Catalytic oxidative carbonylation of arylamines to ureas with W(CO) 6/I2 as catalyst

Article abstract of DOI:10.1002/ejoc.201100657

The oxidative carbonylation of aniline to N,N'-diphenylurea was carried out by using W(CO)₆ as the catalyst, I₂ as the oxidant, CO as the carbonyl source and 4-(dimethylamino)pyridine (DMAP) as base. The reaction conditions were optimized with respect to different bases, molar ratio of DMAP/iodine, temperature, time, and CO pressure. Various p-substituted arylamines can be converted into the respective symmetrical and unsymmetrical N,N'-disubstituted ureas in moderate to good yields. The reaction demonstrated broad tolerance of functionality.

Full text of DOI:10.1002/ejoc.201100657

FULL PAPER
DOI: 10.1002/ejoc.201100657
Catalytic Oxidative Carbonylation of Arylamines to Ureas with W(CO)6/I2 as
Catalyst
Li Zhang,[a,b] Ampofo K. Darko,[a] Jennifer I. Johns,[a] and Lisa McElwee-White*[a]
Keywords: Amines / Amides / Carbonylation / Iodine / Tungsten
The oxidative carbonylation of aniline to N,NЈ-diphenylurea
was carried out by using W(CO)6 as the catalyst, I2 as the
oxidant, CO as the carbonyl source and 4-(dimethylamino)-
pyridine (DMAP) as base. The reaction conditions were opti-
mized with respect to different bases, molar ratio of DMAP/
iodine, temperature, time, and CO pressure. Various p-sub-
stituted arylamines can be converted into the respective sym-
metrical and unsymmetrical N,NЈ-disubstituted ureas in
moderate to good yields. The reaction demonstrated broad
tolerance of functionality.
Introduction
base.[39] Herein, we report conditions for the W(CO)6/I2-
catalyzed oxidative carbonylation of aniline (Scheme 1,
Table 1) and other p-substituted arylamines (Scheme 2,
Table 2) to their respective aromatic ureas. In addition, we
N,NЈ-Disubstituted ureas have numerous applications in
areas such as pharmaceuticals,[1,2] pesticides,[3,4] and
dyes.[5,6] Traditional synthetic routes for the synthesis of
ureas involve the use of phosgene or phosgene derivatives.
However, phosgene poses handling issues due to its toxicity,
while its derivatives produce undesirable byproducts.[7] In
light of these problems, developing a less hazardous syn-
thetic route to ureas has attracted considerable interest over
the years.[7–11] Transition-metal catalysts have shown prom-
ise, because their use offers an alternative route to the syn-
thesis of ureas from amines.[8,12] Reaction conditions typi-
cally involve amines, an oxidant, and CO as the carbonyl
source. Catalysts that include Pd,[13–24] Ni,[25] Co,[26,27]
Ru,[28–30] and Au[31–33] have been employed for the oxidative
carbonylation of amines to ureas. Other conditions beside
standard homogeneous catalysis have also been employed.
For example, Pd(OAc)2 in ionic liquids[34] afforded good to
high yields of ureas from aryl- and alkylamines, as well as
carbamates from amino alcohols. Immobilized palladium
Scheme 1. Oxidative carbonylation of aniline to N,NЈ-diphenylurea.
Table 1. Optimization of the reaction conditions for the W(CO)6/
I2-catalyzed carbonylation of aniline to N,NЈ-diphenylurea.
Entry
Base
Temp. Time
CO
[atm]
I2/base[a]
[equiv.]
Yield
[°C]
[h]
[%][b,c]
1
2
3
4
5
6
7
8
9
10
11
12
13
DBU
pyridine
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
40
40
40
40
40
40
25
60
80
40
40
40
40
20
20
20
20
20
20
20
20
20
4
80
80
80
80
80
80
80
80
80
80
80
40
60
1:2
1:2
1:2
1:1
1:3
0.5:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
trace
trace
81
52
59
79
60
78
72
39
85
34
61
nanoparticles,[9] and silica-gel-confined [Pd(PPh3)2Cl2][35]
have also been utilized. An NiI/[Ru(CO)3I3]NBu4
[28]
cata-
lyst system showed excellent reactivity for the selective for-
mation of N,NЈ-diphenylurea from the oxidative carbon-
ylation of aniline.
We have previously reported the use of W(CO)6 in the
oxidative carbonylation of various aliphatic primary and
secondary diamines.[36–38] However, early experiments sug-
gested that arylamines would not be substrates for this reac-
tion, because the oxidative carbonylation of aniline to N,NЈ-
diphenylurea was unsuccessful when K2CO3 was used as
8
8
20
[a] Based on 1 equiv. of aniline. [b] Isolated yield of diphenylurea
calculated per equivalent of aniline (values are Ϯ5%). [c] Reaction
conditions: aniline (5.0 mmol), W(CO)6 (0.15 mmol), CH2Cl2
(40 mL).
