Regio-selective mono nitration of phenols with ferric nitrate in room temperature ionic liquid

Article abstract of DOI:10.1081/SCC-120016360

The mono nitration of phenols with ferric nitrate has been achieved in high regio-selectivities in 1-3 h at 30-60°C using the ionic liquid 1,3-di-n-butylimidazolium tetraflouroborate [bbim]BF4 as the solvent. In particular, excellent para selectives of the order of 76-86% for unsubstituted, ortho and meta-substituted phenols were observed.

Full text of DOI:10.1081/SCC-120016360

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Regio-selective Mono Nitration of Phenols with Ferric
Nitrate in Room Temperature Ionic Liquid
R. Rajagopal a & K. V. Srinivasan a
a Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune,
Maharashtra, India
Version of record first published: 17 Aug 2006.
To cite this article: R. Rajagopal & K. V. Srinivasan (2003): Regio-selective Mono Nitration of Phenols with Ferric Nitrate in
Room Temperature Ionic Liquid, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 33:6, 961-966
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 6, pp. 961–966, 2003
Regio-selective Mono Nitration of Phenols with
Ferric Nitrate in Room Temperature Ionic Liquid
*
R. Rajagopal and K. V. Srinivasan
Division ofOrganic Chemistry: Technology, National
Chemical Laboratory, Pune, Maharashtra, India
ABSTRACT
The mono nitration ofphenols with ferric nitrate has been achieved
in high regio-selectivities in 1–3 h at 30–60ꢀC using the ionic liquid
1,3-di-n-butylimidazolium tetraflouroborate [bbim]BF4 as the
solvent. In particular, excellent para selectives ofthe order of
76–86% for unsubstituted, ortho and meta-substituted phenols were
observed.
Key Words: Ionic liquid; Mono-nitration; Phenols; Ferric nitrate;
Regio-selective.
*Correspondence: K. V. Srinivasan, Division ofOrganic Chemistry: Technology,
National Chemical Laboratory, Dr. Homi Bhabha Road, Pune-411008,
Maharashtra, India; E-mail: kvsri@dalton.ncl.res.in.
961
DOI: 10.1081/SCC-120016360
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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962
Rajagopal and Srinivasan
The nitration ofphenol is a ufndamental unit process ofgreat
industrial importance generating commercially valuable intermediates
and there is a great need for regio-selective pollution free processes. A
survey ofliterature shows nitration ofphenol lacks positional selectivity
for para isomer with majority of processes giving rise to o-isomer (ꢁ67%)
as the major product along with minor amounts of p-isomer (ꢁ33%).[1]
Among several nitrating agents employed which include mixed acid,
super acids, acyl nitrates and a variety ofmetal nitrates under different
conditions,[2] ferric nitrate in particular either alone or supported on solid
matrices such as clays has enjoyed considerable importance.[3] Likewise,
the use ofroom temperature ionic liquids (I.L.s) as ‘‘green’’ solvents in
organic synthetic processes has gained considerable importance in recent
years due to their negligible vapour pressures, easy recoverability and
reusability.[4] Indeed, a very recent publication reports the electrophilic
nitration ofaromatics other than phenols using ethylmethylimidazolium
salts as ionic liquid solvents.[5] In all cases reported in this recent work,
the isomer distribution in the products was in keeping with those
reported for conventional systems with ortho product being the major
isomer.
Recently, the use of1,3-di-n -butylimidazolium tetrafluroborate
[bbim]BF4 as a new room temperature ionic liquid in catalyzing Heck
and Suzuki reactions at ambient conditions has been reported by us.[6] In
continuation ofour investigations on organic transofrmations in I.Ls,
this communication describes for the first time a new methodology for
the regioselective mono nitration ofphenols with hydrated efrric nitrate
using [bbim]BF4 as the room temperature ionic liquid.
Phenol and substituted phenols were nitrated with Fe(NO3)3. 9H2O
in [bbim]BF4 as shown in the Scheme 1.
The results are summarized in Table 1. The reaction mixtures were
homogeneous and the reactions were monitored by TLC. All the
reactions went to complete conversion except that for p-nitrophenol
(Entry 12) wherein the conversion stabilized at 92% even after much
longer reaction time (6 h). The I.L. [bbim]BF4 could be selectively and
completely extracted with chloroform from the reaction mixture after
it has been made alkaline. The I.L. thus recovered could be used at
least 3 times for the nitration of phenol. Phenol and activated phenols
Scheme 1.

