One-pot synthesis of N,N-dimethylaniline from nitrobenzene and methanol

Article abstract of DOI:10.1039/b905656d

A route for the direct synthesis of N,N-dimethylaniline from nitrobenzene and methanol was developed through the sequential coupling of the hydrogen production from methanol, hydrogenation of nitrobenzene to produce aniline, and N-methylation of aniline over a pretreated Raney-Ni catalyst (at 443 K in methanol). A high yield of N,N-dimethylaniline up to 98% was obtained by the proposed methodology. In this process, aniline was produced from in-situ hydrogenation of nitrobenzene with hydrogen generated from methanol, or transfer hydrogenation of nitrobenzene with methanol as donor, while methanol acted as a hydrogen source, alkylating reagent and solvent, simultaneously. Additionally, a plausible mechanism of this one-pot reaction process has been described.

Full text of DOI:10.1039/b905656d

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PAPER
www.rsc.org/njc | New Journal of Chemistry
One-pot synthesis of N,N-dimethylaniline from nitrobenzene
and methanol
Long Xu,a Xiaonian Li,*a Yifeng Zhuab and Yizhi Xianga
Received (in Victoria, Australia) 20th March 2009, Accepted 22nd June 2009
First published as an Advance Article on the web 21st July 2009
DOI: 10.1039/b905656d
A route for the direct synthesis of N,N-dimethylaniline from nitrobenzene and methanol
was developed through the sequential coupling of the hydrogen production from methanol,
hydrogenation of nitrobenzene to produce aniline, and N-methylation of aniline over a
pretreated Raney-Nis catalyst (at 443 K in methanol). A high yield of N,N-dimethylaniline
up to 98% was obtained by the proposed methodology. In this process, aniline was produced
from in-situ hydrogenation of nitrobenzene with hydrogen generated from methanol, or transfer
hydrogenation of nitrobenzene with methanol as donor, while methanol acted as a hydrogen
source, alkylating reagent and solvent, simultaneously. Additionally, a plausible mechanism
of this one-pot reaction process has been described.
the coupling of the APR of ethanol, hydrogenation of
Introduction
nitrobenzene and N-ethylation of aniline. In this paper, we
report a one-pot synthetic method for NNDMA from
nitrobenzene and methanol (Scheme 2). This process was
realized through the coupling of hydrogen production from
methanol, hydrogenation of nitrobenzene for aniline, and
N-methylation of aniline for NNDMA, simultaneously.
As a valuable intermediate in the synthesis of dyes, paints,
medicines and pesticides,1 N,N-dimethylaniline (NNDMA)
has been traditionally synthesized by N-methylation of aniline
with methylating reagents such as methanol, dimethyl carbonate,2
formaldehyde3 and methyl halides. Formaldehyde and methyl
halides are not eco-friendly reagents due to their highly
noxious nature.4 Dimethyl carbonate and methanol are
both green reagents but methanol is cheaper than dimethyl
carbonate.5 However, the synthesis of NNDMA from aniline
and methanol in the liquid-phase is no longer a preferred route
due to the use of liquid acid, such as sulfuric acid, as the
catalyst. Heterogeneous catalytic synthesis of NNDMA in the
gas-phase over metallic oxide,6 zeolite7 or other solid acid8 is
an environmentally benign process, but it suffers from low
conversion of aniline. Recently, Selva et al.5 suggested that
NNDMA could not be formed from aniline and methanol at a
low temperature (423–473 K) over the NaX-type faujasites,
but they interestingly found that it could be produced through
a sequential coupling of the transesterification of ethylene
carbonate with the selective N-methylation of aniline under
identical conditions. However, it should be noted that aniline
was used as the starting material in all of the aforementioned
routes for the synthesis of NNDMA.
Results and discussion
As shown in Table 1, the conversion rate was significantly
influenced by the temperature and amount of Raney-Nis,
but the selectivity of products was almost unchanged
(Table 1, entries, 1–10). The yield of NNDMA was decreased
with an increase of nitrobenzene or water (Table 1, entries 8
and 11–19). An optimal yield of NNDMA up to 98% (isolated
yield 92.5%) was obtained from nitrobenzene and methanol in
a one-pot reaction at 443 K and 3.0 MPa (N2 pressure) in a
stainless-steel autoclave (500 ml), which was higher than the
yield obtained by Selva et al. (89%) through the sequential
coupling of the transesterification of cyclic carbonates with
selective N-methylation of anilines.5 In particular, the reaction
was not only carried out under a mild condition, but also has
high conversions of aniline (100%) and N-methylaniline
(99.7%).
