Trichloroisocyanuric acid/NaNO2 as a novel heterogeneous system for the selective mononitration of phenols under mild conditions

Article abstract of DOI:10.1055/s-2003-36791

Nitrophenols can be obtained via direct nitration of phenols with trichloroisocyanuric acid, NaNO₂ and wet SiO₂ at room temperature in moderate to high yields.

Full text of DOI:10.1055/s-2003-36791

LETTER
191
Trichloroisocyanuric Acid/NaNO2 as a Novel Heterogeneous System for the
Selective Mononitration of Phenols under Mild Conditions
S
elective Mononitratio
o
n of
P
henols
h
under Mild
aConditionsmmad Ali Zolfigol,* Ezat Ghaemi, Elaheh Madrakian
Chemistry Department, College of Science, Bu-Ali Sina University, Hamadan Zip Code 65174, Post Box No 4135, Iran
Fax +98(811)8272404; E-mail: Zolfi@basu.ac.ir
Received 22 September 2002
have in industry and in development technologies.28 In
Abstract: Nitrophenols can be obtained via direct nitration of phe-
nols with trichloroisocyanuric acid, NaNO2 and wet SiO2 at room
temperature in moderate to high yields.
continuation of our studies in this regard,29 we have found
that trichloroisocyanuric acid,30 a cheap commercially
available reagent used primarily as a disinfectant and de-
odorant, has found little application in organic chemistry
so far.31 Therefore, we were interested in using this re-
agent for the nitration of phenols when used in conjunc-
tion with NaNO2 and wet SiO2 in CH2Cl2. We wish to
report a simple method for the effective mono nitration of
phenols by using trichloroisocyanuric acid, NaNO2 and
wet SiO2 under mild and heterogeneous conditions
(Schemes 1 and 2).
Key words: trichloroisocyanuric acid, nitrophenols, sodium nitrite
The nitration of aromatic compounds is an important in-
dustrial process and nitro aromatic compounds so pro-
duced are widely utilized for the synthesis of dyes,
pharmaceuticals, perfumes, and plastics.1 Therefore, the
nitration of aromatic rings has received considerable at-
tention of late, due to unsolved problems pertaining to re-
gioselectivity, overnitration and competitive oxidation of
substrates.2,3 Nitration of the phenol taken as a special
case has been studied by various nitrating agents under
different conditions.1–27 Very recently, three excellent
procedures have been reported for the nitration of phe-
nols, two of them using microemulsion and surface-medi-
ated system for the regioselective nitration of phenols.22
The third one reported an enzymatic method for the nitra-
tion of phenols.23 Recently, we have reported the applica-
tions and mechanism of reaction of some hydrated metal
nitrates and their dinitrogen tetroxide complex analo-
goues, as well as ionic metal nitrates or nitrites in the pres-
ence of inorganic acidic salts, for the nitration of phenols
under various conditions.24
During the course of our studies on the utilization of NO+
in functional groups transformations,29 we thought that
phenol (1) could be converted into the 4-nitrosoderivative
(2) selectively by trichloroisocyanuric acid (I), NaNO2
(II), and wet SiO2 (50% w/w) in CH2Cl2 via in situ gener-
ation of HNO2. In addition, phenol nitrosation is rapid and
yields almost entirely the para isomer which can be readi-
ly converted to 4-nitrophenol (the desired product which
is precursor of acetaminophene) via a mild oxidation with:
HNO3,32 H2O2/Na2WO433 etc. (Scheme 1, path a). There-
fore, we decided to produce 4-nitrophenol via a nitrosa-
32–34
tion-oxidation strategy
in a one pot reaction under
mild and heterogeneous conditions. We chose trichloro-
isocyanuric acid (I)/wet SiO2 system for the nitrosation of
phenol (Scheme 1, path a). In contrast to the reported pro-
cedures in aqueous media,31–33 we observed that apparent-
ly direct formation of 2-nitrophenol (4) and 4-nitrophenol
(3) occurred (Scheme 1, path b, and Table 1).
Our goal, in undertaking this line of work, was two-fold:
a) to overcome the limitations and drawbacks of the re-
ported methods such as tedious work-up,13,15 strongly
acidic media,8b oxidation ability of the reagents and safety
problems (storage, handling, using and also presence of
toxic transition metal cations such as Cr+3, Hg+2, Cu+2,
within molecular structure of the reagents):25,26 (b) more-
over, to develop a high-yielding one-pot synthesis of ni-
trophenols using a novel combination of reagents.
Different kinds of 4-substituted phenols (5) were also sub-
jected to nitration in the presence of trichloroisocyanuric
acid (I), NaNO2 (II), and wet SiO2 (50% w/w) in dichlo-
romethane (Scheme 2). The nitration reactions were per-
formed under mild and completely heterogeneous
conditions at room temperature with moderate to good
yields (Schemes 1 and 2, Table 1). The present nitration
reactions can be readily carried out by placing the nitrat-
ing agents, phenols (1 or 5) and the solvent used in a reac-
tion vessel and efficiently stirring the resultant
heterogeneous mixture at room temperature. Highly pure
mono nitrophenols can be obtained by simple filtration
and then evaporation of the solvent.
In addition, any reduction in the amount of liquid acids
needed and/or any simplification in handling procedures
would be highly convenient in terms of risk reduction,
economic advantage and environment protection.27 On
the other hand, there is intense current research and gen-
eral interest in heterogeneous systems because of the per-
ceived opportunities such systems present for basic
research and because of the unquestioned importance they
In fact, a combination of sodium nitrite and trichloroiso-
cyanuric acid (I) can act as solid nitrating agent which can
be readily weighed, handled and used for different pur-
poses in the presence of moist SiO2.29
Synlett 2003, No. 2, Print: 31 01 2003.
Art Id.1437-2096,E;2003,0,02,0191,0194,ftx,en;G23202ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

