Nitric acid in the presence of P2O5 supported on silica gel - A useful reagent for nitration of aromatic compounds under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2005.09.178

A variety of aromatic compounds are nitrated to parent nitro aromatic compounds under solvent-free conditions using 65% nitric acid in the presence of P₂O₅ supported on silica gel is described. This methodology is useful for nitration of activated and deactivated aromatic rings.

Full text of DOI:10.1016/j.tetlet.2005.09.178

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8307–8310
Nitric acid in the presence of P O supported on
2
5
silica gel—a useful reagent for nitration of aromatic compounds
under solvent-free conditions
a,b,
b
*
Abdol Reza Hajipour
and Arnold E. Ruoho
a
Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
Department of Pharmacology, University of Wisconsin Medical School, 1300 University Avenue, Madison, WI 53706-1532, USA
b
Received 9 August 2005; revised 27September 2005; accepted 28 September 2005
Available online 14 October 2005
Abstract—A variety of aromatic compounds are nitrated to parent nitro aromatic compounds under solvent-free conditions using
6
5% nitric acid in the presence of P
2
O
5
supported on silica gel is described. This methodology is useful for nitration of activated and
deactivated aromatic rings.
Ó 2005 Published by Elsevier Ltd.
1. Introduction
over conventional classical method is that they are clea-
ner reactions, decreased reaction time, and easier work-
Nitroaromatic compounds are important chemicals that
have application as solvents, dyes, pharmaceuticals,
agrochemicals, explosives, and plastics in industry. They
are also useful intermediates for the preparation of other
compounds, particularly amines, by reduction of nitro
up.
2. Results and discussion
1
groups. Electrophilic aromatic nitration is one of the
In continuation of our ongoing program to develop
environmentally benign methods under solvent-free con-
ditions,
method for nitration of aromatic compounds with 65%
nitric acid in the presence of P O supported on silica
gel under solvent-free conditions. The P O /silica gel
most important reactions in organic chemistry. How-
ever, the majority of the reported methods for nitration
of aromatic compounds suffer from disadvantages such
1
4–16
we wish to report an extremely convenient
2
2b,d
as low regioselectivity, over nitration,
strongly acidic
2
5
3
3
2b,4
media, tedious work-up, oxidation of the reagents,
and safety problems (storage, handling, using toxic tran-
2 5
was prepared by mixing a mixture of P O and silica
2
5
+
2
+2
5
sition metal cations such as Hg , Cu , etc.). These
disadvantages have encouraged the researchers for
extensive efforts to develop alternative procedures such
gel (0.063–0.2 mm) in a mortar and grinding with a
pestle for 1 min to obtain a homogeneous mixture. This
reagent is stable and can be kept at room temperature
1
b,2b,4b,5b,6
+
17
as using solid acids
, other sources of NO
for months without losing its activity.
2
2
a,7a
7b
(
nitronium salts,
N-nitropyridinium salts, nitrogen
and peroxynitrite ), organic nitrating agents
2
b,c
8
oxide,
Aromatic compound 1 is mixed with one molar ratio of
(
acetyl nitrate, benzoyl nitrate, and trimethylsilyl
P O /silica gel in a mortar and then nitrated with one
2
5
9
10
nitrate), etc.
molar ratio of HNO 65% to the corresponding nitro-
3
aromatic compound 2 (Table 1). After extraction of
the product with ether and evaporating the solvent,
the product was purified by column chromatography
to give the product in good to excellent yields and short
reaction time. This method offers a simple, general,
selective, and highly efficient route for converting aro-
matic compounds 1 to the corresponding nitro deriva-
tives 2 in short reaction time.
Reaction under solvent-free conditions has recently
1
1–13
attracted attention.
The advantage of these methods
Keywords: Nitration; Solvent free; Silica gel; P
2
O ; HNO
5
3
.
