Carbamate synthesis by solid-base catalyzed reaction of disubstituted ureas and carbonates

Article abstract of DOI:10.1039/b107947f

A simple and efficient methodology to prepare carbamates has been demonstrated for the first time from symmetrical ureas and organic carbonates in the presence of solid base catalysts.

Full text of DOI:10.1039/b107947f

Carbamate synthesis by solid-base catalyzed reaction of disubstituted
ureas and carbonates
Sunil P. Gupte, Anand B. Shivarkar and Raghunath V. Chaudhari*
Homogeneous Catalysis Division, National Chemical Laboratory, Pune-411008, India.
E-mail: rvc@ems.ncl.res.in
Received (in Cambridge, UK) 5th September 2001, Accepted 31st October 2001
First published as an Advance Article on the web 3rd December 2001
A simple and efficient methodology to prepare carbamates
has been demonstrated for the first time from symmetrical
ureas and organic carbonates in the presence of solid base
catalysts.
carbonates to carbamates utilizing the total functionality of both
the urea and the carbonate. In this communication, we report for
the first time, a new methodology for the synthesis of
carbamates from substituted ureas and organic carbonates using
a highly efficient and simple catalyst system [Scheme 1, eqn.
(iii)].† This novel protocol has 100% atom economy while
using an environmentally benign reactant source.
Carbamates are compounds of growing interest because of their
applications in the agrochemicals industry as herbicides,
fungicides and pesticides, in the pharmaceuticals industry as
drug intermediates and in the polymer industry, in the synthesis
of polyurethane. The commercial production of urethane is
almost exclusively based on phosgene technology, however,
due to worldwide awareness of pollution hazards of phosgene
and pollution prevention laws adopted by Governmental
agencies it is most essential to substitute it by environmentally
benign routes. Efforts have continuously been made for the
replacement of the phosgene route with routes such as reductive
carbonylation of nitro aromatics and oxidative carbonylation of
amines which have shown some promise. However, the former
route will suffer from a lack of economical viability in the near
Surprisingly, the reaction between aromatic ureas and
carbonates has not been studied12 previously. A non-catalytic
reaction between N,NA-diphenylurea and diphenyl carbonate
gave only traces of N-phenyl phenyl carbamate after 24 h at
150 °C (see Table 1, entry 1). During the course of our
investigations for screening of catalysts it was observed that
basic catalysts such as triphenyl phosphine, sodium phenolate
etc. were more effective than classical acid catalysts such as
Lewis acids (FeCl
acidic Al (entry 4). However, heterogeneous basic catalysts
e.g. Mg–Al hydrotalcite, Li–MgO, PbZrO , the Na form of
3 3
, AlCl etc.) and solid acid catalysts such as
2 3
O
3
zeolite ZSM-5 and amorphous catalyst grade silica gel were
found to give excellent results amongst the catalysts examined,
which are summarized in Table 1. Most of the catalyst screening
and recycling of catalyst studies were carried out aiming for
industrially important phenyl N-phenyl carbamate (PPC) as the
product and for this purpose N,NA-diphenyl urea (DPU) and
diphenyl carbonate (DPC) were chosen as model substrates
(entries 2–9). From the catalysts screened, amorphous silica gel
was found to be the most suitable catalyst because of its
commercial availability, low cost and ease in recycling.
Therefore, further studies were carried out using silica gel
catalyst. The generalized applicability of the method is also
verified and is evident from the range of carbamates synthesized
from different ureas and carbonates (Table 1). Aromatic
substituted ureas were also found to react smoothly with DPC
giving the corresponding carbamates in excellent to high yields
(entries 10–14). However, reaction between DPU and dimethyl
carbonate (DMC) gave only a poor yield of N-phenyl methyl
carbamate (entry 15). Interestingly, industrially important N-
methyl methyl carbamate is produced in excellent yield from
dimethyl urea and DMC (entry 16), while dimethyl urea and
dibutyl carbonate require highly basic potassium supported
silica gel catalyst for excellent yields of carbamate (entry 17). In
general it was observed from screening of the substrates that,
excellent yields of carbamates are obtained, when an aromatic
urea was reacted with an aromatic carbonate and likewise for
aliphatic derivatives. Catalyst screening experiments indicated
that the basicity of the catalysts plays a vital role in their
1
future while the latter suffers from hazards in handling of
carbon monoxide and oxygen under high pressures. Carbamate
synthesis has also been accomplished by several-pot reaction
2
methods such as Hofmann rearrangement from amides, by
3
reaction of chloroformates and amines catalyzed by zinc, and
from alcohols to unsubstituted carbamates by treatment with
4
2 3
trichloroacetyl isocyanate, followed by hydrolysis on Al O .
Recently, the use of carbon dioxide to replace phosgene has
been attracting attention of research workers mainly due to its
non-hazardous nature and safety in handling under pressure.
Usually powerful organic bases5 (e.g. N-cyclohexyl-
NA,NA,NB,NB-tetramethylguanidine etc.) or additives such as
crown ethers6 are required to stabilize carbamate anion
2
generated during amine and CO reaction. This difficulty was
partly overcome by using tetraethylammonium hydrogen car-
7
bonates (TEAHC), and a combination of potassium carbonate
8
and onium salts as catalysts for the synthesis of carbamates
from alkyl halides and amines. However, these methods at
present are not attractive for bulk production of carbamates as
they utilize only stoichiometric quantities of reagents and
generate salts as by-products, which are not easy to dispose.
Recently, two industrially very important methods have been
reported for the synthesis of carbamates viz., alcoholysis of
9
10
ureas and carboxylation of amines. We were interested in
developing methods for the synthesis of carbamates utilizing
solid catalysts, as they are industrially important due to their
potential in replacing conventional acid/base catalysts. The use
of solid acid/base catalysts for synthesizing organic inter-
mediates and fine chemicals is gaining increasing awareness
and is a field of intense research activity.11 While, working on
reactions of alcoholysis of urea (i) and carboxylation of amines
(
ii) to carbamic acid esters (Scheme 1), we realized that,
reactions (i) and (ii) both show poor atom economy and in each
case alcohol or amine is produced as a byproduct reducing the
functional group efficiency of the reagent. One way of
improving the atom economy in reactions (i) and (ii) is to
eliminate the use of alcohols and amines. Therefore, we were
interested in effecting the conversion of disubstituted ureas and
Scheme 1 Carbamate synthesis from urea and carbonate.
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Chem. Commun., 2001, 2620–2621
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b107947f

