Synthesis of N-arylureas in water and their N-arylation with aryl halides using copper nanoparticles loaded on natural Natrolite zeolite under ligand-free conditions

Article abstract of DOI:10.1039/c4ra03093a

A new method for the synthesis of N-arylureas and their N-arylation with aryl halides has been developed using copper nanoparticles supported on natural Natrolite zeolite as a reusable heterogeneous catalyst under ligand-free conditions.

Full text of DOI:10.1039/c4ra03093a

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Synthesis of N-arylureas in water and their
N-arylation with aryl halides using copper
nanoparticles loaded on natural Natrolite
zeolite under ligand-free conditions
Cite this: RSC Adv., 2014, 4, 26264
a
a
b
Mahmoud Nasrollahzadeh,* Mojtaba Enayati and Mehdi Khalaj
Received 7th April 2014
Accepted 28th May 2014
A new method for the synthesis of N-arylureas and their N-arylation with aryl halides has been developed
using copper nanoparticles supported on natural Natrolite zeolite as a reusable heterogeneous catalyst
under ligand-free conditions.
DOI: 10.1039/c4ra03093a
www.rsc.org/advances
investigated the hydration of cyanamides in water using triethyl
orthoformate in the absence of additives such as base, acid or
Introduction
The synthesis of N-monosubstituted ureas has been of great catalyst (Scheme 1). To the best of our knowledge, this new
interest, because they are widely used in pharmaceutical and procedure provides the rst example of an efficient approach for
1
agrochemical industry. Also, they are found in many natural the synthesis of N-arylureas. Reactions will take place under
2
products.
reux conditions with good yields and easy operations without
The earliest published methods for the preparation of application of toxic organic solvents, bases, acids and expensive
substituted ureas were reactions including the following: (1) reagents or catalysts. Also, none of the above mentioned
3
4
reaction of amines with toxic phosgene or isocyanates; (2) disadvantages are observed.
insertion of CO or CO into amino compounds using different
Among various catalysts for the carbon–carbon and carbon–
2
5
catalysts in organic solvents at high pressure and temperature;
heteroatom coupling reactions, homogeneous copper catalysts
6
11,12
(
3) acid or base-catalyzed hydration of cyanamides; (4) reaction have been widely investigated,
while less expensive hetero-
of amines with KOCN in aqueous solution of HCl under MW geneous copper catalysts received scanter attention. Thus, the
7
irradiation; (5) reaction of S,S-dimethyl dithiocarbonate with use of ligand-free heterogeneous Cu catalysts is oen desirable
8
ammonia in water–dioxane and (6) hydration of cyanamides by from the perspective of process development due to their easy
9
acetaldoxime and InCl
3
in toluene as a toxic solvent.
handling, simple recovery, and recycling.
However, most of these synthetic methods suffer from
In the second step, we hereby report the N-arylation of
different drawbacks such as employing expensive, toxic and N-arylureas with aryl halides using Natrolite zeolite/Cu nano-
hazardous reagent or catalysts, use of organic solvents, harsh particles (NPs) as a stable heterogeneous catalyst under ligand-
reaction conditions including the use of HF–pyridine complex, free conditions (Scheme 2). This catalyst is safe, environmen-
2 4 2 2
H SO , H O
/NaOH and HCl, expensive and complex catalysts tally benign with fewer disposals problems.
or reagents, long reaction times, many tedious isolation steps
and low yields of the products that restrict their usage in
practical applications. Therefore, it is desirable to develop an
efficient method for the synthesis of N-monosubstituted ureas
without the application of toxic organic solvents, corrosive and
toxic reagents such as acids, phosgene and isocyanates or
expensive catalysts.
Scheme 1
In the rst step and in continuation of our efforts to develop
environmentally friendly synthetic methodologies and
10
synthesis of the nitrogen-containing compounds, we have
a
Department of Chemistry, Faculty of Science, University of Qom, Qom 37185-369,
Iran. E-mail: mahmoudnasr81@gmail.com; Fax: +98 25 32103595; Tel: +98 25
3
2850953
b
Department of Chemistry, Buinzahra Branch, Islamic Azad University, Buinzahra,
Qazvin, Iran
Scheme 2 N-Arylation of N-monosubstituted ureas with aryl halides
under microwave irradiation.
