Cu(acac)2-catalyzed N-arylations of phenylurea with aryl boronic acid

Article abstract of DOI:10.1080/00397911.2010.543747

Cu(acac)₂ activates aryl boronic acids for the reaction with NH₂-phenylurea without additional ligand and heating. The procedure is simple, general, ligand-free, milder than the palladium-catalyzed arylation, and avoids the use of toxic phosphine ligands. Copyright Taylor & Francis Group, LLC.

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Cu(acac)2-Catalyzed N-Arylations of
Phenylurea with Aryl Boronic Acid
Sandip Gavade a , Ravi Balaskar a , Madhav Mane a , Pramod N.
Pabrekar b & Dhananjay Mane a
a P.G. Department of Chemistry and Research Center, S.C.S. College,
Omerga, India
b V.G. Vaze College, Mulund (E), Mumbai, India
Accepted author version posted online: 17 Nov 2011. Version of
record first published: 03 Feb 2012
To cite this article: Sandip Gavade, Ravi Balaskar, Madhav Mane, Pramod N. Pabrekar & Dhananjay
Mane (2012): Cu(acac)2-Catalyzed N-Arylations of Phenylurea with Aryl Boronic Acid, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:11, 1704-1714
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Synthetic Communications1, 42: 1704–1714, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.543747
Cu(acac)2-CATALYZED N-ARYLATIONS OF
PHENYLUREA WITH ARYL BORONIC ACID
Sandip Gavade,1 Ravi Balaskar,1 Madhav Mane,1
Pramod N. Pabrekar,2 and Dhananjay Mane1
1P.G. Department of Chemistry and Research Center,
S.C.S. College, Omerga, India
2V.G. Vaze College, Mulund (E), Mumbai, India
GRAPHICAL ABSTRACT
Abstract Cu(acac)2 activates aryl boronic acids for the reaction with NH2-phenylurea with-
out additional ligand and heating. The procedure is simple, general, ligand-free, milder than
the palladium-catalyzed arylation, and avoids the use of toxic phosphine ligands.
Keywords Aryl boronic acid; copper catalyzed; ligand free; phenylurea
INTRODUCTION
Transition–metal–catalyzed cross coupling of aryl halides and amines provides
an invaluable entry toward the synthesis of a wide range of compounds, including
pharmaceuticals and natural products. The copper-catalyzed variant has emerged
as an important alternative that is promising for large-scale industrial applications
because of lower catalyst cost and toxicity.[1] N,N0-Diarylureas are valuable subunits
for organic synthesis and have found numerous applications as drugs,[2] pesticides,[2]
selective anion-binding receptors,[3] and polymer materials.[4] One of the most
common synthetic protocols for their preparation is the copper-catalyzed Ullmann
reaction[5] and the related Goldberg reaction (copper-catalyzed N-arylation of
amides).[6] Some ligand-free Ullmann-type coupling reactions have also been
reported.[7–11] The palladium-catalyzed reactions are very sensitive to functional
groups such as –OH, –NH2, and exogenous air or moisture and also very expensive
compared to the copper reagent.[12] Kotecki et al. have reported the
palladium-catalyzed amidation of urea with different aryl halides, and Bippyphos
was found to be a suitable ligand for these coupling reactions. However, this method
suffers from the following disadvantages: (1) the use of toxic phosphine ligands, and
Received October 8, 2010.
Address correspondence to Dhananjay Mane, P. G. Department of Chemistry and Research
Center, S.C.S. College, Omerga 413 606, India. E-mail: dr_dvmane@rediffmail.com
1704

N-ARYLATIONS OF PHENYLUREA
1705
Figure 1. Cu=ligand-free catalyzed N-arylation of phenyl-urea and phenylboronic acid in NMP.
Figure 2. Cu(acac)2-catalyzed N-arylation of ureas (1) with aryl boronic acids (2a–r).
