A simple and efficient synthesis of diaryl ureas with reduction of the intermediate isocyanate by triethylamine

Article abstract of DOI:10.3184/174751913X13663925002708

Thirty symmetrical diaryl urea derivatives were synthesised in moderate to excellent yields from arylamine and triphosgene with triethylamine as a reducing agent for the intermediate, isocyanate. It was significant that part of the products could be collected in almost quantitative yield without column chromatography. The procedure under mild reaction conditions was tolerant of a wide range of functional groups. The structures of the compounds were determined by NMR, MS and X-ray crystallographic analyses.

Full text of DOI:10.3184/174751913X13663925002708

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 315
MAY, 315–319
A simple and efficient synthesis of diaryl ureas with reduction of the
intermediate isocyanate by triethylamine
Shuguang Zhou, Ting Yao, Jicheng Yi, Dashuai Li and Jing Xiong*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325035, P. R. China
Thirty symmetrical diaryl urea derivatives were synthesised in moderate to excellent yields from arylamine and
triphosgene with triethylamine as a reducing agent for the intermediate, isocyanate. It was significant that part of the
products could be collected in almost quantitative yield without column chromatography. The procedure under mild
reaction conditions was tolerant of a wide range of functional groups. The structures of the compounds were
determined by NMR, MS and X-ray crystallographic analyses.
Keywords: diaryl ureas, triphosgene, triethylamine
The urea group plays an important role in agricultural,
supramolecular, and medicinal chemistry.1–6 For example,
recent reports have cited examples of ureas as antimalarial
agents,7,8 cardiac-specific myosin activators,9 anaplastic
lymphoma kinase inhibitors,10 tyrosine and Raf kinase
inhibitors,11 soluble epoxide hydrolase inhibitors for the
treatment of diabetes, hypertension, stroke, and inflammatory
diseases.12,13 Moreover, urea derivatives also impart important
function in organic synthesis as intermediates and bifunctional
organocatalysts.14–17
Typically, efficient synthesis of the urea functional group is
achieved through the condensation of an amine with an iso-
cyanate, or the coupling of amines with phosgene or a phosgene
equivalent.18,19 Unfortunately, phosgene poses handling issues
due to its toxicity, so developing a less hazardous synthetic
route to ureas has attracted considerable interest over the
years.20–24 Bis(trichloromethyl) carbonate (BTC) or triphos-
gene, (Cl3CO)2C=O, is a relatively safe substitute for the
notorious toxic gas phosgene. It is stable at room temperature,
and its handling and storage do not demand meticulously
anhydrous conditions, thus making it a very convenient reagent
for typical laboratory and industrial scale operations.25
In addition, this reagent has been used to achieve various
functional group interconversions, particularly the insertion of
the carbonyl moiety.26
(Table 1, entry 4). Then we investigated the reaction in various
solvents, and found that the reaction was tolerant of a wide
variety of both polar and non polar solvents (Table 1).
Furthermore, using dichloromethane not only got the best
yield, but also was the most convenient procedure during the
purification of the products from the reaction mixture.
We next investigated other tertiary amines, pyridine and
inorganic base such as sodium carbonate, sodium bicarbonate,
and found that 1,3-diphenylurea could also be obtained in the
presence of other tertiary amines such as tripropylamine and
tributylamine, instead of triethylamine. However, the yields
were much lower than that with triethylamine. Interestingly,
there was almost no diaryl urea generated when pyridine
or inorganic base was used as a substitute for triethylamine
(Table 2, entries 9–11). Instead, the reaction just produced the
intermediate 1-isocyanatobenzene even if the reaction time
was prolonged.
With our preferred conditions in hand, we investigated a
range of different aryl primary amines. As shown in Tables 3
and 4, the reaction was highly tolerant of the monosubstituted
or disubstituted aromatic primary amine structure, and most
of the products were obtained in excellent yields, even weak
nucleophilic amine such as 2-nitroaniline or 3-nitroaniline
reacted in yield 85% (Table 3, entries 19 and 20), only
Driven by our interest in the utilisation of triphosgene to
synthesise urea-containing compounds, we recently explored a
mild method for the construction of symmetrical diaryl ureas
by triphosgene in the presence of triethylamine, which led to
the rapid and clean production of the target products in good
yields (Scheme 1). In most cases, the reactions proceed to
completion in less than 1 h at room temperature except for the
aryl amine containing nitro group.