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Mono Nitration of Phenols
963
Table 1. Nitration ofphenol and substituted phenols by Fe(NO 3)3ꢀ9H2O in
[bbim][BF4].
Yields (%)c
Nitrophenols
Substrate/
No.
phenola
Time (h)
Conversion (%)
Ortho
Para
Others
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
H
1.5
1.0
1.0
1.5
1.0
2.0
2.0
2.0
1.0
1.0
1.0
6.0
3.0
2.0
100
100
100
100
100
100
100
100
100
100
100
92
9
10
23
8
15
–
80
79
68
76
78
82
83
86
–
–
–
–
–
11
11
9
16
7
18
17
14
18
14
8
o-CH3
o-OCH3
m-CH3
o-Cl
b
o-NO2
o-COCH3
o-COOMe
p-CH3
p-OCH3
p-Cl
p-NO2
–
–
82
86
92
84
88
88
8
12
12
p-COCH3
p-COOMe
100
100
–
aMole ratios phenol/Fe(NO3)3ꢀ9H2O were 1.66 and 1.0 and reaction temperatures
30ꢁC and 60ꢁC for activated and deactivated phenols respectively.
bMole ratio o-methoxyphenol/Fe(NO3)3ꢀ9H2O was 2.
cIsolated yields by column chromatography; all the o- and p-nitrophenols are
known compounds and were characterized by comparison oftheir spectral
data (IR, 1H NMR, MS), TLC and physical data (M.P.) with those of
authentic samples.
could be completely nitrated at 30ꢀC (1–1.5 h) whereas the deactivated
phenols required elevated temperature (60ꢀC) and marginally longer
reaction times (2–3 h).
As is evident from Table 1, phenol, ortho and meta substituted
phenols afforded the p-nitrophenols in very high selectivity and isolated
yields (68–86%) whereas the para substituted phenols afforded selectively
the o-isomer (82–92%). All ofthe isolated nitrophenols are known
compounds and their melting points are reported in literature.[7]
Neither the m-isomer nor the dinitrated products could be detected.
Atfer recovering ofthe mono nitro products, the rest ofthe reaction
mass could only be isolated as a mixture difficult to resolve and separate
into individual components by chromatographic techniques for their
identification. In all probability these constitute a complex mixture of

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964
Rajagopal and Srinivasan
Table 2. Nitration ofphenol with Fe(NO ) ꢀ9H2Oa in various I.L.s as solvents
3 3
at 30ꢁC.
Yields (%)b
Nitrophenol
No.
Solvent
Time (h) Conversion (%)
o-
p-
Others
1
2
3
4
5
bbimBF4
bbimBr
bmimBF4
bmimBr
EtNHþ3 NOÀ3
1
15
1
15
10
100
0
100
60
9.0
–
28.0
80.2
–
63.0
10.8
–
9.0
—complex mixture—
12.0 75.0 13.0
100
aIn all cases, mole ratio ofphenol: Fe(NO ) ꢀ9H2O ¼ 1:0.6.
3 3
bIsolated yields by column chromatography.
polymeric/oxidized products designated as others in the Tables 1 and 2 to
account for the mass balance. It was interesting to study the nitration of
phenol with Fe(NO3)3ꢂ9H2O in other ionic liquids under similar
conditions. The ionic liquids used for the investigation are known and
were prepared following methods reported in literature.[8] The results are
summarized in Table 2. The analogous [bmim]BF4 showed reduced para
selectivity. The I.L [bbim]Br showed no conversion and analogous
[bmim]Br gave rise to a complex mixture ofproducts difficult to separate.
The I.L. EtNHþ3 NOÀ3 showed good para selectivity but the reaction was
sluggish. Attempts are in progress to correlate the polarity ofthe I.Ls with
reaction rates/selectivities.
In conclusion, the mono nitration ofphenols with efrric nitrate has
been achieved with high regio-selectivities in excellent isolated yields
using the I.L. [bbim][BF4] as solvent. In particular, excellent para
selectivities were observed for the unsubstituted, o- and m-substituted
phenols respectively. The complete recovery and reuse ofthe I.L. along
with high selectivities observed makes this
wide synthetic and commercial utility.
a methodology of
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded on
Mattson Research series FTIR spectrometer, mass spectra on Finnigan
Mat-1020 automated GC/MS spectrometer and 1H NMR spectra
on Bruker-200 MHz spectrometer.