*
Corresponding author. Fax: +98 311 391 2350; e-mail: haji@
cc.iut.ac.ir
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.09.178

8308
A. R. Hajipour, A. E. Ruoho / Tetrahedron Letters 46 (2005) 8307–8310
Table 1. Nitration of aromatic compounds 1 with 65% HNO
3
in the presence of P
2
5
O /silica gel to nitroarens 2 under solvent-free conditions at room
temperature
a
b
Entry
ArH (1)
ArNO
2
(2) (o:m:p ratio)
Time (min)
Yield (%)
1
2
3
4
5
6
Anisole
Acetanilide
3-Methylactanilide
3-Chloroacetanilide
1,2-Dimethoxybenzene
Toluene
Nitroanisole (20:0:80)
2
2
4
97
89
95
Nitroacetanilide (10:0:90)
4-Nitro-3-methylactanilide
4-Nitro-3-chloroacetanilide
4-Nitro-1,2-dimethoxybenzene
Nitrotoluene (40:0:60)
780
5
792
90
3
3
3
3
20
10
15
20
15
93
790
790
77
3
96
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
Phenol
Nitrophenol (10:0:90)
3
1,4-Dimethoxybenzene
4-Hydroxybenzaldehyde
1,3,5-Trimethylbenzene
Naphthalene
2-Nitro-1,4-dimethoxybenzene
100
81
83
92
58
82
81
80
78
2-Nitro-4-hydroxybenzaldehyde
2-Nitro-1,3,5-trimethylbenzene
1-Nitronaphthalene
0
1
2
3
4
5
6
C
6
H
5
NO
2
1,3-Dinitrobenzene
4-MeC
6
H
4
NO
CHO
2
4-Me 1,3-(NO
2
6 3
)2C H
C
C
C
6
6
6
H
5
H
5
H
5
3-NO
3-NO
3-NO
2
C
2
C
2
C
6
6
6
H
4
H
4
H
4
CHO
COOH
COPh
COOH
COPh
7Benzylalcohol
Benzaldehyde
10
8
9
0
1
2
C
C
C
C
6
6
6
6
H
4
H
4
H
4
H
4
(CH
(CH
CH
CH
2
)
)
2
2
COOH
COOMe
NO
NO
NO
2
2
2
C
C
C
6
6
6
H
H
H
3
3
3
(CH
(CH
2
)
)
2
2
COOH (10:0:90)
COOMe (12:0:88)
2
2
2
COOH
CH
CH
3-Nitrocoaine
2
COOH (15:0: 80 5)
2
COOMe
NitroC
6
H
3
2
COOMe (15:0:85)
95
68
Cocaine
20
a
18–22
Confirmed by comparison with authentic samples (IR, TLC, and NMR).
Yield of isolated pure product after purification.
b
Activated aromatic compounds were converted to the
corresponding nitro-aromatic compounds under sol-
vent-free conditions at room temperature in excellent
yields in 2–7min; deactivated aromatic compounds
converted to nitrobenzene derivatives with HNO3
site of the electrophilic attack by this reagent was
found to be identical to the conventional methods
(Table 1).
The possible mechanism for nitration of aromatic com-
pounds 1 to the corresponding nitroaromatic com-
pounds 2 using nitric acid in the presence of P O
6
5% in the presence of P O /silica gel in moderate
2 5
to good yields in 15–20 min under solvent-free condi-
tions at room temperature (Scheme 1 and Table 1).
The reagent is not suitable for nitration of aro-
matic compounds with oxidizable functional groups,
such as hydroxyl and amino groups (Table 1). The
2
5
supported on silica gel under solvent-free conditions is
outlined in Scheme 2.
In summary, we report here a novel method for nitra-
tion of aromatic compounds under solvent-free condi-
tions. This procedure is an efficient and novel method
for nitration of activated and deactivated aromatic
compounds to the corresponding nitro derivatives under
solvent-free conditions. This method is not suitable
for nitration aromatic compounds with oxidizable
functional groups.
