Silica sulfuric acid/NaNO2 as a novel heterogeneous system for the nitration of phenols under mild conditions

Article abstract of DOI:10.3390/71000734

Nitrophenols can be obtained in moderate to high yields via nitrosation-oxidation of phenols with silica sulfuric acid, NaNO₂ and wet SiO₂ at room temperature. In situ generation of HNO₂ and a radical cation mechanism via the nitrous acid catalyzed (NAC) pathway appear to be applicable to phenol nitration using these reagents.

Full text of DOI:10.3390/71000734

Molecules 2002, 7, 734-742
molecules
ISSN 1420-3049
http://www.mdpi.org
Silica Sulfuric Acid/ NaNO2 as a Novel Heterogeneous System
for the Nitration of Phenols under Mild Conditions
Mohammad Ali Zolfigol*, Elahe Madrakian and Ezat Ghaemi
Department of Chemistry, College of Science, University of Bu-Ali Sina, Zip Code 65174, Post Box
No. 4135, Hamadan, I.R. Iran; Fax: (+98) 81 8272404.
* Author to whom correspondence should be addressed; e-mail: zolfi@basu.ac.ir
Received: 2 October 2001; in revised form: 14 October 2002/ Accepted: 14 October 2002 /
Published 31 October 2002
Abstract: Nitrophenols can be obtained in moderate to high yields via nitrosation-
oxidation of phenols with silica sulfuric acid, NaNO2 and wet SiO2 at room temperature.
In situ generation of HNO2 and a radical cation mechanism via the nitrous acid catalyzed
(NAC) pathway appear to be applicable to phenol nitration using these reagents.
Keywords: Silica sulfuric acid, nitrosation-oxidation, nitration, nitrophenols.
Introduction
In several industrially important processes (e.g. nitration, nitrosation, etc.) a large excess of sulfuric
acid is required because the water by-product slows the reaction down by diluting the acid. At the end
of these processes, a large amount of “spent acid” is obtained which, in batch reactions, is usually
neutralized and disposed of, while, in continuous processes, it has to be recycled by complex
techniques. Also, the separation of the products from the acid is often a difficult and energy consuming
process that habitually implies a basic aqueous work-up. Moreover, sulfuric acid is corrosive and is
dangerous to transport and handle. Consequently, any reduction in the amount of sulfuric acid needed
and/or any simplification in handling procedures would be highly convenient in terms of risk
reduction, economic advantages and environment protection [1]. On the other hand, there is intense
current research and general interest in heterogeneous systems because of the perceived opportunities

Molecules 2002, 7
735
such systems present for basic research and because of the unquestioned importance such systems have
in industry and in developing technologies [2]. In continuation of our studies on the application of
inorganic acidic salts we found that silica gel reacts with chlorosulfonic acid to give silica sulfuric acid
(I). It is interesting to note that the reaction is easy and clean, not requiring any work-up procedure
because the evolved HCl gas can be removed from the reaction vessel immediately (Scheme 1).
Scheme 1
rt.
+
+
HCl
SiO OH
SiO OSO H
ClSO H (neat)
2
2
3
3
I
We believed that the silica sulfuric acid (I) is a superior proton source to all of the reported acidic
solid supports or acidic resins such as polystyrene sulfonic acid and Nafion-H [3] for running reactions
under heterogeneous conditions. Therefore, we were interested in using this inorganic acidic resin (I)
as a new sulfuric acid function immobilized on the surface of silica gel via covalent bonding for the in-
situ generation of HNO2 when used in conjunction with NaNO2, wet SiO2.
The nitration of aromatic compounds may be achieved with many nitrating reagents and is a very
useful reaction in organic synthesis. Nitration of the phenol as a special case has been studied using
various nitrating agents under different conditions [4-20]. Recently, in this connection we have
reported the applications and mechanism of reaction of some hydrated metal nitrates and their
dinitrogen tetroxide complex analogues for the nitration of phenols under various conditions [21]. We
have also demonstrated that in situ formation of HNO3 is a major factor for effective nitration of
phenols with metal nitrates (containing covalent nitrato groups) [21a].
Our goal, in undertaking this line of work, was two-fold: a) to overcome the limitations and
drawbacks of the reported methods such as: tedious work-up [12,14], strongly acidic media (Ho~ -8)
[7b], oxidation ability of the reagents and safety problems (storage, handling, use and also presence of
toxic transition metal cations such as Cr+3, Hg+2, Cu+2, etc., within molecular structure of the reagents)
[22,23]; (b) moreover, high-yielding one-pot synthesis of nitrophenols using a novel combination of
reagents are our main interest.
Very recently, we among many others, have demonstrated that heterogeneous reagent systems have
many advantages such as simple experimental procedures, mild reaction conditions and minimization
of chemical wastes as compared to their liquid phase counterparts. We have reported simple
procedures for in situ generation of the nitrosonium ion (NO+) under mild and heterogeneous
conditions and also applications of it for different purposes [24]. Therefore, we decided to seek a
heterogeneous system for the nitration of phenols, and we have investigated a number of different
reaction conditions based upon the in situ generation of HNO2 by the relatively strong solid inorganic
acidic resin [silica sulfuric acid (I)] with sodium nitrite. We wish to report here a one-pot
heterogeneous procedure for the nitration of phenols.