[a] Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200, USA
Fax: +1-352-392-8768
E-mail: lmwhite@chem.ufl.edu
[b] College of Environmental Science and Engineering, Tongji
University,
Scheme 2. Oxidative carbonylation of p-substituted arylamines to
symmetrical N,NЈ-diaryl ureas.
1239 Siping Rd, Shanghai 200092, P. R. of China
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L. McElwee-White et al.
FULL PAPER
Table 2. Oxidative carbonylation of various arylamines to symmet- Optimization of Reaction Conditions for the Oxidative
rical N,NЈ-diaryl ureas by using the W(CO)6/I2 catalyst system.
Carbonylation of Aniline to N,NЈ-Diphenylurea
Initial experiments involved the carbonylation of aniline
(0.46 g, 5 mmol) in the presence of 3mmol-% of W(CO)6,
1.0 equiv. of I2, and 2.0 equiv. of base in 40 mL of CH2Cl2
with 80 atm of CO, stirred at 40 °C for 20 h (Table 1). Use
of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or pyridine as
the base only produced trace amounts of the desired prod-
uct (Table 1, Entries 1 and 2). Alternatively, the use of 4-
(dimethylamino)pyridine (DMAP) as the base dramatically
increased the yield to 81% (Table 1, Entry 3). Lowering of
the amount of DMAP to 1 equiv. resulted in a reduced iso-
lated yield of 52% and unreacted starting material (Table 1,
Entry 4); increasing of the amount of DMAP to 3 equiv.
produced a similar yield (59%, Table 1, Entry 5). According
to these experiments, 2.0 equiv. of DMAP was chosen for
further optimization studies.
Having established DMAP as the preferred base, the
quantity of iodine was optimized. Lowering of the amount
of the oxidant to 0.5 equiv. resulted in the formation of the
desired product in 79% yield (Table 1, Entry 6). The highest
activity was obtained when the molar ratio of I2/DMAP
was 1:2. The temperature was then varied from 25 °C to
80 °C (Table 1, Entries 7–9). When temperatures below
40 °C were used, only 60% yields were obtained. The yield
improved when the temperature was increased to 60 °C, but
decreased slightly at 80 °C. Further increases in the tem-
perature caused the yields to decrease, most likely either due
to catalyst degradation and subsequent byproduct forma-
tion or because of partial decomposition of the urea prod-
uct in the complex reaction mixtures.
The carbonylation yields were also determined as a func-
tion of time (Table 1, Entries 10 and 11). At 40 °C and 4 h,
the yield of N,NЈ-diphenylurea decreased significantly to
39%, whereas at 8 h the urea yield was 85%, which was an
improvement upon previous trials at 20 h. Therefore, the
optimal time for the carbonylation was determined to be
8 h.
The CO pressure was found to be critical to the yield of
urea in this reaction (Table 1, Entries 11 and 12). As the
CO pressure was decreased from 80 to 40 atm, the yields
were markedly reduced from 85 to 34%. At 60 atm of CO,
the urea was obtained in moderate yield (Table 1, Entry 13).
[a] Isolated yield based on arylamine (values are Ϯ5%). [b] Rea-
gents and conditions: arylamine (5.0 mmol), W(CO)6 (0.15 mmol),
Therefore, the optimal conditions for the carbonylation re-
action were determined to be 40 °C, 80 atm of CO, 1 equiv.
of I2, 2 equiv. of DMAP, and CH2Cl2 as the solvent. Se-
lected primary arylamines were then converted into their
corresponding N,NЈ-disubstituted ureas under these condi-
tions.
I2 (5.0 mmol), DMAP (10.0 mmol), CH2Cl2 (40 mL), CO (80 atm),
40 °C, 8 h.
found that, in certain cases, arylamines could be carbonyl-
ated to unsymmetrical ureas by using W(CO)6 as precata-
lyst and I2 as the oxidizing agent.
Results and Discussion
Oxidative Carbonylation of p-Substituted Arylamines to
Symmetrical Diarylureas
Initially, carbonylation-reaction conditions for the con-
version of aniline into N,NЈ-diphenylurea were screened.
Variables such as temperature, solvent, CO pressure, and
To explore the scope of the reaction for the possible ap-
equivalents of base were examined; the results are presented plication in organic synthesis, a study of functional-group
in Table 1.
6262
tolerance was undertaken. Various substituted arylamines
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Oxidative Carbonylation of Arylamines to Ureas
Scheme 3. Attempted carbonylation of 1o.