Table 1 Investigation of the effect of various solvents
Entry
Solvent
Yield/%a
1
2
3
4
5
6
7
8
THF
Acetic ether
Acetonitrile
DCM
95
87
76
97
75
80
77
75
Results and discussion
Initially,weinvestigatedthereactionofanilinewithtriphosgene
to synthesise isocyanatobenzene in dichloromethane. After
the aniline reacted completely with triphosgene by GC-MS
monitoring, we added excess triethylamine as a base to the
above mixture, and surprisingly, the symmetrical 1,3-diphenyl-
urea was obtained rapidly in almost quantitative yield, 97%
Pyridine
Toluene
DCM/pyridine = 4/1
THF/pyridine = 4/1
a Isolated yield.
Scheme 1
* Correspondent. E-mail: xiongjing@wzu.edu.cn

316 JOURNAL OF CHEMICAL RESEARCH 2013
Table 2 Investigation of the effect of tertiary amines and
inorganic bases
Table 3 Investigation of the scope of the monosubstituted
aryl primary amine
Entry
Tertiary amine or base
Yield/%a
1
2
Triethylamine
Tripropylamine
97
75
71
61
69
66
65
68
Trace
0
Entry
1
Starting material
2
Yield/%a
97
3
Tributylamine
2a
4
N,N–Dimethylaniline
N,N-Diethylaniline
N,N-Diisopropylethylamine
N,N-dimethylethylamine
N,N-Dimethylbutylamine
Pyridine
5
6
7
2
2b
95
8
9
10
11
NaHCO3
Na2CO3
3
4
5
2c
2d
2e
82
86
99
0
a Isolated yield.
4-methyl-2-nitrobenzenamine and 4-methoxy-2-nitrobenzen-
amine reacted in moderate yield, 77% and 75%, respectively
(Table 4, entries 9 and 10).
All the products were characterised by 1H NMR, 13C NMR
and High-resolution mass spectrometry (HRMS). In order to
confirm the structure of the compounds, the crystal structure
of 1,3-bis(2,5-dichlorophenyl)urea (4a) as a representative
example was determined by X-ray crystallography. Crystal of
4a was obtained from a mixture of ethyl acetate and ethanol
(1:3). An ORTEP view of the molecule together with the atom
numbering is presented in Fig. 1, the crystal data and structure
refinement is shown in Table 5. In the molecule (Fig. 1), both
the two phenyl rings (C1–C6 and C1A–C6A) are almost planar
with the RMS deviations of 0.0036 Å, the dihedral angle
between the two planes is 84.7°. The adjacent molecules are
linked by intermolecular N1–H1…O1 hydrogen bond
interactions to stabilise the crystal structure.
6
7
2f
88
92
2g
8
9
2h
2i
86
82
10
11
2j
87
87
2k
Conclusions
In conclusion, we have developed a highly practical and
convenient synthesis of symmetrical diaryl ureas by the
reaction of triphosgene and various aromatic primary amines
with triethylamine as a reduction for the isocynate-containing
intermediates. Note that the reaction in high yield is tolerant of
a wide range of aromatic primary amines, and could take place
under extremely mild conditions.
12
13
2l
88
94
2m
Experimental
14
2n
97
All reagents were purchased from commercial sources and used
without treatment, unless otherwise indicated. IR spectra were run
on a Bruker Equinox 55 using KBr pellets. 1H NMR (500 MHz) and
13C NMR (125 MHz) analyses were recorded on a Bruker AVANCE
500 spectrometor in DMSO-d6 with TMS as internal standard. Mass
spectra were obtained on a Bruker micrOTOF-Q II instrument. The
crystallographic data were collected on a Bruker Smart-Apex CCD
diffractometer. Melting points were recorded on a digital melting
point apparatus WRS-1B and are uncorrected. The progress of the
reactions was detected by TLC using silica gel GF 254 plates.
15
16
2o
2p
90
82
17
18
2q
2r
84
83
Synthesis of the compounds 2 and 4; general procedure
Bis(trichloromethyl) carbonate (BTC) (5.0 mmol 1.48 g) was dis-
solved in DCM (30 mL). The aromatic primary aniline (10.0 mmol) in
DCM (20 mL) was added dropwise to the above solution at 0 °C over
30 min. After the aryl primary aniline reacted completely (monitored
by GC), triethylamine (25.0 mmol, 2.53g) was added dropwise to the
above mixture and stirred for 1–2 h at room temperature (monitored
by TLC). The solid was obtained after distillation of DCM, washing
by water (2×10 mL), and filtration.
19
2s
2t
85
85
20
1,3-Diphenylurea (2a): White solid; yield 97%, m.p. 245.0–245.4 °C
(lit.1 240–241 °C); IR (KBr, cm−1): 3282, 3046, 1644, 1594, 1547,
a Isolated yield.