(2) the expensive palladium catalyst.[13] Sergeer et al. have reported that the
electron-poor ligand 3,5-(CF3) 2-xantphos is more effective than xantphos, requires
lower catalyst loading, and gives better yields of products than xantphos.[1] An
attempt by the same group for the arylation of urea using a copper catalyst was
unsuccessful.[14]
Recently, Nandakumar[15] and Hosseinzadeh[16] et al. reported a copper
catalyst and Kotecki et al.[13] and Artamkina et al.[17] reported a palladium catalyst
system for the amidation of aryl halides with urea. Chan et al. and Lam et al.[18] also
reported the preparation of C-N bonds via Cu-mediated coupling of amines with
arylboronic acids under milder conditions, where arylboronic acids are used as
arylating agents instead of aryl halides (Figure 1).[19] Xia and Taillefer reported a
Cu(acac)2 as a catalyst for amination of aryl halide.[20] Herein, we report the use
of Cu(acac)2-catalyzed N-arylation of N-phenylurea with aryl boronic acid using t-
BuOK as a suitable base (Figure 2). The present methodology is simple, mild, and
clean and works efficiently without additional ligand and heating.
RESULTS AND DISCUSSION
Optimization experiments involved phenylboronic acid (1) and phenylurea (2a)
as test substrates and focused on determining the effect of the copper salt, the base,
and the amount of boronic acid. Table 1 shows the influence of various copper salts
on this transformation. Both copper(I) and copper(II) salts were catalytically active
in the coupling reaction even at room temperature. Among the tested copper salts,
Cu(acac)2 was found to be the best catalyst, leading to 85% yield of 3a within 24 h
at room temperature (Table 1, entry 9). CuI and Cu(OAc)2 afforded the N-arylated
product[21] in moderate yields (Table 1, entries 1 and 8). However, the employment
of CuSO4, CuO, Cu2O, CuBr2, CuBr, and CuCl resulted in lesser yields (Table 1,
entries 2–7). Increasing the catalyst amount had only a minor effect on the product
yield, and smaller quantities led to longer reaction times and incomplete conversions.
The reactions using t-BuOK as the base gave the desired product in good yields

1706
S. GAVADE ET AL.
Table 1. Cu=ligand-free catalyzed N-arylation of phenyl-urea and phenylboronic acid in NMPa
Entry
Copper salt (10 mol%)
Base
Yieldb (%)
1
2
CuI
CuSO4
CuO
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
K2CO3
K3PO4
DBU
45
22
16
30
20
27
25
65
85
0
3
4
Cu2O
CuBr2
5
6
CuBr
CuCl
7
8
Cu(OAc)2
Cu(acac)2
No catalyst
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2
9
10
11
12
13
14
30
60
10
15
TEA
aCondition: phenylurea 1 (1 equiv), phenylboronic acid 2a (1.5 equiv), t-BuOK (1.5 equiv), Cu salt (0.1
equiv), 0.3 M NMP, rt, 24 h.
bIsolated yields; acac: acetyl acetonate.
(Table 1, entry 9), while K2CO3, K3PO4, 1,8-diazabicyclo[5.4.0] and dec-7-ene
(DBU), or triethylancine (TEA) as the base gave the desired product in poor yields
(Table 1, entries 11–14).
Table 2 shows that the amount of boronic acid was critical to the reaction
outcome. Less than 1.5 equiv of the aryl source drastically reduced the yield of
the N-arylated product. Even with 1 equiv of the copper salt (Table 2, entries 2
and 6) the reaction of equimolar amounts of phenylboronic acid and phenylurea
Table 2. Dependence of the yield of 3a on the amounts of Cu(acac)2
and phenyl boronic acid (2a) used in the N-arylation of phenylurea (1)
Entry
Cu(acac)2 (equiv)
2a (equiv)
Yielda of 3a (%)
1
2
3
4
5
6
7
0.1
1
1
33
42
85
80
45
62
55b
1
0.1
0.1
0.05
1
1.5
2
1.5
1.5
1.5
0.1
aIsolated yield.
bBase (2 eq).

N-ARYLATIONS OF PHENYLUREA
1707
led to only 42% yield. Greater than 1.5 equiv of the base drastically reduced the yield
of the desired product (Table 2, entry 7).