(Scheme 2) were treated with CO and converted into sym- iododeboronation has been observed in the reaction of alk-
metrical N,NЈ-diarylureas under the optimized carbon- enylboranes in the presence of I2 and sodium hydroxide in
ylation conditions (Table 2).
ethereal solvents.[40,41]
The effect of halogen substituents was evaluated first.
The yield of urea 2b from 4-chloroaniline (1b) was good
(66%). Bromo- (1c) and iodo-substituted (1d) anilines af-
forded their respective N,NЈ-disubstituted ureas in nearly
identical yields (Table 2, Entries 3 and 4). In contrast to the
halogenated anilines, substitution with the electron-donat-
Oxidative Carbonylation of Arylamines to Unsymmetrical
Diarylureas
The catalyzed carbonylation of arylamines with various
ing methoxy group (1e) resulted in a significant decrease in functional groups to give symmetrical ureas suggested the
the yield of urea 2e (38%, Table 2, Entry 5); however, other possibility that unsymmetrical ureas might also be synthe-
donating groups gave good yields (Table 2, Entries 6 and sized under the same reaction conditions (Table 3).
7). The phenoxyaniline 1f and thioether 1g produced their
To explore the feasibility of using arylamines with elec-
corresponding ureas in 82 and 72% yields, respectively. The tron-withdrawing groups to produce unsymmetrical ureas,
electron-poor p-nitroaniline 1h was successfully carbony- compounds 1h (p-NO2) and 1i (p-CN) were subjected to the
lated to its urea 2h in 84% yield. This trend of higher yields same reaction conditions. This reaction provided the de-
with electron-withdrawing substituents was followed by sired unsymmetrical urea 3hi as the major product in 58%
ethyl 4-aminobenzoate (1j) (83%). An exception was 4-ami- yield (Table 3, Entry 1), without formation of the symmetri-
nobenzonitrile (1i), which afforded just 48% of the urea cal ureas 2h and 2i in the product mixture. When 1h was
(Table 2, Entry 9), despite its electron-withdrawing cyano paired with 1j (p-CO2Et), the unsymmetrical urea 3hj was
substituent. However, the ability of the nitrile moiety to only slightly favored over symmetrical urea 2j (Table 3, En-
serve as ligand for the catalyst may be affecting the yield. try 2). The equimolar pair of arylamines 1b (R1 = Cl) and
In prior studies on p-substituted benzylamines,[39] amines 1e (R2 = OCH3) featured an electron-withdrawing and an
with coordinating substituents such as carboxylates gave electron-donating substituent; with these starting materials,
poor yields under the original reaction conditions.
the desired unsymmetrical urea 3be was obtained in low
In addition, we investigated the aromatic amine 1k under yield (12%, Table 3, Entry 3). The symmetrical products,
the carbonylation conditions and found that the cyclic urea 1,3-bis(4-chlorophenyl)urea (2b) and 1,3-bis(4-methoxy-
3,4-dihydro-2-quinazolinone 2k formed in 41% yield. This phenyl)urea (2e), were formed as the major products in the
result was an improvement over the original reaction condi- mixture and were obtained in yields of 19% and 24%,
tions with K2CO3 as base.[39] Further functional-group respectively. Although the yield of unsymmetrical urea 3be
studies included 4-aminostyrene, 4-aminobenzyl alcohol, was low, the yield of symmetrical urea from electron-rich
and 4-aminobenzoic acid (1l–n). Unfortunately, none of 1e was also relatively low, and it is possible that 1e is simply
the corresponding ureas could be detected in the reaction moderately unreactive. However, the presence of the unsym-
mixtures (Table 2, entries 12–14). These results are also con- metrical urea suggests that manipulation of the reaction
sistent with the previous study on substituted benzylamines, conditions could tip the product mixture in its favor. When
in which the same substituents also resulted in lower yields the ratio was 1:2 in favor of 1e, however, the symmetrical
of the dibenzylureas.
urea 2e was formed exclusively in 36% yield (Table 3, En-
Boronic esters were also tested for compatibility under try 4). Use of more of the p-chloroaniline (1b) (2:1; Table 3,
the carbonylation conditions. Attempted catalytic carbon- Entry 5) resulted in 43% yield of the unsymmetrical urea
ylation of (4-aminophenyl)boronic ester (1o) did not result 3be and 11% of 2b (Table 3, Entry 5). A large excess of 1b
in the formation of the expected urea, but rather p-iodoan- resulted in the formation of its respective symmetrical urea
iline (1c) was formed (Scheme 3). Control experiments re- 2b, and a low yield of the unsymmetrical urea (Table 3, En-
vealed that the p-iodoaniline (1c) was also formed from 1o try 6). Compound 3be is of interest, because it represents a
at room temperature in the absence of CO and W(CO)6 substructure of the anticancer drug sorafenib.[42] When the
catalyst. This observation is not unprecedented, because less electron-rich 4-phenoxyaniline (1f) was used in place of
Eur. J. Org. Chem. 2011, 6261–6268
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L. McElwee-White et al.
