a-2i)
yield: 86%. IR (n, cm-1): 3336 (N-H), 1666 (C=O). MS: 335
(M+), 170, 155, 138. 1H NMR (d, ppm): 9.58-9.94 (2H, NH),
7.17-8.25 (8H, Ar-H). Anal. Calc.: C, 46.57; H, 2.99; N,
12.54. Found: C, 46.55; H, 3.13; N, 12.64.
2-Nitroisocyanate (1 mmol) and substituted aniline (1
mmol) were milled respectively and mixed thoroughly in an
agate mortar. Then the mixture was placed in a beaker and ir-
radiated by microwave for 2-5 min. in a household micro-
wave oven. The procedure of the reaction was monitored by
thin-layer chromatography. The crude products were recrys-
tallized with ethanol or acetone and dried under vacuum to
yield the pure products.
N-(2-nitrophenyl)-N¢-(4-iodophenyl)urea (2f)
Pale yellow needles. mp (°C): 220-222 (lit.:12 223-224).
yield: 90%. IR (n, cm-1): 3328, 3286 (NH), 1651(C=O).
N-(2-nitrophenyl)-N¢-(2-nitrophenyl)urea (2g)
Pale yellow needles. mp (°C): 226-228 (lit.:13 225).
yield: 80%. IR (n, cm-1): 3298 (NH), 1659 (C=O).
N-(2-nitrophenyl)-N¢-(4-methylphenyl)urea (2a)
Yellow needles. mp (°C): 192-193 (lit.:10 191-193).
yield: 93%. IR (n, cm-1): 3326, 3302 (NH), 1652 (C= O).
N-(2-nitrophenyl)-N¢-(3-nitrophenyl)urea (2h)
Orange sticks. mp (°C): 240-243 (lit.:7 246-247) yield:
88%. IR (n, cm-1): 3381 (NH), 1729 (C=O).
N-(2-nitrophenyl)-N¢-(4-methyoxyphenyl)urea (2b)
Pale yellow sticks. mp (°C): 176-179 (no lit. mp re-
ported). yield: 90%. IR (n, cm-1): 3296 (NH), 1642 (C=O).
N-(2-nitrophenyl)-N¢-(4-nitrophenyl)urea (2i)
MS: 287 (M+), 138, 122, 91. H NMR (d, ppm): 9.56-9.69
Yellow needles. mp (°C): 270 (dec.) [lit.:13 270-275
(dec.)]. yield: 90%. IR (n, cm-1): 3375 (NH), 1611(C=O).
1
(2H, NH), 6.88-7.41 (8H, Ar-H), 3.72 (3H, OCH3-H). Anal.
Calc.: C, 58.54; H, 4.53; N, 14.63. Found: C, 58.51; H, 4.72;
N, 14.63.
Received June 12, 2002.
N-(2-nitrophenyl)-N¢-(3,4-dimethylphenyl)urea (2c)
Pale yellow silk needles. mp (°C): 190-192 (no lit. mp
reported). yield: 95%. IR (n, cm-1): 3296 (NH), 1648 (C=O).
MS: 285 (M+), 147, 138, 121. 1H NMR (d, ppm): 9.56-9.68
(2H, NH), 7.04-8.32 (7H, Ar-H), 2.16-2.19 (6H, CH3-H).
Anal. Calc.: C, 63.16; H, 5.26; N, 14.74. Found: C, 63.07; H,
5.44; N, 14.84.
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N-(2-nitrophenyl)-N¢-(4-chlorophenyl)urea (2d)
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N-(2-nitrophenyl)-N¢-(4-bromophenyl)urea (2e)
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Solvent-free Synthesis of N,N¢-Diarylureas
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