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(
42%). When the reaction carried out at reux, product was
Result and discussion
obtained in 73% isolated yield aer 6 hours. The optimized
In order to examine the feasibility of our rationale and nd reaction conditions (cyanamide (2 mmol), triethyl orthoformate
optimum conditions, we carried out the reaction of 4-methyl- (4 mmol) and 10 mL water) were used for the synthesis of a
phenylcyanamide with triethyl orthoformate in water under series of N-arylureas (Table 1). To study the effects of the nature
various temperature conditions. The reaction at room temper- of the substituents on the benzene ring of the cyanamide,
ature required a long reaction time (80 h) and gave low yield various N-arylureas were synthesized from different aromatic
cyanamides containing both electron-releasing and electron-
withdrawing groups with triethyl orthoformate in water in good
yields under reux conditions. As shown in Table 1, cyanamides
having electron-withdrawing groups require higher reaction
times. In addition, ortho substituents have not effects on
cyanamides hydrolysis.
Table 1 Formation of N-arylureas via hydration of cyanamides
a
Ref.
Entry
R
C
Time (h) Yield (%) M.p. (lit. m.p.)
9
1
2
3
4
5
6
7
8
6
H
5
8
6
70
73
73
71
70
69
64
70
142–144 (143–145)
The mechanism of the reaction may originate from the
hydrolysis of triethyl orthoformate to formic acid and then
treatment with CN group in cyanamide. The nitrile group in
cyanamides is probably coordinated to the proton of the formic
acid, so its reactivity will be enhanced in reaction with water.
The products were characterized by melting points, CHN, IR
and NMR. Elimination of one sharp absorption band (CN
stretching band) and appearance of the two absorption bands in
commercial
9
4-MeC
4-OMeC
2-MeC
3-BrC
4-ClC
4-NO
1-Naphthyl
6
H
4
178–180 (180)
6
H
4
6
6
8
9
11
7
165–168 (166–167)
194–196 (this work)
165–167 (this work)
6
H
4
6
H
4
9
6
H
4
208–210 (204–206)
13
2
C
6
H
4
236–238 (238)
220–221 (this work)
a
Yields are aer work-up.
ꢀ
1
the range of 3200–3400 cm (NH stretching bands) and one
ꢀ1
absorption band in the range of 1640–1670 cm (C]O) in the
IR spectrum conrmed formation of the N-arylureas.
Among various methods for the N-arylation of ureas,
homogeneous palladium and copper catalysts in the presence
of Xantphos and diamine ligands have been widely investi-
14
gated, while less expensive heterogeneous copper catalysts
received scanter attention. Thus, the use of ligand-free
Fig. 1 Aluminosilicate framework of zeolite.
Fig. 2 XRD diffraction pattern of Natrolite zeolite.
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heterogeneous Cu catalysts is oen desirable from the aqueous solution of Cu(OAc)
2
and was characterized by using
16
perspective of process development due to their easy handling, the powder XRD, SEM, EDS and FT-IR spectroscopy. The
simple recovery, and recycling. crystalline structure of Natrolite zeolite/Cu NPs was conrmed
0
Due to the importance of N,N -diarylureas in synthetic with powder XRD (X-ray Powder Diffraction) measurements.
organic chemistry and in industry for the manufacture of The X-ray diffraction pattern revealed that Cu nanoparticles are
pharmaceuticals and medicinal compounds and in continua- very air-sensitive and easily oxidized to CuO. X-Ray diffraction
tion of our recent studies on application of Natrolite zeolite as pattern of Natrolite zeolite and Natrolite zeolite/Cu NPs was
15
catalyst, we next turned our attention to applying Natrolite shown in Fig. 2 and 3, respectively. The purity of the solid crystal
16
0
zeolite/Cu nanoparticles to the synthesis of N,N -diarylureas will be measured by comparing the X-ray diffractogram pattern
via the arylation reaction of N-arylureas with aryl halides. of the sample with X-ray diffractogram pattern of the standard
The framework structure of zeolite consists of a three sample. The XRD powder patterns of a sample show very good
dimensional network of SiO4 and AlO4 tetrahedra linked crystallinity (Fig. 2). The X-ray powder diffraction was applied
+
together by oxygen (Fig. 1) which the ordered Na ions and H
2
O
for its phase purity in which its pattern was completely matched
The Natrolite with that of the Natrolite zeolite (according to the JCPDS le no.
