Formanilide and carbanilide from aniline and carbon dioxide

Article abstract of DOI:10.1016/S0040-4039(03)00384-8

Earlier syntheses of formamides from the catalytic hydrogenation of CO₂ in the presence of amines were only successful for the preparation of dialkylformamides. After an analysis of the reason for the failure of the reaction using aniline as a starting material, formanilide has been prepared, for the first time, from CO₂, H₂ and aniline with the use of 1,8-diazabicyclo[5.4.0]undec-7-ene. Omission of the H₂ reductant causes the selectivity to switch to the production of carbanilide (1,3-diphenylurea).

Full text of DOI:10.1016/S0040-4039(03)00384-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2725–2727
Formanilide and carbanilide from aniline and carbon dioxide
Pradip Munshi, David J. Heldebrant, Erin P. McKoon, Patrick A. Kelly, Chih-Cheng Tai and
Philip G. Jessop*
Department of Chemistry, University of California, Davis, CA 95616-5295, USA
Received 9 May 2002; revised 31 January 2003; accepted 4 February 2003
Abstract—Earlier syntheses of formamides from the catalytic hydrogenation of CO in the presence of amines were only successful
2
for the preparation of dialkylformamides. After an analysis of the reason for the failure of the reaction using aniline as a starting
material, formanilide has been prepared, for the first time, from CO , H and aniline with the use of 1,8-diazabicyclo[5.4.0]undec-
2
2
7
-ene. Omission of the H reductant causes the selectivity to switch to the production of carbanilide (1,3-diphenylurea). © 2003
2
Elsevier Science Ltd. All rights reserved.
Carbon dioxide, by virtue of its great abundance, has
attracted continuing attention as a useful C1 building
block. There have been many reports describing the
lidine and piperidine using RhCl(PPh3)3 could be
achieved at 125°C but no yields were given and the
reaction was ‘not fast’. Supercritical pressures of CO2,
combined with trans-RuCl (PMe ) catalyst, were
1
conversion of CO to a small range of useful chemicals
2
2
3 4
2–5
with the help of homogeneous catalysts.
However,
found to be highly effective for the conversion of CO
2
further work is required to extend the range. For
example, highly efficient homogeneous catalysts have
been identified for the synthesis of dialkylformamides
6–8,11–14
and dialkylamines to dialkylformamides.
Unfor-
tunately, even the supercritical CO2 protocol was
unable to prepare a significant yield of formanilide
from aniline. Although formanilides, which are used as
6–8
from CO and amines,
but no catalysts have been
2
found for the preparation of formanilides from CO2
and anilines (Eq. (1)). We have now observed the
homogeneously catalyzed conversion of aniline, CO2,
15
antioxidants and in the pharmaceutical industry, rep-
resent an important class of formamides, their prepara-
tion by CO hydrogenation in the presence of anilines
2
and H into formanilide with high selectivity. In the
2
has not been reported.
absence of H , carbanilide is formed (Eq. (2)).
2
The N,N-dialkylformamide synthesis with trans-
(
(
1)
2)
6,7
RuCl (PMe ) catalyst precursor is known to proceed
2
3 4
by Ru-catalyzed and alcohol-cocatalyzed hydrogena-
tion of CO to the ammonium formate salt, which is
2
then thermally dehydrated in situ to the corresponding
formamide (Eq. (3)). The failure of less basic amines
such as aniline to be converted to formamides is a
result of their inability to promote the hydrogenation of
Synthetic methods for the preparation of formamide
derivatives via hydrogenation of CO in the presence of
2
CO in the first step, not any inability of the formate
2
ammonia, a primary amine, or a secondary amine were
salt to be dehydrated to the formamide. This was
confirmed by heating a 1:1 mixture of formic acid and
aniline to 100°C for 10 h (in the absence of solvent or
catalyst); 76% of the aniline was found to be converted
to formanilide. Therefore, the reason for the poor yield
9
first developed in 1935. However, the method has so
far been essentially restricted to the preparation of
N,N-dimethylformamide (from dimethylamine) and
other simple formamides from mono- or dialkylamines
of similar basicity and with very small alkyl groups.
1
0
of formamide from CO
2
, with these more difficult
Haynes et al. reported that the conversion of pyrro-
amines, must lie in the hydrogenation step of Eq. (3).
*
Corresponding author. Tel.: +1-530-754-9426; fax: +1-530-752-8995;
e-mail: jessop@chem.ucdavis.edu
(3)
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00384-8