192
M. A. Zolfigol et al.
LETTER
A competitive reaction was performed between phenol (1) available reagent (slightly soluble in CH2Cl2) was used for
and anisole. It was observed that exclusive phenol nitra- the in situ generation of HOCl in the presence of wet
tion proceeded, anisole remaining intact in the reaction SiO2.35 It was converted to cyanuric acid as a highly polar
mixture after 24 hours. Selective mononitration of 4,4′-di- compound which is completely insoluble in CH2Cl2 and
hydroxydiphenyl (5l) was also achieved by controlling the was adsorbed by silica gel. However, highly pure mono-
stoichiometry of reagents (Table 1, entry 15).
nitrophenols were obtained by simple filtration and subse-
quent evaporation of the solvent.
This new system, i. e. a combination of trichloroisocyanu-
ric acid (I) and sodium nitrite is similar to N2O4 (N2O4 ⇔
– 36
NO+NO3 ) as a nitrosating agent via in situ generation of
HNO2 and NO+. Therefore, on the basis of our observa-
tions, in order to explain the previously reported results
concerning the applications of N2O4,29,36,37 metal nitrate
dinitrogen tetroxide complexes [M(NO3)m⋅nN2O4],24a oxi-
dation of HNO2 with oxygen and production of N2O4,38
well recent reported mechanism for nitration of
phenols39–41 and the products which are obtained, the
nitrous acid catalyzed mechanism (NAC) may be pro-
posed (see ref.24f).
In conclusion, cheapness and availability of reagents, easy
and clean work-up and good yields make this method at-
tractive for organic chemists.
Scheme 1
General: Chemicals were purchased from Fluka, Merck and Ald-
rich chemical companies. Yields refer to isolated pure products. The
nitration products were characterized by comparison of their spec-
tral (IR, 1H NMR), TLC and physical data with authentic samples.
Mononitration of Phenol (1) with trichloroisocyanuric acid (I),
NaNO2 (II) and wet SiO2: A Typical Procedure
A suspension of compound 1 (0.188 g, 2 mmol), I (0.928 g, 4
mmol), II (0.276 g, 4 mmol) and wet SiO2 (50% w/w, 0.4 g) in
CH2Cl2 (10 mL) was magnetically stirred at room temperature. The
reaction was complete after 15 min and then filtered, bring the res-
idue washed with CH2Cl2 (2 × 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)43
and simple distillation. The residue is a mixture of 2- and 4-nitro-
phenol. 4-Nitrophenol (3) is insoluble in n-pentane, 0.120 g, 42%
mp 110–113 °C [Lit.8 mp 114 °C]. The n-pentane fraction was evap-
orated by water bath (35–40 °C),43 to give 2-nitrophenol (4), 0.080
g, 30%, mp 44–45 °C [Lit.8 mp 44 °C] (Table 1, Scheme 1).
Mononitration of 4-Chlorophenol (5b) with trichloroisocyan-
uric acid (I), NaNO2 (II) and wet SiO2: A Typical Procedure
A suspension of compound 5b (0.257 g, 2 mmol), I (0.464 g, 2
mmol), wet SiO2 (50% w/w, 0.4 g) and II (0.138 g, 2 mmol) in
dichloromethane (10 mL) was stirred at room temperature for 15