JOURNAL OF CHEMICAL RESEARCH 2013 317
Table 4 Investigation of the scope of the disubstituted aryl
primary amine
Entry
1
Starting material
4
Yield/%a
82
Fig. 1 X-ray crystal structure of 4a, showing displacement
ellipsoids at the 50% probability.
4a
(t, 2H, J = 7.5 Hz), 6.94 (dd, 2H, J = 7.5, 1.0 Hz), 2.26 (s, 6H); 13C
NMR (125 MHz, DMSO-d6) δ 153.1, 137.7, 130.3, 127.9, 126.2,
122.8, 121.7, 18.2; HRMS (ESI) exact mass calcd for (C15H17N2O)+
requires m/z 241.1341, found m/z 241.1324.
1,3-Di-m-tolylurea (2f): White solid; yield 88%, m.p. 225.6–226.1 °C
(lit.1 262–263 °C); IR (KBr, cm−1): 3255, 3056, 2961, 2931, 2869,
1635, 1550, 1401, 1290, 1227, 763, 748; 1H NMR (500 MHz,
DMSO-d6) δ 8.59 (s, 2H), 7.34 (s, 2H), 7.26 (d, 2H, J = 8.5 Hz), 7.16
(t, 2H, J = 8.0 Hz), 6.78 (d, 2H, J = 7.5 Hz), 2.28 (s, 6H); 13C NMR
(125 MHz, DMSO-d6) δ 152.7, 139.9, 138.1, 128.8, 122.7, 118.9,
115.6, 21.4; HRMS (ESI) exact mass calcd for (C15H17N2O)+ requires
m/z 241.1335, found m/z 241.1325.
2
3
4b
4c
98
91
4
5
4d
4e
87
85
1,3-Di-p-tolylurea (2g): White solid; yield 92%; m.p. 271.6–
273.3 °C (lit.1 268–269 °C); IR (KBr, cm−1): 3319, 3056, 2933, 2869,
1
1635, 1594, 1556, 1516, 1406, 1305, 1230, 814, 776, 751; H NMR
6
7
4f
80
84
(500 MHz, DMSO-d6) δ 8.50 (s, 2H), 7.35 (d, 4H, J = 8.0 Hz), 7.08 (d,
4H, J = 7.5 Hz), 2.24 (s, 6H); 13C NMR (125 MHz, DMSO-d6)
δ 152.8, 137.4, 130.7, 129.3, 118.4, 20.5; HRMS (ESI) exact mass
calcd for (C15H17N2O)+ requires m/z 241.1341, found m/z 241.1324.
1,3-Bis(2-ethylphenyl)urea (2h): White solid; yield 86%, m.p.
237.9–238.3 °C (lit.2 177–179 °C); IR (KBr, cm−1): 3255, 3056, 2961,
2931, 2870, 2831, 1631, 1585, 1537, 1446, 1290, 1118, 751; 1H NMR
(500 MHz, DMSO-d6) δ 8.21 (s, 2H), 7.75 (d, 2H, J = 8.0 Hz), 7.19 (d,
2H, J = 7.5 Hz), 7.14 (t, 2H, J = 7.5 Hz), 7.01 (t, 2H, J = 7.5 Hz), 2.64
(q, 4H, J = 7.5 Hz), 1.19 (t, 6H, J = 7.5 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 153.7, 136.9, 134.4, 128.5, 126.1, 123.4, 123.0, 24.0,
14.4. HRMS (ESI) exact mass calcd for (C17H21N2O)+ requires m/z
269.1650, found m/z 269.1647.
4g
8
9
4h
4i
82
77
75
10
4j
1,3-Bis(4-ethylphenyl)urea (2i): White solid; yield 82%, m.p.
224.2–224.4 °C; IR (KBr, cm−1): 3268, 3016, 2912, 2872, 2855,
1631, 1585, 1547, 1456, 1406, 1296, 1230, 1064, 826, 760; 1H NMR
(500 MHz, DMSO-d6) δ 8.52 (s, 2H), 7.37(d, 4H, J = 8.0 Hz), 7.10 (d,
a Isolated yield.
4H, J = 8.0 Hz), 2.54 (q, 4H, J = 7.5 Hz), 1.15 (t, 6H, J = 7.5 Hz); 13
C
1
1497, 1315, 1227, 895, 781, 691; H NMR (500 MHz, DMSO-d6)
δ 8.68 (s, 2H), 7.48 (d, 4H, J = 8.0 Hz), 7.29 (t, 4H, J = 8.0 Hz), 6.97
(t, 2H, J = 7.5 Hz); 13C NMR (125 MHz, DMSO-d6) δ 152.7, 139.9,
128.9, 122.0, 118.4; HRMS (ESI) exact mass calcd for (C13H13N2O)+
requires m/z 213.1028, found m/z 213.1017.