10 main structural unit. The 33-1205). The results reveal that actual phases for this catalyst
15d
molecules ll the voids of the framework.
zeolite is one of zeolites with Al Si
2
3
O
Natrolite zeolite can be classied as brous zeolites with small were silicon oxide cristabolite-SiO
2
ꢁ
(cubic) and aluminium
ꢁ
ꢁ
pores (channels in the framework structure) which mostly silicate zeolite. Peaks at 34.97 , 38.95 and 51.96 are attributed
consist of 8 members of oxygen ring systems (the diameter of to CuO and appears because of oxidation of Cu nanoparticles.
+
˚
their pores < 4.5 A), and the Na cations occupy positions in the These results indicate that Cu nanoparticles have been
eight-ring channels. Our recent study has shown that the combined with Natrolite zeolite.
Natrolite zeolite can be used as a very active catalyst in the
organic synthesis.
The shape and size of the Natrolite zeolite/Cu NPs was
determined by scanning electron microscopy (SEM). Fig. 4
15
Natural Natrolite zeolite was obtained from Puna city, Iran. shows SEM images of Natrolite zeolite/Cu NPs. The surface of
The Natrolite zeolite/Cu NPs was prepared by supporting in an the zeolite specimens is highly heterogeneous due to the coex-
istence of different zeolite phases together with other crystalline
and amorphous materials. The morphology of zeolite demon-
strates a surface with a cubic shape, which is a typical structure
16,17
for zeolite.
The presence of copper has caused changes,
demonstrated by change in the roughness of the surface. It is
clearly observed that the Cu grain pervaded on zeolite surface,
which displays a good combination between natural Natrolite
zeolite and Cu NPs. Hence, Cu particles appear as bright dots
over the surface of Natrolite zeolite with average sizes of less
than 60 nm.
Energy Dispersive X-ray Spectroscopy (EDS) was used to
determine chemical composition of catalyst. EDS results show
that copper concentrations is about 13 wt%.
To demonstrate the scope of the application of Natrolite
zeolite/Cu NPs, a wide range of functionalized aryl halides were
Fig. 3 XRD diffraction pattern of Natrolite zeolite/Cu NPs.
Fig. 4 SEM image of Natrolite zeolite/Cu NPs.
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Table 2 Formation of N,N -diarylureas via N-arylation of N-arylureas
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0
a
b
Entry
1
N-Monosubstituted ureas
Aryl halide
Product
Yield (%)
c
94, 90
c
2
3
4
92, 89
91
88
5
89
6
7
87
85
8
84
a
3 4
Reaction conditions: 0.6 mmol of aryl halide, 0.5 mmol of N-arylureas, 1.0 mmol of K PO and 0.05 g Natrolite zeolite/Cu NPs (0.05 g), DMF (1.0
ꢁ
b
c
mL), 120 C, MW, 1 h. Yields are aer work-up. Yield aer the 4th cycle.
coupled with N-arylureas under ligand-free conditions and
microwave irradiation. As expected, both aryl halides with
electron-rich or electron-poor substituents and neutral aryl-
boronic acids afforded good to excellent yields (Table 2) when
reacted with N-arylureas.
Finally, the reusability of the catalyst was checked in the
reaction of N-phenylurea with phenyl iodide under the present
reaction conditions (Table 2, entries 1 and 2). Aer the
completion of the reaction, the insoluble catalyst was separated
from the reaction mixture by ltration. The catalyst was washed
with water and ethyl acetate several times, dried and employed
for the next reaction. The catalytic activity did not decrease
considerably aer four catalytic cycles (Fig. 5). The XRD analysis
of the recovered catalyst indicated that its structural integrity
remains intact aer separation from the reaction mixture and
thus proves the heterogeneous nature and the efficiency of
Natrolite zeolite/Cu NPs as a recyclable catalyst. This reusability
demonstrates the high stability and turnover of catalyst under
operating conditions.
Fig. 5 Reusability of Natrolite zeolite/Cu NPs for the N-arylation of
N-phenylurea.
making it a useful and attractive strategy for the synthesis of
0
N,N -diarylureas. Zeolites have denite advantages over
conventional solid catalysts: less or no corrosion, no waste or
disposal problems, high thermostability, easy setup of contin-
uous processes, etc.