To evaluate the substrate scope of this new approach toward N-arylated
phenylurea, we investigated cross couplings of various commercially available aryl
boronic acids and phenylurea. In all cases, the optimized condition described
previously proved to be applicable. Reaction of the bulky aryl 1-naphthyl boronic
acid with phenyl urea gave N-(1-naphthyl)-N0-phenylurea in excellent yield
(Table 3, entry 2). Good to excellent results were achieved with para-substituted
boronic acids (Table 3, entries 3–6), irrespective of the electronic nature of the sub-
stituent of the boronic acid. Ortho-substituted boronic acids gave good yields
(Table 3, entries 7 and 8). In the case of meta-substituted boronic acids, excellent
results were achieved with CF3 and Me (Table 3, entries 10 and 11) but Cl and Br
gave poor yields (Table 3, entries 9 and 12). Reaction of heteroaryl boronic acid
2-pyridineboronic acid and 3-pyridineboronic acid gave moderate yield (Table 3,
entries 13 and 14). The lower yields in most couplings of ortho-substituted aryl boro-
nic acids indicated the importance of steric effects. The product was characterized on
Table 3. Cu(acac)2-catalyzed N-arylation of ureas (1) with aryl boronic acids (2a–r)a
Entry
ArB(OH)2
Ar
R1
P
Yieldc (%)
1
2
2a
2b
2c
2d
2e
2f
C6H5-
1-napthyl-
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
3a
3b
3c
3d
3e
3f
85
82
3
4-Me-C6H4-
4-OMe-C6H4-
4-F-C6H4-
76
70
4
5
90
92
6
4-NO2-C6H4
2-Me-C6H4-
2-OMe-C6H4-
3-Cl-C6H4-
3-CF3-C6H4-
3-Me-C6H4-
3-Br-C6H4-
3-Pyridine
7
2g
2h
2i
3g
3h
3i
65
67
8
9
30
87
10
11
12
13
14
15
16
17
18
2j
3j
2k
2l
3k
3l
78
32
2m
2n
2o
2p
2q
2r
3m
3n
3o
3p
3q
3r
50
4-Pyridine
C6H5-
42
77b
72b
40b
66b
4-Me-C6H4-
4-Cl-C6H4-
4-OMe-C6H4-
H
H
H
aReactions condition: phenylurea 1a (1 equiv), aryl boronic acid 2a–n (1.5 equiv), t-BuOK (1.5 equiv),
Cu(acac)2 (0.1 equiv), 0.3 M NMP, rt, 24 h.
bReaction condition: urea 1o (1 equiv), aryl boronic acid 2o–r (3.0 equiv), t-BuOK (3.0 equiv), Cu(acac)2
(0.2 equiv), 0.3 M NMP, rt, 24 h.
cIsolated yields; products were characterized by 1H NMR and mp. P: Products.

1708
S. GAVADE ET AL.
the basis of its spectral data and by comparison of its melting point with the litera-
ture.[22–27] 2,4,6-Trimethylphenylboronic acid, 3-furanboronic acid, and 3-thiophe-
neboronic acid failed to give the corresponding N-arylated product. The reaction
could also be extended to achieve the coupling of urea with aryl boronic acid such
as phenyl, 4-methyl phenyl, 4-chloro phenyl, and 4-methoxy phenyl boronic acid
(Table 3, entries 15–18).
In conclusion, we reported a novel Cu(acac)2-catalyzed N-arylation of
phenylurea using boronic acids as arylating agents. The cross couplings proceed
under mild reaction conditions at room temperature without additional ligand.
Considering the structural diversity and the huge number of boronic acid derivatives,
we foresee that this new method will find broad application for the synthesis of a
wide variety of phenyl ureas with as-yet-unknown properties.
EXPERIMENTAL
All reagents and solvents were purchased and used without further purification.