NMR (125 MHz, DMSO-d6) δ 152.8, 137.6, 137.2, 128.1, 118.5, 27.7,
15.9. HRMS (ESI) exact mass calcd for (C17H21N2O)+ requires m/z
269.1654, found m/z 269.1646.
1,3-Bis(2-methoxyphenyl)urea (2j): Light yellow solid; yield 87%,
m.p. 187.6–188.1 °C (lit.1 187–188 °C); IR (KBr, cm−1): 3292, 2936,
2834, 1644, 1591, 1534, 1456, 1321, 1286, 1252, 1227, 1108, 1024,
1,3-Bis(2-chlorophenyl)urea (2b): White solid; yield 95%, m.p.
242.0–242.3 °C (lit.1 226–227 °C); IR (KBr, cm−1): 3248, 3016, 1640,
1580, 1460, 1405, 1264, 1222, 1080, 871, 800, 729; 1H NMR
(500 MHz, DMSO-d6) δ 9.07 (s, 2H), 8.10 (d, 2H, J = 8.0 Hz), 7.45 (d,
2H, J = 7.5 Hz), 7.30 (t, 2H, J = 7.5 Hz), 7.04 (t, 2H, J = 8.0 Hz); 13
C
Table 5 Crystal data and structure refinement for 4a
NMR (125 MHz, DMSO-d6) δ 152.4, 136.0, 129.5, 127.6, 123.9,
123.0, 122.7; HRMS (ESI) exact mass calcd for (C13H10Cl2N2ONa)+
requires m/z 303.0068, found m/z 303.0060.
Empirical formula
Formula weight
Temperature/K
Wavelength/Å
Crystal system
Space group
C13 H8 Cl4 N2 O
350.01
298(2)
0.71073
1,3-Bis(3-chlorophenyl)urea (2c): White solid; yield 82%, m.p.
253.2–252.6 °C (lit.1 245–246.5 °C); IR (KBr, cm−1): 3324, 3076,
1635, 1578, 1550, 1478, 1403, 1284, 1224, 1070, 870, 789; 1H NMR
(500 MHz, DMSO-d6) δ 8.96 (s, 2H), 7.74 (s, 2H), 7.29–7.28 (m, 4H),
7.02–7.00 (m, 2H); 13C NMR (125 MHz, DMSO-d6) δ 152.5, 141.2,
133.5, 130.5, 121.9, 118.0, 117.0; HRMS (ESI) exact mass calcd for
(C13H10Cl2N2ONa)+ requires m/z 303.0068, found m/z 303.0060.
1,3-Bis(4-chlorophenyl)urea (2d): White solid; yield 86%, m.p.
284.3–284.7 °C (lit.1 301–302 °C); IR (KBr, cm−1): 3240, 3056, 1655,
1605, 1568, 1500, 1448, 1401, 1294, 1214, 1075, 826, 729; 1H NMR
(500 MHz, DMSO-d6) δ 8.87 (s, 2H), 7.51 (d, 4H, J = 9.0 Hz), 7.33 (d,
4H, J = 8.5 Hz); 13C NMR (125 MHz, DMSO-d6) δ 152.5, 138.7, 128.8,
125.7, 120.0; HRMS (ESI) exact mass calcd for (C13H10Cl2N2ONa)+
requires m/z 303.0068, found m/z 303.0059.
Monoclinic
C 2
Volume/Å3
670.76(13)
Z
2
Calculated density/Mg m−3
Unit cell dimensions
1.733
a = 24.874(3) Å,
b = 4.6225(5) Å
c = 5.8692(7) Å
α = 90 °, β = 96.310(2)°, γ = 90°
Absorption coefficient/mm−1 0.876
F(000)
Index ranges
352
–30 ≤ h ≤ 25
–5 ≤ k ≤ 5
–6 ≤ l ≤ 7
1,3-Di-o-tolylurea (2e): White solid; yield 99%, m.p. 258.4–258.9 °C
Goodness-of-fit on F2
Final R indices
R indices (all data)
1.012
(lit.1 235–236 °C); IR (KBr, cm−1): 3215, 3086, 2966, 2863, 1652,
R1 = 0.0225, wR2 = 0.0808
R1= 0.0255, wR2 = 0.0971
1
1562, 1438, 1294, 1200, 906, 751; H NMR (500 MHz, DMSO-d6)
δ 8.26 (s, 2H), 7.79 (d, 2H, J = 7.5 Hz), 7.17 (d, 2H, J = 7.0 Hz), 7.13

318 JOURNAL OF CHEMICAL RESEARCH 2013
1
735; H NMR (500 MHz, DMSO-d6) δ 8.94 (s, 2H), 8.18 (dd, 2H,
(s, 2H), 8.05 (dd, 2H, J = 8.0, 1.5 Hz), 7.97 (d, 2H, J = 8.0 Hz), 7.71
(t, 2H, J = 8.5 Hz), 7.30 (t, 2H, J = 8.5 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 152.1, 140.1, 134.7, 133.2, 125.4, 124.1, 123.8. HRMS
(ESI) exact mass calcd for (C13H10N4O5Na)+ requires m/z 325.0549,
found m/z 325.0543.