In previous work, we9 have coupled the aqueous-
phase-reforming (APR) of alcohols10 and the liquid-phase
To investigate the hydrogen source of the nitrobenzene
hydrogenation for aniline, methanol (with or without water)
was tested for hydrogen production. Catalyzed by the
Raney-Nis catalyst, more H2 (8.3%) and CO2 (10.4%) were
produced from methanol and water than from only methanol
hydrogenation of unsaturated compounds to realize
a
novel method of liquid-phase hydrogenation (Scheme 1).
Additionally, N-monoethylaniline was obtained from
nitrobenzene and ethanol directly with a yield up to 86% via
a Industrial Catalysis Institute of Zhejiang University of Technology,
State Key Laboratory Breeding Base of Green Chemistry Synthesis
Technology, Hangzhou 310032, P. R. China.
E-mail: xnli@zjut.edu.cn; Fax: +86 571-88320409;
Tel: +86 571-88320409
b West Branch of Zhejiang University of Technology, Quzhou 324000,
P. R. China
Scheme 1 Liquid-phase hydrogenation of nitrobenzene.
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Table 2 Reduction of nitrobenzene with H2 or methanola
Entry Reactants
T/K Conv. (%) Selectivity (%)
1b
PhNO2 + H2
443 100
Scheme 2 One-pot synthetic method for NNDMA.
2c
PhNO2 + CH3OH 353
45.6
0
(4.9% and 2.6%, respectively). The amount of CO2 shows that
more H2 was produced from methanol through APR with the
addition of water.
3d
PhNH2 + CH3OH 353
—
The hydrogenation of nitrobenzene with H2 and methanol,
respectively, as the hydrogen source was investigated. Using
H2 as hydrogen source will result in the formation of aniline
(Table 2, entry 1), cyclohexylamine,11 and cyclohexanol10b
etc., simultaneously. While the hydrogenation of nitrobenzene
with methanol as hydrogen source could produce aniline,
N-methyleneaniline and N-methylaniline, simultaneously at
353 K (Table 2, entry 2), N-methylaniline could not be
produced from aniline and methanol under the identical
conditions (Table 2, entry 3), because formaldehyde can not
be produced from methanol over the Raney-Nis catalyst
without a hydrogen acceptor.12 These results suggested that
the catalytic transfer hydrogenation of nitrobenzene using
methanol as hydrogen donor could lead to the formation
of aniline and formaldehyde together.13a This transfer
hydrogenation process could favor the formation of N-methylene-
aniline and N-methylaniline due to the formation of
formaldehyde.
Reaction time = 5 h, 5 g Raney-Nis as catalyst. 60 ml cyclo-
a
b
c
hexane as solvent, 2 ml PhNO2, under 3 MPa H2. 2 ml PhNO2,
d
60 ml CH3OH. 2 ml PhNH2, 60 ml CH3OH.
hexanol and N-methylaniline (Table 3, entry 2). In the case of
using formaldehyde as methylating reagent, the results show
that N-methyleneaniline could be produced from aniline
and sequentially hydrogenated into N-methylaniline with
methanol as hydrogen source (Table 3, entries 3, 4).
As shown above, the generation of NNDMA from nitro-
benzene and methanol was carried out by multi-step reaction
pathways in one reactor over a multifunctional catalyst.
