Synthesis of N,N′-disubstituted urea from ethylene carbonate and amine using CaO

Article abstract of DOI:10.1246/cl.2004.742

Calcium oxide has been proved to be an excellent solid catalyst for the synthesis of N,N′-disubstituted ureas from ethylene carbonate and primary amines under mild conditions.

Full text of DOI:10.1246/cl.2004.742

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Chemistry Letters Vol.33, No.6 (2004)
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Synthesis of N,N -Disubstituted Urea from Ethylene Carbonate and Amine Using CaO
ꢀ
y
y;yy
y;yy
and Masahiko Arai
Division of Materials Science and Engineering, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628
Shin-ichiro Fujita, Bhalchandra M. Bhanage,
y
yy
CREST, JST
(Received March 22, 2004; CL-040318)
Calcium oxide has been proved to be an excellent solid cat-
0
0
a
Table 1. N,N -Dibutylurea synthesis using various catalysts
alyst for the synthesis of N,N -disubstituted ureas from ethylene
carbonate and primary amines under mild conditions.
Entry
Catalyst
CaO
Yield / %
1
2
3
4
5
49
78
6
0
0
b
CaO
Substituted ureas have found extensive applications such as
dyes, antioxidants, corrosion inhibitor, intermediates for the
ZnO
MgO
ZrO2
1
preparation of pharmaceuticals, and agricultural chemicals.
2
They can be synthesized from amines via phosgenation, reduc-
a
Catalyst, 0.5 g; EC, 40 mmol; butylamine 80 mmol; temper-
ature, 100 C; time 1 h. The reaction was carried out for 3 h.
3
4
tive carbonylation, or oxidative carbonylation. However, these
reactions are not eco-friendly because of risks associated with
using the poisonous compounds of phosgene and carbon monox-
ide and/or a potentially explosive mixture of carbon monoxide
and oxygen. The reactions of amines with dialkyl or diaryl car-
bonate also produce substituted ureas or substituted carba-
mates.5 The latter compounds further reacts with amines pro-
ducing substituted ureas. However, the carbonates are
currently produced via similar hazardous routes of phosgenation
ꢁ
b
the other catalysts, resulting in its higher activity observed.
The reactions of EC with various amines were also carried
out using CaO. The results obtained are represented in
Table 2. It is seen that CaO is effective for the synthesis of var-
ious disubstituted amines. Propylamine and butylamine give
good yields for the corresponding disubstituted ureas at a reac-
1
1
,6
ꢁ
tion temperature of 100 C (Entries 1 and 2). Slightly higher re-
5
,6
0
or oxidative carbonylation. N,N -Disubstituted ureas can be
synthesized via the reaction of ethylene carbonate and amine
in the presence of homogeneous base catalysts such as sodium
action temperatures are required to obtain the substituted ureas
from hexylamine and benzylamine with good yields (Entries 3
and 5). Unfortunately, from aniline, diphenylurea was not pro-
duced even at 125 C (Entry 6). The product observed was 2-
(phenylamino)ethanol. Probably, EC should decompose to eth-
ylene oxide and this decomposition product should further re-
act with aniline, producing 2-(phenylamino)ethanol. Aniline
might catalyze the former reaction.
7
ꢁ
methoxide and triethylamine (Scheme 1). However, no one
has used solid base catalysts for this reaction. The solid base cat-
alysts are more easily separable and recyclable than the homoge-
1
2
8
neous catalysts and are still gaining much attension. In the pres-
ent work, it has been shown that calcium oxide is an excellent
solid catalyst for the synthesis of the disubstituted ureas from
ethylene carbonate and primary amines.
