A New Method for Nitration of Phenolic Compounds

Article abstract of DOI:10.1002/adsc.200303111

Phenolic compounds can be nitrated by 65% nitric acid in the presence of catalytic amounts of montmorillonite KSF and bismuth(III) nitrate to give the corresponding nitrated products in good yields in a heterogeneous phase. The co-catalyst of KSF and Bi(NO₃)₃ can be easily recovered and reused in the next batch of nitration.

Full text of DOI:10.1002/adsc.200303111

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A New Method for Nitration of Phenolic Compounds
Min Shi,* Shi-Cong Cui
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354Fenglin Lu, Shanghai 200032, P. R. China
Fax: ( ‡ 86)-21-64166128, e-mail: mshi@pub.sioc.ac.cn
Received: June 9, 2003; Accepted: August 8, 2003
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de or from the author.
for the preparation of nitrophenols is the hydrolysis of
Abstract: Phenolic compounds can be nitrated by
5% nitric acid in the presence of catalytic amounts
the corresponding nitrochlorobenzene with dilute alkali
using aqueous sodium hydroxide at elevated temper-
ature of 160 8C for 4hours. But these ways are all
inconvenient.
Much effort has been expended by many chemists to
solve the problem in the nitration of phenolic substrates.
6
of montmorillonite KSF and bismuth(III) nitrate to
give the corresponding nitrated products in good
yields in a heterogeneous phase. The co-catalyst of
KSF and Bi(NO ) can be easily recovered and
3
3
reused in the next batch of nitration.
There is a large body of literature so far. Using HNO
3
,
‡
AgNO , NaNO or Ca(NO ) as an NO carrier and
3
3
3
2
2
Keywords: bismuth(III) nitrate; catalytic nitration;
montmorillonite KSF; nitric acid; phenols; synthetic
methods
H
2
SO
4
or BF
3
as an acid catalyst in CH
3
CN, CHCl or
3
aromatic solvents, the nitrated phenolic compounds
were obtained in good yields. Some other methods, for
example, using Cu(NO ) /K10 as a catalyst and 100%
HNO as an NO carrier in acetic anhydride are also
useful in the nitration of phenolic substrates. In
addition, Fe(NO ) ¥ 1.5 N O , Cr(NO ) ¥ 2 N O and
[
5]
3
2
‡
3
2
[6]
3
3
2
4
3
3
2
4
‡
Nitration of aromatic compounds is one of the most Cu(NO ) ¥ N O can be used as NO carrier in this
important industrial processes. Especially, nitrated nitration reaction. Recently, the nitration of phenol
phenolic compounds are very useful intermediates in with 6 wt % nitric acid in the presence of a phase-
3
2
2
4
2
[
1]
[7]
[
2±4]
[8]
the preparation of fine chemicals.
transfer catalyst has also been reported. However,
In fact, nitration of phenolic compounds is very most of the methods have some drawbacks, such as
effortless. It is readily carried out at room temperature regioselectivity, over-nitration, and competitive oxida-
[
9]
with dilute nitric(V) acid (6 wt % HNO ). A particular tion of the phenolic substrates. In this paper, we report
3
case is that in the nitration of phenol, a mixture of 2- a new method for the nitration of phenolic compounds
nitrophenol and 4-nitrophenol is usually formed. How- under mild conditions.
‡
‡
ever, since the concentration of nitronium ions (NO )
present in dilute nitric(V) acid is very small, the NO2
4,6-Dinitroresorcinol is used to prepare 4,6-diamino-
resorcinol, which is a precursor to polybenzoxazoles
2
ion is unlikely to play a significant part in the nitration (PBOs), polymers that are useful as insulators, solar
process. There is evidence that the electrophile involved arrays, and cut-resistant gloves. They are usually pre-
‡
is the nitrosonium ion (NO ), namely, the electrophilic pared by the reactions of 4,6-diaminoresorcinol with
substitution of a hydrogen atom with ÀNO group is a bisacids, bisacid halides, bisesters, bisamides, or bisni-
[
10]
major reaction path. The nitric(V) acid present oxidizes triles. Efforts to prepare 4,6-dinitroresorcinol in one
the ÀNO group to the ÀNO group forming the desired step from resorcinol and nitric acid in yields exceeding
2
2
- and 4-nitrophenols. On the other hand, phenolic 30 percent have been unsuccessful due to the formation
compounds are in general very sensitive to oxidants. It is of high levels of undesirable by-products such as 2,4-
very difficult to find a good means to nitrate them in high dinitroresorcinol and 2,4,6-trinitroresorcinol.