1H NMR and 13C NMR spectra were measured on a 300-MHz and 400-MHz Bruker
spectrometer (1H 300 MHz and 400 MHz, 13C 75 MHz and 101 MHz), using
dimethylsulfoxide (DMSO) as the solvent with tetramethylsilane (TMS) as the
internal standard at room temperature. NMR chemical shifts were reported in d
(ppm) using the d 2.54 signal of DMSO (1H NMR) and the d 39.94 signal of DMSO
(13C NMR) as internal standards. High-resolution mass spectra (HRMS) spectra
were recorded on a Jeol JMS-DX300 instrument. Melting points were determined
in a capillary tube and are uncorrected. Thin-layer chromatography (TLC) was car-
ried out on SiO2 (silica gel 60F254, Merck), and the spots were located with ultra-
violet (UV) light. Flash chromatography was carried out on SiO2 (silica gel 60,
Merck, 100 to 200-mesh ASTM). Drying of organic extracts after workup of reac-
tions was performed over anhydrous Na2SO4. Evaporation of solvents was
accomplished with a Buchi rotatory evaporator.
¨
Typical Procedure for N-Arylation of Aryl Ureas
A screw-capped tube was charged with the phenylurea (1.0 mmol), aryl
boronic acid (1.5 mmol), t-BuOK (1.5 mmol), Cu(acac)2 (10 mol%), and anhydrous
N-methyl-2 pyrrolidone (NMP) (3 mL). The vial was degassed with N2, sealed, and
stirred at room temperature for 24 h. After completion, the reaction mixture was
quenched with water (100 mL), extracted with diethyl ether (3 ꢀ 100 mL), and dried
over anhydrous MgSO4. The solvents were removed under vacuum, and the residue
was purified by silica-gel chromatography (hexane–ethyl acetate, 8:2). The identity
and purity of the known products was confirmed by 1H and 13C NMR spectroscopic
analysis, and the new products were fully characterized.
Typical Procedure for N-Arylation of Ureas
A screw-capped tube was charged with the urea (1.0 mmol), aryl boronic acid
(3.0 mmol), t-BuOK (3.0 mmol), Cu(acac)2 (20 mol%), and anhydrous NMP (3 mL).
The vial was degassed with N2, sealed, and stirred at room temperature for 24 h.

N-ARYLATIONS OF PHENYLUREA
1709
After completion, the reaction mixture was quenched with water (100 mL), extracted
with diethyl ether (3 ꢀ 100 mL), and dried over anhydrous MgSO4. The solvents were
removed under vacuum, and the residue was purified by silica-gel chromatography
(hexane–ethyl acetate, 8:2). The identity and purity of the known products was
1
confirmed by H and 13C NMR spectroscopic analysis, and the new products were
fully characterized.
1,3-Diphenylurea (Carbanilide) (3a). White solid in 85% isolated yield; mp
237.5 ꢁC (lit. 238 ꢁC); 1H NMR (400 MHz, DMSO): d ¼ 8.63 (s, 2H), 7.45 (d,
J ¼ 8.6, Hz, 4H), 7.27 (t, J ¼ 7.9 Hz, 4H), 6.96 (t, J ¼ 7.3 Hz, 2H). 13C NMR
(101 MHz, DMSO): d ¼ 151.9, 139.1, 128.2, 121.3, 117.7. HRMS (ESI): m=z [M]þ
calcd. for C13H12N2O: 212.2512; found: 212.2514.
N-(1-Naphthalenyl)-N’-phenyl-urea (3b). White solid in 80% isolated yield;
mp 221–223 ꢁC; 1H NMR (300 MHz, DMSO): d ¼ 9.08 (s, 1H), 8.79 (s, 1H), 8.15 (d,
J ¼ 8.7 Hz, 1H), 8.05 (d, J ¼ 7.6 Hz, 1H), 7.93 (d, J ¼ 7.6 Hz, 1H), 7.45–7.72 (m, 6H),
7.32 (t, J ¼ 7.9 Hz, 2H), 6.96–7.09 (m, 1H). 13C NMR (300 MHz, DMSO): d ¼ 153.38,
140.23, 134.75, 129.31, 128.88, 126.37, 123.37, 122.30, 121.75, 118.57, 117.84. HRMS
(ESI): m=z [M]þ calcd. for C17H14N2O: 262.3178; found: 262.3175.
