Synthesis of urea derivatives from amines and CO2 in the absence of catalyst and solvent

Article abstract of DOI:10.1039/c0gc00059k

Urea derivatives are obtained in mild to good yield from the reactions of primary aliphatic amines with CO₂ in the absence of any catalysts, organic solvents or other additives. To optimize reaction conditions, experimental variables including temperature, pressure, the concentration of amine, reaction time etc. were studied. Satisfactory yields were obtained at the optimized conditions that are comparable to the presence of catalyst and solvent. The preliminary investigation of the reaction mechanism showed that alkyl ammonium alkyl carbamate was quickly formed as the intermediate, and then the final product was formed by the intramolecular dehydration.

Full text of DOI:10.1039/c0gc00059k

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www.rsc.org/greenchem | Green Chemistry
Synthesis of urea derivatives from amines and CO2 in the absence of
catalyst and solvent†
Chaoyong Wu,a,b Haiyang Cheng,a,b Ruixia Liu,a,b Qiang Wang,a,b Yufen Hao,a,b Yancun Yua and
Fengyu Zhao*a
Received 29th April 2010, Accepted 12th August 2010
DOI: 10.1039/c0gc00059k
Urea derivatives are obtained in mild to good yield from the reactions of primary aliphatic amines
with CO2 in the absence of any catalysts, organic solvents or other additives. To optimize reaction
conditions, experimental variables including temperature, pressure, the concentration of amine,
reaction time etc. were studied. Satisfactory yields were obtained at the optimized conditions that
are comparable to the presence of catalyst and solvent. The preliminary investigation of the
reaction mechanism showed that alkyl ammonium alkyl carbamate was quickly formed as the
intermediate, and then the final product was formed by the intramolecular dehydration.
a neat and effective route for the synthesis of urea derivatives
Introduction
from amines and CO2 in the absence of any catalyst, organic
The increasing levels of carbon dioxide in the atmosphere has a
solvent or other additives, with satisfactory yields comparable
detrimental effect on the climate and is the major contributing
to that reported in literature with these additives.
factor to recent global warming.1 It is imperative that new
reactions and processes are developed for the efficient storage
or utilization of the abundant and renewable CO2 resource in
Results and discussion
an environmentally friendly manner. For the carbon dioxide
capture and storage (CCS),2 amine scrubbing3 will probably
be the dominant technology for CO2 capture from coal-fired
During the initial research of this work, we tried to perform
the reaction by using solid base catalysts. A lot of product was
formed when a blank reaction was carried out in the absence
of catalyst. With the assurance that no impurities or other
factors could promote the reaction, we examined the catalytic
possibility of the stainless steel wall of the reactor as our previous
observation.22 Similar yields of 29.8% and 30.2% were obtained
for n-butylamine (BA) reacting with CO2 in a stainless steel
reactor with and without setting Teflon inner liner at conditions
of 180 ◦C, 10 MPa, 1.0 mmol ml-1 BA for 4 h. Thus, there was no
reactor wall effect and the reaction could occur in the absence of
any catalyst. So the effect of reaction parameters were studied
using BA as a model substrate with the formation of N,N¢-
dibutylurea (DBU) as the main-product and no by-products
detected except water (Scheme 1).
4–8
power plants. Chemical utilization of CO2 could also help to
reduce its concentration in the atmosphere while at the same
time exploiting it as a carbon feedstock for the production of
useful organic compounds. Herein we describe a technology
that combines CO2 capture and utilization into one process with
the formation of useful urea derivatives but not for geologic
sequestration.
Urea derivatives are widely used in a variety of areas,9
such as pharmaceuticals, agricultural pesticides, antioxidants
in gasoline and corrosion inhibitors. Traditional synthesis of
urea derivatives involves the reaction of amines with phosgene,
CO10 or isocyanate,11 which has tremendous toxicological and
environmental problems. Alternative routes have also been
developed, which involve amines reacting with urea,12 ethylene
carbonate13 or diethyl carbonate.14 However, these expensive
reagents originate from CO2 reacting with ammonium,15 ethy-
lene oxide or ethanol.5 Some researchers have synthesized urea
derivatives through amines reacting with CO2 in the presence of
catalysts, such as 1,8-diazabicyclo[5.4.0]undec-7-ene,16 CsOH,17
Cs2CO3,18 Au/poly,19 [Bmim]OH20 or KOH/PEG1000,21 using
ionic liquids, N-methylpyrrolidone or CO2 as solvent. We show
Scheme 1 Reaction of n-butylamine with CO2.