P O /silica gel
2
5
Ar-NO2
Ar-H + HNO (65%)
3
Solid-state
2
1
Scheme 1.
silica gel
grinding
2
H PO + N O
3 4 2 5
+
P2O5 + 2H O
2
HNO3
2
N O
NO3-
+ NO +
2
2
5
R1
NO2
NO2
R1
R2
R1
H
+ NO +
2
R2
NO2+
+
+
NO3-
R2
2
R and R functional groups
1
2
1
Scheme 2.

A. R. Hajipour, A. E. Ruoho / Tetrahedron Letters 46 (2005) 8307–8310
8309
3
. Experimental section
2001, 42, 4357; (c) Bak, R. R.; Smallridge, A. J. Tetra-
hedron Lett. 2001, 42, 6767; (d) Irabpoor, N.; Firouzabadi,
H.; Heydari, R. Synth. Commun. 1999, 29, 3295.
. (a) Ramana, M. M. V.; Malik, S. S.; Parihar, J. A.
Tetrahedron Lett. 2004, 45, 8681; (b) Strazzolini, P.;
Giumanini, A. G.; Runcio, A. Tetrahedron Lett. 2001, 42,
3
.1. General
3
4
Yields refer to isolated pure products after column chro-
matography. The products were characterized by com-
parison of their spectral (IR and H NMR) and
physical data with those of authentic samples.
All H NMR spectra were recorded at 300 and
00 MHz in CDCl relative to TMS (0.00 ppm) and
IR spectra were recorded on Shimadzu 435 IR spec-
trometer. All reactions were carried out under solvent-
free conditions at room temperature in a hood with
strong ventilation.
1
387.
. (a) Bozell, J. J.; Hoberg, J. O. Tetrahedron Lett. 1988, 39,
261; (b) Bahulayan, D.; Narayan, G.; Sreekumar, V.;
Lalithambika, M. Synth. Commun. 2002, 32, 3565.
1
1
8–22
2
1
5
5. (a) Olah, G. A.; Krishnamurthy, V. V.; Narang, S. C. J.
Org. Chem. 1982, 47, 596; (b) Cornelis, A.; Laszlo, P.
Synthesis 1985, 909; (c) Mellor, J. M.; Mittoo, S.; Parkes,
R.; Millar, R. W. Tetrahedron 2000, 56, 8019.
. (a) Riego, J. M.; Sedin, Z.; Zaldivar, J. M.; Marziano, N.
C.; Tortato, C. Tetrahedron Lett. 1996, 37, 513; (b)
Zolfigol, M. A.; Ghasemi, E.; Madrakian, E. Synlett 2003,
3
6
3
.2. Preparation of reagent [P O /silica gel (64%w/w)]
2 5
1
91; (c) Zolfigol, M. A.; Madrakian, E.; Ghasemi, E.
Molecules 2002, 7, 734.
In a mortar, 4.5 g of P O (31.69 mmol) and 2.5 g of sil-
ica gel (0.063–0.2 mm) was ground for 1 min to a homo-
geneous mixture.
2
5
7. (a) Olah, G. A.; Reddy, V.; Prakash, S. Synthesis 1992,
1087; (b) Bosnich, B.; Nyholm, R. S.; Pauling, P. J.; Tobe,
M. L. J. Am. Chem. Soc. 1968, 90, 4742.
8
. Nonoyama, N.; Chiba, K.; Hisatome, K.; Suzuki, H.;
Shintani, F. Tetrahedron Lett. 1999, 40, 6933.
3
.3. Typical experimental procedure: nitration of 1,4-di-
9
. (a) Rodrigues, J. A. R.; Filho, A. P. D. O.; Moran, P. J. S.;
Custodio, R. Tetrahedron 1999, 55, 6733; (b) Kimura, M.;
Kajita, K.; Naoyuki, O.; Morosawa, S. J. Org. Chem.
methoxybenzene with 65% nitric acid in the presence of
P O supported on silica gel to 2-nitro-1,4-dimethoxy-
benzene
2
5
1
990, 55, 4887.
