Regioselectivity nitration of aromatics with N2O5 in PEG-based dicationic ionic liquid

Article abstract of DOI:10.1016/j.tetlet.2011.01.053

Regioselective mononitration of simple aromatic compounds has been investigated with N₂O₅ as nitrating agent and a new PEG200-based dicationic acidic ionic liquid (PEG₂₀₀-DAIL) as catalyst. The results of experiments show that this nitration system can significantly improve the para-selectivity of alkyl-benzenes and the ortho-selectivity of halogenated-benzenes. The PEG₂₀₀-DAIL exhibits recyclable temperature-dependant phase behavior in CCl₄ solvent, and it can be recycled without apparent loss of catalytic activity, and only 5% loss of weight is observed after six times recycling.

Full text of DOI:10.1016/j.tetlet.2011.01.053

Tetrahedron Letters 52 (2011) 1452–1455
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regioselectivity nitration of aromatics with N2O5 in PEG-based dicationic
ionic liquid
⇑
Peng-Cheng Wang, Ming Lu
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing 210094, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Regioselective mononitration of simple aromatic compounds has been investigated with N2O5 as nitrat-
ing agent and a new PEG200-based dicationic acidic ionic liquid (PEG200-DAIL) as catalyst. The results of
experiments show that this nitration system can significantly improve the para-selectivity of alkyl-ben-
zenes and the ortho-selectivity of halogenated-benzenes. The PEG200-DAIL exhibits recyclable tempera-
ture-dependant phase behavior in CCl4 solvent, and it can be recycled without apparent loss of
catalytic activity, and only 5% loss of weight is observed after six times recycling.
Received 24 November 2010
Revised 1 January 2011
Accepted 14 January 2011
Available online 26 January 2011
Keywords:
Aromatic nitration
N2O5
Ó 2011 Elsevier Ltd. All rights reserved.
PEG200-DAIL
Regioselective
Recyclable
1. Introduction
sulfonic acid group in an acyclic trialkanylammonium cation could
efficiently catalyze the nitration of aromatic compounds. Never-
Nitration of aromatic compounds is a ubiquitous reaction to
realize organic intermediates required in large tonnages for the
fine chemical industry. However, most of these reactions, employ-
ing a nitrating mixture of nitric and sulfuric acid, are facing the
problems of waste acid cauterization and poor selectivity.1 So,
finding green catalysts and nitrating reagents to selective synthesis
of the desired isomer in the nitration of substituted aromatic com-
pounds is of topical interest, with the purpose to reduce environ-
ment pollution and specifically to respond to market demand.
Strategies for improving this notoriously ‘ungreen’ reaction had
included the use of clays2,3 or zeolites4–6 as solid supports or
perfluorocarbons7 as solvents.
theless, the traditional mixed acid systems as HNO3/Ac2O and
HNO3/H2SO4 were still widely applied.
N2O5 employed as a green nitrating reagent had been studied
for several years. Millar and Philbin14 introduced N2O5 in an inert
solvent into syntheses of nitramines and nitrate esters. Talawar
et al.15 succeed in finding several N2O5-inert solvents as green
and moderate systems. Qian et al16 reported that HZSM-5 solid
acid with N2O5 promoted an excellent para-selective nitration of
chlorobenzene.
Here we combined a novel polyethylene glycol (PEG)-200-
based dicationic acidic ionic liquid (PEG200-DAIL)17 with N2O5
(Scheme 1). Nitration in ionic liquids was surveyed using a host
of aromatic substrates with similar reactivity. And ionic liquid
recycling procedures had also been devised. The easily recovered
ionic liquid opened up the possibility of a more economic process.
In the past few years, a growing interest had been witnessed in
ionic liquids as solvents or catalysts for aromatic nitration. Laali
and Gettwert8 first reported 1-ethyl-3-methylimidazolium salts
[emim] [X] with X = OTfꢀ and CF3COOꢀ as ionic liquids for electro-
philic nitration of aromatics. Smith et al.9 reported that [bmim] [X]
2. Results and discussion
ꢀ
with X ¼ BF4ꢀandPF6 performed better than CCl4 in reaction rate.