Scheme 3 illustrates the essential features of the one-pot
synthesis of NNDMA. It involves first formation of aniline
from the in-situ and/or transfer hydrogenation of nitrobenzene
as described in the follows, these initial steps were followed by
stepwise N-methylations of aniline to produce NNDMA
finally. Methanol in this reaction system could be versatile,
since it acted as a hydrogen source, alkylating reagent and
solvent, simultaneously. Additionally, the simply pretreated
commercial Raney-Nis catalyst seems to be multifunctional
for its feasibility on hydrogen production from methanol,10d
Finally, the N-methylation of aniline with methanol
or formaldehyde as the methylating reagent was also
investigated. When the methanol was used as methylating
reagent, a high yield of NNDMA (95.0%) was obtained
(Table 3, entry 1). The addition of water, however, decreased
the yield of NNDMA (90.8%) with the increase of cyclo-
Table 1 Results of one-pot synthesis of N,N-dimethylaniline
Yield (%)
Reactants (ml)
Entry
CH3OH
PhNO2
H2O
T/K
Catalyst/g
t/h
P/MPa
Others
1
2
3
4
5
6
7
8
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
1
1
1
1
1
1
2
2
2
2
3
4
5
5
2
2
2
2
2
—
—
—
—
—
—
—
—
—
—
—
—
—
—
1
413
423
433
443
453
463
443
443
443
443
443
443
443
443
443
443
443
443
443
3.0
3.0
3.0
3.0
3.0
3.0
2.5
5.0
7.5
10.0
5.0
5.0
5.0
10.0
5.0
5.0
5.0
5.0
5.0
25
18
10
7
5
4
15
7
5
2.0
2.0
2.5
3.0
3.5
4.4
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
4.8
2.1
2.6
1.8
2.1
2.3
0.8
0.4
0.3
0.3
2.1
3.6
3.1
1.6
0.8
0.8
1.3
2.7
4.9
89.4
91.8
91.8
94.4
93.3
91.0
95.7
97.0
98.0
96.7
94.0
91.2
89.2
88.5
95.0
96.0
93.3
92.8
89.0
2.2
3.1
2.6
0.3
2.5
2.2
0.3
0.6
0.1
0.1
0.2
0.7
0.4
1.0
0.3
0.2
0.2
0.5
0.9
0.6
0.7
1.1
0.7
0.7
1.4
1.2
0.9
0.8
1.1
1.1
0.9
2.8
5.4
1.4
1.2
2.7
2.3
3.9
3.0
2.3
1.9
2.8
1.4
3.1
2.0
1.1
0.8
1.8
2.6
3.6
4.5
2.5
2.5
1.8
2.5
1.7
1.3
9
10
11
12
13
14
15
16
17
18
19
4
10
16
20
9
8
9
9
9
10
2
3
4
5
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Table 3 N-Methylations of aniline with methanol or formaldehyde
Selectivity (%)
Entry
Reactants
Conv. aniline (%)
Others
1a
2b
3c
4d
PhNH2 + CH3OH
100
100
68.7
95.7
o0.1
o0.1
94.8
o0.1
2.2
3.8
—
37.0
95.0
90.8
—
1.8
0.5
—
o0.1
0.2
2.3
—
o0.1
0.8
2.6
5.2
2.0
PhNH2 + CH3OH + H2O
PhNH2 + CH2O + CH3OH
PhNH2 + CH2O + CH3OH
60.8
a
b
Reaction conditions: 2 ml PhNH2, 60 ml CH3OH, 5 g catalyst, 9 h, at 443 K, under 3 MPa Ar. Reaction conditions: 2 ml PhNH2, 60 ml
c
CH3OH, 10 ml H2O, 5 g catalyst, 9 h, 443 K, 3 MPa Ar. Reaction conditions: 2 ml PhNH2, 8 ml CH2O, 100 ml CH3OH, 1 min, at room
d
temperature. Reaction conditions: 5 g catalyst, 5 h, 443 K, under 3 MPa Ar.
Scheme 3 Reaction pathways for the one-pot synthesis of NNDMA.
hydrogenation of nitrobenzene for aniline14 and N-methylation
of aniline (Table 3, entry 1) in the one-pot concurrent catalysis
manner. It can also be reused directly after separation from the
products (at least six times).
as alkylating reagent. The substitution N-alkylation of aniline
with methanol could take place more easily and effectively
than with ethanol etc. because the C–O bond dissociation
energy of methanol is lower (384.93 Æ 0.71 kJ molÀ1 15
)
Two plausible routes for the reduction of nitrobenzene are
considered to be involved in the proposed methodology.
Initially (anhydrous system), aniline is partially produced by
the catalytic transfer hydrogenation of nitrobenzene with
methanol as hydrogen donor (accompanied with the formation
of formaldehyde and water as the by-products). Hydrogen is
produced by APR of methanol with water (Scheme 4, eqn (1),
and subsequently the produced hydrogen could be used in-situ
for the hydrogenation of nitrobenzene into aniline.