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Mono Nitration of Phenols
965
Materials
All chemicals were ofresearch grade and were used as obtained from
Aldrich or Fluka.
Typical Procedures
Preparation of[bbim]BF 4. A mixture of N-n-butyl imidazole
(12.4 g. 0.1 mol) and n-butyl bromide (15.0 g. 0.11 mol) was heated
with stirring at 70ꢀC for 4 h. Excess n-butyl bromide was distilled off
under reduced pressure. To the resulting thick liquid consisting of1,3-
n-dibutyl imidazolium bromide ([bbim]Br), water (100 mL) was added
under stirring. A solution ofsodium tetraflouroborate (22 g. 0.2 mol)
in water (80 mL.) was then added to the above solution and the mixture
was stirred at 30ꢀC for 5 h. The ionic liquid [bbim]BF4 separates out as an
immiscible layer. The mixture was extracted with dichloromethane
(3 Â 50 mL.). The combined DCM layer which was separated
was washed with 2% hydrochloric acid, water, brine and dried over
sodium sulphate. The solvent DCM was distilled off under reduced
pressure leaving behind the pure I.L [bbim]BF4 (23 g. 85%). The
I.L was fully characterized by 1H/13C NMR and Mass
spectral analysis. Its elemental analysis for C, H, N was in conformity
with its structure.
1H NMR (CDCl3). ꢀ ¼ 0.94 (t, J ¼ 7.0 Hz, 6H, CH3), 1.36 (sept,
J ¼7.6 Hz,
4H,
CH3CH2(CH2)2N),
1.86
(pent,
J ¼ 7.5 Hz,
4H, NCH2CH2), 4.20 (t, J ¼ 7.0 Hz, 4H, NCH2), 7.38 (s, 2H,
NCHCHN), 8.87 (s, 1H, NCHN). 13C NMR (CDCl3): ꢀ ¼ 13.18, 19.21,
31.89, 49.57, 122.61, 135.29. Mass (m/z) 268 (Mþ). Anal. calcd.
for C11H21N2BF4 (268): C ¼ 49.25%, H ¼ 7.84%, N ¼ 10.45%; found
C ¼ 49.08%, H ¼ 7.59, N ¼ 10.25.
Nitration ofphenol.
A
solution ofthe phenol (2 mmol)
and Fe(NO3)3ꢂ9H2O (1.2 mmol) in [bbim]BF4 (1 g) was strirred
vigorously under argon atmosphere. After completion of reaction (mon-
itored by T.L.C.), sodium carbonate solution (10% w/v, 5 mL.)
was added. The I.L layer was separated and extracted with dichloro-
methane (DCM). The DCM layer was separated, washed with 10%
sodium carbonate solution (5 mL Â 2) and brine. The DCM was evapo-
rated under reduced pressure to afford the pure I.L for recycle. The
combined aqueous alkaline layer was filtered, acidified and extracted
with ethyl acetate (10 mL Â 3). The ethyl acetate layer was dried
over sodium sulphate and the solvent evaporated under reduced pressure

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966
Rajagopal and Srinivasan
to furnish crude product. The crude product was subjected to column
chromatography, to isolate pure products.
ACKNOWLEDGMENT
RR thanks CSIR, New Delhi for senior research fellowship.
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Received in the UK February 17, 2002