Increasing the temperature led to a rise then fall in the isolated
yield of DBU, reaching a maximum yield at around 180 ◦C
(Fig. 1). The decrease of the yield at high temperatures was
ascribed to the idea that it is a reversible and exothermic reaction;
its equilibrium constant decreases as temperature increases. The
reactions of 5 mmol DBU and 100 mmol H2O were examined
at different temperatures from 180 to 220 ◦C. The hydrolyzation
content increased with increasing and nearly completed at
220 ◦C(data not shown), indicating that it is a reversible reaction.
The industrial production of urea from NH3 and CO2 occurs
aSate Key Laboratory of Electroanalytical Chemistry, Laboratory of
Green Chemistry and Process, Changchun Institute of Applied
Chemistry, Chinese Academy of Sciences, Changchun, 130022, Jilin, P.
R. China
bGraduate university of the Chinese Academy of Sciences, Beijing,
100049, P. R. China
† Electronic supplementary information (ESI) available: Spectroscopic
data for the products. See DOI: 10.1039/c0gc00059k
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(Fig. 3). The results for the reactions of hexylamine (HA) and
cyclohexylamine (CHA) with CO2 showed that the yield of the
product was also greatly dependent on the concentration of the
reactant similar to BA. Aria and co-workers24 have reported that
cyclic ureas could be formed from alkylene diamines and CO2
at 150 ◦C in the absence of catalyst in methanol solvent. The
industrial production of urea also operates at elevated tempera-
tures (150–220 ◦C) and pressures (15–25 MPa) with the precise
control of the amount of ammonia and CO2 without using any
catalyst.15 So it seems to be reasonable for synthesizing urea
derivatives without catalyst by finely controlling the reaction
conditions.
Fig. 1 Effect of temperature on the isolated yield of DBU. The
selectivity of DBU was 100% at all the conversion values. Conditions:
BA 1.0 mmol ml-1; pressure 10 MPa; time 4 h.
in two steps via the intermediate ammonium carbamate. The
conversion of NH3 and CO2 into ammonium carbamate is highly
exothermic, while the dehydration to urea is endothermic. The
overall process is exothermic and no urea was formed at high
temperatures.15,18 The production of DBU may have a similar
thermal effect. As the overall process is exothermic, a shift of
the equilibrium to the left with the increase in temperature is
reasonable.
The isolated yield of DBU reached a maximum value at super-
critical region, ca. 10 MPa, and then decreased with increasing
pressure (Fig. 2). At pressures above 10 MPa, the superfluous
CO2 dissolved into the liquid phase of butyl ammonium butyl
carbamate (BABC), this resulted in an expansion of the liquid
and then caused a dilution effect as observed in our previous
work.23 The dilution effect was less obvious for the case of 1.0
mmol ml-1 BA and the yield decreased slowly at higher pressures
compared with 0.8 mmol ml-1 BA. Based on the role of amine,
it is a reactant and also a promoter or catalyst of the reaction
(as discussed later). The catalytic effect is more obvious for the
high concentrations of BA, so the negative dilution effect is less
obvious, leading to a slow decrease of the yield.
Fig. 3 Effect of quantity of amines on the isolated yield of urea
derivatives. The selectivity of DBU was 100% at all the conversion
values. Conditions: temperature 180 ◦C; pressure 10 MPa; time 4 h.
HA: hexylamine, CHA: cyclohexylamine.
The isolated yield of DBU could be enhanced by adding a
small amount of water, especially at low concentrations of BA,
but it decreased slightly at large quantity of water (Fig. 4). The
positive effect of water was ascribed to the interaction of water
with BABC; while the reaction equilibrium would shift to the
left with an excess amount of water, resulting in a reduction of
the yield of DBU.
