A fast and mild method for nitration of aromatic rings

Article abstract of DOI:10.1080/10426500490274655

The use of benzyltriphenylphosphonium nitrate (PhCH₂Ph ₃P⁺NO₃^-) (BTPPN) as a useful reagent for nitration aromatic compounds in the presence of methanesulfonic anhydride under solvent-free conditions is described. This methodology is useful for nitration of activated aromatic rings.

Full text of DOI:10.1080/10426500490274655

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A FAST AND MILD METHOD FOR NITRATION OF
AROMATIC RINGS
a
b
Abdol R. Hajipour & Arnold E. Ruoho
a
Isfahan University of Technology, Isfahan, Iran
b
University of Wisconsin Medical School, Madison, Wisconsin, USA
Version of record first published: 11 Aug 2010.
To cite this article: Abdol R. Hajipour & Arnold E. Ruoho (2004): A FAST AND MILD METHOD FOR NITRATION OF AROMATIC
RINGS, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:2, 221-226
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Phosphorus, Sulfur, and Silicon, 179:221–226, 2004
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490274655
A FAST AND MILD METHOD FOR NITRATION
OF AROMATIC RINGS
Abdol R. Hajipoura,b and Arnold E. Ruoho
b
a
Isfahan University of Technology, Isfahan, Iran; and University
b
of Wisconsin Medical School, Madison, Wisconsin, USA
(
Received November 11, 2002; accepted July 26, 2003)
+
−
The use of benzyltriphenylphosphonium nitrate (PhCH Ph P NO )
2
3
3
(
BTPPN) as a useful reagent for nitration aromatic compounds in the
presence of methanesulfonic anhydride under solvent-free conditions
is described. This methodology is useful for nitration of activated aro-
matic rings.
Keywords: Aromatic compounds; benzyltriphenylphosphonium
nitrate; methanesulfonic anhydride; nitration; solvent-free conditions
Conventional methods for the nitration of aromatic rings utilize a
mixture of nitric and sulphuric acids or nitronium tetrafluroborate
1
methods. These conditions are incompatible with a range of compounds
that are sensitive to oxidizing or strongly acidic conditions. In the case
1
of borane/nitronium salt, HF and BF3 are liberated. We have been
engaged in the synthesis of azido aromatic compounds as photoaffin-
2
ity ligands. The nitro compounds required for the synthesis of these
derivatives were prepared by the conventional nitric-sulphoric acid or
3
nitronium tetraborate methods. We became concerned about the dis-
posal of the large amount of acid waste that resulted, sensitivity of
starting material, and low yields of product. To avoid this complication
and the associated hazards, we set out to test the nitrating ability of
benzyltriphenylphosphonium nitrate under solvent-free conditions in
a projected route to develop a simple synthesis of the nitro compound
in a relatively short period.
We gratefully acknowledge the funding support received for this project from the
Isfahan University of Technology, IR Iran (A.R.H.) and grant GM 33138 (A.E.R.) from
the National Institutes of Health, USA.
Address correspondence to A. R. Hajipour, Department of Pharmacology, University
of Wisconsin Medical School, 1300 University Ave., Madison, WI 53706-1532. E-mail:
haji@cc.iut.ac.ir
2
21