Later researchers mainly focused on the modified methods of for-
mer ionic liquids. Qiao et al.10,11 immobilized ionic liquids to mod-
ified silica gel and got an excellent ortho/para ratio. Rajagopal and
Srinivasan12 reported that ultrasound promoted para-selective
nitration of phenols in ionic liquid. Fang et al.13 reported that hal-
ogen-free SO3H-functional Br¢nsted-acidic ILs that bear an alkane
Our initial effort aimed to use PEG200-DAILas catalystand N2O5 as
the nitrating agent (Fig. 1). The typical reaction with toluene was
investigated to optimize the reaction conditions (Fig. 2, Table 1). It
was observed that the variation in the amount of PEG200-DAIL had
an effective influence. When the amount of catalyst was increased
to 3 g (5.6 mmol) at 50 °C, the conversion and the para-selectivity
of the nitrotoluene got the best result. And then the effect would
glissade in both sides with conditions changed. We supposed
that an increasing of by-products as 2,4-dinitrobenzene and
⇑
Corresponding author. Tel.: +86 025 84315514; fax: +86 025 84315030.
E-mail address: luming@mail.njust.edu.cn (M. Lu).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.053

P.-C. Wang, M. Lu / Tetrahedron Letters 52 (2011) 1452–1455
1453
NaN
N
SOCl2
HO
O
n
Cl
O
n
O
OH
O
Cl
pyridine
HO3S
O
O
O
S
N
N
O
n
N
+
O
N
-
N
N
O
2HSO4
n
O
N
H2SO4
N
+
SO3H
Scheme 1. Synthesis of PEG200-DAIL.
Homogeneous
Biphase
Biphase
Table 1
Effect of catalyst’s amount in toluene nitrationa
ILs: ionic liquids
Os: organic solvent
S: substrate
PEG200-DAIL (g) Conv. (%) m-MNT (%) o-MNT (%) p-MNT (%) o/pb
55ºC
Cooling
ILs
ILs
P: product
1
2
3
4
5
97.1
97.7
98.5
97.2
97.9
2.0
2.0
1.9
1.9
2
54.2
52.5
51.2
53.7
54.6
43.8
45.5
46.9
44.4
43.4
1.24
1.15
1.09
1.21
1.26
Mixture
Os+ S+N2O5
Os +P
separatory funnel
a
Toluene (0.48 mmol), N2O5 (1 equiv), CCl4 (15 ml), 50 °C, 2 h.
Ratio of para/ortho calculated from original GC data.
Figure 1. Reaction process with N2O5 in PEG200-DAIL.
b
2,6-dinitrobenzene might be the major factor of this phenomenon.
Temperature was another important factor. The conversion
increased to 98.5% until 50 °C with temperature rising, but then
decreased rapidly for the decomposition of N2O5.
Then the reaction was compared with several reported IL sys-
tems in the nitration of toluene, and the results were summarized
in Table 2. As can be seen from Table 2, PEG200-DAIL successfully
decreased the ratio of o/p to 1.09, while the conversion was still
kept at 98.5%. But the traditional ILs could not remain competitive
both in terms of conversion and selectivity. The IL of highest selec-
tivity was [emim] CF3COOꢀ; a pity that its conversion was only
65%.
Table 2
Regioselective nitration of toluene in various IL
IL
Conv. (%) m-MNT (%) o-MNT (%) p-MNT (%) o/p
HNO3/H2SO4
[emim]OTfa
92.2
60.0
4.6
3.5
3.1
5.5
5.1
5.3
1.9
61.3
57.2
48.9
53.1
53.3
53.9
51.2
34.1
39.3
48.0
41.4
41.6
40.8
46.9
1.79
1.45
1.02
1.28
1.28
1.32
1.09
[emim] CF3COO-a 65.0
b
[MIMPS]HSO4
[p-SABPy]HSO4
[TEPSA]HSO4
PEG200-DAIL
90.0
97.4
94.8
98.5
b
b
a
Ref. 8.
Ref. 9.
b
But the nitration of chlorobenzene was out of our expectation:
the result was significantly opposed with toluene in selectivity
(Table 3). It showed a strongly ortho-selectivity and the p/o ratio
decreased to 1.04.