1
0. (a) Frost, C. G.; Hartley, J. P.; Griffin, D. Tetrahedron
Lett. 2002, 43, 4789; (b) Parac-Vogt, T. N.; Binnemans, K.
Tetrahedron Lett. 2004, 45, 3137; (c) Rajagopal, R.;
Srinivasan, K. V. Ultrason. Sonochem. 2003, 10, 41.
Two grams of P O /silica gel (64% w/w) (1 mmol) and
2
5
1
,4-dimethoxybenzene (1 mmol, 0.14 g) were ground
for 30 s, and then 0.5 mL of HNO 65% was added
3
and the mixture was ground with a pestle at rt for
the time specified in Table 1 until a deep-yellow color
appeared. When TLC (n-hexane/EtOAc 80:20) showed
complete disappearance of 1,4-dimethoxybenzene, to
the reaction mixture was added ether (10 mL) and the
solid was separated through a short pad of silica gel
and washed with ether (15 mL). The filtrate was washed
with NaHCO 10% (20 mL) and dried (MgSO ). The
solvent was evaporated under reduced pressure and
the residue was purified by short column chromato-
graphy (n-Hexane/EtOAc, 3:1), 1,4-dimethoxybenzene
was obtained (1 mmol, 0.18 g 100%) as a yellow solid.
11. (a) Caddick, S. Tetrahedron 1995, 51, 10403; (b) Michael,
D.; Mingos, P.; Baghurst, D. R. Chem. Soc. Rev. 1991, 20,
1
; (c) Gedye, R. J.; Westaway, K.; Ali, H.; Baldisera, L.;
Laberge, L.; Rousell, J. Tetrahedron Lett. 1986, 27, 279;
d) Giguere, R. J.; Bray, T. L.; Duncan, S. M.; Majetich,
(
G. Tetrahedron Lett. 1986, 27, 4945.
1
1
2. (a) Abramovitch, A. Org. Prep. Proc. Int. 1991, 23, 685;
(
1
b) Migos, D. M. P.; Baghurst, D. R. I. Chem. Soc. Rev.
991, 20, 1; (c) Caddick, S. Tetrahedron 1995, 51, 10403.
3
4
3. (a) Loupy, A.; Petit, A.; Ramdiani, M.; Yvanaeff, C.;
Majdoud, M.; Labiad, B.; Villemin, D. Can. J. Chem.
1993, 71, 90; (b) Varma, R. S.; Chatterjee, A. K.; Varma,
M. Tetrahedron Lett. 1993, 34, 3207.
1
4. (a) Hajipour, A. R.; Arbabian, M.; Ruoho, A. E. J. Org.
Chem. 2002, 67, 8622; (b) Hajipour, A. R.; Ruoho, A. E.
Org. Prep. Proced. Int. 2002, 34, 647; (c) Hajipour, A. R.;
Mazloumi, G. Synth. Commun. 2002, 32, 23; (d) Hajipour,
A. R.; Ruoho, A. E. J. Chem. Res. (S) 2002, 547; (e)
Hajipour, A. R.; Adibi, H.; Ruoho, A. E. J. Org. Chem.
Acknowledgements
We gratefully acknowledge the funding support received
for this project from the Isfahan University of Technol-
ogy (IUT), IR Iran (A.R.H.) and Grants GM 033138,
MH 065503, NS 033650 (A.E.R.) from the National
Institutes of Health, USA. Further financial support
from Center of Excellency in Chemistry Research
2
003, 68, 4553; (f) Hajipour, A. R.; Bageri, H.; Ruoho, A.
E. Bull. Korean Chem. Soc. 2004, 25, 1238; (g) Hajipour,
A. R.; Malakutikhah, M. Org. Prep. Proced. Int. 2004,
3
64, 647; (h) Hajipour, A. R.; Ruoho, A. E. Sulfur Lett.
2
002, 25, 151; (i) Hajipour, A. R.; Mirjalili, B. F.; Zarei,
(
IUT) is gratefully acknowledged.