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Table 3. Oxidative carbonylation of arylamines to give unsymmetrical ureas.
[a] Isolated yield based on arylamine (values are Ϯ5%). [b] Reagents and conditions: arylamines (1.0 mmol + 1.0 mmol), W(CO)6
(0.06 mmol), I2 (2.0 mmol), DMAP (4.0 mmol), CH2Cl2 (40 mL), 40 °C, CO (80 atm), 20 h. [c] Yield determined by NMR analysis.
the methoxy compound 1e in a reaction with p-chloro-
To probe whether the reaction proceeds through an iso-
aniline (1b) the unsymmetrical urea 3bf was obtained as the cyanate intermediate, the secondary amine N-methylaniline
major product (41%, Table 3, Entry 8). Symmetrical urea (1q), which cannot form an isocyanate, was subjected to the
2f was obtained in 23% yield, whereas 2b was present in carbonylation conditions.[37] After 20 h under 80 atm of CO
small quantities (4%).
at 40 °C, formation of urea 2q was not observed in the
Because the electron-poor aniline 1h gave the highest product mixture. Most of the starting material was reco-
yields of unsymmetrical ureas (3hi and 3hj), we investigated vered, along with trace quantities of p-iodo-N-methylani-
adding the CF3 group that is present in the diarylamine line (1r), which formed as a result of the electrophilic aro-
moiety of sorafenib (Figure 1). Coupling of 4-chloro-3-(tri- matic substitution of N-methylaniline with elemental iodine
fluoromethyl)aniline (1p) with anisidine (1e) by using a 2:1 (Scheme 4). The lack of urea in the product mixture is con-
ratio of 1p/1e produced a mixture of products (Table 3, En- sistent with the intermediacy of an isocyanate in the reac-
try 7). The symmetrical urea 2e was formed as the major tion pathway.
product (24% yield), whereas the unsymmetrical urea 3pe
was produced in low yield (12%). Only trace amounts of
symmetrical urea 2p was detected. Although arylamines
with one electron-withdrawing substituent give good yields
of ureas, it is possible that the increased electron deficiency
of the parent aniline 2p renders it insufficiently nucleophilic
for facile urea formation. Urea 3pf is a better model for
sorafenib, and this was obtained in 45% yield from a 5:1
ratio of 1p/1f without competitive formation of 2p (Table 3,
Entry 9). For unsymmetrical urea synthesis using aniline 2p,
an excess of 2p was required to shift the product mixtures
toward the unsymmetrical product.
Scheme 4. Attempted carbonylation of N-methylaniline.
Furthermore, when N-methylaniline (1q) and aniline (1a)
were combined under the optimized conditions, the major
product was the unsymmetrical urea 3aq (31% yield,
Table 4, Entry 1) when excess 1q was used. Diphenylurea
(2a) was detected in only trace amounts. Some aniline was
also recovered due to incomplete conversion. Although the
yield was modest, formation of the unsymmetrical urea is
Figure 1. Structure of sorafenib.
6264
consistent with formation of an isocyanate from the pri-
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Oxidative Carbonylation of Arylamines to Ureas
Table 4. Synthesis of trisubstituted arylureas.
[a] Isolated yield based on arylamine. [b] Reagents and conditions: arylamines (1.0 mmol each, unless otherwise noted), W(CO)6
(0.06 mmol), I2 (2.0 mmol), DMAP (4 mmol), CH2Cl2 (40 mL), 80 °C, CO (80 atm), 20 h. [c] Yield determined by NMR analysis.
N,NЈ-Diphenylurea (2a): Aniline (0.46 g, 5.0 mmol) was added to a
glass-lined 300 mL Parr high-pressure vessel containing W(CO)6
(0.053 g, 0.15 mmol), I2 (1.27 g, 5.00 mmol), and DMAP (1.22 g,
10.0 mmol) in CH2Cl2 (40 mL). The vessel was charged with CO
(80 atm), and the reaction mixture was stirred at 40 °C for 8 h.
The autoclave was cooled, the excess CO gas was released, and the
reaction mixture was filtered and washed with saturated aq.