1,3-Bis(3-nitrophenyl)urea (2t): Yellow solid; yield 85%, m.p.
242.0–243.5 °C (lit.1 231–232 °C); IR (KBr, cm−1): 3312, 3029, 1669,
1576, 1510, 1475, 1257, 1217, 829, 741; 1H NMR (500 MHz,
DMSO-d6) δ 9.40 (s, 2H), 8.57 (s, 2H), 7.86 (dd, 2H, J = 8.0, 1.5 Hz),
7.77 (d, 2H, J = 8.0 Hz), 7.59 (t, 2H, J = 8.0 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 152.6, 148.3, 140.8, 130.2, 124.8, 116.9, 112.7. HRMS
(ESI) exact mass calcd for (C13H10N4O5Na)+ requires m/z 325.0549,
found m/z 325.0545.
1,3-Bis(2,5-dichlorophenyl)urea (4a): White solid; yield 82%, m.p.
292.0–292.6 °C; IR (KBr, cm−1): 3289, 3084, 1641, 1581, 1549, 1461,
1406, 1262, 1217, 1089, 873, 804, 738; 1H NMR (500 MHz, DMSO-
d6) δ 9.31 (s, 2H), 8.23 (d, 2H, J = 2.5 Hz), 7.52 (d, 2H, J = 8.5 Hz),
7.14 (dd, 2H, J = 8.5, 2.5 Hz); 13C NMR (125 MHz, DMSO-d6) δ
152.1, 137.0, 132.0, 130.8, 123.6, 121.5, 121.2. HRMS (ESI) exact
mass calcd for (C13H935Cl337ClN2O)+ requires m/z 350.9440, found m/z
350.9419.
1,3-Bis(3,5-dimethylphenyl)urea (4b): White solid; yield 98%, m.p.
281.7–282.0 °C; IR (KBr, cm−1): 3284, 3081, 2963, 2916, 2857,
2823, 1635, 1553, 1513,1444, 1312, 1274, 1218, 851, 839; 1H NMR
(500 MHz, DMSO-d6) δ 8.46 (s, 2H), 7.06 (s, 4H), 6.60 (s, 2H),
2.23 (s, 12H); 13C NMR (125 MHz, DMSO-d6) δ 152.6, 139.7, 137.9,
123.5, 116.0, 21.3. HRMS (ESI) exact mass calcd for (C17H21N2O)+
requires m/z 269.1654, found m/z 269.1645.
1,3-Bis(3,4-dimethylphenyl)urea (4c): White solid; yield 91%, m.p.
243.4–243.9 °C; IR (KBr, cm−1): 3292, 3151, 2964, 2914, 2852, 2808,
1638, 1588, 1534, 1444, 1403, 1301, 1218, 1024, 999, 870, 801, 782;
1H NMR (500 MHz, DMSO-d6) δ 8.43 (s, 2H), 7.26 (s, 2H), 7.19 (d,
2H, J = 8.0 Hz), 7.02 (d, 2H, J = 8.5 Hz), 2.20 (s, 6H), 2.16 (s, 6H);
13C NMR (125 MHz, DMSO-d6) δ 152.8, 137.7, 136.5, 129.8, 129.5,
119.7,115.9,19.8,18.8.HRMS(ESI)exactmasscalcdfor(C17H21N2O)+
requires m/z 269.1654, found m/z 269.1642.
1,3-Bis(3-chloro-4-methylphenyl)urea (4d): White solid; yield
87%, m.p. 271.1–271.3 °C; IR (KBr, cm−1): 3275, 3062, 2948, 1628,
1553, 1491, 1440, 1378, 1271, 1045, 867, 820; 1H NMR (500 MHz,
DMSO-d6) δ 8.79 (s, 2H), 7.70 (d, 2H, J = 2.0 Hz), 7.23 (d, 2H, J =
8.0 Hz), 7.20 (dd, 2H, J = 8.0, 2.0 Hz), 2.26 (s, 6H); 13C NMR
(125 MHz, DMSO-d6) δ 152.5, 138.9, 133.3, 131.3, 128.5, 118.5,
117.2, 18.9. HRMS (ESI) exact mass calcd for (C15H15Cl2N2O)+
requires m/z 309.0554, found m/z 309.0561.