0
Table 2. N,N -Disubstituted urea synthesis from EC with vari-
a
ous amines
O
O
Entry
Amine
Yield / %
R
R
O
O
+ 2RNH2
OH
1
2
3
4
5
Propylamine
Butylamine
Hexylamine
Benzylamine
Benzylamine
Anilineb
68
78
77
38
55
0
+
N
H
N
H
HO
b
0
Scheme 1. Synthesis of N,N -disubstituted urea from EC and
amine.
b
c
0
6
Table 1 lists the reaction results for the N,N -dibutylurea
synthesis from ethylene carbonate (EC) and butylamine using
a
CaO, 0.5 g; EC, 40 mmol; amine 80 mmol; temperature,
100 C; time 3 h. at 125 C. at 150 C.
9
ꢁ
b
ꢁ
c
ꢁ
various catalysts. It is seen that among the catalysts used only
0
CaO is a good catalyst. N,N -Dibutylurea is obtained in a yield
0
of 49% after the reaction for 1 h with CaO (Entry 1). When
the reaction time is lengthened from 1 to 3 h, the yield increases
from 49 to 78% (Entry 2). In contrast to these, ZnO gives a very
poor yield and the other catalysts do not produce the disubstitut-
ed urea (Entries 3–5). To elucidate the difference among the cat-
alysts, basic properties of the catalysts were examined by tem-
CaO was reused for the N,N -dibenzylurea synthesis three
times.13 The yields of N,N -dibenzylurea obtained for the second
and third runs were 56 and 55%, respectively. Thus, CaO retains
its activity during the recycles. It is noted that the procedures for
the recycle runs were carried out under ambient atmosphere. Ex-
posing solid base catalysts to air sometimes causes their severe
0
1
0
8
perature programmed desorption of adsorbed CO2. For CaO,
ꢁ
deactivation. However, such deactivation was not observed
for the present reaction system.
For the experiment of Entry 1 in Table 1, compounds dis-
solved in water used for the post-reaction treatment were ana-
lyzed. It was found that all of EC was consumed and unreacted
CO2 desorption peaks were observed at 585 and 650 C. For
ꢁ
ZnO and MgO, peaks appeared below 500 C. ZrO2 had a trace
ꢁ
amount of CO2 desorption at 580 C. These results suggest that
CaO has larger amounts of strongly basic sites as compared with
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.6 (2004)
743
amine, ethylene glycol, and 2-hydroxyethyl butylcarbamate pre-
sented in the water phase. This carbamate was considered to be
intermediates species for the N,N -dibutylurea formation. A
(1951).
A. M. Lee and C. W. Lee, J. Mol. Catal., 61, L15 (1990); C. W.
Lee, S. M. Lee, and J. S. Oh, Ind. Eng. Chem. Res., 30, 6344
3
0
(
1991); S. M. Lee, N. S. Cho, K. D. Kim, J. S. Oh, C. W.
plausible reaction mechanism for the title reaction is illustrated
in Scheme 2. EC reacts with one molecule of amine, transform-
ing to 2-hydroxyethyl alkylcarbamate. The carbamate reacts
with another amine molecule, producing ethylene glycol and
Lee, and J. S. Lee, J. Mol. Catal., 73, 43 (1992); K. D. Kim,
S. M. Lee, N. S. Cho, J. S. Oh, C. W. Lee, and J. S. Lee, J.
Mol. Catal., 81, 163 (1993); Y. Yang and S. Lu, Tetrahedron
Lett., 40, 4845 (1999); A. M. Tafesh and J. Weiguny, Chem.
Rev., 96, 2035 (1996) and references cited therein.
N. Sonoda, T. Yasuhara, K. Kondo, T. Ikeda, and S. Tsutsumi,
J. Am. Chem. Soc., 93, 6344 (1971); P. Giannoccaro, J. Orga-
nomet. Chem., 336, 271 (1987); P. Giannoccaro, C. F. Nobile,
P. Mastrorilli, and N. Ravasio, J. Organomet. Chem., 419, 251
0
N,N -dialkylurea. Since the carbamate formation from EC and
amine proceeds rapidly around room temperature without any
4
1
4
catalyst, as Kaupp et al. reported, the second reaction of carba-
mate and amine would be catalyzed by CaO and the rate deter-
mining step. CaO should activate both the amine and the carba-
mate as illustrated in Scheme 2.
(
1991); B. M. Choudary, K. K. A. Rao, S. D. Pirozhokov, and
A. L. Lapidus, Synth. Commun., 21, 1923 (1991); A. A. Kelkar,
D. S. Kolhe, S. Kanagasabapathy, and R. V. Chaudari, Ind.
Eng. Chem. Res., 31, 172 (1992); J. E. McCusker, A. D. Main,
K. S. Johnson, C. A. Grasso, and L. McElwee-White, J. Org.
Chem., 65, 5216 (2000); F. Shi, Y. Deng, T. SiMa, and H.