Na2SO3. The resulting solution was then dried with MgSO4, fil-
tered, and the excess solvent was removed by evaporation. The
crude residue was purified by flash chromatography on silica gel
with mixtures of ethyl acetate and CH2Cl2 as eluent to recover 2a
in 85% yield (0.45 g). The product was identified by comparison
mary arylamine followed by attack of the more nucleophilic
secondary arylamine. When N-methylaniline was coupled
with 4-phenoxyaniline (1f), competitive formation of the
symmetrical urea 2f was observed because of the increased
nucleophilicity of 1f due to the presence of the phenoxy
substituent (Table 4, Entry 2). In contrast, coupling of an
electron-deficient arylamine (1p) with 1q provided the un-
symmetrical urea 3pq as the only product in 25% yield
(Table 4, Entry 3).
with literature data.[43] IR (neat): ν = 1635 (CO) cm–1. 1H NMR
˜
Conclusions
(300 MHz, [D6]DMSO): δ = 8.60 (s, 2 H, NH), 7.40 (d, J = 8.47 Hz,
2 H, ArH), 7.22 (t, J = 7.59 Hz, 2 H, ArH), 6.84–6.97 (m, 1 H,
ArH) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 153.1, 140.3,
We have demonstrated the catalytic carbonylation of an-
iline to N,NЈ-diphenylurea with the W(CO)6/I2 catalyst sys-
tem. After optimizing the conditions for the carbonylation 129.4, 122.4, 118.8 ppm.
of aniline, various p-substituted arylamines were also oxi-
datively carbonylated to generate symmetrical and unsym-
metrical diaryl ureas. Coupling of N-methylaniline with
arylamines produced results that are consistent with the in-
termediacy of an isocyanate in the mechanism. These re-
sults demonstrate the moderately broad tolerance of func-
tionality during the oxidative carbonylation reaction and
provide an alternative to the reaction of amines with phos-
gene and phosgene derivatives. Further work on related car-
bonylation reactions with the W(CO)6/I2 system is in pro-
gress.
1,3-Bis(4-chlorophenyl)urea (2b): Procedure A afforded urea 2b
from 4-chloroaniline (1b; 0.255 g, 2.00 mmol) in 68% yield
(0.190 g). The product was identified by comparison with literature
data.[44] IR (neat): ν = 1643 (CO) cm–1. 1H NMR (300 MHz, [D ]-
˜
6
DMSO): δ = 8.81 (s, 2 H), 7.45 (d, J = 8.78 Hz, 4 H), 7.30 (d, J =
8.78 Hz, 4 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 153.0,
139.2, 129.3, 126.2, 120.5 ppm. HRMS (ESI): calcd. for
C13H10Cl2N2O [M + Na]+ 303.0062; found 303.0061.
1,3-Bis(4-iodophenyl)urea (2c): Procedure A afforded urea 2c from
4-iodoaniline (1c; 0.219 g, 1.00 mmol) in 76% yield (0.176 g). IR
(neat): ν = 1634 (CO) cm–1. 1H NMR (300 MHz, [D ]DMSO): δ =
˜
6
8.77 (s, 2 H), 7.55 (d, J = 8.47 Hz, 4 H), 7.25 (d, J = 8.47 Hz, 4 H)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 152.8, 140.1, 138.0,
121.2, 85.5 ppm. HRMS (ESI): calcd. for C13H10I2N2O
[M + Na]+ 486.8775; found 486.8780.
Experimental Section
General: All solvents were dried by standard procedures, distilled,
and stored under nitrogen before use. All other chemicals were pur-
chased in reagent grade and used with no further purification un-
less stated otherwise. The p-substituted diarylurea products were
identified by comparison to authentic samples purchased from
Sigma–Aldrich or by comparison of their spectroscopic data to lit-
erature values. 1H and 13C NMR spectra were recorded with Varian
Gemini 300 and Mercury 300 spectrometers. IR spectra were re-
corded with a Perkin–Elmer 1600 FTIR instrument. High-resolu-
tion mass spectrometry (HRMS) was performed by the University
of Florida analytical service.
1,3-Bis(4-bromophenyl)urea (2d): Procedure A afforded urea 2d
from 4-bromoaniline (1d; 0.172 g, 1.00 mmol) in 64% yield
(0.120 g). The compound was identified by comparison with litera-
1
ture data.[45] IR (neat): ν = 1644 (CO) cm–1. H NMR (300 MHz,
˜
[D6]DMSO): δ = 8.80 (s, 1 H, NH), 7.38 (s, 4 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 152.9, 139.6, 132.2, 120.9, 114.0 ppm.
HRMS (ESI): calcd. for C13H10Br2N2O [M + Na]+ 392.9032; found
392.9062.
1,3-Bis(4-methoxyphenyl)urea (2e): Procedure A afforded urea 2e
from p-anisidine (1e; 0.615 g, 5.00 mmol) in 38% yield (0.260 g).
