Alternatives to phosgene and carbon monoxide: Synthesis of symmetric urea derivatives with carbon dioxide in ionic liquids

Article abstract of DOI:10.1002/anie.200351098

Simple, clean, safe, reproducible, and practical describes the synthesis of disubstituted urea derivatives, which are effectively synthesized from amines and carbon dioxide with a CsOH/ionic-liquid catalyst system. The products are easily separated and the catalytic system can be reused without deactivation (see picture).

Full text of DOI:10.1002/anie.200351098

Angewandte
Chemie
CO2 Activation in an Ionic Liquid
Alternatives to Phosgene and Carbon Monoxide:
Synthesis of Symmetric Urea Derivatives with
Carbon Dioxide in Ionic Liquids**
Feng Shi, Youquan Deng,* Tianlong SiMa, Jiajian Peng,
Yanlong Gu, and Botao Qiao
N-containing compounds such as isocyanates, carbamates,
and N,N’-disubstituted urea derivatives are important chem-
icals. For example, the world production of isocyanates
exceeded 5 megatons in 2001. Currently, these chemicals are
mainly manufactured by the phosgenation of amines . The
worldwide production of phosgene ranges from 6–8 megatons
per year, which have been used mainly (> 85%) for the
synthesis of isocyanates and their derivatives. Therefore, as a
first step, the use of an alternative to phosgene in the synthesis
of isocyanates should be found to help eliminate the use of
phosgene altogether.[1–2]
Many strategies for nonphosgene routes, including reduc-
tive carbonylation[3] and oxidative carbonylation[4] by using
CO as carbonyl source, and the use of Pd,[5] Ru,[6] Rh,[7] Fe,[8]
Ni,[9] Co,[10] Mn,[11] Se,[12] Au,[13] and W[14] catalysts, have been
extensively studied. The progress in this field of research,
however, is relatively slow. Carbon monoxide is also poison-
ous and the mixing of CO and O2 for oxidative carbonylation
is potentially explosive. As an alternative, the use of dimethyl
carbonate or dimethyl sulfate as phosgene substitutes are
relatively expensive for commercial applications.[15] There-
fore, the most desirable option to avoid phosgene is to replace
it with CO2 directly. Besides the abundance of CO2 and its
environmentally benign nature, a process that uses CO2 has
the benefit of recycling carbon from the atmosphere when its
use is linked with other processes that emit CO2. The
detrimental influence of CO2 as a “green house” gas has
[*] Prof. Y. Deng, Dr. F. Shi, T. SiMa, J. Peng, Y. Gu, B. Qiao
Centre for Green Chemistry andCatalysis
Lanzhou Institute of Chemical Physics
Chinese Academy of Sciences, Lanzhou, 730000 (China)
Fax: (+86)931-8277088
E-mail: ydeng@ns.lzb.ac.cn
[**] This work was financially supportedby the National Natural Science
Foundation of China (No.20225309)
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DOI: 10.1002/anie.200351098
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3257