Yang, Tetrahedron Lett., 42, 2161 (2001).
H
R
O
N
H
O
R
OH
O
O
N
H
O
5
6
J. Izdebski and D. Pawlak, Synthesis, 1989, 423; N. Nagaraju
and G. Kuriakose, Green Chem., 4, 269 (2002).
OH
Y. Ono, Catal. Today, 35, 15 (1997); M. A. Pachenco and C. L.
Marshall, Energy Fuels, 11, 2 (1997); D. Delledonne, F.
Rivetti, and U. Romano, Appl. Catal., A, 221, 241 (2001).
T. Hayashi and J. Yasuoka, Eur. Pat., EP 846679 (1998);
Chem. Abstr., 129, 40921q (1998).
O
H
N
R
R
OH
δ+ O
H
7
+ HO
R
N
H
N
H
δ− R
N
O
H δ+
8
9
H. Hattori, Chem. Rev., 95, 537 (1995).
Experimental: CaO, ZnO, and ZrO2 were prepared by decom-
O
Ca
O
O
Ca
O
ꢁ
position of calcium hydroxide at 550 C for 4 h, hydroxy zinc
ꢁ
0
ꢁ
Scheme 2. Reaction mechanism for N,N -disubstituted urea
synthesis from EC and amine.
carbonate at 350 C for 4 h and zirconium oxynitrate at 500 C
for 3 h, respectively. MgO was a commercially available re-
agent. BET surface areas of CaO, ZnO, ZrO2, and MgO were
2
1
3, 49, 49, and 14 m /g, respectively. The reaction was per-
O
formed in a 50-mL-stainless steel autoclave attached with a
mechanical agitator. After EC (40 mmol), amine (80 mmol),
and the catalyst (0.5 g) were charged into the reactor, the reac-
O
+
CO2
O
O
ꢁ
tor was heated to 100 C and kept for 1 h. After the reactor was
cooled to room temperature, the reaction mixture was dis-
persed in 50 mL of water and stirred for 1 h at room tempera-
ture to remove remaining substrates, carbamate and ethylene
glycol co-generated. The solid mixture of the urea formed
and the catalyst in the resultant suspension was filtered off
and washed with water. The product yield was determined
from the weight of the solid mixture by subtracting the catalyst
weight. The product was characterized by gas-chromatogra-
phy, mass spectrometry and H NMR.
0 B. M. Bhanage, S. Fujita, Y. Ikushima, and M. Arai, Appl.
Catal., A, 219, 259 (2001).
1 For the experiments with hexylamine and benzylamine, 50 mL
of acetone was used instead of water for the post-reaction treat-
ment of the products. The products were characterized by gas-
O
O
OH
O
O
+
2RNH2
R
R
+
HO
N
H
N
H
Scheme 3. EC based carbon dioxide fixation.
In summary, this is the first paper reporting that CaO is an
1
0
efficient solid catalyst for the synthesis of various N,N -disubsti-
tuted ureas under mild conditions. It is noted that excess amine is
not required under the present reaction conditions. This is more
preferable from the viewpoint of economics. It should be noted
that, since EC is prepared industrially from ethylene oxide and
carbon dioxide, the title reaction will be EC based carbon diox-
ide fixation to important chemicals (Scheme 3).
1
1
chromatography, mass spectrometry, melting point measure-
ments, 1H NMR, and comparison with authentic samples
whenever possible.
A part of this work is supported by a Grant-in-Aid from
Japan Society for the Promotion of Science.
12 B. M. Bhanage, S. Fujita, Y. Ikushima, and M. Arai, Green
Chem., 5, 71 (2003).
1
3 After being weighed, the product was dissolved in DMF. Then,
the catalyst was separated by filtration, washed with acetone,
dried under vacuum, and used for the next run.
References and Notes
1
F. Bigi, R. Maggi, and G. Sartori, Green Chem., 2, 140 (2000)
and references cited therein.
V. Papesch and E. F. Schroeder, J. Org. Chem., 16, 1879
14 G. Kaupp, J. Schmeyers, and J. Boy, Tetrahedron, 56, 6899
(2000).
2
Published on the web (Advance View) May 24, 2004; DOI 10.1246/cl.2004.742