A fast and mild method for the nitration of aromatic rings

Article abstract of DOI:10.1016/S0040-4039(01)01378-8

The use of N₂O₅ and a Fe(III) catalyst for the nitration of aromatic rings is described. This methodology is compatible with most functional groups and results in near quantitative yields in 4 min. The reaction conditions are non-oxidising: benzaldehyde and benzyl alcohols are readily nitrated with little or no oxidation (<4%) occurring. The addition of the iron catalyst activates the system to such an extent that nitration of an activated aromatic ring, such as toluene, occurs quantitatively at -100°C. This high activity allows compounds with sensitive functional groups such as alkenes to be smoothly nitrated.

Full text of DOI:10.1016/S0040-4039(01)01378-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6767–6769
A fast and mild method for the nitration of aromatic rings
Radoslaw R. Bak and Andrew J. Smallridge*
School of Life Sciences and Technology, Victoria University of Technology, PO Box 14428, Melbourne 8001, Australia
Received 20 June 2001; revised 18 July 2001; accepted 26 July 2001
Abstract—The use of N O and a Fe(III) catalyst for the nitration of aromatic rings is described. This methodology is compatible
2
5
with most functional groups and results in near quantitative yields in 4 min. The reaction conditions are non-oxidising:
benzaldehyde and benzyl alcohols are readily nitrated with little or no oxidation (<4%) occurring. The addition of the iron catalyst
activates the system to such an extent that nitration of an activated aromatic ring, such as toluene, occurs quantitatively at
−
100°C. This high activity allows compounds with sensitive functional groups such as alkenes to be smoothly nitrated. © 2001
Published by Elsevier Science Ltd.
Conventional methods for the nitration of aromatic
rings utilize nitric acid or mixtures of nitric and sul-
phuric acids. These conditions are incompatible with a
range of compounds which are sensitive to oxidising
or strongly acidic conditions. Use of nitronium salts,
quantitative yield of o- and p-nitrotoluene after only
10 min. Attempts to nitrate less activated aromatic
rings, such as acetophenone, using this methodology
resulted in recovery of unreacted starting material.
1
such as those formed from methane sulfonic acid, or
The use of an Fe(III) catalyst for the nitration of
2
from Lewis acids, such as boron trifluoride, are also
aromatic rings using NO in the presence of oxygen has
2
hampered by liberation of strong acids; in the case of
6
been reported. The iron activates the NO although
2
the boron trifluoride/nitronium salt, HF and BF are
3
long reaction times, up to 72 h, are required and
moderately deactivated substrates are not nitrated. It
was thought that Fe(III) might also be capable of
catalysing nitration reactions using the more active
N O .
2
liberated.
For our studies a mild nitrating agent was required,
which could nitrate moderately deactivated aromatic
rings in the presence of a variety of functional groups.
Recent developments in aromatic nitration methodol-
ogy using NO /O (Kyodai nitration) demonstrated
2
5
2
3
Table 1. Nitration of aromatic rings using N O and
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5
excellent conversions for a variety of aromatic com-
Fe(acac) for 4 min
3
3
pounds. In the Kyodai nitration the active nitrating
R
R
agent is thought to be N O which is formed in situ
2
5
N O
2
5
from NO2 and O . The drawbacks to this method
3
Fe(acac)3
include the necessity to generate ozone, which
limits the reaction rate, and long induction periods,
during which sensitive compounds may undergo degra-
dation.
NO2
R
o:m:p
Isolated yield (%)
CHO
COCH3
18:60:22
50:44:6
21:B1:79
33:B1:67
19:32:49
93
98
96
91
99
94
The direct use of N O as a nitrating reagent, instead
2
5
of generating it in situ, has been previously reported
CH CN
2
4
5
for activated aromatic rings. In our hands N O5
CH
2
OH
2
a
Br
NO2
CN
readily nitrated toluene at 0°C to give a virtually
b
B1:99:B1
68:32:B1
b
95
a
Reaction conducted at 20°C.
Reaction conducted at 40°C.
b
*
0
Corresponding author.
040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)01378-8