The present method offers several notable features,
14
compared with the other literature works on the N-arylation of
N-arylureas, i.e., (1) use of Natrolite zeolite as a natural, efficient
and reusable heterogeneous catalyst with high activity, (2)
avoidance of the toxic ligands, (3) wide substrate scope and
generality, (4) higher yields and purity and shorter reaction
time, (5) effective reusability and recycling of the catalyst,
Conclusions
In conclusion, we have developed an efficient and simple
procedure for the hydration of cyanamides using triethyl
orthoformate in water. The advantages of this environmentally
benign and safe protocol include a simple reaction setup, very
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ꢁ
mild reaction conditions, easy work-up, elimination of toxic and
N-(4-Methoxyphenyl)urea (Table 1, entry 3). M.p. 167–169 C;
ꢀ1
corrosive acids and moderate to good yields. We also demon- FT-IR (KBr, cm ) 3471, 3337, 3195, 2955, 2837, 1645, 1616,
strated the preparation of Natrolite zeolite/Cu NPs as a new 1592, 1547, 1512, 1417, 1347, 1302, 1247, 1137, 1108, 1038, 823,
1
highly separable catalyst for N-arylation of N-arylureas with aryl 785, 675, 563, 519; H NMR (300 MHz, DMSO-d ) d ¼ 8.27 (s,
6
H
halides. Interestingly, the prepared catalyst showed improved 1H), 7.26 (d, J ¼ 7.2 Hz, 2H), 6.78 (d, J ¼ 7.2 Hz, 2H), 5.68 (s, 2H),
activity in the N-arylation reaction, affording the corresponding 3.67 (s, 3H).
0
N,N -diarylureas products in excellent yields under ligand-free
N-(2-Methylphenyl)urea (Table 1, entry 4). White color; yield
conditions and microwave irradiation. Aer the completion of 73%; M.p. 198–200 C; FT-IR (KBr, cm ) 3438, 3315, 3218,
ꢁ
ꢀ1
the reaction, the catalyst could be recovered and reused without 1650, 1613, 1582, 1547, 1459, 1354, 1289, 1258, 1117, 1041, 844,
1
affecting the reactivity.
747, 596, 480; H NMR (250 MHz, DMSO-d ) d ¼ 7.79 (t, J ¼ 6.4
6
H
Hz, 1H), 7.69 (s, 1H), 7.13–7.07 (dd, J ¼ 8.0 Hz, J ¼ 7.6 Hz, 2H),
1
3
6
.88 (d, J ¼ 7.4 Hz, 1H), 6.03 (s, 2H), 2.19 (s, 3H); C NMR (62.5
MHz, DMSO-d ) d
¼ 156.6, 138.6, 130.5, 127.4, 126.4, 122.5,
21.4, 18.36; anal. calcd for C H N O: C, 63.98; H, 6.71; N,
Experimental section
6
H
1
1
All reagents were purchased from the Merck and Aldrich
chemical companies and used without further purication.
8
10 2
8.65. Found: C, 63.85; H, 6.61; N, 18.52%.
N-(3-Bromophenyl)urea (Table 1, entry 5). White color; yield
70%; M.p. 141–143 C; FT-IR (KBr, cm ) 3375, 3333, 3189,
1679, 1578, 1476, 1410, 1091, 861, 777, 674, 599; H NMR
250 MHz, DMSO-d
m, 2H), 7.07 (d, J ¼ 8.1 Hz, 1H), 5.97 (s, 2H); C NMR
62.5 MHz, DMSO-d ) d
20.2, 116.8; anal. calcd for C H N OBr: C, 39.10; H, 3.28; N,
7.16. Found: C, 39.20; H, 3.34; N, 37.26%.
N-(4-Chlorophenyl)urea (Table 1, entry 6). M.p. 208–210 C;
Products were characterized by different spectroscopic methods
ꢁ
ꢀ1
1
(
FT-IR and H NMR spectra), elemental analysis (CHN) and
1
1
melting points. H NMR spectra were recorded on a Bruker
Avance DRX 250, 300, 400 and 500 MHz instruments. The
chemical shis (d) are reported in ppm relative to the TMS as
internal standard. J values are given in Hz. IR (KBr) spectra were
recorded on a Perkin-Elmer 781 spectrophotometer. Melting
points were taken in open capillary tubes with a BUCHI 510
melting point apparatus and were uncorrected. The elemental
analysis was performed using Heraeus CHN–O-Rapid analyzer.