2
726
P. Munshi et al. / Tetrahedron Letters 44 (2003) 2725–2727
a
7
Table 1. The reactions of aniline with CO and H
concentration, at least at lower base concentrations.
Adding both C F OH and DBU simultaneously does
2
2
6
5
Base
Alcohol
Formanilide
Carbanilide (mol%)
not further increase the yield. The greatest spectro-
scopic yield of formanilide was 85% (1,400 TON),
obtained by increasing both the reaction time and the
amount of DBU. The product was isolated by washing
the vessel contents with 5% HCl, extracting three times
from the acid washes with ether, combining the ether
extracts with the organic residue from the vessel, drying
with MgSO , filtering and removing volatiles in vacuo.
The formanilide product was obtained as white crystals
in 72% isolated yield.
(
mol%)
None
None
None
None
5
2
14
1
35
85
35
0
0.3
0
0
0
MeOH
C F OH
6
5
Barton’s
DBU
None
None
None
b
DBU
0
6
4
DBU
C F OH
6
5
a
All experiments with 3 mmol RuCl (PMe ) , 120 bar CO , 80 bar
H , 0.1 mmol alcohol (where used), 5 mmol base (where used), 5
mmol aniline, 31 mL stainless steel vessel at 100°C for 10 h.
2
3 4
2
2
Omitting H gas from the reaction mixture during the
formanilide preparation completely reverses the selec-
tivity to carbanilide, rather than formanilide, synthesis
2
b
1
0 mmol DBU, 23 h.
(
Table 2). Carbanilides, which are used as antimicro-
More efficient conversion of these amines into for-
mamides by the hydrogenation of CO2 therefore
requires an increase in the rate of the hydrogenation
step. We recently discovered that use of particularly
acidic alcohols has a favorable effect on the rate of that
17–19
bials and dyes,
aniline and either phosgene or arylisocyanates, both
highly toxic. Uncatalyzed syntheses from aniline and
are traditionally prepared from
CO include the use of unusual drying agents such as
2
2
0
21
1
6
[BuP(OPh) ]Br or SO ·NMe , usually in conjunction
step. In the presence of weakly basic amines such as
3 3 3
with organic bases such as DBU. Of course, in the
absence of a strong dehydrating agent, it is difficult to
obtain a high yield of carbanilide. Although the extent
of conversion, after 10 h at 100°C, is low, the selectivity
is very high; no formanilide or other aromatic products
aniline derivatives, the rate of CO hydrogenation is
2
increased by the use of C F OH rather than methanol
6
5
or water as the cocatalyst. We found in the present
system that addition of C F OH did indeed increase the
6
5
yield of formanilide (Table 1). However, adding a stoi-
chiometric amount of the base DBU (1,8-diazabicyclo-
1
are detected by H NMR spectroscopy. The synthesis
[
5.4.0]undec-7-ene) increases the yield by an order of
requires DBU, does not require the Ru complex, and is
inhibited by the addition of an acidic alcohol. Decreas-
ing the amount of DBU 5-fold caused the yield of
magnitude, probably because DBU is a better base than
aniline and therefore is better able to stabilize the
formate salt intermediate in Eq. (3). DBU is used in
stoichiometric quantities because the rate of the hydro-
genation step is known to be proportional to base
carbanilide to drop by half. Decreasing the CO pres-
2
sure to only 10 bar CO caused only a small decrease in
2
the yield of carbanilide. Attempts to obtain a greater
a
2
Table 2. The reactions of aniline with CO in the absence of H
2
DBU (mmol)
Additive
T (°C)
Formanilide (mol%)
Carbanilide (% of theoretical yield)
0
0
1
5
5
5
5
5
5
5
5
5
5
1
1
1
1
None
100
100
100
60
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
10
0
18
15
11
20
13
17
17
15
4
C F OH
6
5
None
None
None
Mol. sieve
DMSO
DMSO & mol. sieve
None
None
100
100
100
100
100
100
100
100
100
100
100
120
100
c
c
d
c,e
b
None
c
[bmim]BF4
C F OH
6
5
c,e
0
0
0
0
None
None
None
17
46
39
f
c,e
c
g
C F OH
23
6
5
a
Conditions: 120 bar CO , 5 mmol aniline, 0.1 mmol C F OH (where used), 3–4 mL DMSO (where used), 1.5 mL 1,3-butylmethylimidazolium
2
6 5
tetrafluoroborate (where used), 3 mmol RuCl (PMe ) , 31 mL stainless steel vessel at 100°C for 10 h.
2
3 4
b
c
d
e
f
No RuCl (PMe ) added.
2
3 4
1
8–22 h.
Only 10 bar CO2.
mmol RuCl (PMe ) .
9
2
3 4
4
8 h.
g
Other unidentified products also observed.

P. Munshi et al. / Tetrahedron Letters 44 (2003) 2725–2727
2727
yield of carbanilide, by adding molecular sieves, more
DBU, or a solvent (DMSO or N,N-butylmethylimida-
zolium tetrafluoroborate) were unsuccessful. Raising
the temperature to 120°C more than doubled the yield
of carbanilide but unidentified other products were also
observed. The reaction did not proceed appreciably at
State University, http://prof.ucdavis.edu, grant number
K12GM00697.
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6
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obtained at 100°C with a 48 h reaction time and using
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2
3,24
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1
1
1
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2
3 4
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2
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Acknowledgement is made to the Division of Chemical
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Science, US Department of Energy (grant number DE-
FG03-99ER14986). This support does not constitute an
endorsement by DOE of the views expressed in this
article. NMR spectrometers used in this study were
funded by NSF CRIF program (CHE-9808183).
Patrick A. Kelly was supported in part by an NIGMS
MORE Institutional Research and Academic Career
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