Fig. 4 Effect of additional water on the isolated yield of DBU. The
selectivity of DBU was 100% at all the conversion values. Conditions:
temperature 180 ◦C; pressure 10 MPa; time 4 h.
Fig. 2 Effect of pressure on the isolated yield of DBU. The selectivity
of DBU was 100% at all the conversion values. Conditions: BA 1.0 mmol
ml-1; temperature 180 ◦C; time 4 h.
The concentration of BA had a great effect on the isolated
yield of DBU, which increased drastically and then reached
a plateau slightly with increasing of the concentration of BA
The yield increased smoothly with the reaction time and
reached to 72.9% after 24 h (Fig. 5). The control experiments
with catalysts and solvents showed that the yield was enhanced
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Table 1 The results for the reaction of BA and CO2 in the presence of
various additivesa
Entry
Catalyst & additive
Quantity/mmol
Yield/%
1
2
3
4
5
6
7
8
None
NaOH
KOH
CsOH
Na2CO3
K2CO3
Cs2CO3
NMP
Cs2CO3 + NMP
[Bmim]Cl
[Bmim]OH
—
1
1
1
1
1
1
100
30.2
31.2
33.4
37.8
36.6
38.7
41.3
37.5
55.3
31.8
37.0
9
10
11
1 + 100
1
1
Fig. 5 Effect of reaction time on the isolated yield of DBU. The
selectivity of DBU was 100% at all the conversion values. Conditions:
BA 1.0 mmol ml-1; temperature 180 ◦C; pressure 10 MPa.
a Conditions: BA 1.0 mmol ml-1; temperature 180 ◦C; pressure 10 MPa;
time 4 h. The selectivity of DBU was 100% at all the conversion values.
appropriate amount of amine without any catalyst, solvent or
additives.
slightly with the presence of these additives (Table 1). But
the increase was at the expense of additional procedure to
separate the catalyst and additives from product and the cost of
economy etc. Additives are necessary only when a remarkable
enhancement of the yield could compensate these drawbacks.
So the optimized reaction condition is ca. 180 ◦C, 10 MPa,
The scope of this reaction was examined (Table 2). A wide
range of primary aliphatic amines bearing different chain length
and/or substituents could undergo the target reaction smoothly,
delivering the corresponding dialkyl ureas in moderate to good
yields (entries 1–12). The conversions of isopropylamine and
a
Table 2 Synthesis of symmetric and cyclic urea derivatives from amines and CO2
Entry
Product
R
Yield/%
1
2
3
4
5
6
7
8
propyl
isopropyl
butyl
isobutyl
sec-butyl
hexyl
67.5
1.7
72.9
57.0
1.6
77.1
62.6
36.0
60.4
64.7
51.9
67.3
96.9
94.6
86.4
95.9
octyl
allyl
9
2-methoxyethyl
cyclohexyl
benzyl
phenethyl
R = H, n = 1
R = methyl, n = 1
R = H, n = 2
R = 1,2-cyclohexylene, n = 1
10
11
12
13
14
15
16
17
18
19
20
R1 = H, R2 = H, n = 1
3.5 : 58.8
R1 = methyl, R2 = H, n = 1
R1 = H, R2 = methyl, n = 1
R1 = H, R2 = H, n = 2
37.9 : 13.6
12.3 : 52.3
24.3 : 13.3
a Conditions: amine 1.0 mmol ml-1; temperature 180 ◦C; pressure 10 MPa; time 24 h. The selectivity of listed product was 100% at all the conversion
values.