The compound was identified by comparison with literature
Typical Procedure A. Catalytic Carbonylation of p-Substituted Aryl-
data.[46] IR (neat): ν = 1631 (CO) cm–1. 1H NMR (300 MHz,
˜
amines
[D6]DMSO): δ = 8.31 (s, 2 H), 7.28 (d, J = 9.06 Hz, 4 H), 6.80 (d,
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L. McElwee-White et al.
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J = 8.91 Hz, 4 H), 3.29 (s, 2 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 154.9, 153.6, 133.6, 120.5, 115.6, 114.6, 55.8 ppm.
HRMS (ESI): calcd. for C15H16N2O3 [M + Na]+ 295.1053; found
295.1063.
benzocaine (1j; 0.165 g, 1.00 mmol) in 46% yield (0.150 g). IR
(neat): ν = 1668, 1706 cm–1. 1H NMR (300 MHz, [D6]DMSO): δ
˜
= 9.52 (s, 1 H), 9.31 (s, 1 H), 8.20 (d, J = 7.6 Hz, 2 H), 7.92 (d, J
= 7.3 Hz, 2 H), 7.71 (d, J = 7.6 Hz, 2 H), 7.62 (d, J = 7.3 Hz, 2
H), 4.29 (q, J = 6.8 Hz, 2 H), 1.31 (t, J = 6.4 Hz, 3 H) ppm. 13C
NMR (75 MHz, [D6]DMSO): δ = 166.0, 152.4, 146.6, 144.3, 142.0,
138.3, 131.0, 125.8, 124.1, 118.4, 61.0, 14.9 ppm. HRMS (ESI):
calcd. for C16H15N3O5 [M + H]+ 330.1084; found 330.1079.
1,3-Bis(4-phenoxyphenyl)urea (2f): Procedure A afforded urea 2f[27]
from 4-phenoxyaniline (1f; 0.185 g, 1.00 mmol) in 82% yield
(0.163 g). IR (neat): ν = 1643 cm–1. 1H NMR (300 MHz, [D6]-
˜
DMSO): δ = 8.67 (s, 2 H), 7.48 (d, J = 8.8 Hz, 4 H), 7.36 (t, J =
7.8 Hz, 4 H), 7.15–6.91 (m, 10 H) ppm. 13C NMR (75 MHz, [D6]- 1-(4-Chlorophenyl)-3-(4-methoxyphenyl)urea (3be): Procedure A af-
DMSO): δ = 158.4, 153.4, 151.3, 136.4, 130.6, 123.4, 120.6, 120.5,
118.3 ppm. HRMS (ESI): calcd. for C25H20N2O3 [M + Na]+
419.1366; found 419.1369.
forded urea 3be[52] from 4-chloroaniline (1b; 0.255 g, 2.00 mmol)
and p-anisidine (1e; 0.123 g, 1.00 mmol) in 43% yield (0.118 g). IR
1
(neat): ν˜ = 1633 cm–1. H NMR (300 MHz, [D6]DMSO): δ = 8.66
(s, 1 H), 8.44 (s, 1 H), 7.41 (d, J = 8.91 Hz, 4 H), 7.16–7.34 (m, 4
H), 6.81 (d, J = 8.91 Hz, 2 H), 3.66 (s, 3 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 154.6, 152.6, 138.9, 132.5, 128.5, 125.1,
120.2, 119.6, 114.0, 55.2 ppm. HRMS (DART): calcd.
C14H13ClN2O2 [M + H]+ 277.0738; found 277.0742.
1,3-Bis[4-(methylthio)phenyl]urea (2g): Procedure A afforded urea
2g from 4-(methylthio)aniline (1g; 0.139 g, 1.00 mmol) in 76% yield
(0.116 g). IR (neat): ν = 1638 cm–1. 1H NMR (300 MHz, [D6]-
˜
DMSO): δ = 8.65 (s, 2 H), 7.41 (d, J = 8.8 Hz, 4 H), 7.22 (d, J =
8.5 Hz, 4 H), 2.45–2.41 (m, 6 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 153.1, 138.1, 130.6, 128.4, 119.6, 16.7 ppm. HRMS
(ESI): calcd. for C15H16N2OS2 [M + Na]+ 327.0596; found
327.0608.
1-[4-Chloro-3-(trifluoromethyl)phenyl]-3-(4-methoxyphenyl)urea
(3pe): Procedure A produced urea 3pe from p-anisidine (1e; 0.123 g,
1.00 mmol) and 4-chloro-3-(trifluoromethyl)aniline (1p; 0.391 g,
2.00 mmol) in 12% yield (0.042 g). IR (neat): ν = 1627 (CO) cm–1.