Communications
received more and more attention, so its use as raw
material for basic chemical production is an attractive
subject. Until now, the studies of carbonylation reac-
tions of nitrogen containing compounds by using CO2
are relatively few in comparison with those that make
use of CO, probably because of the chemical inertness of
CO2. Nevertheless, only four kinds of carbonylations of
N-containing compounds that make use of CO2 as the
carbonyl source have been reported[16] (Scheme 1).
Although the desired products are obtained in good
yields by these routes (ca. 60–90%), large amounts of
dehydrating agents, such as PCl5, POCl3, dicyclohexyl-
carbodiimide (reactions a, b and c) and/or an appropriate
base, such as Et3N (reaction c), or relatively expensive alkyl
chlorides, R’Cl (reaction d) are needed. Furthermore, large
amounts of by-products, such as Et3NHCl, Et3NHPOCl, HCl
are inevitably formed. Although CO2 was used as a carbonyl
source as an alternative to phosgene in the synthesis of
isocyanate and its derivatives, this route was not only more
expensive but also environmentally less friendly.
Scheme 1. Carbonylations of N-containing compounds with CO2 as the car-
bonyl source.
quantities of dehydrating agents should imply a breakthrough
in the synthesis of isocyanates with CO2 and amine without
the need of stoichiometric quantities dehydrating agent.
These processes are illustrated in Scheme 2.
A series of aliphatic amines, and even aromatic amines,
react with CO2 to afford corresponding urea derivatives with
moderate to high yields in the presence of the CsOH/ionic-
liquid catalyst system (Table 1).[20] The type of cations and
anions of the ionic liquids have a strong impact on the
Recently, room-temperature
ionic liquids,
a reaction media
with very low vapor pressure, pecu-
liar physicochemical properties,
and selective solubility towards
many organic and inorganic sub-
stances, have attracted growing
interest. Many catalytic reactions
that proceed in ionic liquids were
reported, with satisfactory per-
formances in many cases.[17] The
combination of ionic liquids as
versatile and novel reaction media
with a suitable catalyst, such as
acid, base, nanostructures, or
metal-complex, may result in a
more diverse and flexible “plat-
form” to establish a highly effec-
tive and easily separable catalytic
system.
Scheme 2. The transformations between urea, carbamate, andisocyanate derivedfrom amine and
CO2.
Table 1: Results for synthesis of symmetric urea derivatives with carbon dioxide.
Herein, we report an effective
process for the direct synthesis and
separation of symmetric urea
derivatives in good yield from
amines by using CO2 as the car-
bonyl source. The recyclable cata-
lytic system consists of an ionic
liquid and base and avoids the need
for stoichiometric quantities of
dehydrating agent. As it was dem-
onstrated that N,N’-disubstituted
urea derivatives could easily be
converted into the corresponding
carbamates,[18] and the carbamates
can be thermally decomposed to
form isocyanates,[19] thus, the
breakthrough in the synthesis of
N,N’-disubstituted urea derivatives
in the absence of stoichiometric
Entry Substrates
Ionic liquidCatalysts
t [h] Product
Yield [%,
isolated]
1
BMImBF4
BMImPF6
BMImCl
BMImCl
CMImCl
CsOH
CsOH
CsOH
CsOH
CsOH
4
4
4
4
4
84.5
56.6
98
2
3
4[a]
5
93
–
6
7
8
BMImCl
BMImCl
BMImCl
KOH
4
6
6
53.5
93
CsOH
CsOH
86
9
BMImCl
BMImCl
CsOH
CsOH
36
36
27
33
10
[a] The catalyst system hadbeen twice recoveredandusedfor a thirdtime.
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Chemie
formation of urea derivatives when cyclohexylamine is the
substrate (Table 1 entries 1–6).[21] If the conversion is suffi-
ciently high, the desired product precipitates on adding about
10 mL water into the reaction mixture as urea is insoluble in
water,[22] whereas CsOH and the ionic liquid are water-soluble
(Figure 1). The solid product could be recovered by filtration
and dried. A yield of 98% was obtained when BMImCl ionic
liquid containing CsOH was employed (Table 1 entry 3).
nates. The concept of reaction and separation has been
fulfilled with a simple CsOH/ionic liquid catalyst system that
takes advantage of the nonvolatility and selective solubility of
the ionic liquid. This concept may be expanded to other
catalysis systems.
Received: February 4, 2003 [Z51098]
Keywords: amines · carbon dioxide · carbonylation · green
.
chemistry · ionic liquids
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The use of a weaker base was found to disfavor the
formation of urea derivatives; a yield of only 53.5% was
obtained when CsOH was replaced with KOH, a relatively
weak base. The ionic liquid was indispensable for the
formation of the desired product as the yield of dicyclohexyl
urea was almost zero in the absence of ionic liquid.
As to primary amines with a linear chain, a longer reaction
time was needed to obtain similar yields to those of cyclo-
hexylamine, (Table 1 entries 7, 8).
Surprisingly, good results were also achieved with aro-
matic amines, which have never been effectively carbonylated
directly by carbon dioxide, although longer reaction times
were required. Yields of 27% and 33% were obtained with
aniline and p-methoxylaniline, respectively, (Table 1entries 9,
10). No urea derivative was afforded with m-nitroaniline,
which may be attributed to the strong electron-withdrawing
property of the nitro group.
The recycling of BMImCl/CsOH catalyst system was also
tested. Ionic liquid containing CsOH could be recovered and
reused after it was distillated to remove water, and a yield of
93% of urea was obtained when CsOH/BMImCl system was
used for a third time.
In summary, the organic-solvent- and dehydrating-agent-
free process for carbonylation of both aliphatic and aromatic
amines with carbon dioxide to afford urea derivatives is
simple, clean, safe, reproducible, and even practical. Further-
more, urea derivatives are potential precursors for the
phosgene- and carbon monoxide-free synthesis of isocya-
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Communications
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[20] The ionic liquids were synthesized according to reported
procedures (P. Bonhote, A. P. Dias, N. Papageorgiou, K.
Kalyanasundaram, M. Grꢀtzel, Inorg. Chem. 1996, 35, 1168)
with slight modifications. The following ionic liquids were
synthesized: 1-n-butyl-3-methyl imidazolium tetrafluoroborate
(BMImBF4), 1-n-butyl-3-methyl imidazolium hexafluorophos-
phate (BMImPF6), 1-n-butyl-3-methyl imidazolium chloride
(BMImCl) and 1-n-cetic-3-methyl imidazolium chloride
(CMImCl).
A typical procedure for the carbonylation of
amines with CO2 is as follows. 2 ml (or 2 g) of amine, 3 ml of
ionic liquid and 0.05 g of base were put into an autoclave
(100 ml) with a magnetic stirring bar. Carbon dioxide (60 atm,
purity > 99%) was introduced into the reactor, and the reaction
was stirred and heated at 1708Cfor 4–36 h. Water (10 mL) was
added into the resulting reaction mixture, and the desired
resulted product precipitated out. The solid product was
recovered by filtration, washing and drying. Ionic liquid
containing CsOH could also be recovered and reused after the
filtrate was distillated to remove water. All products were
qualitatively analyzed with
a HP 6890/5973 GC–MS and
quantitatively analyzed with HP 1790GC(flame ion detector).
[21] When using CsOH/CMImCl, a foamy mixture resulted that
could not be separated effectively, although the conversion of
cyclohexylamine was analyzed by GCand found to be > 95%.
[22] The by-products formed in the reactions were only carbamic
salts, which readily dissolved in water.
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