Molecules 2002, 7
736
Results and Discussion
During the course of our studies on the utilization of NO+ in functional groups transformations, we
thought that phenol (1) must be converted in to the p-nitrosophenol selectively in CH2Cl2 as solvent by
silica sulfuric acid (I) [(2 eq), one equivalent of I was needed for oxidation step], NaNO2 [(II), (1 eq)]
and wet SiO2 (50% w/w) via in situ generation of HNO2. On the other hand, we also thought that
phenol nitrosation is rapid and yields almost entirely the para- isomer which can be readily converted
to p-nitrophenol via a mild oxidation with HNO3 [25], H2O2/Na2WO4 [26], etc. Therefore, we decided
to produce p-nitrophenol via a nitrosation-oxidation strategy [22-24] in a one pot reaction under mild
and heterogeneous conditions. We chose silica sulfuric acid (I) because it is an excellent acid source(a
proton source for the in situ generation of HNO2 and NO+ under compeletly heterogeneous
conditions). NaNO3 (1eq) was needed for the second step, i.e., in situ generation of HNO3 for the
oxidation of p-nitrosophenol. (Scheme 2, path a). In contrast to the reported procedures in aqueous
media [26- 27], we observed that nitrosation and oxidation were occurring simultaneously. Hence, in
this reaction mono nitration has occurred and o-nitrophenol (4) and o-nitrophenol (2) were obtained
(Scheme 2, Table 1, path b).
Scheme 2
OH
OH
NaNO3
a
OH
NO
NO2
I or II
III
2
3
OH
OH
1
NO2
b
+
NO2
4
3
Different kinds of 4-substituted phenols (5) were also subjected to nitration reaction in the presence
of silica sulfuric acid (I), NaNO2 (II), and wet SiO2 (50% w/w) in dichloromethane (Scheme 3). The
nitration reactions were performed under mild and completely heterogeneous conditions at room
temperature in moderate to excellent yields (Scheme 3, Table 1). The present nitration reactions can be
readily carried out by placing the nitrating agents, phenols (1 or 5) and the solvent used in a reaction
vessel and efficiently stirring the resultant heterogeneous mixture at room temperature. The mono
nitrophenols can be obtained by simple filtration and then evaporation of the solvent. This method
provides nitrated phenols directly, in short reaction times and good yields.

Molecules 2002, 7
737
Scheme 3
OH
OH
NO
2
I
II
X
X
5
6
5
a
b
c
d
e
f
g
h
i
j
k
X
F
Cl Br CN Ph CH3 OCH3
COCH3
CH2Ph NHOAc
4-HOC6H4-
Table 1. Mononitration of Phenols to Their Corresponding Nitro derivatives with a
Combination with Silica Sulfuric acid (I), NaNO2 (II) and Wet SiO2 (50% w/w) in
Dichloromethane at Room Temperature.
Time
(h)
Yieldsb
%
M.p. (oC)
Reported
Entry
Substrate
1
Products
Found
110-113
44-45
73
3
4
1.5
20
115 [10]
44 [10]
1
30
5a
5b
5c
5d
5e
5f
5g
5h
5i
6a
6b
6c
6d
6e
6f
1.5
30
73-74 [7c]
91 [14, 31]
84 [14, 31]
2
3
2
45
89
2
90
87
4
2
80
140-142
61-63
29-31
54-56
122-124
61-6
145 [7c, 31]
66 [34]
5
2
86
6
2
2
70
31 [14, 31]
-- [31, 35]
123 [14, 31]
---[35]
7
6g
6h
6i
54
8
3
62
9
3
70
10
11
12
13
5j
6j
24
3
60
180
---[16, 37]
---[34]
5k
1
6k
3, 4
25
180-184
24(h)
No reactionc
---
---
b
c
a Wet SiO2 : substrate (1) (0.2 g : 1mmol) . Isolated Yields. Reaction did not occur in
the absence of Silica Sulfuric acid (I).
In fact, a combination of sodium nitrite and silica sulfuric acid (I) can act as solid HNO2 which can
be readily weighed, handled and used for different purposes in the presence of moist SiO2 [24]. A
competitive reaction was performed between phenol and anisole. It was observed that exclusive phenol
nitration proceeded, anisole remaining intact in the reaction mixtures after 24 hours (Scheme 4).
Selective mononitration of 4,4’-dihydroxydiphenyl (5k) was also achieved by controlling the
stoichiometry of reagents (Table 1, Entry 12).