A.; Khazdooz, L.; Ruoho, A. E. Tetrahedron Lett. 2004,
5, 6607.
4
1
5. (a) Hajipour, A. R.; Mallakpour, E.; Imanzadeh, G. J.
Chem. Res. 1999, 228; (b) Hajipour, A. R.; Mallakpour,
E.; Adibi, H. Chem. Lett. 2000, 460; (c) Hajipour, A. R.;
Mallakpour, E.; Afrousheh, A. Tetrahedron 1999, 55,
2311; (d) Hajipour, A. R.; Islami, F. Ind. J. Chem. 1999,
38B, 461; (e) Hajipour, A. R.; Mallakpour, E.; Imanzadeh,
G. Chem. Lett. 1999, 99; (f) Hajipour, A. R.; Hanteh-
zadeh, M. J. Org. Chem. 1999, 64, 8475; (g) Hajipour, A.
R.; Mallakpour, E.; Backnejad, H. Synth. Commun. 2000,
30, 3855; (h) Hajipour, A. R.; Mallakpour, E.; Afrousheh,
A. Phosphorus Sulfur Silicon 2000, 160, 67; (i) Hajipour,
References and notes
1
. (a) Esakkidurai, T.; Pitchumani, K. J. Mol. Catal. A:
Chem. 2002, 185, 305; (b) Samajdar, S.; Becker, F. F.;
Banik, B. K. Tetrahedron Lett. 2000, 41, 8017; (c) Botvay,
A.; Mathe, A.; Poppl, L. Polymer 1999, 40, 4965; (d)
Tasneem, A. M. M.; Rajanna, K. C.; Saiparakash, P. K.
Synth. Commun. 2001, 31, 1123.
2
. (a) Olah, G. A.; Kuhn, S. J. J. Am. Chem. Soc. 1962, 84,
3
684; (b) Peng, X.; Suzuki, H.; Lu, C. Tetrahedron Lett.

8310
A. R. Hajipour, A. E. Ruoho / Tetrahedron Letters 46 (2005) 8307–8310
A. R.; Mallakpour, E.; Khoee, S. Synlett 2000, 740; (j)
Hajipour, A. R.; Mallakpour, E.; Khoee, S. Chem. Lett.
000, 120; (k) Hajipour, A. R.; Baltork, I. M.; Nikbaghat,
K.; Imanzadeh, Gh. Synth. Commun. 1999, 29, 1697.
6. (a) Hajipour, A. R.; Mahboubkhah, N. J. Chem. Res. (S)
998, 122; (b) Hajipour, A. R.; Mallakpour, E.; Adibi, H.
17. Hajipour, A. R.; Kooshki, B.; Ruoho, A. E. Tetrahedron
Lett. 2005, 46, 5503.
18. Frost, C. G.; Hartley, J. P.; Griffin, D. Tetrahedron Lett.
2002, 43, 4789.
19. Parac-Vogt, T. N.; Binnemans, K. Tetrahedron Lett. 2004,
45, 3137.
2
1
1
Chem. Lett. 2000, 460; (c) Hajipour, A. R.; Mallakpour,
E.; Khoee, S. Chem. Lett. 2000, 120; (d) Hajipour, A. R.;
Mallakpour, E.; Khoee, S. Synlett 2000, 740; (e) Hajipour,
A. R.; Ruoho, A. E. Org. Prep. Proced. Int. 2005, 37, 298;
20. Olah, G. A.; Malhotra, R.; Narang, S. C. J. Org. Chem.
1978, 43, 4628.
21. Olah, G. A.; Gupta, B. G. B.; Narang, S. C. J. Am. Chem.
Soc. 1979, 101, 5317.
(
2
f) Hajipour, A. R.; Ruoho, A. E. Org. Prep. Proced. Int.
005, 37, 279.
22. Dictionary of Organic Compounds, 5th ed.; Chapman and
Hall, 1982.