6
768
R. R. Bak, A. J. Smallridge / Tetrahedron Letters 42 (2001) 6767–6769
Nitration of acetophenone at 0°C using Fe(acac) and
of 2,4- and 2,6-dinitrotoluene. The mono-nitrated
product can be obtained by conducting the nitration
reaction at −100°C (dry ice/ether bath) (Scheme 1). In
the absence of the iron the reaction occurs at 0°C,
this dramatic difference in reaction temperature
clearly illustrates the activating effect of the iron cata-
lyst.
3
N O in dichloromethane resulted in a near quantita-
2
5
tive yield of o- and m-nitroacetophenone after only 4
7
min.
This nitrating procedure was found to be applicable
to a range of aromatic compounds (Table 1).
In all cases complete nitration was observed after
only 4 min and the products were readily isolated in
near quantitative yields. For some deactivated aro-
The ability to conduct the nitration reaction at such
low temperatures allows the nitration of compounds
containing functional groups which are themselves
susceptible to nitration. Nitration of ethyl cinnamate
at 0°C resulted in attack at the double bond leading
to a complex mixture of products. However, conduct-
ing the nitration reaction at −100°C (dry ice/ether
bath) for 4 min gave a quantitative yield of nitrated
product, indicating the high reactivity of this method-
ology (Scheme 2).
8
matic rings (R=Br, NO , CN) incomplete nitration
2
was observed at 0°C. Conducting these reactions at
slightly elevated temperatures (20–40°C) resulted in
quantitative yields of nitrated product. These reaction
conditions are extremely mild as exemplified by the
ready formation of nitrobenzaldehyde, from benzalde-
hyde, with no evidence of oxidation of the aldehyde
functionality. In the case of benzyl alcohol a small
amount of benzaldehyde (<4%) is formed.
The structure of the active nitrating complex is not
clear nor is the mechanism of the reaction. Unlike
9
other nitrating systems involving Lewis acids, such as
The regioselectivity of the nitration reaction is similar
to that observed for reactions conducted under stan-
dard nitrating conditions, HNO /H SO , except for
BF , this reaction is clearly catalytic. Addition of
3
N O to a solution of Fe(acac) results in the forma-
2
5
3
3
2
4
tion of a pale pink solid. Attempts to isolate and
characterise this complex have to date been unsuc-
cessful as the complex decomposes readily in moist
air although it can be filtered and washed with
dichloromethane under nitrogen. This washed com-
plex does not nitrate aromatic rings stoichiometrically
in the absence of N O but the reaction proceeds nor-
nitration of compounds containing a carbonyl group,
e.g. benzaldehyde and acetophenone, which produce
increased amounts of the o-isomer. Reactions con-
ducted under non-acidic conditions using N O have
2
5
also been reported to exhibit this enhanced o-nitra-
3
tion. It has been postulated that in the absence of
2
5
acidic protons the carbonyl group is not protonated
leading to o-nitration whilst the protonated carbonyl
group is meta directing.
mally upon the addition of further amounts of N O .
2
5
It is also critical to add the N O to the Fe(III) to
2
5
form the complex prior to the addition of the aro-
matic substrate. If the complex is not preformed the
nitration reaction is significantly slower, and similar
results are obtained to those in reactions conducted in
the absence of the Fe(III). Addition of substrate to
the nitrating complex causes an immediate colour
change to an intense red/brown colour, and the com-
plex dissolves. The nitration reaction is self-indicating
as the mixture reverts to a lighter colour and the
solid catalyst is reformed once nitration is complete.
Whilst deactivated aromatic rings are readily mono-
nitrated under these conditions, nitration of toluene, a
mildly activated aromatic ring, leads to the formation
NO2
CH3
CH3
CH3
N O
2
5
+
:
Fe(acac)3
100°C
-
NO2
The use of N O and Fe(acac) is a simple, fast and
2
5
3
mild procedure for the nitration of aromatic rings.
The reaction is tolerant of a range of functional
groups and gives virtually quantitative yields in less
than 4 min.
65
35
Scheme 1.
NO2
CO Et
CO Et
2
CO Et
2
2
N O
2
5
+
:
Fe(acac)3
100°C
-
NO2
63
37
Scheme 2.

R. R. Bak, A. J. Smallridge / Tetrahedron Letters 42 (2001) 6767–6769
6769
References
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2
5
CH Cl2 and Fe(acac)3 (0.1 mmol) at 0°C results in the
2
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2
3
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4
10
2
2
affords N O with liberation of nitrogen oxides. The col-
Removal of solvent afforded the pure nitrated compounds
in near quantitative yields.
2
5
lected N O is placed in a freezer until a solid is formed,
2
5
1
13
the product is then warmed slowly to 10°C at which time
any liquid nitrogen oxides are discarded, to leave a white/
yellow solid. It is important that the N O used is free of
8. All compounds were fully characterized using H and
C
NMR.
9. Bachman, G. B.; Dever, J. L. J. Am. Chem. Soc. 1958, 80,
2
5
nitrogen oxide(s) CAUTION: N O is highly corrosive and
5871.
2
5