˜
1,3-Bis(4-nitrophenyl)urea (2h): Procedure A afforded urea 2h from
p-nitroaniline (1h; 0.691 g, 5.00 mmol) in 84% yield (0.638 g). The
1H NMR (300 MHz, [D6]DMSO): δ = 9.04 (s, 1 H), 8.61 (s, 1 H),
8.04 (s, 1 H), 7.64–7.48 (m, 2 H), 7.31 (d, J = 8.9 Hz, 2 H), 6.82
(d, J = 8.9 Hz, 2 H), 3.67 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 155.4, 153.2, 140.2, 132.6, 123.5, 121.2, 117.2, 114.6,
55.8, 23.4 ppm. HRMS (ESI): calcd. C15H12ClF3N2O2 [M + Na]+
367.0439; found 367.0432.
compound was identified by comparison with literature data.[47,48]
1
IR (neat): ν = 1635 (CO) cm–1. H NMR (300 MHz, [D ]DMSO):
˜
6
δ = 9.58 (br. s, 2 H), 7.93–8.24 (m, 4 H), 7.30–7.79 (m, 4 H) ppm.
13C NMR (75 MHz, [D6]DMSO): δ = 151.7, 145.7, 141.6, 125.2,
118.0 ppm. HRMS (APCI): calcd. for C13H10N4O5 [M – H]–
301.0578; found 301.0579.
1-(4-Chlorophenyl)-3-(4-phenoxyphenyl)urea (3bf): Procedure A af-
forded 3bf from 4-phenoxyaniline (1f; 0.185 g, 0.999 mmol) and 4-
chloroaniline (1b; 0.255 g, 2.00 mmol) in 41% yield (0.138 g) ac-
1,3-Bis(4-cyanophenyl)urea (2i): Procedure A afforded urea 2i[49]
from 4-aminobenzonitrile (1i; 0.295 g, 2.50 mmol) in 48% yield
cording to NMR spectroscopy. IR (neat): ν = 1633 cm–1. 1H NMR
˜
(0.160 g). IR (neat): ν = 1643 (CO) cm–1. 1H NMR (300 MHz, [D ]-
˜
6
(300 MHz, [D6]DMSO): δ = 8.79 (s, 1 H), 8.71 (s, 1 H), 7.51–7.45
(m, 4 H), 7.40–7.27 (m, 4 H), 7.14–7.03 (m, 1 H), 7.01–6.91 (m, 4
H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 158.2, 153.1, 151.4,
139.4, 136.1, 130.5, 125.9, 123.4, 120.7, 120.4, 120.3, 118.3 ppm.
HRMS (ESI): calcd. for C19H15ClN2O2 [M + Na]+ 361.0706; found
361.0706.
DMSO): δ = 9.33 (s, 2 H), 7.66–7.78 (m, 4 H), 7.59 (d, J = 8.76 Hz,
4 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 152.4, 144.3,
134.0, 119.9, 119.0, 104.5 ppm. HRMS (ESI): calcd. for
C15H10N4O [M + Na]+ 285.0747; found 285.0747.
Diethyl 4,4Ј-[Carbonylbis(azanediyl)]dibenzoate (2j): Procedure A
afforded urea 2j[49] from ethyl p-aminobenzoate (1j; 0.331 g,
1-[4-Chloro-3-(trifluoromethyl)phenyl]-3-(4-phenoxyphenyl)urea
(3pf): Procedure A afforded 3pf from 4-chloro-3-(trifluoromethyl)
aniline (1p; 0.978 g, 5.00 mmol) and 4-phenoxyaniline (1f; 0.185 g,
2.00 mmol) in 74% yield (0.263 g). IR (neat): ν = 1642 (CO) cm–1.
˜
1H NMR (300 MHz, CDCl3): δ = 7.85 (d, J = 8.62 Hz, 4 H), 7.41
(d, J = 8.62 Hz, 4 H), 4.23 (t, J = 7.10 Hz, 4 H), 3.53 (br. s, 2 H),
1.27 (t, J = 7.08 Hz, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
170.9, 156.5, 147.5, 134.9, 128.2, 121.8, 65.0, 18.3 ppm. HRMS
(ESI): calcd. for C19H20N2O5 [M + Na]+ 379.1264; found 379.1266.
1.00 mmol) in 45% yield (0.183 g). IR (neat): ν = 1649 (CO) cm–1.
˜
1H NMR (300 MHz, [D6]DMSO): δ = 9.12 (s, 1 H), 8.83 (s, 1 H),
8.09 (d, J = 2.1 Hz, 1 H), 7.71–7.53 (m, 2 H), 7.46 (d, J = 9.1 Hz,
2 H), 7.34 (t, J = 7.9 Hz, 2 H), 7.14–7.03 (m, 1 H), 7.01–6.88 (m,
3 H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 158.2, 153.2,
151.8, 140.1, 135.8, 132.6, 130.6, 123.5, 121.2, 120.4, 118.4 ppm.