N-(4-Methylphenyl)-N’-phenyl-urea (3c). White solid in 76% isolated yield;
mp 219–220 ꢁC (lit. 221–222 ꢁC); 1H NMR (400 MHz, DMSO): d ¼ 8.58 (s, 1H), 8.52
(s, 1H), 7.43 (d, J ¼ 8.6 Hz, 2H), 7.32 (d, J ¼ 8.4 Hz, 2H), 7.25 (t, J ¼ 7.9 Hz, 2H), 7.07
(d, J ¼ 8.6 Hz, 2H), 6.94 (t, J ¼ 7.3 Hz, 1H), 2.24 (s, 3H). 13C NMR (101 MHz,
DMSO): d ¼ 151.9, 139.2, 136.5, 130.1, 128.6, 128.2, 121.2, 117.8, 117.6, 20.4. HRMS
(ESI): m=z [M]þ calcd. for C14H14N2O: 226.2825; found: 226.2830.
N-(4-Methoxyphenyl)-N’-phenyl-urea (3d). White solid in 70% isolated
1
yield; mp 195–196 ꢁC (lit. 193–194 ꢁC); H NMR (400 MHz, DMSO): d ¼ 8.54 (s,
1H), 8.43 (s, 1H), 7.42 (d, J ¼ 8.7 Hz, 2H), 7.34 (d, J ¼ 9.1 Hz, 2H), 7.25 (t, J ¼ 7.9 Hz,
2H), 6.93 (t, J ¼ 7.3 Hz, 1H), 6.85 (d, J ¼ 9.1 Hz, 2H), 3.71 (s, 3H). 13C NMR
(101 MHz, DMSO): d ¼ 153.8, 152.1, 139.3, 132.2, 128.2, 121.1, 119.5, 117.6, 113.5,
55.0. HRMS (ESI): m=z [M]þ calcd. for C14H14N2O2: 242.2856; found: 242.2855.
N-(4-Fluorophenyl)-N’-phenyl-urea (3e). White solid in 90% isolated yield;
1
mp 240–242 ꢁC (lit. 241 ꢁC); H NMR (300MHz, DMSO): d ¼ 8.68 (s, 1H), 8.64 (s,
1H), 7.41–7.52 (m, 4H), 7.27 (t, J ¼ 7.9 Hz, 2H), 7.06–7.17 (m, 2H), 6.92-7.01 (m,
1H). 13C NMR (300MHz, DMSO): d ¼ 159.35, 156.2, 153.07, 140.07, 136.45, 129.2,
122.28, 120.46, 118.69, 115.83. HRMS (ESI): m=z [M]þ calcd. for C13H11FN2O:
230.2443; found: 230.2442.
N-(4-Nitrophenyl)-N’-phenyl-urea (3f). Orange solid in 92% isolated yield;
1
mp 210–211 ꢁC (lit. 209 ꢁC); H NMR (400 MHz, DMSO): d ¼ 9.40 (s, 1H), 8.89 (s,
1H), 8.18 (d, J¼ 9.3 Hz, 2H), 7.68 (d, J¼ 9.3 Hz, 2H), 7.47 (d, J¼ 8.6 Hz, 2H), 7.30
(t, J¼ 7.9 Hz, 2H), 7.01 (t, J¼ 7.4 Hz, 1H). 13C NMR (101 MHz, DMSO): d ¼ 151.3,
145.8, 140.4, 138.4, 128.3, 124.6, 122.0, 118.2, 117.0. HRMS (ESI): m=z [M]þ calcd.
for C13H11N3O3: 257.2532; found: 257.2537.

1710
S. GAVADE ET AL.
N-(2-Methylphenyl)-N’-phenyl-urea (3g). White solid in 67% isolated yield;
mp 199–200 ꢁC (lit. 201–203 ꢁC); 1H NMR (400 MHz, DMSO): d ¼ 8.99 (s, 1H), 7.90
(s, 1H), 7.83 (dd, J ¼ 1.1, 8.1 Hz, 1H), 7.45 (dt, J ¼ 1.6, 8.7 Hz, 2H), 7.30 ꢂ 7.24 (m,
2H), 7.18 ꢂ 7.10 (m, J ¼ 7.6, 15.5 Hz, 2H), 6.99 ꢂ 6.90 (m, 2H), 2.24 (s, 3H). 13C
NMR (101 MHz, DMSO): d ¼ 152.0, 139.3, 136.8, 129.6, 128.3, 126.9, 125.6,
122.1, 121.2, 120.5, 117.5, 18.0). HRMS (ESI): m=z [M]þ calcd. for C14H14N2O:
226.2827; found: 226.2831.