1,3-Bis(2,5-dimethoxyphenyl)urea (4e): Grey solid; yield 85%,
m.p. 206.5–207.5 °C; IR (KBr, cm−1): 3292, 3092, 2936, 2834, 1669,
1598, 1535, 1454, 1417, 1279, 1198, 1123, 1045, 867, 820; 1H NMR
(500 MHz, DMSO-d6) δ 8.99 (s, 2H), 7.85 (d, 2H, J = 2.5 Hz), 6.90 (d,
2H, J = 9.0Hz), 6.50 (dd, 2H, J = 9.0, 3.0Hz), 3.81 (s, 6H), 3.70 (s,
6H); 13C NMR (125 MHz, DMSO-d6) δ 153.5, 152.8, 142.6, 129.9,
111.7, 106.2, 105.7, 56.4, 55.4. HRMS (ESI) exact mass calcd for
(C17H21N2O5)+ requires m/z 333.1450, found m/z 333.1441.
1,3-Bis(2-methyl-3-nitrophenyl)urea (4f): Light yellow solid; yield
80%, m.p. 290.6–291.6 °C; IR (KBr, cm−1): 3316, 3067, 2923, 2831,
1659, 1585, 1515, 1464, 1345, 1251, 1084, 832, 781; 1H NMR
(500 MHz, DMSO-d6) δ 8.74 (s, 2H), 8.04 (d, 2H, J = 8.0 Hz), 7.59
(d, 2H, J = 7.5 Hz), 7.41 (t, 2H, J = 8.0 Hz), 2.34 (s, 6H); 13C NMR
(125 MHz, DMSO-d6) δ 153.0, 151.2, 139.1, 126.9, 126.8, 123.2,
118.8, 13.7. HRMS (ESI) exact mass calcd for (C15H14N4O5Na)+
requires m/z 353.0862, found m/z 353.0854.
J = 8.0, 1.5 Hz), 7.00 (dd, 2H, J = 8.0, 1.5 Hz), 6.96 (td, 2H, J = 8.0,
1.5 Hz), 6.91 (td, 2H, J = 7.5, 1.5 Hz), 3.87 (s, 6H). 13C NMR
(125 MHz, DMSO-d6) δ 152.9, 148.4, 129.1, 122.1, 120.6, 119.4,
111.0, 55.8. HRMS (ESI) exact mass calcd for (C15H16N2O3Na)+
requires m/z 295.1059, found m/z 295.1046.
1,3-Bis(4-methoxyphenyl)urea (2k): White solid; yield 87%, m.p.
242.4–242.7 °C (lit.1 240 °C); IR (KBr, cm−1): 3309, 3065, 2956,
2844, 1638, 1603, 1553, 1503, 1301, 1243, 1105, 1027, 823, 723; 1H
NMR (500 MHz, DMSO-d6) δ 8.39 (s, 2H), 7.36 (d, 4H, J = 8.5 Hz),
6.87 (d, 4H, J = 8.0 Hz), 3.71(s, 6H); 13C NMR (125 MHz, DMSO-d6)
δ 154.6, 153.2, 133.1, 120.1, 114.2, 55.3. HRMS (ESI) exact mass
calcd for (C15H16N2O3Na)+ requires m/z 295.1059, found m/z
295.1045.
1,3-Bis(3-fluorophenyl)urea (2l): White solid; yield 88%, m.p.
197.1–197.4 °C; IR (KBr, cm−1): 3314, 3277, 3065, 1649, 1597, 1541,
1
1485, 1442, 1312, 1270, 1178, 1135, 1046, 940, 864, 762; H NMR
(500 MHz, DMSO-d6) δ 9.00 (s, 2H), 7.53(dt, 2H, J = 11.5, 2.0 Hz),
7.32 (dd, 2H, J = 15.0, 8.0 Hz), 7.16 (dd, 2H, J = 8.0, 1.5 Hz), 6.81
(td, 2H, J = 8.5, 2.5 Hz); 13C NMR (125 MHz, DMSO-d6) δ 162.6
(d, 1JFC = 240.0 Hz), 152.5, 141.5 (d, 3JFC = 11.3 Hz), 130.5 (d, 3JFC
=
8.8 Hz), 114.3 (d, 4J FC = 2.5 Hz), 118.5 (d, 2J FC = 21.3 Hz), 105.3 (d,
2J = 26.3 Hz); HRMS (ESI) exact mass calcd for (C13H11F2N2O)+
FC
requires m/z 249.0839, found m/z 249.0816.
1,3-Bis(4-fluorophenyl)urea (2m): White solid; yield 94%, m.p.