In order to investigate the roles of different constituents, such
as PEG200-DAIL and N2O5 each played in reaction, a comparison
of the results obtained by five various nitration systems was car-
ried. Toluene and chlorobenzene were chosen as the typical com-
pounds for activated and deactivated substituent benzenes
separately (Figs. 3 and 4). As can be seen in the nitration of toluene,
two main phenomena were attractive: first, mixed acid systems
both HNO3/H2SO4 and N2O5/H2SO4 were poor in selectivity (o/p
ratio is 1.79 and 1.8), they are very close to the theoretical value
(o/p ratio is 2); second, the effect of para-selectivity would be
obviously increased with an existence of PEG200-DAIL (o/p ratio is
1.22 and 1.09). While in nitration of chlorobenzene, the p/o ratio
increased to 3.09 with the existence of PEG200-DAIL in PEG200
-
DAIL/ HNO3 system, but p/o ratio decreased to 1.04 in N2O5/CCl4
system for this system was facilitated in producing o-MNCB. The
causation of complicated diversification could be explained with
100
95
þ
two different nitration mechanisms. In mixed acid systems, NO2
þ
would generate quickly, NO2 was the main body attacking
benzene ring (Eq. (1)); in organic solvent system, the dissociation
of N2O5 became so slight that the main body attacking benzene
ring was N2O5 itself (Eqs. ()()()(2)–(4)). And PEG200-DAIL per-
90
50°C
55°C
Table 3
85
45°C
Effect of catalyst’s amount in chlorobenzene nitrationa
65°C
PEG200-DAIL/g Conv. (%) m-MNCB (%) o-MNCB (%) p-MNCB (%) p/ob
60°C
80
75
1
2
3
4
5
91.1
91.7
92.8
91.3
90.9
0.7
0.5
0.4
0.4
0.6
42.8
46.7
48.8
47.2
46.8
56.5
52.8
50.8
52.4
52.6
1.32
1.13
1.04
1.11
1.12
0.3
0.8
1.3
1.8
2.3
Reaction time / h
a
Chlorobenzene (0.48 mmol), N2O5 (1 equiv), CCl4 (15 ml), 50 °C, 2 h.
Ratio of para/ortho calculated from original GC data.
Figure 2. Nitration of toluene at different temperatures. Reaction condition:
toluene (0.48 mmol), N2O5 (1 equiv), PEG200-DAIL (3 g), CCl4 (15 ml).
b

1454
P.-C. Wang, M. Lu / Tetrahedron Letters 52 (2011) 1452–1455
PEG200-DAIL/N2O5/CCl4
N2O5/H2SO4
Table 4
PEG200-DAIL/HNO3
HNO3/H2SO4
100
90
Selectivity on nitration of various aromatic with amides20
Substrate
Products
Selectivity
Conv. (%)
97.16
1.8
1.6
1.4
1.2
1.0
N2O5/CCl4
Ethylbenzene
2-Nitroethylbenzene
3-Nitroethylbenzene
39.15
4.99
4-Nitroethylbenzene
55.86
8.12
6.85
85.03
52.45
0.70
46.85
88.97
0.24
tert-Butylbenzene
Bromobenzene
Fluorobenzene
1-tert-Butyl-2-nitrobenzene
1-tert-Butyl-3-nitrobenzene
1-tert-Butyl-4-nitrobenzene
2-Nitrobromobenzene
3-Nitrobromobenzene
4-Nitrobromobenzene
2-Nitrofluorobenzene
3-Nitrofluorobenzene
4-Nitrofluorobenzene
3-Nirtobenzoic acid
89.9
80
91.96
95.77
70
10.79
100
Benzoic acid
Nitrobenzene
87.35
78.36
60
1,3-Dinitrobenzene
1,2-Dinitrobenzene
1,4-Dinitrobenzene
89.26
10.13
0.61
1
2
3
4
5
Cov.
Nitration system
o / p
p-Nitrotoluene
m-Toluic acid
2,4-Dinitrotoluene
100
86.27
89.87
3-Me-6-nitrobenzoic acid
3-Me-2-nitrobenzoic acid
3-Me-4-nitrobenzoic acid
2-Me-5-nitrobenzoic acid
2-Me-3-nitrobenzoic acid
3,5-Dinitro-o-toluic acid
44.96
44.58
10.46
74.58
23.32
2.10
Figure 3. Nitration of toluene in different systems.18
o-Toluic acid
93.32
PEG200-DAIL/HNO3
PEG200-DAIL/N2O5/CCl4
N2O5/H2SO4
100
90
HNO3/H2SO4
3.0
2.5
2.0
1.5
1.0
1.20
1.15
1.10
1.05
1.00
100
98
96
94
92
90
N2O5/CCl4
80
70
60
Cov.
p / o
1
2
3
4
5
1
2
3
4
5
6
Cov
o/p
Nitration system
recycle times
Figure 4. Nitration of chlorobenzene in different systems.19
Figure 5. Repeating reaction using recovered PEG200-DAIL.
