KHSO4 as an efficient catalytic system for the regiospecific nitration of phenols with metal nitrates

Article abstract of DOI:10.1002/cjoc.201090085

Highly regiospecific mononitration of phenol and substituted phenols was accomplished employing a metal nitrate and a catalytic amount of KHSO₄ in acetonitrile. An exclusive ortho-selectivity was observed with excellent yields. A variety of metal nitrates were used to obtain o-nitrophenols exclusively in good to excellent yields. The use of KHSO₄ is key for the selectivity observed.

Full text of DOI:10.1002/cjoc.201090085

FULL PAPER
KHSO as an Efficient Catalytic System for the Regiospecific Nitra-
4
tion of Phenols with Metal Nitrates
Baghernejad, Bita
Oskooie, Hossein A.*
Heravi, Majid M.
Beheshtiha, Yahia Sh.
Department of Chemistry, School of Science, Azzahra University, Vanak, Tehran, Iran
Highly regiospecific mononitration of phenol and substituted phenols was accomplished employing a metal ni-
trate and a catalytic amount of KHSO in acetonitrile. An exclusive ortho-selectivity was observed with excellent
4
yields. A variety of metal nitrates were used to obtain o-nitrophenols exclusively in good to excellent yields. The
use of KHSO is key for the selectivity observed.
4
4
Keywords KHSO , phenol, nitration, regiospecific
Introduction
cantly, enhancing the scope of the nitration process
however, there are concerns regarding achieving effi-
cient regioselectivity. All these methods also suffer from
other drawbacks, for example, some of the nitrates must
be prepared from dinitrogen pentoxide, or they must
either use the clay supported or absorbed on silica gel
prior to their use as nitrating agents. Recently, solid ac-
ids have attracted much attention to organic synthesis
owing to their easy work-up procedures, easy filtration,
and minimization of cost and waste generation due to
Aromatic nitro compounds are important starting
materials for the manufacture of various industrial
products such as pharmaceuticals, dyes and plastics.
Some aromatic compounds as anti-tumor drugs have
shown structure-activity relationship with several di-
amides and diamines to which a polycyclic aromatic
1
ring was bound and which nitro compounds required
for the synthesis of these derivatives. The nitration of
aromatics is one of the oldest and most important proc-
esses in the chemical industry for the production of in-
termediates. Extensive and well-documented reviews
have been published about the mechanisms using
various nitrating agents under different conditions,
36
reuse and recycling of these catalysts. As the continua-
tion of our studies towards the development of new
37-42
routes to the synthesis of heterocyclic compounds
2
,3
and the application of KHSO
ganic synthesis,
4
as a green catalyst to or-
herein we report nitration of phe-
nols in the presence of a catalytic amount of KHSO
4-25
43,44
but most of them are usually not selective and cause
environmental concerns regarding the disposal of large
volumes of mixed acids typically employed in this
4
with metal nitrates (Scheme 1) in good yields (Table 1
and 2).
2
6,27
process.
A mixture of concentrated nitric acid and
sulfuric acid is used as the most common nitrating re-
agent for the nitration of benzene, alkyl benzene, and
Scheme 1
2
8,29
less reactive aromatic compounds,
but highly reac-
tive aromatic compounds, phenols and pyrroles, require
mild nitration condition, thus a wide variety of nitration
2
4,25,30,31
methods have been developed.
Regarding the
nitration of phenols, concentrated nitric acid or mixture
of acids is promising. However their use is always asso-
ciated with the formation of dinitro compounds, oxi-
dized products and unspecified resinous tarry materials
resulting from over-oxidation of the substrate. Further-
more, it is noteworthy that the typical yield of direct
Results and discussion
Nitration of phenol in the presence of a catalytic
amount of KHSO
4
with a variety of metal nitrates was
screened and the results are summarized in Table 1. The
use of a catalytic amount of KHSO
action to proceed with high regiospecificity and each of
the metal nitrates used afforded o-nitrophenols as a sin-
gle regioisomer in good to excellent yields. KHSO
one of the components of a triple salt with formula
2
6
nitration never exceeds 60% because of the above
mentioned side reactions in most cases, which makes
these existing processes uneconomical. On the other
hand, the use of metal nitrates like ceric ammonium
34
4
is key for the re-
8
32,33
7,34
4
is
nitrate, copper nitrate,
ferric nitrate
and vana-
3
5
dium nitrate has contributed to this nitration signifi-
2
KHSO
5
•KHSO
4
•K
2
SO
4
so called oxone, which is used
*
E-mail: mmh1331@yahoo.com (M. M. Heravi); Tel.: 0098-2188041344; Fax: 00982188047861
Received November 21, 2008; revised July 10, 2009; accepted September 2, 2009.
Chin. J. Chem. 2010, 28, 393— 396
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
393

