Aromatic nitration under neutral conditions using N-bromosuccinimide/ silver(I) nitrate

Article abstract of DOI:10.1016/j.tetlet.2012.06.126

The use of N-bromosuccinimide and silver nitrate as a convenient reagent system for the nitration of aromatic compounds under neutral and environmentally safer reaction conditions is described.

Full text of DOI:10.1016/j.tetlet.2012.06.126

Tetrahedron Letters 53 (2012) 4841–4842
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Tetrahedron Letters
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Aromatic nitration under neutral conditions using
N-bromosuccinimide/silver(I) nitrate
⇑
Najmeh Nowrouzi , Abdol Mohammad Mehranpour, Elham Bashiri, Zohre Shayan
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of N-bromosuccinimide and silver nitrate as a convenient reagent system for the nitration of
aromatic compounds under neutral and environmentally safer reaction conditions is described.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 18 April 2012
Revised 24 May 2012
Accepted 27 June 2012
Available online 4 July 2012
Keywords:
N-Bromosuccinimide (NBS)
Silver nitrate (AgNO
Nitration
3
)
Aromatic compounds
Aromatic nitro compounds are key intermediates in organic
synthesis. This important class of industrial chemicals is widely
used in the synthesis of many diverse products, including dyes,
polymers, pesticides, and explosives. Aromatic nitration is com-
monly achieved using a mixture of nitric and sulfuric acids, called
NMe2
NMe2
NO2
NMe2
NO2
NBS (1.0 eq), AgNO (1.0 eq)
3
+
CH3CN, reflux
1
.0 eq
‘
mixed acid’, which is expensive to treat, creates pollution, and is
hazardous to the environment. These disadvantages have encour-
1
Scheme 1.
aged researchers to develop procedures using solid acid catalysts,
2
3
4
metal nitrates, organic nitrating agents, inorganic acidic salts,
+
5
2
and other sources of NO .
molar ratio of NBS/AgNO
3
/N,N-dimethylaniline of 1:1:1 in reflux-
However, many of these reactions have been carried out in the
presence of protic and Lewis acids, and most suffer from draw-
backs, such as regioselectivity issues, over nitration, and competi-
tive oxidation of substrates. Hence, there is still a need for the
design and execution of mild methods for aromatic nitration.
ing CH CN (Scheme 1).
3
Having established optimized reaction conditions, various aro-
matic compounds with electron-donating and electron-withdraw-
ing groups were examined and the results are summarized in
Table 1.
In the case of reactive aromatic compounds nitrated products
were obtained in high yields. The reactions were selective, and
no dinitro or side-chain substitution products were detected. Deac-
tivated aromatic compounds failed to undergo nitration with this
reagent system, even after prolonged reaction times under reflux
6
In continuation of our recent work on aromatic nitration, here-
3
in, we report the application of NBS/AgNO as a novel reagent sys-
tem for the efficient and selective nitration of aromatic compounds
under essentially neutral conditions. This method minimizes waste
products compared to traditional methods and gives the corre-
sponding mononitro derivatives in good to excellent yields.
Initially, N,N-dimethylaniline was chosen as the substrate for
model reactions and several common solvents were tested in the
presence of different amounts of N-bromosuccinimide and silver
nitrate. We found that the reaction afforded high yields of the
corresponding nitro derivatives after three hours, when using a
(
Table 1, entries 13–16).
Nitrophenols are important intermediates for the manufacture
7
of drugs and pharmaceuticals. Phenols are highly reactive, there-
fore the nitration of phenols by mixed acids is always associated
with the formation of dinitro compounds, oxidized products, and
unspecified resinous materials. Thus, many mild nitration pro-
cesses for phenols have been developed to overcome these short-
8
⇑
Corresponding author. Tel.: +98 771 4222341; fax: +98 771 4541494.
E-mail address: nowrouzi@pgu.ac.ir (N. Nowrouzi).
comings. However, some of the nitrating reagents are poorly
regioselective and uneconomical.
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.126