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a
Table 3 Synthesis of urea derivatives from different amines and CO2
Conv./%
Select./%
A–A
Entry
B
A
B
A–B
B–B
1
2
3
4
5
6
7
8
isopropylamine
sec-butylamine
hexylamine
cyclohexylamine
benzylamine
diethylamine
dipropylamine
dibutylamine
pyrrolidine
74.3
40.5
72.7
77.5
76.9
62.5
39.2
39.4
51.0
46.7
58.1
41.4
26.1
80.1
60.3
56.6
7.8
6.6
4.2
33.8
13.9
13.3
42.9
37.3
18.6
27.8
24.2
77.8
68.1
78.1
20.4
52.5
60.8
46.4
47.1
51.4
50.3
57.8
22.2
31.9
21.9
79.6
47.5
39.2
10.6
15.6
30.1
21.8
18.0
—
—
—
—
—
9
10
11
piperidine
morpholine
—
a Conditions: A (BA) 1.0 mmol ml-1; B 1.0 mmol ml-1; temperature 180 ◦C; pressure 10 MPa; time 24 h.
Scheme 2 Proposed reaction mechanism.
sec-butylamine were low due to the steric hindrance effect
(entries 2 & 5). Alkylene diamines or alcohol amines reacted
with CO2 under the same conditions producing corresponding
cyclic ureas (entries 13–16) and urethanes (entries 17–20) as
reported in literature.24 The observation that diamine is more
reactive than nomoamine was ascribed to it bearing two amino
groups with the formation of stable five- or six-membered
rings. However, no products were detected at the same reaction
conditions for the secondary and aromatic amines. Based on
the reaction mechanism, the formation of the intermediate of
alkyl isocyanate (vide infra) was the prerequisite of the reaction,
which could not form in the case of secondary amines. The base
dissociation constant of aromatic amines is 106 times smaller
aliphatic amines with BA and CO2, but B–B products were
not detected (entries 6–11). As shown in the above paragraph,
the secondary aliphatic amines could not react with CO2, but
the asymmetric A–B products were formed in the presence of
primary aliphatic amine (BA). It could illustrate the reaction
mechanism as discussed below.
The reaction mechanism is proposed in Scheme 2. Primary
aliphatic amine 1 reacted with CO2 rapidly to form alkyl
ammonium alkyl carbamate (AAAC) 3, an intermediate, and
then form the final product 2 via the subsequent dehydration.
Two possible dehydrating steps were proposed, intermolecular
route A and intramolecular route B through the intermediate 4
or 5. It was witnessed through the following experiments.
First of all, the phase-behavior of the reaction of BA and
CO2 was observed in a high pressure view-cell. 15 ml BA was
preset into an 80 ml view-cell at room temperature (Fig. 6A).
With charging CO2 into the reactor, the gas phase turned into
black rapidly (Fig. 6B). As the pressure reached to 2 MPa, at
which the charging was stopped, the black phase turned into
gray gradually (Fig. 6C) and finally into bright within 2 min
and the pressure decreased to ca. 1 MPa (Fig. 6D). The color
change of the gas phase was due to the quick formation of
BABC, the intermediate, and then sank down to the bottom,
forming a viscous liquid. It indicates that the formation of the
intermediate 3 is a fast step. The existence of 3 was examined by
the experiment of using 5 ml cyclohexylamine or piperidine to
than the aliphatic amines (aniline pKb = 9.37 vs. BA pKb
=
3.34), which may be the reason for the inactivity of aromatic
amines. Therefore, the reaction largely depends on the structure
and the basicity of the reactant.
Moreover, urea derivatives were synthesized from different
amines with CO2 under the same reaction conditions (Table
3). Amine A and amine B with different substituents could react
with CO2 to produce, theoretically, three kinds of corresponding
urea derivatives, i.e. symmetric A–A, B–B and asymmetric A–B.
Different primary aliphatic amines reacted with BA to produce
urea derivatives, and the selectivity of the asymmetric products
was higher (entries 1–5). Interestingly, the corresponding A–A
and A–B urea derivatives could be produced from the secondary
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Scheme 3 Reaction of cyclohexylisocyanate with different amines.
Now we give a brief comparison of the two possible dehydrat-
ing routes. Route A seems to be the only possible pathway for the
secondary amines since they cannot form intermediate 5 through
route B, while it is unlikely as no products were formed for the
secondary amines. The two dehydrating routes are possible for
primary aliphatic amines, but the formation of intermediate 4
needs two molecules, in contrast only one molecule is needed
to form intermediate 5. Moreover, intermediate 5 is more
stable and readily formed compared to 4, since it is difficult
to form a four-substituted carbon atom bearing two hydroxyl
groups. Intermediate 5 can react with another primary or
secondary aliphatic amine to form the corresponding symmetric
or asymmetric urea derivatives. And thus, the route B might be
the predominant pathway.