268.3–269.1 °C; IR (KBr, cm−1): 3267, 3151, 1625, 1606, 1562, 1503,
1
1409, 1296, 1205, 1152, 1088, 829, 789, 729; H NMR (500 MHz,
DMSO-d6) δ 8.73 (s, 2H), 7.52 (dd, 4H, J = 9.0, 5.0 Hz), 7.13 (t, 4H,
J = 9.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 157.6 (d, 1JFC = 236.3
Hz), 153.0, 136.3 (d, 4JFC = 2.25 Hz), 120.3 (d, 3JFC = 7.5 Hz), 115.4
(d, 2JFC = 22.3 Hz); HRMS (ESI) exact mass calcd for (C13H11F2N2O)+
requires m/z 249.0839, found m/z 249.0816.
1,3-Bis(2-isopropylphenyl)urea (2n): White solid; yield 97%, m.p.
229.5–229.6 °C; IR (KBr, cm−1): 3317, 3046, 2933, 2835, 1643, 1605,
1542, 1501, 1418, 1300, 1227, 1049, 863, 725; 1H NMR (500 MHz,
DMSO-d6) δ 8.19 (s, 2H), 7.62 (dd, 2H, J = 8.0, 1.5 Hz), 7.28 (dd, 2H,
J = 7.5, 1.5 Hz), 7.13 (dd, 2H, J = 7.5, 1.5 Hz), 7.07 (dd, 2H, J = 7.5,
1.0 Hz), 3.20 (hept, 2H, J = 6.5 Hz), 1.21 (d, 12H, J = 6.5 Hz);
13C NMR (125 MHz, DMSO-d6) δ 154.2, 139.9, 135.9, 125.8, 125.4,
124.2,124.1,27.0,23.3.HRMS(ESI)exactmasscalcdfor(C19H25N2O)+
requires m/z 297.1967, found m/z 297.1957.
1,3-Bis(4-isopropylphenyl)urea (2o): White solid; yield 90%, m.p.
237.9–238.6 °C; IR (KBr, cm−1): 3267, 3080, 2930, 2831, 1641, 1591,
1547, 1506, 1415, 1302, 1234, 1049, 833, 785; 1H NMR (500 MHz,
DMSO-d6) δ 8.54 (s, 2H), 7.40 (d, 4H, J = 8.0 Hz), 7.14 (d, 4H, J =
8.5 Hz), 2.82 (hept, 2H, J = 7.0Hz), 1.19 (d, 12H, J = 7.0 Hz); 13C
NMR (125 MHz, DMSO-d6) δ 152.8, 141.9, 137.7, 126.6, 118.5, 33.0,
24.2. HRMS (ESI) exact mass calcd for (C19H25N2O)+ requires m/z
297.1967, found m/z 297.1959.
1,3-Bis(2-bromophenyl)urea (2p): White solid; yield 82%, m.p.
232.2–232.8 °C (lit.2 229–232 °C); IR (KBr, cm−1): 3319, 3059, 1644,
1581, 1534, 1475, 1434, 1280, 1224, 1027, 748, 732; 1H NMR
(500 MHz, DMSO-d6) δ 8.91 (s, 2H), 7.97 (d, 2H, J = 8.0 Hz), 7.63
(d, 2H, J = 8.0 Hz), 7.35 (t, 2H, J = 7.5 Hz), 7.01 (t, 2H, J = 7.5 Hz);
13C NMR (125 MHz, DMSO-d6) δ 152.6, 137.1, 132.7, 128.1, 124.8,
123.8, 114.3. HRMS (ESI) exact mass calcd for (C13H11Br2N2O)+
requires m/z 368.9238, found m/z 368.9232.
1,3-Bis(3-bromophenyl)urea (2q): Light yellow solid; yield 84%,
m.p. 275.5–276.4 °C; IR (KBr, cm−1): 3279, 3059, 1631, 1572, 1539,
1475, 1396, 1284, 1224, 1064, 873, 851, 785, 682; 1H NMR
(500 MHz, DMSO-d6) δ 8.95 (s, 2H), 7.89 (s, 2H), 7.34 (d, 2H, J =
8.5 Hz), 7.23 (t, 2H, J = 8.0 Hz), 7.15 (d, 2H, J = 7.5 Hz); 13C NMR
(125 MHz, DMSO-d6) δ 152.4, 141.3, 130.8, 124.8, 121.9, 120.9,
117.4. HRMS (ESI) exact mass calcd for (C13H11Br2N2O)+ requires
m/z 368.9238, found m/z 368.9231.
1,3-Bis(3,4-dichlorophenyl)urea (4g): White solid; yield 84%, m.p.