[
11]
Im-
yields because this nitration process is usually accom- proved yields of the desired 4,6-isomer have been
panied by oxidized by-products of nitric(V) acid. In obtained by introducing bulky protecting groups at the
industry, the nitration of phenol may be achieved in a l- and 3-positions of resorcinol, thereby inhibiting
[
12]
two-step process involving the sulphonation of phenol nitration at the 2-position. Based on these previous
and subsequent nitration with mixed acid. The replace- results, it is very clear that the preparation of mono- or
ment of sulphonic acid groups must be completed to dinitrated resorcinol as a sole product in high yield is
minimize the losses due to the solubility of the sulpho- difficult by using nitric acid. Thus, from the beginning we
nated compounds in water. The other popular method decide to select resorcinol as a substrate in our experi-
Adv. Synth. Catal. 2003, 345, 1197 ± 1202
DOI: 10.1002/adsc.200303111
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1197

COMMUNICATIONS
Min Shi, Shi-Cong Cui
Table 1. The nitration of resorcinol catalyzed by Bi(NO ) /
3
3
KSF.
Figure 1. The yields of the nitration of resorcinol in the
presence or absence of catalyst versus time with 65% HNO .
3
!
Bi(NO ) /KSF; * only KSF;
&
only Bi(NO ) ;
&
no catalyst.
3
3
3 3
Table 2. The concentration of nitric acid on the nitration of
resorcinol[
a]
ments to seek out a mild nitration method in the
preparation of the corresponding nitrated phenolic
compounds.
In 2000, Susanta reported that the nitration of
aromatic compounds can be achieved by using
[
13]
Bi(NO ) as a nitration reagent and KSFas a catalyst.
3
3
[
14]
tigations on the nitration of aromatic compounds, we
found that Bi(NO ) /KSF [(39 mg, 0.1 mmol)/500 mg] is
3
3
a good catalyst for nitration. First of all, we utilized
Bi(NO ) /KSFas a catalyst to nitrate resorcinol in ether
3
3
with 65% nitric acid. The mono-nitrated product was
obtained in 50% after 1 h, and in 61% after 16 h at room
temperature (208C) (Table 1, entries 1 and 2). This
result suggests that Bi(NO ) /KSF is a very effective
3
3
catalyst for mono-nitration of phenolic compounds.
Then we examined the effects of solvent on this
nitration. These results are summarized in Table 1. As
can be seen from Table 1, we found that this nitration
process proceeded very well in ether, DME or THF changed from 20% to 65% and 95%, we found that the
Table 1, entries 1, 4, and 5). The best result was nitration reaction rate became faster. The results are
(
obtained when using THF as a solvent in which the listed in Table 2. Using 20% nitric acid, the nitration
corresponding mono-nitrated product was obtained in reaction is sluggish. The nitrated resorcinol was ob-
5
2% after 1 h and in 70% after 16 h. Nevertheless, in the tained in 50% at higher temperature (308C) and in the
[
15]
other kinds of solvents, for example, dichloromethane or presence of 1.0 g of KSF (Table 2, entry 1). Using
nitromethane, the yields are very low (Table 1, entries 6 95% of nitric acid, the nitration reaction proceeded
and 7).
quickly to give the corresponding nitrated product 1
The control experiment showed that using only along with many unidentified products at room temper-
Bi(NO ) as a catalyst or without a catalyst, no reaction ature because of the further oxidation with 95% nitric
2
3
occurred under the same conditions (Figure 1). The acid. But at 08C, the reaction proceeded very well to give
combination of Bi(NO ) /KSF is more efficient than 1 in 75% (Table 2, entry 3). Considering the safety of the
2
3
only using KSFas a catalyst in the nitration of resorcinol operation, we decided to use 65% nitric acid in the
(
Figure 1).
nitration of the phenolic compounds.
It should be emphasized here that the Bi(NO ) /KSF
We also examined this catalytic nitration reaction with
3
3
different concentrations of nitric acid under the same catalyst can be easily recovered from the reaction
conditions. When the concentration of nitric acid was mixture just by filtration and reused many times after
1198
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Nitration of Phenolic Compounds
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Table 3. The recovered catalyst in the nitration of resorcinol.
Table 5. Nitration of resorcinol catalyzed by Bi(NO ) /car-
rier.
3
3
Table 4. Nitration of resorcinol catalyzed by catalyst/KSF.
Figure 2. The yields of the nitration of p-chlorophenol in the
presence or absence of catalyst versus time with 65% HNO .