4
842
N. Nowrouzi et al. / Tetrahedron Letters 53 (2012) 4841–4842
Table 1
Supplementary data
Nitration of aromatic compounds using NBS/AgNO
3
in refluxing CH
3
CN
Yielda (%)
Entry
1
Aromatic compound
Time
3 h
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.06.
126. These data include MOL files and InChiKeys of the most
important compounds described in this article.
N,N-Dimethylaniline
ortho: 16
para: 69
ortho: 15
para: 74
ortho: 20
para: 66
2-Nitro: 88
3-Nitro: 91
3-Nitro: 87
1-Nitro: 80
ortho: 20
para: 67
2-Nitro: 81
2-Nitro: 92
2-Nitro: 76
4-Nitro: 75
—
2
3
Anisole
Toluene
3.5 h
4.5 h
References and notes
4
5
6
7
8
4-Iodoanisole
Indole
2-Methylindole
Naphthalene
Phenol
5 h
2 h
1.5 h
3.5 h
2.5 h
1.
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988; (f) Choudary, B. M.; Sarma, M. R.; Vijayakumar, K. J. Mol. Catal. 1994, 87,
3; (g) Riego, J. M.; Sedin, Z.; Zaldivar, J. M.; Marziano, N. C.; Torato, C.
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987, 2273; (i) Min, S.; Shi-Cong, C. J. Fluorine Chem. 2002, 113, 207; (j)
1
(
1
3
9
4-Bromophenol
4-Methoxyphenol
4-Nitrophenol
2-Nitrophenol
Cyanobenzene
Chlorobenzene
Bromobenzene
Iodobenzene
4 h
50 min
7 h
7.5 h
24 h
24 h
24 h
24 h
1
1
1
1
1
1
1
0
1
2
3
4
5
6
1
Esakkidurai, T.; Pitchumani, K. J. Mol. Cat. A: Chem. 2002, 185, 305; (k)
Kogelbauer, A.; Vassena, D.; Prins, R.; Armor, J. N. Catal. Today 2000, 55, 151; (l)
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226, 49; (m) Peng, X.; Suzuki, H.; Lu, C. Tetrahedron Lett. 2001, 42, 4357;
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Shokrolahi, A.; Zali, A.; Keshavarz, M. H. Chin. Chem. Lett. 2007, 1064, 18.
—
—
—
a
Isolated yield.
2. (a) Delaude, L.; Laszlo, P.; Smith, K. Acc. Chem. Res. 1993, 26, 607; (b) Laszlo, P.
Acc. Chem. Res. 1986, 19, 121; (c) Cornelis, A.; Laszlo, P.; Pennetreau, P. Bull. Soc.
Chim. Belg. 1984, 93, 961; (d) Zolfigol, M. A.; Iranpoor, N.; Firouzabadi, H. Orient.
J. Chem. 1998, 14, 369; (e) Firouzabadi, H.; Iranpoor, N.; Zolfigol, M. A.; Iran, J.
Chem. Chem. Eng. 1997, 16, 48; (f) Firouzabadi, H.; Iranpoor, N.; Zolfigol, M. A.
Synth. Commun. 1997, 27, 3301; (g) Iranpoor, N.; Firouzabadi, H.; Zolfigol, M. A.
Synth. Commun. 1998, 28, 2773; (h) Mellor, J. M.; Mittoo, S.; Parkes, R.; Millar, R.
W. Tetrahedron 2000, 56, 8019.
O
O
O
ArH
AgNO3
AgBr
NBr
O
_
ArNO2
+
NOH
O
NO NO2
-
3.
(a) Rodrigues, J. A. R.; Oliveria Filho, A. P.; Moran, P. J. S.; Custodio, R.
Tetrahedron 1999, 55, 6733; (b) Rodrigues, J. A. R.; Oliveria Filho, A. P.; Moran, P.
J. S. Synth. Commun. 1999, 29, 2169; (c) Ramana, M. M. V.; Malik, S. S.; Parihar, J.
A. Tetrahedron Lett. 2004, 45, 8681.
O
(
I)
Scheme 2.
4. (a) Zolfigol, M. A.; Bagherzadeh, M.; Madrakian, E.; Ghaemi, E.; Taqian-nasab, A.
J. Chem. Res. Synop. 2001, 140; (b) Zolfigol, M. A.; Madrakian, E.; Ghaemi, E.
Indian J. Chem. 2001, 40B, 1191; (c) Hosseini-Sarvari, M.; Tavakolian, M.;
Ashenagar, S. Iran. J. Sci. Technol. Trans. A 2010, 34, 215.
Here, treatment of phenols under similar conditions to those
5.
(a) Parac-Vogt, T. N.; Binnemans, K. Tetrahedron Lett. 2004, 45, 3137; (b)
Hajipour, A. R.; Ruoho, A. E. Tetrahedron Lett. 2005, 46, 8307; (c) Shi, M.; Shi-
Cong, C. J. Fluorine Chem. 2002, 113, 207; (d) Rajanna, K. C.; Kumar, M. S.;
Venkanna, P.; Ramgopal, S.; Venkateswarlu, M. Int. J. Org. Chem. 2011, 1, 250;
described above gave the nitro derivatives in good to excellent
yields. Phenols with electron-donating or electron-withdrawing
groups reacted smoothly under mild conditions, and in all cases,
mononitration was observed. For example, 4-methoxy-2-nitrophe-
nol was isolated in 92% yield following nitration of 4-methoxyphe-