Fig. 6 Phase behavior of the reaction of BA with CO2 to form
butylammonium butylcarbamate (BABC).
react with 5 MPa CO2 at room temperature for 10 min, with the
subsequent characterization by solid-state 13C CP/MAS NMR.
The peaks at 162.23 ppm and 161.99 ppm clearly indicate the
carbonyl group in 3 (Fig. 7). Thus amines reacted rapidly with
CO2 to form 3, and it is not rate-determining step.
Tsipis and co-worker investigated the mechanism of the
production of urea from NH3 and CO2 by using electronic
structure calculation methods.26 They indicated that NH3 and
H2O could interact with the intermediate ammonium carbamate
forming an active species, which acted as a catalyst to promote
the reaction. A similar mechanism should be applicable to the
present reaction, that amines interacted with AAAC through
hydrogen bonding or other means, and the interaction increased
with increasing the concentration of amine, thus accelerated the
dehydration to produce urea derivatives. Base was always used as
a catalyst to accelerate this reaction in literature. As illustrated
in Fig. 3, the amount of amine has a decisive effect on the
reaction. Herein amine may therefore play a role of catalyst in
present reaction, as amine is also a kind of strong base. More
detailed mechanism is under investigation by using theoretical
calculation methods.
Conclusions
In summary, we developed a simple and green process that
utilizes the captured CO2 to synthesize useful urea derivates,
which avoids the use of toxic or expensive substrates. It is a
parameter sensitive reaction, especially the concentration of the
reactant. Satisfactory yields were obtained in the absence of
any additives, which are comparable to those in the presence
of catalyst and solvent. The preliminarily study of the reaction
mechanism showed that the formation of the intermediate 5
from 3 is the rate-determining step and the intramolecular
dehydrating step (route B) is preferred. It is a green and facile
route to the synthesis of urea derivates, which has great potential
for industrial application.
Fig. 7 Solid-state 13C CP/MAS NMR spectrum of the products of
(a) cyclohexylamine and (b) piperidine reacted with CO2 at room
temperature for 10 min.
Isocyanate was suspected to be the intermediate in the
formation or the hydrolyzation of urea.24,25 So alkyl isocyanate
5 was supposed to be the intermediate in this reaction. The
reactivity of 5 was checked by using cyclohexylisocyanate to
react with different amines at room temperature (Scheme 3).
The reaction performed drastically to form the corresponding
urea derivatives. It is widely accepted that 5 is very active and
often used as building blocks to the synthesis of organics or
polymers.27,28 The intermediate 4 is not stable due to it bearing
two hydroxy groups. The above results suggest that the rate-
determining step is the formation of 4 or 5 from 3.
Experimental
All the chemicals were used as received from commercial
sources without further purification except aniline which was
distilled before use. All the reactions were conducted in a 50
mL autoclave. The reactor was firstly charged with amines
and/or additives, flushed with CO2 three times, and then placed
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into an oil batch preset to the reaction temperature. After
heating for 20 min, CO2 was introduced into the reactor with
a high-pressure liquid pump (Jasco SCF-Get) to the desired
pressure. The reaction was conducted while the mixture was
stirred vigorously with a magnetic stirrer. After the reaction,
the reactor was cooled to room temperature with an ice-water
bath and then depressurized carefully. The products were washed
with deionized (DI) water, recovered by filtration or rotary
evaporation (depending on the solubility of product in water)
and then dried in vacuum thoroughly. The powders were weighed
to determine the isolated yields. All the samples were analyzed
by gas chromatograph (Shimadzu GC-2010, Rtx-50 capillary
column). The products were characterized by GC-MS (Agilent
5975/6890N). The solid-state 13C CP/MAS NMR spectra were
obtained on a Bruker Avance 400 WB spectrometer.
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This work was financially supported by the One Hundred Talent
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