min (the progress of the reaction was monitored by TLC) and then
filtered. Anhydrous Na2SO4 (3 g) was added to the filtrate. After 15
min the resulting mixture was also filtered. Dichloromethane was
removed by water bath (35–40 °C) under simple distillation. The
yield was 0.319 g (99%) of crystalline pale yellow solid (6b), mp
88–90 °C, [Lit.8c mp 91 °C]. 1H NMR (FT-90 MHz, CDCl3, TMS):
Scheme 2
Phenol nitration did not occur in the absence of trichloro-
isocyanuric acid (Table 1, entry 17). On the other hand,
the water molecules or wet SiO2 are necessary for the ni-
tration of phenols (Table 1, entries 6 and 18). In order to
further clarify the action of wet SiO2 reaction was carried
out in the presence of water under two phase system
(CH2Cl2–H2O). It led to similar yields but without the ease
in the separation. Therefore, we think that the presence of
wet SiO2 acts as a heterogeneous effective surface area for
in situ generation of HNO2, efficiently making work-up
easy. Trichloroisocyanuric acid (I) as a commercially
1
δ 7.12 (dd, 1 H), 7.42 (dd, 1 H), 8.02 (s, 1 H), 10.31 (b, 1 H). H
NMR spectrum was identical with reference one.8c
Acknowledgement
The authors gratefully acknowledge partial support to this work by
the Research Affair of Bu-Ali Sina University, Hamadan, I. R Iran.
Synlett 2003, No. 2, 191–194 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Selective Mononitration of Phenols under Mild Conditions
193
Table 1 Mononitration of Phenols to Their Corresponding Nitro Derivatives with a Combination of Trichloroisocyanuric Acid (I), NaNO2
(II) and Wet SiO2 (50% w/w) in Dichloromethane at Room Temperature
Entry
Substrate
Product
Subst./Reagents (mmol)a
Time (min)
Yieldb%
Mp (°C)
I
II
Found
Reported
1
1
3
4
30
42
111–113
44–46
11511
4411
2
2
15
2
3
5a
5b
5c
5c
5c
5d
5e
5f
5g
5h
5i
6a
6b
6c
6c
6c
6d
6e
6f
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
–
2
1
1
1
1
1
1
1
1
1
1
1
1
1
2
1
2
2
15
15
98
99
92
82c
84d
91
74
74
80
97
78
91
70
80
87
73
89
73–48c
9115,39
4
15
87
8415,39
5
20
87
8415,39
6
20
87
8415,39
7
30
140–142
61–63
1458c,39
6642
8
20
9
30
29–31
3115,39
10
11
12
13
14
15
16
17
18
6g
6h
6i
15
57–58
54–624h
12315,39
140–428c
61–624h
18024h
20
122–124
143–145
63–65
20
5j
5k
5l
6j
30
6k
6l
30
178–180
183–186
180–182
no reactione
no reactionf
20
183–18424h
180–18424h
5m
1
6m
3, 4
3, 4
20
12 (h)
12 (h)
1
a Wet SiO2: substrate (1 and 5) (0.2 g:1 mmol).
b Isolated yields.
c Reaction was performed under two phase system (CH2Cl2–H2O).
d Reaction was performed by addition of two drops of water (instead of wet SiO2) to the reaction mixture.
e Reaction did not occur in the absence of trichloroisocyanuric acid (I).
f Reaction did not occur in the absence of wet SiO2.
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Synlett 2003, No. 2, 191–194 ISSN 0936-5214 © Thieme Stuttgart · New York