3
!
Bi(NO ) /KSF; * only KSF;
&
only Bi(NO ) ; ~ no catalyst.
3
3
3 3
it has been re-activated by heating in an oven at 1208C.
In our experiment, we reused the catalyst for three times
and it still has good activity (Table 3, entries 1 ± 3).
phenol as a substrate for this method. The yield of
We also examined other metal salts (BiCl ) or metal nitrophenol is 88% (p-:o- ˆ 31:49). If phenol was
3
oxides (Bi O , SeO , Sb O , GeO ) in this nitration directly nitrated only by nitric acid, the product was a
2
3
2
2
3
2
process. The results are summarized in Table 4. Among black solid and no nitrophenol was formed. In order to
all our examined metal salts and metal oxides, Bi O also further clarify the effects of the catalyst Bi(NO ) /KSF
2
3
3 3
gave a good result. The yield of nitrated resorcinol is in other phenolic compounds control experiments were
3% (Table 4, entry 2). carried out using Bi(NO ) , KSFor Bi(NO ) /KSFas the
In addition, we also tried to find other carriers to catalysts in the nitration of p-chlorophenol and p-
7
3
3
3 3
replace KSF. During our own examinations, we found bromophenol. The results are shown in Figures 2 and 3.
that Bi(NO ) /SiO can catalyze this nitration reaction at We found that the nitration of p-chlorophenol did not
3
3
2
a higher temperature (508C) to give the corresponding 1 occur in the absence of catalyst or using only Bi(NO ) as
3
3
in similar yield as that of Bi(NO ) /KSFalong with some catalyst. The catalyst Bi(NO ) /KSF is better than KSF
3
3
3 3
unidentified by-products, although it has no activity at alone as catalyst in this nitration process. The difference
room temperature (208C) (Table 5, entries 1 and 2). is very distinctive. The yield reached 98% within 16 h
However, molecular sieves 4ä showed no activity
under mild conditions. Similar results were obtained in
(
Table 5, entry 3). From our experiments, the best the nitration of p-bromophenol (Figure 3).
catalyst is Bi(NO ) /KSF for nitration of phenolic
substrates at room temperature.
This electrophilic aromatic nitration reaction pro-
ceeded very well for many phenolic substrates. The
3
3
Based on the above investigations, we decided to use results are shown in Table 6. p-Chlorophenol, p-bromo-
Bi(NO ) /KSF as a catalyst to nitrate other phenolic phenol and p-fluorophenol reacted smoothly to afford a
3
3
substrates under mild conditions. We first utilized single mono-nitrated product in excellent yields (Ta-
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Table 7. Nitration of cresols catalyzed by Bi(NO ) /KSF.
3
3
Figure 3. The yields of the nitration of p-bromophenol in the
presence or absence of catalyst versus time with 65% HNO .
3
!
Bi(NO ) /KSF; * only KSF;
&
only Bi(NO ) ; ~ no catalyst.
3
3
3 3
Table 6. Nitration of phenolic compounds catalyzed by
Bi(NO ) /KSF.
3
3
nitration of 4-iso-propylphenol and 1,4-dimethoxyben-
zene, the corresponding mono-nitrated phenolic com-
pound was exclusively formed (Table 6, entries 8 and 9).
On the other hand, we also examined the nitration
reaction of 2-cresol, 3-cresol and 4-cresol. In the case of
3
-cresol, two mono-nitrated phenolic products 4j and 4j'
were obtained in good yields (Table 7, entry 2). How-
ever, in the nitration of 4-cresol and 2-cresol, both
mono-nitrated and dinitrated products were obtained at
the same time (Table 7, entries 1 and 3).
In conclusion, we have found a good method for the
nitration of phenolic compounds under mild conditions.
In the presence of Bi(NO ) /KSF catalyst, 65% nitric
3
3
acid can be used in the nitration of phenolic compounds
to give the nitrated products in good yields. The use of
concentrated or fuming nitric acid can be avoided by this
catalytic system. Moreover, Bi(NO ) and KSF are very
3
3
cheap catalysts in industry and can be recovered and
reused by simple treatment. This nitration method was
ble 6, entries 2 ± 4). For the nitration of 4-tert-butylphe- carried out in ether or THF, an environmentally safer
nol, two products, mono-nitrated and dinitrated, were solvent. Overall we believe this method is an eco-safer
obtained in total 96% yield and the yield of dinitrated and environment-benign way for the nitration of
product 3e increased when the reaction time was phenolic compounds.