Baghernejad et al.
FULL PAPER
Table 1 Nitration of phenol with metal nitrates using KHSO
a catalyst under refluxing condition
4
as
effect of various solvents on the nitratiom reaction. The
performances of various solvents are in the following
order: acetonitrile＞ethyl acetate＞acetone＞THF＞
chloroform＞dichloromethane. Acetonitrile shows bet-
ter yield compared with other solvents. In addition, the
time required for completion of the reaction was found
to be less in acetonitrile. Maybe it is because of high
polarity of acetonitrile.
Time/ Yields of o-nitro-
Entry M(NO
3
)
n
•xH
2
O
Catalyst
o/p
a
min
25
30
40
50
50
50
phenol /%
1
2
3
4
5
6
Th(NO
Ni(NO
Hg (NO
Bi(NO
Fe(NO
NaNO
3
)
4
•5H
2
O
KHSO
KHSO
4
4
4
4
4
4
95
90
88
85
85
80
19
10
3
)
2
•6H
2
O
2
3
)
2
•2H
2
O KHSO
7.33
5.66
5.66
4
3
)
3
•5H
2
O
KHSO
KHSO
KHSO
Effect of reaction temperature
3 3 2
) •9H O
The temperature effect on the nitration of phenol in
the solvent of choice (acetonitrile) was also carefully
investigated. The reaction was carried out in the pres-
3
a
Yields were obtained by GC.
4
5
4
ence of KHSO and the temperature varied from room
as highly efficient catalyst in many organic reagents.
Very recently, we have reported the use of KHSO as an
temperature (25 to 82 ℃). The results are shown in Ta-
ble 2. As can be seen in Table 2 the highest yield is ob-
tained at 82 ℃ (reflux temperature), and the yields are
lower when the reactions are carried out at temperatures
lower than reflux temperature. We believe that increas-
ing in the temperature is apparently favorable for accel-
erating the reaction.
4
4
3
efficient catalyst for the synthesis of 1,1-diacetates and
synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-
4
4
1
H-indole-4(5H)-ones. Even though the reaction pro-
ceeded with various metal nitrates, the time required for
completion of the reaction was found to be less and the
yields higher with Th(NO
treated with a metal nitrate and KHSO
3
)
4
•5H
2
O. Phenols were
in acetonitrile at
4
Experimental
reflux to afford o-nitrophenol as the exclusive product
in satisfactory to good yields (Scheme 1). The scope and
generality of the method are illustrated with several
examples in Table 2 and all of them yielded the
o-nitroproduct exclusively in good to excellent yields.
Phenols with electron donating groups (Entries 2, 6, 7 in
Table 2) behaved very well to afford the o-nitrophenols
as the exclusive products in excellent GC yields. Phe-
nols with moderately deactivating groups (Entries 3, 4
in Table 2) also yielded the o-nitrophenols in good
yields.
Materials and methods
All the chemicals were obtained from Merck Com-
pany and used as received. All products are known com-
1
pounds and were characterized by m.p., IR, H NMR
and GC/MS. Melting points were measured by using the
capillary tube method with an electrothermal 9200 ap-
1
paratus. H NMR spectra were recorded on a Bruker
AQS AVANCE-300 MHz spectrometer using TMS as an
internal standard (CDCl solution). IR spectra were re-
3
corded from KBr disks on an FT-IR Bruker Tensor 27
spectrometer. GC/MS data were recorded on an Agilent
Technologies 6890 network GC system and an Agilent
In a systematic study and aimed work, the reaction
has been examined with KHSO and the effects of the
4
reaction temperature and solvent have also been studied.
5973 network mass selective detector. Thin layer chro-
Effect of the solvent
matography (TLC) on commercial aluminum backed
plates of silica gel, 60 F254, was used to monitor the
progress of reactions.
Influences of solvents are important for the determi-
nation of yield of the product. Table 3 shows the
Table 2 Nitration of phenols with Th(NO
Product
o-Nitrophenol
3
)
4
•5H
2
O and KHSO
Time/min
4
a
Yield /%
Entry
Substrate
Phenol
2
5 ℃
75
50 ℃
82 ℃
95
1
2
3
4
5
6
7
8
9
25
10
60
60
25
20
10
25
25
85
4-Methoxyphenol
4-Nitrophenol
4-Bromophenol
1,3-Benzenediol
2-Methylphenol
4-Methylphenol
2-Naphthol
4-Methoxy-2-nitrophenol
2,4-Dinitrophenol
80
90
98
70
79
88
4-Bromo-2-nitrophenol
2-Nitro-2,5-benzenediol
2-Methyl-6-nitrophenol
4-Methyl-2-nitrophenol
1-Nitro-2-naphthol
70
80
87
70
81
80
80
87
88
98
86
98
72
80
93
1-Naphthol
2-Nitro-1-naphthol
71
80
93
a
Yields were obtained by GC.
3
94
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 393— 396