nol for 50 min (Table 1, entry 10).
(
e) Cheng, G.; Duan, X.; Qi, X.; Lu, C. Catal. Commun. 2008, 10, 201; (f) Olah, G.
A.; Narang, S. C.; Olah, J. A.; Pearson, R. L.; Cupas, C. A. J. Am. Chem. Soc. 1980,
02, 3507.
1
6
7
.
.
Nowrouzi, N.; Zareh Jonaghani, M. Tetrahedron Lett. 2011, 52, 5081.
Conlon, D. A.; Lynch, J. E.; Hartner, F. W.; Reamer, R. A.; Volante, R. P. J. Org.
Chem. 1996, 61, 6425.
A possible mechanism for the nitration process is shown in
Scheme 2. Addition of AgNO
3
to N-bromosuccinimide produces
8. (a) Zolfigol, M. A.; Ghaemi, E.; Madrakian, E. Molecules 2001, 6, 614; (b) Sun, H.
B.; Hua, R.; Yin, Y. J. Org. Chem. 2005, 70, 9071; (c) Ganguly, N. C.; Dutta, S.;
Datta, M.; De, P. J. Chem. Res. 2005, 733; (d) Rajagopal, R.; Srinivasan, K. V.
Ultrason. Sonochem. 2003, 10, 41; (e) Baghernejad, B.; Oskooie, H. A.; Heravi, M.
M.; Beheshtiha, Y. S. Chin. J. Chem. 2010, 28, 393; (f) Selvam, J. J. P.; Suresh, V.;
Rajesh, K.; Reddy, S. R.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 2507; (g)
Zolfigol, M. A.; Madrakian, E.; Ghaemi, E. Synlett 2003, 2222.
the intermediate I which is accompanied by the precipitation of
AgBr. This reactive intermediate then reacts with the aromatic ring
of the substrate to produce the corresponding nitro aromatic com-
pound along with N-hydroxysuccinimide. N-hydroxysuccinimide
can be removed from the organic phase by washing with an aque-
ous solution of sodium bicarbonate.
The precipitation of AgBr and formation of N-hydroxy-
succinimide during the reaction are considered strong evidence
for the proposed mechanism. In this reaction, the silver salt is
recovered as AgBr by filtration of the reaction mixture.
In summary, we have described a simple and convenient meth-
od for the nitration of aromatic compounds using NBS/AgNO
reactions occur under mild and environmentally safer conditions
and can be applied to a wide range of acid-sensitive substrates in
comparison to traditional methods. Further, the absence of dinitrat-
ed and polynitrated products is another advantage of our system.
9.
Typical procedure for the nitration of N,N-dimethylaniline: To a stirred mixture of
CH CN (5 mL) and NBS (1.0 mmol, 0.177 g) at reflux, was added AgNO
1.0 mmol, 0.169 g). N,N-Dimethylaniline (1 mmol, 0.126 mL) was then added
to the mixture. After 3 h, the mixture was filtered to remove AgBr. The solvent
was evaporated and the residue dissolved in CH Cl (10 mL) and washed with
aqueous 4% NaHCO
3
3
(
2
2
3
(2 Â 5 mL) to remove N-hydroxysuccinimide from the
organic phase. The aqueous phase was separated and the organic phase dried
and concentrated. The residue was subjected to column chromatography over
silica gel using n-hexane/EtOAc (4:1) as eluent to give 4-nitro- and 2-nitro-N,N-
dimethylaniline in 69% and 16% yields, respectively. 4-Nitro-N,N-
9
3
. The
10
dimethylaniline (Table 1, entry 1): Yellow powder; mp 162–165 °C (Lit 163–
À1
1
165 °C); IR (KBr) 800, 1300, 1350, 1500, 1525, 1600, 2900–3000 cm
; H NMR
(
250 MHz, CDCl ): d (ppm) 2.89 (6H, s), 6.32 (2H, d, J = 5.49 Hz), 7.8 (2H, d,
3
13
J = 5.5 Hz); C NMR (62.9 MHz, CDCl ): d (ppm) 30.2, 110.5, 126.4, 138.0,
3
154.4. The aqueous phase was treated with 4% HCl solution and extracted with
CH Cl (10 mL). The organic layer was separated and evaporated. The melting
2 2
point of the obtained product (colourless crystals) was 93–95 °C, which was in
accordance with the melting point of N-hydroxysuccinimide (mp 95 °C).
Acknowledgement
10. (a) www.sigmaaldrich.com.; (b) www.chemexper.com.
We thank the Persian Gulf University Research Council for
generous partial financial support of this study.