271.0–271.9 °C; IR (KBr, cm−1): 3324, 3086, 1670, 1607, 1577, 1544,
1471, 1390, 1290, 1026, 884, 854, 808; 1H NMR (500 MHz, DMSO-
d6) δ 9.10 (s, 2H), 7.87(s, 2H), 7.50 (d, 2H, J = 9.5 Hz), 7.35 (d, 2H,
J = 9.0 Hz); 13C NMR (125 MHz, DMSO-d6) δ 152.2, 139.7, 131.2,
130.7, 123.7, 119.8, 118.7. HRMS (ESI) exact mass calcd for
(C13H935Cl337ClN2O)+ requires m/z 350.9440, found m/z 350.9419.
1,3-Bis(3-chloro-4-fluorophenyl)urea (4h): White solid; yield 82%,
m.p. 237.1–237.6 °C; IR (KBr, cm−1): 3322, 3027, 1649, 1600, 1554,
1494, 1402, 1217, 1053, 868, 825, 755; 1H NMR (500 MHz, DMSO-
d6) δ 8.95 (s, 2H), 7.80–7.78 (m, 2H), 7.36–7.30 (m, 4H); 13C NMR
1,3-Bis(4-bromophenyl)urea (2r): Light yellow solid; yield 83%,
m.p. 283.0–283.3 °C (lit.1 292–293 °C); IR (KBr, cm−1): 3239, 3039,
1
1719, 1687, 1581, 1509, 1431, 1287, 1177, 1024, 742; H NMR
(500 MHz, DMSO-d6) δ 8.89 (s, 2H), 7.45 (d, 8H, J = 9.0 Hz). 13C
NMR (125 MHz, DMSO-d6) δ 152.4, 139.1, 131.7, 120.4, 113.6.
HRMS (ESI) exact mass calcd for (C13H11Br2N2O)+ requires m/z
368.9238, found m/z 368.9232.
(125 MHz, DMSO-d6) δ 152.7 (1JFC = 240.0 Hz), 152.6, 136.9 (4JFC
=
2.5 Hz), 120.0, 119.3 (2JFC = 17.5 Hz), 118.9 (3JFC = 6.25 Hz), 117.0
(2JFC = 22.5 Hz). HRMS (ESI) exact mass calcd for (C13H9Cl2F2N2O)+
requires m/z 317.0060, found m/z 317.0036.
1,3-Bis(2-nitrophenyl)urea (2s): Light yellow solid; yield 85%,
m.p. 225.4–226.1 °C; IR (KBr, cm−1): 3342, 3049, 1667, 1579, 1515,
1471, 1277, 1227, 899, 801; 1H NMR (500 MHz, DMSO-d6) δ 10.08

JOURNAL OF CHEMICAL RESEARCH 2013 319
References
1,3-Bis(4-methyl-2-nitrophenyl)urea (4i): Light yellow solid; yield
77%, m.p. 234.6–235.0 °C; IR (KBr, cm−1): 3305, 3077, 2933, 2823,
1657, 1575, 1512, 1474, 1337, 1271, 1234, 1153, 1088, 892, 829, 801;
1H NMR (500 MHz, DMSO-d6) δ 9.92 (s, 2H), 7.86 (s, 2H), 7.82
(d, 1H, J = 8.5 Hz), 7.52 (d, 2H, J = 8.5 Hz), 2.35 (s, 6H); 13C NMR
(125 MHz, DMSO-d6) δ 152.2, 139.9, 135.3, 133.6, 130.8, 125.0,
124.1, 20.0. HRMS (ESI) exact mass calcd for (C15H14N4O5Na)+
requires m/z 353.0862, found m/z 353.0854.
1,3-Bis(4-methoxy-2-nitrophenyl)urea (4j): Light yellow solid;
yield 75%, m.p.229.3–229.8 °C; IR (KBr, cm−1): 3307, 3112, 2958,
2849, 1650, 1578, 1503, 1479, 1350, 1268, 1209, 1027, 836, 801, 751;
1H NMR (500 MHz, DMSO-d6) δ 9.71 (s, 2H), 7.83 (d, 2H, J =
9.0 Hz), 7.53 (d, 2H, J = 2.5 Hz), 7.33 (dd, 2H, J = 9.0, 3.0Hz), 3.84
(s, 6H); 13C NMR (125 MHz, DMSO-d6) δ 155.0, 152.6, 141.0, 126.4,
126.2, 121.6, 121.5, 108.9, 108.8, 56.1. HRMS (ESI) exact mass calcd
for (C15H14N4O7Na)+ requires m/z 385.0760, found m/z 385.0734.
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Received 6 January 2013; accepted 1 March 2013
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