Mendeleev Commun., 2006, 16(1), 41–42
1,3-Dihalo-5,5-dimethylhydantoin or citric acid/NaNO2 as a heterogeneous system
for the selective mononitration of phenols under mild conditions
Mohammad A. Zolfigol,* Ezat Ghaemi, Elaheh Madrakian and Arash G. Choghamarani
Department of Chemistry, College of Science, Bu-Ali Sina University, Hamadan 65174, Iran.
Fax: +98 811 827 2404; e-mail: Zolfi@basu.ac.ir
DOI: 10.1070/MC2006v016n01ABEH002116
Direct nitration of phenols was performed using 1,3-dichloro-5,5-dimethylhydantoin, 1,3-dibromo-5,5-dimethylhydantoin or
citric acid/NaNO2 in the presence of wet SiO2 at room temperature.
The nitration of aromatic compounds is an important industrial
process.1 However, the nitration of aromatic rings involves
OH
OH
I–III
unsolved problems of regioselectivity, overnitration and com-
petitive oxidation of substrates.2 The nitration of phenol under
various conditions has been studied.3 Recently, three proce-
dures have been reported for the nitration of phenols with the
use of microemulsion and surface-mediated systems for regio-
selective nitration4 or an enzymatic method.5 We have reported
the reactions of hydrated metal nitrates and their dinitrogen
tetroxide complex analogues, as well as ionic metal nitrates or
nitrites, in the presence of inorganic acidic salts, for the nitration
of phenols under various conditions.6 The nitration of phenols
using nitric acid under phase-transfer and ultrasonic conditions
is also known.7,8
wet SiO2
NO2
NaNO2
n-hexane
room temperature
Y
Y
4a–m
5a–m
a Y = F
h Y = COMe
i Y = CHO
j Y = CH2Ph
k Y = NHOAc
l Y = 4-HOC6H4
m Y = COOH
b Y = Cl
c Y = Br
d Y = CN
e Y = Ph
f Y = Me
g Y = OMe
Scheme 2
O
O
Cl
Cl Br
Br
A combination of sodium nitrite and one of the I–III can act
as a solid nitrating agent, which can be readily weighed, handled
and used in the presence of moist SiO2.
N
N
N
N
O
O
Phenol nitration did not occur in the absence of I–III (Table 1,
entry 15). On the other hand, water molecules or wet SiO2
are necessary for the nitration of phenols (Table 1, entry 16).
Therefore, we think that wet SiO2 acts as a heterogeneous
effective surface area for in situ generation of HNO2, efficiently
making work-up easy. DCH or DBH (slightly soluble in n-hexane)
was used for the in situ generation of HOX in the presence of
wet SiO2.11 It was converted to 5,5-dimethylhydantoin (IV) as
a highly polar compound, which is completely insoluble in
n-hexane, adsorbed by silica gel (Scheme 3). However, highly
I
II
COOH
H
O
H
HO
H
COOH
H
H
N
N
H
COOH
III
O
IV
We found that commercially available 1,3-dichloro(bromo)-
5,5-dimethylhydantoin (I or II)9,10 and citric acid (III) can be
used as a green source of H+. Therefore, we report a simple,
cheap and convenient method for the effective mononitration of
phenols using 1,3-dichloro-5,5-dimethylhydantoin (DCH, I),
1,3-dibromo-5,5-dimethylhydantoin (DBH, II) or citric acid
(CA, III) with NaNO2 in the presence of wet SiO2 under mild
and heterogeneous conditions (Schemes 1 and 2).†
†
Chemicals from Fluka, Merck and Aldrich were used. Yields refer to
isolated pure products. Silica gel (70–230 mesh) from Merck was used.
The nitration products were characterised by a comparison of their
1
spectral (IR, H NMR), TLC and physical data with those of authentic
samples.12,13
A typical procedure for mononitration of phenol 1 with 1,3-dibromo-
5,5-dimethylhydantoin I, NaNO2 and wet SiO2. A suspension of com-
pound 1 (0.188 g, 2 mmol), I (0.572 g, 2 mmol), NaNO2 (0.276 g,
4 mmol) and wet SiO2 (50% w/w, 0.4 g) in n-hexane (10 ml) was
magnetically stirred at room temperature. The reaction was complete
after 45 min. The reaction mixture was filtered; the residue was washed
with n-hexane (20 ml). Anhydrous Na2SO4 (3 g) was added to the
filtrate. After 15 min, the resulting mixture was also filtered; n-hexane
was removed in a water bath (35–40 °C) by distillation. The residue
is a mixture of 2- and 4-nitrophenol. 4-Nitrophenol (2) is insoluble in
n-pentane, yield 0.077 g (28%), mp 111–113 °C (lit.,13 mp 114 °C).
The n-pentane fraction was evaporated in a water bath (35–40 °C) to
give 2-nitrophenol (3), yield 0.166 g (60%), mp 44–46 °C (lit.,13 mp 44 °C)
(Table 1, Scheme 1).
OH
OH
OH
I–III
wet SiO2
NaNO2
NO2
n-hexane
room temperature
NO2
1
2
3
Scheme 1
A typical procedure for mononitration of 4-chlorophenol 4b with
1,3-dibromo-5,5-dimethylhydantoin I, NaNO2 and wet SiO2. A suspen-
sion of compound 4b (0.257 g, 2 mmol), I (0.572 g, 2 mmol), wet SiO2
(50% w/w, 0.4 g) and NaNO2 (0.138 g, 2 mmol) in n-hexane (10 ml)
was stirred at room temperature for 30 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; n-hexane was removed by distillation in a water bath. The yield
of 5b 0.312 g (90%), crystalline pale yellow solid, mp 88–89 °C, (lit.,13
mp 91 °C).
A range of 4-substituted phenols (4) were also nitrated
using I–III/NaNO2 in the presence of wet SiO2 (50%, w/w)
in n-hexane (Scheme 2). The nitration reactions were performed
at room temperature with moderate to good yields (Schemes 1
and 2, Table 1). They can be readily carried out by placing the
nitrating agents, phenols (1 or 4) and the solvent in a reaction
vessel and stirring the resulting heterogeneous mixture at room
temperature. Highly pure mono nitrophenols can be obtained
by filtration and subsequent evaporation of the solvent.
Mendeleev Commun. 2006 41