N-(2-Methoxyphenyl)-N’-phenyl-urea (3h). White solid in 65% isolated
yield; mp 149–150 ꢁC (lit. 148.2–148.8 ꢁC); 1H NMR (500 MHz, acetone-d6):
d ¼ 8.59 (s, 1H), 8.30 (d, J ¼ 7.7 Hz, 1H), 7.86 (s, 1H), 7.55 (d, J ¼ 8.1 Hz, 2H),
7.27 (t, J ¼ 7.5 Hz, 2H), 6.98–6.90 (m, 4H), 3.87 (s, 3H). HRMS (ESI): m=z [M]þ
calcd. for C14H14N2O2: 242.2856; found: 242.2853.
N-(3-Chlorophenyl)-N’-phenyl-urea (3i). Off-white solid in 30% isolated
1
yield; mp 184–186 ꢁC; H NMR (300 MHz, DMSO): d ¼ 8.87 (s, 1H), 8.72(s, 1H),
7.64–7.77 (m, 1H), 7.44 (d, J ¼ 7.6 Hz, 2H), 7.14–7.33 (m, 4H), 6.93–7.04 (m, 2H).
13C NMR (300 MHz, DMSO): d ¼ 152.8, 141.7, 139.8, 133.6, 130.8, 129.2, 122.5,
121.8, 118.8, 117.9, 117.0. HRMS (ESI): m=z [M]þ calcd. for C13H11ClN2O:
246.7045; found: 246.7047.
N-(3-Trifluoromethylphenyl)-N’-phenyl-urea (3j). White solid in 87% iso-
1
lated yield; mp 203–205 ꢁC; H NMR (300 MHz, DMSO): d ¼ 9.02 (s, 1H), 8.77 (s,
1H), 8.00 (s, 1H), 7.40–7.61 (m, 4H), 7.23–7.37 (m, 3H), 6.92–7.07 (m, 1H). 13C
NMR (300 MHz, DMSO): d ¼ 152.9, 141.0, 139.7, 130.4, 130.1, 129.2, 122.6,
122.2, 118.9, 118.6, 118.5, 114.5. HRMS (ESI): m=z [M]þ calcd. for C14H11F3N2O:
280.2567; found: 280.2562.
N-(3-Methylphenyl)-N’-phenyl-urea (3k). White solid in 78% isolated yield;
mp 174–175 ꢁC; 1H NMR (300 MHz, DMSO): d ¼ 8.62 (s, 1H), 8.56 (s, 1H), 7.44 (d,
J ¼ 7.6 Hz, 1H), 7.11–7.31 (m, 5H), 6.92–7.01 (m, 2H), 6.77 (d, J ¼ 7.6 Hz, 1H), 2.26
(s, 3H). 13C NMR (300 MHz, DMSO): d ¼ 152.9, 140.1, 140.0, 138.4, 129.2, 129.0,
123.0, 122.2, 119.1, 118.5, 115.8, 21.6. HRMS (ESI): m=z [M]þ calcd. for
C14H14N2O: 226.2825; found: 226.2822.
N-(3-Bromophenyl)-N’-phenyl-urea (3l). Off-white solid in 35% isolated
1
yield; mp 171–174 ꢁC; H NMR (300 MHz, DMSO): d ¼ 8.87 (s, 1H), 8.72 (s, 1H),
7.85 (s, 1H), 7.35–7.48 (m, 2H), 7.08–7.31 (m, 5H), 6.74–7.02 (m, 1H). 13C NMR
(300 MHz, DMSO): d ¼ 152.8, 141.8, 140.1, 131.1, 129.2, 124.7, 122.5, 122.2,
120.8, 118.8, 117.4. HRMS (ESI): m=z [M]þ calcd. for C13H11BrN2O: 291.1512;
found: 291.1516.