HRMS (DIP-Cl): calcd. for C20H14ClF3N2O2 [M + H]+ 407.0769;
found 407.0774.
3,4-Dihydroquinazolin-2(1H)-one (2k): Procedure A afforded urea
2k from 2-aminobenzylamine (1k; 0.122 g, 1.00 mmol) in 41% yield
(0.060 g). The product was identified by comparison with literature
data.[50] IR (neat): ν = 1643 (CO) cm–1. 1H NMR (300 MHz, [D ]-
˜
6
DMSO): δ = 8.95 (br. s, 2 H), 6.94–7.15 (m, 2 H), 6.64–6.86 (m, 2
H), 4.25 (br. s, 2 H) ppm. HRMS (ESI): calcd. for C15H18N4O [M
+ Na]+ 171.0529; found 171.0536.
1-Methyl-1,3-diphenylurea (3aq): Procedure A afforded 3aq[53] from
aniline (1a; 0.093 g, 1.00 mmol) and N-methylaniline (1q; 0.536 g,
5.00 mmol) in 31% yield (0.070 g). IR (neat): ν = 1662 cm–1. 1H
˜
1-(4-Cyanophenyl)-3-(4-nitrophenyl)urea (3hi): Procedure A af-
forded urea 3hi from p-nitroaniline (1h; 0.138 g, 1.00 mmol) and 4-
aminobenzonitrile (1i; 0.118 g, 1.00 mmol) in 58% yield (0.150 g).
NMR (300 MHz, CDCl3): δ = 7.56–7.16 (m, 9 H), 7.04–6.94 (m, 1
H), 6.25 (br. s, 1 H), 3.34 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 154.5, 143.1, 139.0, 130.5, 128.9, 128.0, 127.6, 123.0,
119.4, 37.4 ppm.
The product was identified by comparison with literature data.[51]
1
IR (neat): ν = 1644 cm–1. H NMR (300 MHz, CDCl ): δ = 7.90
˜
3
1-Methyl-3-(4-phenoxyphenyl)-1-phenylurea (3fq): Procedure A af-
forded urea 3fq from 4-phenoxyaniline (1f; 0.093 g, 0.500 mmol)
and N-methylaniline (1q; 0.161 g, 1.50 mmol) in 19 % yield
(d, J = 9.1 Hz, 2 H), 7.32 (d, J = 3.6 Hz, 4 H), 7.22 (s, 4 H) ppm.
HRMS (ESI): calcd. for C14H10N4O3 [M + Na]+ 305.0645; found
305.0653.
(0.030 g). IR (neat): ν = 1645 cm–1 1H NMR (300 MHz, [D6]-
.
˜
Ethyl 4-[3-(4-Nitrophenyl)ureido]benzoate (3hj): Procedure A af-
forded urea 3hj from p-nitroaniline (1h; 0.138 g, 1.00 mmol) and
DMSO): δ = 8.20 (s, 1 H), 7.54–7.29 (m, 9 H), 7.28–7.19 (m, 1 H),
7.13–7.03 (m, 3 H), 3.36 (s, 3 H) ppm. 13C NMR (75 MHz, [D6]-
6266
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Eur. J. Org. Chem. 2011, 6261–6268

Oxidative Carbonylation of Arylamines to Ureas
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1H NMR (300 MHz, CDCl3): δ = 7.62–7.15 (m, 8 H), 6.33 (br. s,
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δ = 154.1, 142.4, 137.9, 131.9, 130.8, 128.6, 127.7, 123.3, 118.4,
109.9, 37.6 ppm. HRMS (ESI): calcd. for C15H12ClF3N2O [M +
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1-(4-Chlorophenyl)-3-(4-methoxyphenyl)urea (3be; authentic sam-
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(0.700 g, 4.31 mmol) was slurried in anhydrous THF (6 mL), fol-
lowed by dropwise addition of 4-chloroaniline (0.500 g, 3.93 mmol)
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1-(4-Chlorophenyl)-3-(4-phenoxyphenyl)urea (3bf; authentic sample):
In
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[24]
[25]
[26]
[27]
[28]
[29]
[30]
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recrystallized from ethanol to give a white solid (0.984 g, 74%).
Acknowledgments
We thank the donors of the American Chemical Society Petroleum
Research Fund for support of this work through the Green Chem-
istry Institute. L. Z. sincerely thanks the China Scholarship Council
for funding her exchange visit to the University of Florida.
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Eur. J. Org. Chem. 2011, 6261–6268