prolonged (Table 6, entries 5 and 6). In the case of the
activated phenolic aromatic compound, p-methoxyphe-
nol, a single dinitrated product was observed in 71%
yield under mild conditions (Table 6, entry 7). For the
1200
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Nitration of Phenolic Compounds
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Experimental Section
Acknowledgements
We thank the State Key Project of Basic Research (Project 973)
No. G2000048007), Shanghai Municipal Committee of Science
General Remarks
(
and Technology, and the National Natural Science Foundation
of China for financial support (20025206, 203900502, and
Mp×s were obtained with a Yanagimoto micro melting point
apparatus and are uncorrected. H NMR spectra were record-
1
2
0272069).
ed on a Bruker AM-300 spectrometer for solutions in CDCl3
with tetramethylsilane (TMS) as internal standard; J values are
in Hz. All of the solid compounds reported in this paper gave
satisfactory C,H,N microanalyses with a Carlo-Erba 1106
analyzer. Mass spectra were recorded with an HP-5989 instru-
References and Notes
‡
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spectrometer. Organic solvents were dried by standard meth-
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used without further purification. All reactions were moni-
tored by TLC with Huanghai GF254silica gel coated plates.
The orientation of nitration was determined by NMR analysis.
Flash column chromatography was carried out using 200 ± 300
mesh silica gel.
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1
[
[
[
1
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110 mg, 1.0 mmol) and bismuth nitrate (39 mg, 0.1 mmol ) in
THF (or other solvent, 5 mL) was added into the dried glass
vessel. Nitric acid (65%, 0.10 mL, 1.4mmol) was slowly added
dropwise and the mixture was stirred for 16 hours at room
temperature. After filtration, the catalyst was recovered and
the reaction mixture was extracted with dichloromethane
[
6] B. Gigante, A. O. Prazeres, M. J. Marcelo-Curto, A.
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(
CH Cl ). The solvent was removed under reduced pressure
2 2
and the residue was purified by a silica gel column chromato-
graph (eluent: petroleum ether/EtOAc, 10/l) to give the
product as a yellow solid; yield: 108 mg (70%).
[
2
773 ± 2781.
[
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6
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13 ± 516.
The catalyst can be easily recovered from the reaction mixture
just by filtration and reused for many times after it had been
activated by heating in an oven at 1208C. The recovered
catalyst was employed in the same manner as that described
above. After filtration, the catalyst was recovered and the
reaction mixture was extracted with dichloromethane
5
[
10] F. M. Herman et. al. The Encyclopedia of Polymer
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[
[
(
CH Cl ). The solvent was removed under reduced pressure
2 2
and the residue was purified by a silica gel column chromato-
graph (eluent: petroleum ether/EtOAc, 10/l) to give the
product as a yellow solid; yield: 110 mg (71%).
[
13] S. Susanta, F. B. Frederick, K. B. Bimal, Tetrahedron Lett.
2
000, 41, 8017 ± 8020; for more examples using mont-
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4
-Nitro-resorcinol (1): A yellow solid; yield: 170 mg (73%);
mp 117 ± 1198C, IR (KCl): n ˆ 1532, 1397 (NO ), 3354,
2
À1
1
1
(
8
255 cm (OH); H NMR (CDCl , 300 MHz, TMS): d ˆ 6.47
3
1H, dd, J ˆ 9.2 Hz, 3.4Hz, Ar), 6.52 (1H, d, J ˆ 3.4Hz, Ar ),
.05 (1H, d, J ˆ 9.2 Hz, Ar), 10.97 (1H, s, ArOH); MS (EI): m/
‡ ‡ ‡
z ˆ 155 (M , 47.40), 125 (M ± 30, 100), 97 (M ± 58, 94.90), 77
‡
‡
(
(
M ± 78, 6.77) 51 (M ± 104, 65.02); anal. calcd. for C H NO
6 5 4
%): C 46.46, H 3.25, N 9.03; found: C 46.48, H 3.44, N 9.02.
Adv. Synth. Catal. 2003, 345, 1197 ± 1202
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¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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COMMUNICATIONS
Min Shi, Shi-Cong Cui
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[15] When the nitration was carried out at>308C, the
reaction gave many unidentified by-products.
1
999, 23, 955 ± 956; f) J. S. Yadav, B. V. S. Reddy, A.
Krishnam Raju, D. Gnaneshwar, Adv. Synth. Catal. 2002,
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3
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Adv. Synth. Catal. 2003, 345, 1197 ± 1202