Additionally, the formaldehyde and water could also result
in the formation of formic acid and H2 (Scheme 4, eqn (3)
and (4)).13 In summary, aniline is produced from the in-situ
hydrogenation of nitrobenzene with hydrogen (from any
processes that result in the formation of hydrogen as shown
in Scheme 4), and the transfer hydrogenation of nitrobenzene
with methanol or formic acid as donor.
than those of other primary aliphatic alcohols (ethanol
391.2 Æ 2.9 kJ molÀ1, 1-butanol 392.0 Æ 2.9 kJ molÀ1).15
In the stepwise N-methylations of aniline for NNDMA
production, N-monomethylaniline is first produced through
two individual pathways with methanol and formaldehyde
as methylating reagents, respectively. The produced N-mono-
methylaniline further underwent substitution N-methylation
with methanol as methylating reagent, resulting finally in the
formation of NNDMA.
The main by-products are cyclohexanol and N,N-dimethyl-
cyclohexanamine and their formation mechanisms are shown
in Scheme 5. It suggested that rich H2 and water conditions
should thus be avoided for the proposed methodology.
However, much H2 and water remained on the fresh
Raney-Nis, so that pretreatment of Raney-Nis was essential.
The N-methylation of aniline was realized by two pathways
including substitution N-alkylation with methanol as alkylating
reagent and reductive N-alkylation with formaldehyde
Scheme
5
Formation of cyclohexanol and N,N-dimethylcyclo-
Scheme 4 Hydrogen production from methanol.
hexanamine.
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Porapak Q column and TCD detector. Liquid products
Conclusions
were analyzed by GC-MS (Agilen GC-6890-MS-5973)
(for qualitative analysis) and/or Gas-Chromatogram (Japan
Shimadzu GC-2014B) equipped with a 30 m HP-5 capillary
column (for quantitative analysis). The content of products
was determined by the peak area normalization method.
A novel one-pot synthesis of NNDMA from nitrobenzene and
methanol in the presence of pretreated Raney-Nis at 443 K
and 3 MPa N2 with an overall yield of up to 98% was
described. During the reaction procedure, aniline was produced
in-situ from the hydrogenation of nitrobenzene. Methanol
acted as a hydrogen source, alkylating reagent and solvent,
simultaneously.
Isolation of N,N-dimethylaniline (Table 1, entry 9)
The liquid product mixture was filtered after reaction, and
5 ml of the mixture (total 60 ml) was selected for isolation.
Methanol was removed by rotary evaporation, the residues
were purified by column chromatography on silica gel
(200–300 mesh, eluent: petroleum ether–ethyl acetate, 15 : 1 v/v).
0.185 g (92.5%) N,N-dimethylaniline was obtained.
Experimental
Reagents and apparatus
Nitrobenzene (AR/99.0%) and aniline (AR/99.0%) were
purchased from Shanghai Chemical Reagents Factory.
Methanol (AR/99.5%) and aqueous formaldehyde (37–40%)
were purchased from Juhua Group Corporation, Cyclo-
hexylamine (AR/99.5%) was purchased from Hangzhou
Shuanglin Corporation.
Notes and references
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Catalyst
The Raney-Nis catalyst was obtained from Hangzhou Jiali
metal Co. Ind. Before reaction, the Raney-Nis was pretreated
with methanol at 443 K under about 2 MPa N2 for 8 h, and
then stored in methanol.
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and pretreated Raney-Nis catalyst were calculated from the
hydrogenation of nitrobenzene at 323 K without the supply of
extra hydrogen. The BET surface area, pore volume, and pore
size of Raney-Nis were not changed after the pretreatment.
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Raney-Nis catalyst were significantly decreased from
108.7 to 22.2 ml gÀ1 after the pretreatment.
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Reactions
A stainless-steel autoclave (500 ml) was charged with the
mixture of reagents and catalyst, air was purged for 3–4 times
with 1 MPa N2, and kept under N2 pressure (0.5–1 MPa) at
room temperature, and subsequently heated to the desired
temperature in about 1 h. Finally, the N2 pressure was
adjusted to a desired value, and the reactions were initiated
by starting magnetic stirring and set for a given time. After
each reaction, gaseous products were analyzed in-situ by a
Gas-Chromatogram (Fuli GC-9790) equipped with 2 m
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This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
2054 | New J. Chem., 2009, 33, 2051–2054