Regiospecific Nitration of Phenols with Metal Nitrates
Table 3 Synthesis of o-nitrophenol in the presence of different
Synlett 2000, 1485.
solvents with Th(NO ) •5H O using KHSO as a catalyst under
refluxing condition
8
9
0
1
2
Gu, S.; Jing, H.; Wu, J.; Liang, Y. Synth. Commun. 1997, 27,
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Smith, K.; Musson, A.; DeBoos, G. A. Chem. Commun.
3
4
2
4
a
Entry Solvent Catalyst Temperature/℃ Time/min Yield /%
1
996, 469.
1
2
3
4
5
6
Acetonitrile KHSO
Ethyl acetate KHSO
4
4
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25
30
35
45
50
50
95
92
90
89
87
86
1
1
1
Waller, G.; Barrett, A. G. M.; Braddock, D. C.; Ramprasad,
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Acetone
THF
KHSO4
6
07.
KHSO4
KHSO4
KHSO4
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CHCl3
CH Cl
13 Cornelis, A.; Laszlo, P.; Pennetreau, P. Bull. Soc. Chim. Belg.
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1
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4
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a
Yields were obtained by GC.
Typical experimental procedure
1
6
7
To a stirred solution of phenol (1 mmol) in acetoni-
trile (5 mL) was added metal nitrate (1 mmol) followed
by a catalytic amount of KHSO (0.012 mmol) and the
4
1
reaction mixture was refluxed until all the phenol was
consumed The progress of the reaction was monitored
by TLC using petroleum ether/ethyl acetate (V∶V＝
1
1
8
9
Crivello, J. V. J. Org. Chem. 1981, 46, 3056.
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1
982, 23, 4315.
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saturated sodium hydrogen carbonate (10 mL) and the
product extracted into dichloromethane (5 mL×2). The
combined organic extracts were washed with distilled
20
21
22
Poirier, J. M.; Vottero, C. Tetrahedron 1989, 45, 1415.
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986, 16, 63.
4
water (10 mL), dried over anhydrous MgSO and the
23
24
25
26
27
28
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1
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In conclusion, the mono-nitration of phenols with a
4
metal nitrate and KHSO has been achieved with high
regiospecificity in excellent GC yields. In general, ex-
clusive ortho-selectivity was observed for all the phe-
nols subjected to this protocol. The high regiospecificity,
with excellent GC yields and the use of inexpensive and
4
easily accessible KHSO as the catalyst makes this
2
3
9
0
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Chin. J. Chem. 2010, 28, 393— 396