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Table 1 Solid base catalysed carbamate synthesis from ureas and carbonatesa
1
2
b
Entry
R (urea)
R (carbonate)
Catalyst
Time/h
Yield (%)
1
2
C
C
6
H
H
5
C
C
6
H
H
5
None
24
3
8
3
3
3
3
3
4
3
8
8
8
8
8
8
8
8
Trace
81
96
23
0
Silica gelc
6
5
6
5
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
C
6
C
6
C
6
C
6
C
6
C
6
C
6
H
5
H
5
H
5
H
5
H
5
H
5
H
5
C
6
C
6
C
6
C
6
C
6
C
6
C
6
C
6
C
6
C
6
C
6
C
6
H
H
H
H
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
5
5
5
Silica geld
2 3
O
(acidic)e
Al
5% Pb on silica gel
c
18
92
95
79
90
89
73
79
89
91
18
81
80
f
PbZrO
Mg–Al hydrotalcite
Na-ZSM-5 (Si/Al = 130)
3
g,h
h
i
Li–MgO
1
1
1
1
1
1
1
1
4-CH
3
C
H
6 4
6
H
4
Silica gelc
Silica gelc
Silica gelc
2-ClC
3-ClC
4-ClC
6
H
H
4
c
6
4
Silica gel
4-NO
2
C
6
H
4
5
j
Silica gelc
Silica gelc
Silica gelc
C
6
H
5
CH
CH
3
j
CH
CH
3
3
c,k
3
C
4
H
9
5%K-Silica gel
a
c
b
Reaction conditions: urea: 3.16 mmol; carbonate: 15.4 mmol; catalyst: 200 mg; solvent: carbonate; temperature: 150 °C; agitation: 1000 rpm. Isolated.
Silica gel from W.R.Grace, USA. Silica gel from Davisil, Aldrich. Activated, Brockmann-1, Aldrich. 0.9 mmol. Mg/Al ratio: 3+1. h Synthesized in
d
e
f
g
i
our laboratory using a standard procedure. Prepared by wet impregnation of lithium acetate on magnesium acetate followed by calcination in air at 750 °C
j
3
3
k
(
Li/Mg = 0.1). A 50 cm autoclave was used with 30 bar nitrogen pressure and 15 cm of dimethyl carbonate. Wet impregnation of K
2 3
CO on silica gel
followed by calcinations in air at 500 °C.
show excellent reusability of both the catalysts for up to five
recycles. Calcination for silica gel considerably improves the
catalyst activity over simply drying and recycling of the
catalyst.
In summary the protocol presented here is environmentally
benign, simple and involves inexpensive reagents and can be
effectively applied to large-scale synthesis of carbamates in
high yield.
Notes and references
†
Experimental procedure: A symmetrical urea (3.16 mmol), aromatic
dicarbonate (155.6 mmol) and W.R.Grace silica gel catalyst (200 mg) were
3
added to a well flushed and dried reaction vessel (50 cm ) equipped with a
stirrer and reflux condenser. The contents were heated under stirring up to
1
50 °C and kept for 8 h while an inert atmosphere was maintained. After
cooling to room temperature, the solid mass was dissolved in acetone,
filtered to separate the catalyst and the carbamate isolated in pure form by
column chromatography (silica gel, ethyl acetate–chloroform 0.2+9.8). All
1
13
the products were fully characterized by elemental analysis, H NMR,
C
Fig. 1 Catalyst recycle runs.
NMR, IR, GC–IR and comparison with authentic samples whenever
possible. Recycling of catalyst was carried out by filtration of catalyst from
the crude reaction mixture in acetone followed by drying of catalyst and
calcination 500 °C for 3 h.
activity. Also, from the earlier literature, it is known that basic