2
22
A. R. Hajipour and A. E. Ruoho
RESULTS AND DISCUSSION
Heterogeneous reactions that are facilitated by supported reagents
on various solid inorganic surfaces have received attention in recent
4−6
years.
The advantage of these methods over conventional homoge-
nous reactions is that they provide greater selectivity, enhanced reac-
tion rates, cleaner products, and manipulative simplicity. In connection
with our ongoing program to develop environmentally benign meth-
7
ods using solvent-free conditions, herein we report on an extremely
convenient method for nitration of a variety of aromatic compounds
with BTPPN 1 under solvent-free conditions. The reagent is readily
prepared by addition of an aqueous solution of KNO3 to an aque-
ous solution of benzyltriphenylphosphonium chloride at room temper-
ature (Scheme 1). The resulting white powder, which can be stored for
months without loss of its reactivity, is soluble in polar solvents such as
methanol, THF, acetonitrile, acetone, DMF, chloroform, ethyl acetate,
and dichloromethane, but insoluble in nonpolar solvents such as carbon
tetrachloride, n-hexane, and diethyl ether.
H2O/20 min
+
−
PhCH2P Ph3NO3 + KCl
+
−
PhCH2 P Ph3Cl + KNO3 −−−−−−−−−−−−→
1
room temperature 95%
SCHEME 1
Here we report on the nitration of activated aromatic compounds to
the corresponding nitrobenzene derivatives under solvent-free condi-
tions with reagent 1. The process in its entirety involves a simple mixing
of one molar ratio of aromatic compounds, methanesulfonic anhydride,
and reagent 1 in a mortar and grinding the mixture with a pestle for the
time specified in Table I at room temperature. This reaction proceeds
rapidly and purification of the product is very straightforward.
Activated aromatic compounds 2 were converted to the correspond-
ing nitro aromatic compounds 3 under solvent-free conditions at room
temperature in excellent yields in 5–20 min; deactivated aromatic com-
pounds were not converted to nitrobenzene derivatives with reagent 1
in the presence of methanesulfonic anhydride after 60–120 min grind-
ing at room temperature (Scheme 2 and Table I). The reagent does not
affect oxidizable groups, such as hydroxyl and amino groups (Table I).
After extraction of the nitro aromatic compounds and acidified aqueous
layer with aqueous 5% HCl and treatment with a fresh batch of the
aqueous KNO3, the reagent 1 could be recovered in quantitative yield.

Phosphonium Nitration of Aromatic Rings
223
TABLE I Nitration of Aromatic Compounds 2 with Reagent 1 to Nitroarens
a,b
3
Under Solvent-Free Conditions at Room Temperature
Time Yieldc
Entry
ArH (2)
ArNO2 (3) (o:m:p ratio)
Nitroanisole (15:0:85)
Nitroacetanilide (20:0:80)
4-Nitro-3-methylactanilide
4-Nitro-3-chloroacetanilide
4-Nitro-1,2-dimethoxybenzene
Nitrotluene (40:0:60)
(min)
(%)
1
2
3
4
5
6
7
8
9
Anisole
5
10
5
20
5
15
5
5
20
20
20
120
60
120
120
120
15
15
15
20
20
120
95
89
90
88
92
98
90
100
85
80
99
0
0
0
0
0
83
83
85
80
85
10
Acetanilide
3-Methylactanilide
3-Cloroacetanilide
1,2-Dimethoxybenzene
Toluene
Phenol
Nitrophenol
2-Nitro-1,4-dimethoxybenzene
1,4-Dimethoxybenzene
4-Hydroxybenzaldehyde 2-Nitro-4-hydroxybenzaldehyde
1,3,5-Trimethylbenzene 2-Nitro-1,3,5-trimethylbenzene
Naphthalene
C6H5NO2
4-MeC6H4NO2
C6H5CHO
10
11
12
13
14
15
16
17
18
19
20
21
22
1-Nitronaphthalene
NR
NR
NR
NR
NR
Nitrobenzylalcohol (18:0:82)
NO2C6H4(CH2)2COOH (10:0:90)
NO2C6H4(CH2)2COOMe (12:0:88)
NO2C6H4CH2COOH (15:0:85)
NO2C6H4CH2COOMe (15:0:85)
3-Nitrocoaine
C6H5COOH
C6H5COPh
Benzylalcohol
C6H5(CH2)2COOH
C6H5(CH2)2COOMe
C6H5CH2COOH
C6H5CH2COOMe
Cocaine
a
Confirmed by comparison with authentic samples (IR, TLC, and NMR).
Molar ratio of 1:2 (1:1).
b
c
Yield of isolated pure product after purification.
Interestingly, the site of the electrophilic attack by this reagent was
found to be identical to the conventional nitric acid or acetyl nitrate-
mediated nitration reaction (Table I).
To evaluate the efficiency of this reaction under solvent-free con-
ditions in comparison to the reaction in solution several experiments
were performed. We performed the reaction of anisole in several sol-
vents, such as methanol, acetone, ether, dichloromethane, THF, and
Solid-State
+
−
+
−
PhCH2P Ph3NO + ArH −−−−−−→ PhCH2P Ph3MeSO
3
3
1
2
(MeSO2)2O
+
MeSO3H + ArNO2
3
SCHEME 2