TLC was performed on silica gel polygram SIL G/UV 254 plates.
X-ray diffraction measurements were performed with a Philips
powder diffractometer type PW 1373 goniometer. It was
equipped with a graphite monochromator crystal. The X-ray
(
(
(
1
3
6
) d
H
¼ 8.74 (s, 1H), 7.83 (s, 1H), 7.23–7.15
13
6
C
¼ 156.2, 142.7, 131.0, 123.0, 120.4,
7
7 2
ꢁ
ꢀ1
FT-IR (KBr, cm ) 3427, 3314, 3215, 1654, 1611, 1587, 1549,
1
1
492, 1401, 1357, 1091, 821, 731, 503; H NMR (250 MHz,
DMSO-d ) d
¼ 8.80 (s, 1H), 7.41 (d, J ¼ 8.1 Hz, 2H), 7.25 (d, J ¼
.1 Hz, 2H), 5.93 (s, 2H).
N-(4-Nitrophenyl)urea (Table 1, entry 7). M.p. 226–229 C;
FT-IR (KBr, cm ) 3488, 3381, 3317, 3247, 3218, 3152, 1690,
1595, 1550, 1488, 1414, 1359, 1322, 1299, 1261, 1179, 1111,
6
H
8
ꢁ
ꢀ1
ꢁ
wavelength was 1.5405 A and the diffraction patterns were
ꢁ
recorded in the 2q range (10–60) with scanning speed of 2
1
ꢀ
1
1097, 1005, 855, 839, 750, 718, 632, 566, 473, 434, 411; H NMR
min . Morphology and particle dispersion was investigated by
scanning electron microscopy (SEM) (Cam scan MV2300).
(
7
300 MHz, DMSO-d
.60 (d, J ¼ 9.0 Hz, 2H), 6.20 (s, 2H).
N-(1-Naphthyl)urea (Table 1, entry 8). White color; yield 70%;
) d
6 H
¼ 9.30 (s, 1H), 8.10 (d, J ¼ 9.0 Hz, 2H),
General experimental procedure for the synthesis of
N-arylureas
ꢁ
ꢀ1
M.p. 220–222 C; FT-IR (KBr, cm ) 3444, 33 055, 3206, 3052,
922, 1651, 1608, 1555, 1530, 1505, 1360, 1335, 1278, 1101, 785,
2
1
The cyanamide (2 mmol) and triethyl orthoformate (4 mmol) was 772, 608, 530; H NMR (250 MHz, DMSO-d ) d ¼ 8.70 (s, 1H),
6
H
added to H O (10 mL), and the solution was stirred for the 8.17 (s, 1H), 8.00 (d, J ¼ 7.3 Hz, 1H), 7.85 (s, 1H), 7.73–7.37 (m,
2
1
3
appropriate times under reux conditions. Aer stirring for the 4H), 6.22 (s, 2H); C NMR (62.5 MHz, DMSO-d ) d ¼ 157.1,
6
C
requisite period (Table 1), the reaction mixture was cooled. The 135.9, 134.5, 128.9, 126.6, 126.4, 126.0, 122.7, 122.3, 117.5; anal.
resulting mixture was recrystallized with aqueous ethanol to give calcd for C H N O : C, 70.95; H, 5.41; N, 15.04. Found: C,
1
1
10 2 2
pure products in good yields. The physical data of known 70.82; H, 5.34; N, 14.91%.
compounds were found to be identical with those reported in the
9
,13,18
1
13
literature.
The elemental analysis (CHN), IR, H NMR and
C
16
Preparation of the Natrolite zeolite/Cu NPs
The Cu–Natrolite zeolite was prepared by supporting in an
aqueous solution of Cu(OAc) . Approximately, 2 g of Natrolite
NMR data of the unknown substituted ureas are given as below.