Molecules 2002, 7
738
Scheme 4
OH
X
OCH
OCH
OH
X
3
3
I
NO
NO
2
+
2
+
II
or
1
5
,
3 4 or 6
7
8
100%
0%
Although the reaction occurs without wet SiO2, the reaction times are very long, taking several
days to go to completion. Therefore, we think that the wet SiO2 acts as an effective heterogeneous
surface for in situ generation of HNO2. It also makes work-up easy. This new system i.e. a
-
combination of silica sulfuric acid (I) and sodium nitrite is similar to N2O4 (N2O4 NO+NO3 ) [30] as
a nitrosating agent via in situ generation of HNO2 (eq 1) and NO+ (eq 2). Thus, on the basis of our
observations, the previously reported results concerning the applications of N2O4 [28, 29], metal nitrate
dinitrogen tetroxide complexes [M(NO3)m.nN2O4] [20a], oxidation of HNO2 with oxygen and
production of N2O4 (eq 3-6) [30], the very recent reported mechanism for nitration of phenols [31-33]
and the products which are obtained, the following nitrous acid catalyzed mechanism (NAC) may be
proposed (Scheme 5).
Scheme 5
-
H+ + NO2 → HNO2
HNO2 + 2H+ → NO+
2HNO2 → N2O3 + H2O
(eq 1)
(eq 2)
(eq 3)
(eq 4)
(eq 5)
(eq 6)
+ H3O+
N2O3
2NO2 → N2O4
2NO → N2O2 + O2 → N2O4
→ NO + NO2
.
OH
OH
O
OH
+
_
+
+
NO
NO
NO
2
H
.
_
+
NO
2
+
H
+
X
X
X
X
or
1
5
,
or 6
3 4
Conclusions
The cheapness and the availability of the reagents, easy and clean work-ups and good yields make
this method attractive for large-scale operations. Moreover, a new feature here is the fact that the
reaction is heterogeneous. This could be worthwhile in an industrial setting [20].

Molecules 2002, 7
739
Acknowledgements
The authors gratefully acknowledge partial support of this work by the Research Affairs Office of
Bu-Ali Sina University, Hamadan, I.R Iran.
Experimental
General
Chemicals were purchased from the Fluka, Merck and Aldrich chemical companies. Yields refer to
isolated pure products. The nitration products were characterized by comparison of their spectral (IR,
1H-NMR, 13C-NMR), TLC and physical data with the authentic samples [7, 21].
Preparation of silica sulfuric acid (I) [38]
A 500 mL suction flask equipped with a constant-pressure dropping funnel and a gas inlet tube for
conducting of HCl gas over an adsorbing solution (i.e. water) was used. It was charged with silica gel
(60.0 g). Chlorosulfonic acid (23.3 g, 0.2 mol) was added dropwise over a period of 30 min at room
temperature. HCl gas immediately evolved from the reaction vessel (Scheme 1). After the addition was
completed the mixture was shaken for 30 min. A white solid of silica sulfuric acid (76.0 g, ~100%)
was obtained.
Typical procedure for the mononitration of phenol (1) with silica sulfuric acid (I), NaNO2 (II) and wet
SiO2
A suspension of compound 1 (0.188 g, 2 mmol), I (1.25 g), II (0.138 g, 2 mmol) and wet SiO2
(50% w/w, 0.2 g) in CH2Cl2 (10 mL) was stirred magnetically at room temperature. The reaction was
completed after 1. 5 hours and then filtered. The residue was washed with CH2Cl2 (2 x 10 mL).
Anhydrous Na2SO4 (3 g) was added to the filtrate. After 15 minutes the resulting mixture was also
filtered. Dichloromethane was removed by water bath (35-40 °C) and simple distillation. The residue is
a mixture of 2- and 4-nitrophenols. 4-Nitrophenol (3) is insoluble in n-pentane, 0056 g, 20% mp
112-113 °C (lit. [10] mp 114 °C). The n-pentane was evaporated by water bath (35-40 °C), to give
2-nitrophenol (4), 0.082 g, 30%, mp 43-45 °C (lit. [10] mp 44 °C) (Table 1, Scheme 2).
Typical procedure for the mononitration of 4-chlorophenol (5b) with silica sulfuric acid (I), NaNO2
(II) and wet SiO2.
A suspension of compound 5b (0.257 g, 2 mmol), I (1.25 g), wet SiO2 (50% w/w, 0.2 g) and II
(0.138 g, 2 mmol) in dichloromethane (10 mL) was stirred at room temperature for 1.5 hours (the

Molecules 2002, 7
740
progress of the reaction was monitored by TLC) and then filtered. Anhydrous Na2SO4 (3 g) was added
to the filtrate. After 15 minutes the resulting mixture was also filtered. Dichloromethane was removed
by water bath (35-40 °C) and simple distillation. The yield of crystalline pale yellow solid (6b) was
0.156 g, (45%), mp 88 oC, (lit.[7c] mp 91 oC]. 1H-NMR (FT-90 MHz, CDCl3, TMS) : δ 7.12 (dd, 1H),
7.42 (dd, 1H), 8.02 (s, 1H), 10.31 (b, 1H). 1H-NMR spectra were identical with reference spectra [7c].
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Sample Availability: Samples of compounds 3, 4, 6a, 6b, 6d, 6h, 6k, 3-nitro-4-hydroxybenzoic acid
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