2
24
A. R. Hajipour and A. E. Ruoho
1,4-dioxane. We determined that 1,4-dioxane is the best solvent for this
reaction. When anisole was treated with one molar ratio of this reagent,
only 30% of anisole was converted to nitroanisole after 24 h stirring at
room temperature in the presence of 1 molar ratio of methanesulfonic
anhydride. By increasing the amount of the reagent 1 to 2 molar ratios
in the presence of 2 molar ratio of methanesulfonic anhydride, the yield
of the reaction did not increased. When anisole was treated with a mo-
lar ratio of this reagent and allowed to reflux in 1,4-dioxane for 24 h in
the presence of 1 molar ratio of methanesulfonic anhydride only 45% of
anisole was converted to nitroanisole.
We believe that the effect of methanesulfonic anhydride is to react
with the nitrate ion to produce methanesulfonyl nitrate. This reac-
tive intermediate then reacts with the aromatic ring to produce the
corresponding nitro aromatic compounds. We also tried the nitration
of anisole with KNO3 or NH4NO3 in the presence methanesulfonic
anhydride under solvent-free conditions instead to the benzyltriph-
enylphosphonium nitrate, the yield of product after 60 min was only
1
0%. It is possible that the soft phosphonium cation is required to
form a weakly associated The methanesulfonic anhydride reacted with
this weakly associated ion of nitrate anion to produce methanesul-
fonyl nitrate and that for potassium and ammonium nitrate would not
work.
In summary, we report here the preparation of benzyltriphenylphos-
phonium nitrate 1 as a mild, inexpensive, and selective nitration
reagent. This reagent is easily prepared from low-cost and commercially
available starting materials, and could be stored at room temperature
for months without losing its activity. The reagent is soluble in polar
solvents and slightly soluble in nonpolar solvents. This reagent is an ef-
ficient and novel reagent for nitration of activated aromatic compounds
to the corresponding nitrobenzene derivatives in the presence of other
oxidizable functional groups under solvent-free conditions.
EXPERIMENTAL
General
All yields refer to isolated products after purification by column chro-
matography. Products were characterized by comparison with authentic
1
samples (IR and H-NMR spectra, TLC, melting and boiling points). All
1
H-NMR spectra were recorded at 300 MHz in CDCl3 relative to TMS.
All reactions were carried out under solvent-free conditions at room
temperature.

Phosphonium Nitration of Aromatic Rings
225
Preparation of Benzyltriphenylphosphonium
Nitrate 1 (BTPPN)
A solution of benzyltriphenylphosphonium chloride (19.0 g, 49 mmol)
in 100 ml of water was prepared, and then KNO3 (4.95 g, 49 mmol) in
water (100 ml) was added dropwise to the above solution and stirred
for 1 h at room temperature. The resulting precipitate was filtered and
washed with cooled, distilled water (50 ml), and dried in a desiccator
under vacuum over calcium chloride to afford a white powder (19.92 g,
◦
9
8% yield), which decomposed at 181–182 C to a dark-brown material.
1
13
H-NMR: δ 7.93–6.87 (m, 20 H), 4.7(d, J = 25.6 Hz, CH2-P). C-NMR: δ
1
35.28, 135.25, 134.32, 134.24, 131.o7, 131.03, 130.19, 130.09, 128.99,
1
28.97, 128.69, 128.66, 127.45, 127.43, 118.01, 117.36, 29.68 (d, J =
−
1
193 Hz, C-P). IR (KBr): 1298, 1269, 1098, 1060, 700, 658, 590 cm
.
Anal Calcd for C25H22NO3P: C, 72.29; H, 5.30; N, 3.37%. Found: C,
2.50; H, 5.34; N, 3.31%.
7
Nitration of 1,4-Dimethoxybezene with Reagent (1)
to 2-Nitro-1,4-dimethoxybenzene
A mixture of 1,4-dimethoxybezene (1 mmol, 0.14 g), reagent (1)
1 mmol, 0.42 g), and methanesulfonic anhydride (1 mmol, 0.17 g) in a
(
mortar was ground with a pestle for the time specified in Table I until a
deep-yellow color appeared. When TLC (hexane:EtOAc 70:30) showed
complete disappearance of 1,4-dimethoxybezene, the mixture was ex-
tracted with CH2Cl2 and washed with aqueous HCl (10%). Evaporation
of the solvent gave 2-nitro-1,4-dimethoxybenzene. The yield was 0.18 g
(
100%) of crystalline yellow solid.
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