N-Phenylurea (Table 1, entry 1). M.p. 143–145 C; FT-IR (KBr,
cm ) 3346, 3268, 3243, 3193, 3057, 1740, 1656, 1597, 1561,
ꢁ
ꢀ
1
2
zeolite was dispersed in an aqueous solution of 0.01 M Cu(OAc)
and irradiated with ultrasonic for 15 min at room temperature.
Then, the mixture was reuxed at 100 C for 12 h, followed by
ltration, washing, and drying. This procedure was carried out
2
1
1
(
7
493, 1447, 1369, 1319, 1238, 1068, 737, 691, 605, 491; H NMR
300 MHz, DMSO-d ) d
¼ 8.55 (s, 1H), 7.38 (d, J ¼ 7.8 Hz, 2H),
.20 (t, J ¼ 7.6 Hz, 2H), 6.87 (t, J ¼ 7.2 Hz, 1H), 5.84 (s, 2H).
6
H
ꢁ

ꢁ
N-(4-Methylphenyl)urea (Table 1, entry 2). M.p. 182–184 C;
twice without intermediate calcinations.
ꢀ1
FT-IR (KBr, cm ) 3431, 3311, 3041, 2920, 1655, 1620, 1591,
1
5
551, 1514, 1408, 1357, 1256, 1109, 1024, 824, 811, 708, 638,
1
Typical procedure for the N-arylation of N-arylureas
51, 501; H NMR (300 MHz, DMSO-d ) d ¼ 8.35 (s, 1H), 7.24
6
H
(
(
d, J ¼ 7.8 Hz, 2H), 7.00 (d, J ¼ 7.8 Hz, 2H), 5.73 (s, 2H), 2.20 A Smith process vial was charged with 0.05 g Natrolite zeolite/
s, 3H).
3 4
Cu NPs and K PO (1 mmol). Aer sealing the cap and twice
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purging with N
2
, the vial was charged with 0.5 mL of DMF and
S. Knapp, J. J. Hale, M. Bastos, A. Molina and K. Y. Cheng,
J. Org. Chem., 1992, 57, 6239.
stirred at room temperature for 10 min. A solution of 0.6 mmol
of aryl halide and 0.5 mmol of N-arylurea in 0.5 mL of DMF was
introduced via syringe. The resulting mixture was stirred at
room temperature for 30 min and then was irradiated by
5 (a) X. Peng, F. Li and C. Xia, Synlett, 2006, 1161; and
references cited therein; (b) T. Mizuno, M. Mihara, T. Iwai,
T. Ito and Y. Issino, Synthesis, 2006, 2825; and references
cited therein; (c) K. Orito, M. Miyazawa, T. Nakamura,
A. Horibata, H. Uscito, H. Nagasaki, M. Yuguchi,
S. Yamashita, T. Yamazaki and M. Tokuda, J. Org. Chem.,
2006, 71, 5951; (d) B. Zhu and R. J. Angelici, J. Am. Chem.
Soc., 2006, 128, 14460; (e) Y. Nishiyama, H. Kawamatsu and
N. Sonoda, J. Org. Chem., 2005, 70, 2551; (f) P.-A. Enquist,
P. Nilsson, J. Edin and M. Larhed, Tetrahedron Lett., 2005,
46, 3335; and references cited therein; (g) F. Bigi, R. Maggi
and G. Sartori, Green Chem., 2000, 2, 140.
ꢁ
microwave at 120 C for 1 h in the Smith synthesizer. The
reaction mixture was cooled to room temperature, ltered
through a pad of Celite and extracted with water and ethyl
acetate. The combined organic extracts were dried with anhy-
drous Na SO and the solvent was removed under reduced
2
4
pressure. The crude product was puried by silica gel column
chromatography to afford the N,N -diarylureas product. All
products are known in the literature and were characterized by
IR, NMR and melting points and their spectroscopic data
0
14
identical to that reported in the literature.
,3-Diphenylurea (Table 2, entries 1 and 2). H NMR
400 MHz, DMSO-d ) d
¼ 8.60 (s, 2H), 7.43 (d, J ¼ 8.5 Hz, 4H),
.25 (t, J ¼ 7.7 Hz, 4H), 6.95 (t, J ¼ 7.2 Hz, 2H).