catalysts are highly efficient for reactions involving carbonates
e.g. carbomethoxylation, trans-esterification and methyla-
(
1
2
F. Paul, Coord. Chem. Rev., 2000, 203, 310.
Y. Matsumura, T. Maki and Y. Satoh, Tetrahedron Lett., 1997, 38,
1
3
tion). The solid-base catalysts tested were all found to give
excellent yields of carbamates, however, we believe that for
exceptional activity, dual acid/base sites on the solid support are
8
879.
3
J. Yadav, G. Reddy, M. Reddy and H. Meshram, Tetrahedron Lett.,
1998, 39, 3259.
3
necessary. For catalysts having only basic sites (e.g. PPh ,
K
2
CO
3
, NaOH) only moderate yields of carbamates could be
4 P. Kocovsky, Tetrahedron Lett., 1986, 27, 5521.
5 W. D. McGhee, Y. Pan and D. P. Riley, J. Chem. Soc., Chem. Commun.,
14
realised. The activity of silica gel catalyst can be attributed to
1
994, 699.
the interactions of organic urea and carbonate with silanol
groups on the silica gel surface.15 The variation in activity of
6 M. Aresta and E. Quaranta, Tetrahedron, 1992, 48, 1515.
7
8
A. Inesi, V. Mucciante and L. Rossi, J. Org. Chem., 1998, 63, 1337.
M. Yoshida, N. Hara and S. Okuyama, J. Chem. Soc., Chem. Commun.,
silica gel catalysts procured from two different sources viz.
W.R.Grace & Co., and Davisil (entries 2 and 3 of Table 1) is
thought to be due to the difference in distribution of silanol
groups in these two silica gels. Na-ZSM-5 catalysts with Si/Al
2
000, 151.
9
K. Kongen, C. Arihito, S. Kashun and R. Akyasu, Jpn. Kokai Tokkyo
Koho, JP 08198815 A2 6th Aug, 1996.
ratio of 130 essentially behaved like SiO
2
since at these high
10 A. E. Gurgiolo, US Pat., 4 268 683, 1981; Z. H. Fu and Y. Ono, J. Mol.
Catal., 1994, 91, 399; I. Vauthey, F. Valot, C. Gozzi and M. Lemaire,
Tetrahedron Lett., 2000, 41, 6347.
ratios of Si/Al, Al atoms no longer contribute to a major extent
to the framework structure of the zeolite. The activity in these
1
1 K. Tanabe and W. F. Holderich, Appl.Catal. A, 1999, 181, 399.
zeolites is likely to be due to basic sites created by oxygen atoms
while Al contributes to the Lewis acid sites.16 Common urea
12 P. Molina and A. Tarraga, Comprehensive Organic Functional Group
Transformations, Pergamon Press, Oxford, 1997, vol. 5, p. 981.
and N-methyl urea were also examined for carbamate synthesis
from DPC, however, the carbamates formed were unstable and
at the end of the reaction ill characterized white solids could
only be isolated.
1
1
3 Y. Ono, App.Catal. A, 1997, 155, 133.
4 These catalysts gave a PPC yield of 25–30% under the experimental
conditions employed in this work.
1
5 T. Suzuki, H. Tomon and M. Okazaki, Chem. Lett., 1994, 2151.
The reusability of catalysts was tested for silica gel and Na-
ZSM-5 catalyst and the results are shown in Fig. 1. The results
16 D. Barthomeuf, J. Phys. Chem, 1984, 88, 42; M. Selva, P. Undo and A.
Perosa, J. Org. Chem., 2001, 66, 677.
Chem. Commun., 2001, 2620–2621
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