tle difference was that the product of para-position increased
significantly with the steric effect of the substituted group. The
nitration of deactivated substrates showed greater impact of using
the ionic liquid and N2O5. As is shown in the table, under the reac-
tion conditions employed, the conversion of bromobenzene was
91.96%. And the rare ortho-selectivity gave a possible approach to
meet the industry need of several ortho-products. For some substi-
tuted aromatics which had no other products, their conversions
were improved in this nitration system more or less. Another
praiseworthy advantage was that the mononitro-products were
predominant in this N2O5/PEG200-DAIL system. Dinitration and
multinitration made up only about 1% in conversion.
formed excellent in processing nitration. It accelerated the reac-
tion, in the case of not changing the trend of selectivity. Simulta-
neously, dissimilarity in conversion was also observed. When
N2O5 was added, its oxidation and decomposition made the con-
version decreased by about 2%. But with respect to its significant
selectivity, this shortcoming could be ignored. According to the
marvelous effects, the use of N2O5 and PEG200-DAIL in nitration
was attractive.
Equations: Suggested mechanism for aromatics nitration.
H2SO4 : N2O5 þ 2H2SO4ꢀ ꢀ 2NO2þ þ 2HSO4ꢀ þ H2O
ð1Þ
ð2Þ
ð3Þ
ð4Þ
ꢀ
CCl4 : NO2þNO3ꢀ ꢀ NO2þ þ NO3
R
R
R
R
NO2
PEG200-DAIL
CCl4 , 50 o
N2O5 þ PhCH3 ꢀ PhCH3NO2 þ HNO3
HNO3 þ PhCH3 ꢀ PhCH3NO2 þ H2O
+
+
+
N2O5
C
NO2
NO2
Encouraged by the remarkable results obtained with the above
reaction conditions, and in order to show the generality and scope
of this new protocol, we used various substituted aromatics. The
results obtained were summarized in Table 4. In the nitration of
activated substrates, they showed the same phenomenon of tolu-
ene: higher conversion and para-selectivity than mixed acid. A lit-
The procedure was repeated six times and the results indicated
that PEG200-DAIL could be recycled without the apparent loss of
catalytic activity (Fig. 5) and only 5% loss of weight was observed
after six times of recycling. With the recycle times increased, the

P.-C. Wang, M. Lu / Tetrahedron Letters 52 (2011) 1452–1455
1455
9. Smith, K.; Liu, S.; El-Hiti, G. A. Ind. Eng. Chem. Res. 2005, 44, 8611.
10. Qiao, K.; Hagiwara, H.; Yokoyama, C. J. Mol. Catal. A: Chem. 2006, 246, 65.
11. Qiao, K.; Yokoyama, C. Chem. Lett. 2004, 33, 808.
12. Rajagopal, R.; Srinivasan, K. V. Ultrason. Sonochem. 2003, 101, 41.
13. Fang, D.; Shi, Q. R.; Cheng, J. Appl. Catal., A 2008, 345, 158.
14. Millar, R. W.; Philbin, S. P. Tetrahedron 1997, 53, 4371.
15. Talawar, M. B.; Sivabalan, R.; Polke, B. G.; Nair, U. R.; Gore, G. M.; Asthana, S. N.
J. Hazard. Mater. 2005, 124, 153.
color of ionic liquid turned from brown to yellow at room temper-
ꢀ
ature. It was surmised that a few NO3 generated in the reaction
ꢀ
ꢀ
replaced the HSO4 as anionic group. We prepared this NO3
-
based ionic liquid, and its character was the same with the ionic li-
quid after numerous recycle.
16. Qian, H.; Ye, Z. W.; Lv, C. X. Ultrason. Sonochem. 2008, 15, 326.
17. (a) Zhi, H. Z.; Lv, C.; Zhang, Q.; Luo, J. Chem. Commun. 2009, 2878; (b) Zhi, H. Z.;
Luo, J.; Feng, G. A.; Lv, C. X. Chin. Chem. Lett. 2009, 20, 379.
18. Reaction conditions of five systems in toluene nitration. HNO3/H2SO4 system:
toluene (0.48 mmol), HNO3 (65%, 1 equiv), H2SO4 (98%, 5 equiv), 60 °C, 4 h.
Supplementary data
Supplementary data (experimental details for the synthesis and
characteristic data for key intermediates are provided. 1H NMR
spectra of PEG200-DAIL and GC/LC of aromatic compounds) associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2011.01.053.