N-(3-Pyridinyl)-N’-phenyl-urea (3m). White solid in 50% isolated yield; mp
164–166 ꢁC (lit. 164 ꢁC); 1H NMR (400 MHz, DMSO): d ¼ 8.83 (s, 1H), 8.79 (s, 1H),
8.18 (d, J ¼ 3.5 Hz, 1H), 7.93 (ddd, J ¼ 1.5, 2.5, 8.3 Hz, 1H), 7.41–7.49 (m, 3H),
7.24–7.34 (m, 3H), 6.98 (t, J ¼ 7.3 Hz, 1H). 13C NMR (101 MHz, DMSO):
d ¼ 151.9, 142.2, 139.5, 138.8, 135.9, 128.3, 124.6, 123.1, 121.6, 117.9. HRMS
(ESI): m=z [M]þ calcd. for C12H11N3O: 213.2415; found: 213.2416.

N-ARYLATIONS OF PHENYLUREA
1711
N-(4-Pyridinyl)-N’-phenyl-urea (3n). White solid in 42% isolated yield; mp
1
181-183 ꢁC (lit. 184 ꢁC); H NMR (300 MHz, DMSO): d ¼ 9.15 (s, 1H), 8.89 (s,
1H), 8.36 (d, J ¼ 5.5, 2H), 7.39–7.48 (m, 4H), 7.27–7.33 (m, 2H), 6.99–7.05 (m,
1H). 13C NMR (300 MHz, DMSO): d ¼ 151.5, 149.5, 145.9, 138.5, 128.3, 121.9,
118.1, 111.8. HRMS (ESI): m=z [M]þ calcd. for C12H11N3O: 213.2415; found:
213.2418.
1,3-Diphenylurea (carbanilide) (3o). White solid in 85% isolated yield; mp
237.0 ꢁC (lit. 238 ꢁC); 1H NMR (400 MHz, DMSO): d ¼ 8.65 (s, 2H), 7.47 (d,
J ¼ 8.6, Hz, 4H), 7.30 (t, J ¼ 7.9 Hz, 4H), 6.96 (t, J ¼ 7.3 Hz, 2H). 13C NMR
(101 MHz, DMSO): d ¼ 152.1, 139.4, 128.2, 121.5, 117.8. HRMS (ESI): m=z [M]þ
calcd. for C13H12N2O: 212.2512; found: 212.2515.
1,3-Bis(4-methylphenyl)urea (3p). White solid in 72% isolated yield; mp
1
267–268 ꢁC (lit. 267–268 ꢁC); H NMR (300 MHz, DMSO): d ¼ 8.49 (s, 2H), 7.31
(d, J ¼ 8.4, 4H), 7.07(d, J ¼ 8.2, 4H), 2.23(s, 6H). 13C NMR (300 MHz, DMSO):
d ¼ 153.07, 137.68, 130.94, 129.60, 118.66, 20.79. HRMS (ESI): m=z [M]þ calcd.
for C15H16N2O: 240.3115; found: 240.3118.
1,3-Bis(4-chlorophenyl)urea (3q). White solid in 40% isolated yield; mp
1
304–305 ꢁC (lit. 303–305 ꢁC); H NMR (300 MHz, DMSO): d ¼ 8.84 (s, 2H), 7.48
(d, J ¼ 8.8, 4H), 7.32(d, J ¼ 8.8, 4H). 13C NMR (101 MHz, DMSO): d ¼ 152.80,
139.00, 129.08, 125.97, 120.29. HRMS (ESI): m=z [M]þ calcd. for C13H10Cl2N2O:
281.1421; found: 281.1423.
1,3-Bis(4-methoxyphenyl)urea (3r). White solid in 66% isolated yield; mp
239–240 ꢁC (lit. 240–241 ꢁC); 1H NMR (300 MHz, DMSO): d ¼ 8.36 (s, 2H), 7.34 (d,
J ¼ 9.0, 4H), 6.85 (d, J ¼ 9.0, 4H), 3.71 (s, 6H). 13C NMR (101 MHz, DMSO):
d ¼ 154.81, 153.42, 133.40, 120.39, 114.42, 55.61. HRMS (ESI): m=z [M]þ calcd. for
C15H16N2O3: 272.3117; found: 272.3115.
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