6 (a) A. A. Nirschl, Y. Zou, S. R. Krystek Jr, J. C. Sutton,
L. M. Simpkins, J. A. Lupisella, J. E. Kuhns, R. Seethala,
R. Golla, P. G. Sleph, B. C. Beehler, G. J. Grover, D. Egan,
A. Fura, V. P. Vyas, Y.-X. Li, J. S. Sack, K. F. Kish, Y. An,
J. A. Bryson, J. Z. Gougoutas, J. DiMarco, R. Zahler,
J. Ostrowski and L. G. Hamann, J. Med. Chem., 2009, 52,
1
1
(
7
6
H
0
1
N-(4-Methoxyphenyl)-N -phenylurea (Table 2, entry 3).
H
NMR (300 MHz, DMSO-d ) d ¼ 8.52 (s, 1H), 8.41 (s, 1H), 7.40 (d,
6
H
J ¼ 8.5 Hz, 2H), 7.34 (d, J ¼ 9.0 Hz, 2H), 7.25 (t, J ¼ 7.7 Hz, 2H),
.92 (t, J ¼ 7.4 Hz, 1H), 6.83 (d, J ¼ 9.0 Hz, 2H), 3.70 (s, 3H).
2794;
(b)
V.
D.
Jadhav,
E.
Herdtweck
and
6
F. P. Schmidtchen, Chem.–Eur. J., 2008, 14, 6098; (c)
D. Schade, K. Topker-Lehmann, J. Kotthaus and
B. Clement, J. Org. Chem., 2008, 73, 1025; (d) G. Haufe,
U. Rolle, E. Kleinpeter, J. Kivikoski and K. Rissanen, J. Org.
Chem., 1993, 58, 7084; (e) S.-H. Jung and H. Kohn, J. Am.
Chem. Soc., 1985, 107, 2931; (f) B. B. Snider and
J. R. Duvall, Org. Lett., 2005, 7, 4519; (g) J. R. Duvall, F. Wu
and B. B. Snider, J. Org. Chem., 2006, 71, 8579; (h) S. Nag,
G. P. Yadav, P. R. Maulik and S. Batra, Synthesis, 2007, 911.
7 E. Wertheim, J. Am. Chem. Soc., 1931, 53, 200.
8 E. Artuso, I. Degani, R. Fochi and C. Magistris, Synthesis,
2007, 3497.
0
1
N-(4-Nitrophenyl)-N -phenylurea (Table 2, entry 4). H NMR
500 MHz, DMSO-d ) d
¼ 9.42 (s, 1H), 8.92 (s, 1H), 8.20 (d, J ¼
(
9
6
H
.0 Hz, 2H), 7.70 (d, J ¼ 9.0 Hz, 2H), 7.07 (d, J ¼ 7.3 Hz, 2H), 7.31
(t, J ¼ 7.7 Hz, 2H), 7.04 (t, J ¼ 7.5 Hz, 1H).
0
N-(2-Methylphenyl)-N -phenylurea (Table 2, entries 5 and 6).
1
H NMR (300 MHz, DMSO-d ) d ¼ 8.97 (s, 1H), 7.89 (s, 1H), 7.81
6
H
(
dd, J ¼ 1.0, 8.0 Hz, 1H), 7.43 (dt, J ¼ 1.4, 8.5 Hz, 3H), 7.28–7.23
m, 3H), 7.16–7.08 (m, J ¼ 7.5, 15.0 Hz, 3H), 6.97–6.88 (m, 2H),
(
2
.22 (s, 3H).
0
N-(4-Chlorophenyl)-N -phenylurea (Table 2, entries 7 and 8).
H NMR (300 MHz, DMSO-d ) d
¼ 8.81 (s, 1H), 8.70 (s, 1H), 7.50
1
6
H
(d, J ¼ 8.5 Hz, 2H), 7.45 (d, J ¼ 8.1 Hz, 2H), 7.32 (d, J ¼ 8.5 Hz,
9 S. H. Kim, B. R. Park and J. N. Kim, Bull. Korean Chem. Soc.,
2011, 32, 716.
2H), 7.29 (d, J ¼ 7.6 Hz, J ¼ 8.1 Hz, 2H), 6.98 (d, J ¼ 7.6 Hz, 1H).
1
0 (a) M. Nasrollahzadeh, M. Maham, A. Ehsani and M. Khalaj,
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Acknowledgements
We gratefully acknowledge the Iranian Nano Council and
University of Qom for the support of this work.
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