PEG200-DAIL/ HNO3 system: toluene (0.48 mmol), HNO3 (65%, 1 equiv), PEG200
-
DAIL (3 g), H2SO4 (98%, 5 equiv), 50 °C, 3 h. N2O5/CCl4 system: toluene
(0.48 mmol), N2O5 (1 equiv), CCl4 (15 ml), 0 °C, 3 h. N2O5/H2SO4 system:
toluene (0.48 mmol), N2O5 (1 equiv), H2SO4 (98%, 3 equiv), 0 °C, 3 h. PEG200
-
DAIL/ N2O5/CCl4 system: toluene (0.48 mmol), N2O5 (1 equiv), PEG200-DAIL
(3 g), CCl4 (15 ml), 50 °C, 2 h.
References and notes
19. Reaction conditions of five systems in chlorobenzene nitration. HNO3/H2SO4
system: chlorobenzene (0.48 mmol), HNO3 (65%, 1 equiv), H2SO4 (98%,
5 equiv), 70 °C, 4 h. PEG200-DAIL/ HNO3 system: chlorobenzene (0.48 mmol),
HNO3 (65%, 1 equiv), PEG200-DAIL (3vg), H2SO4 (98%, 5 equiv), 50 °C, 3 h. N2O5/
CCl4 system: chlorobenzene (0.48 mmol), N2O5 (1vequiv), CCl4 (15 ml), 0 °C,
3 h. N2O5/H2SO4 system: chlorobenzene (0.48 mmol), N2O5 (1 equiv), H2SO4
(98%, 3 equiv), 0 °C, 3 h. PEG200-DAIL/ N2O5/CCl4 system: chlorobenzene
(0.48 mmol), N2O5 (1 equiv), PEG200-DAIL (3 g), CCl4 (15 ml), 50 °C, 2 h.
20. All chemicals were purchased from Sinopharm Chemical Reagent Co. Ltd and
used without further purification, N2O5 was prepared with Ref. 14 General
1. Olah, G. A.; Malhotra, R.; Narang, S. C. Nitration, Methods and Mechanisms; VCH:
New York, 1989; Schofield, K. Aromatic Nitration; Cambridge University Press:
Cambridge, 1980; Taylor, R. Electrophilic Aromatic Substitution; John Wiley and
Sons: Chichester, 1990.
2. Cornelis, A.; Delaude, L.; Gerstmanns, A.; Laszlo, P. Tetrahedron Lett. 1988, 29,
5909.
3. Choudary, B. M.; Ravichandra Sarma, M.; Vijaya Kumar, K. J. Mol. Catal. 1994, 87,
33.
4. (a) Claridge, R. P.; Lancaster, N. L.; Millar, R. W.; Moodie, R. B.; Sandall, J. P. B. J.
Chem. Soc., Perkin Trans. 2 2001, 197; (b) Claridge, R. P.; Lancaster, N. L.; Millar,
R. W.; Moodie, R. B.; Sandall, J. P. B. J. Chem. Soc., Perkin Trans. 2 1999, 1815.
5. Smith, K.; Almeer, S.; Peters, C. Chem. Commun. 2001, 2748.
6. (a) Vassena, D.; Kogelbauer, A.; Prins, R. Catal. Today 2000, 60, 275; (b) Haouas,
M.; Bernasconi, S.; Kogelbauer, A.; Prins, R. Phys. Chem. Chem. Phys. 2001, 3,
5067.
7. (a) Crampton, M. R.; Gibbons, L. M.; Millar, R. J. Chem. Soc., Perkin Trans. 2 2001,
1662; (b) Crampton, M. R.; Cropper, E. L.; Gibbons, L. M.; Millar, R. W. Green
Chem. 2002, 4, 275.
procedure: In a typical reaction protocol, 15 ml CCl4, 0.48 mmol aromatic
compound and PEG200-DAIL were placed in a 50 ml three-necked flask. Then
the flask was put in a constant temperature water bath and N2O5 was added
with stirring. After adding, temperature was raised to 50 °C and kept for 2 h.
The final solution was cooled to room temperature and separated. Then the
organic phase was washed once with 10%M sodium bicarbonate solution
(50 ml) and twice with distilled water (50 ml). After dried over magnesium
sulfate, the solvent was evaporated to spontaneously crystallize after several
hours. The constituents were confirmed based on GC or LC analysis
(comparison with an authentic sample).
8. Laali, K. K.; Gettwert, V. J. J. Org. Chem. 2001, 66, 35.