Synthesis of p-aminophenol by catalytic hydrogenation of nitrobenzene

Article abstract of DOI:10.1021/op990040r

The present work describes the preparation of p-aminophenol via single-step catalytic hydrogenation of nitrobenzene in acid medium. A conventional method of synthesis of p-aminophenol is a two-step reaction involving iron-acid reduction of p-nitrophenol. This method causes serious effluent disposal problems due to the stoichiometric use of iron-acid, which leads to the formation of Fe-FeO sludge (?2 kg/kg of product) in the process, which cannot be recycled. The single-step hydrogenation of nitrobenzene was carried out using platinum catalyst, and the process conditions were optimized. Complete conversion of nitrobenzene was achieved with selectivity to p-aminophenol as high as 75% under the best set of conditions. Furthermore, the catalyst can be easily recovered and efficiently recycled giving the TON as high as 1.38 κ' 10.⁵ This paper presents studies on the effect of various process parameters such as temperature, hydrogen pressure, and substrate and acid concentration on the rate of reaction and selectivity to p-aminophenol.

Full text of DOI:10.1021/op990040r

Organic Process Research & Development 1999, 3, 465−470
Synthesis of p-Aminophenol by Catalytic Hydrogenation of Nitrobenzene
C. V. Rode,* M. J. Vaidya, and R. V. Chaudhari
Homogeneous Catalysis DiVision, National Chemical Laboratory, Pune-411008, India
Abstract:
change in the scenario in chemical industry, pertaining to
the efficient and ecofriendly processes demanded by the
statutory authorities, the conventional iron-acid reduction
process needs to be replaced by a catalytic hydrogenation
route. The catalytic route will minimize the effluent disposal
problems to a great extent and is also expected to improve
the overall process economics as well as the product quality.
The catalytic route involves hydrogenation of nitroben-
zene in a single step to p-aminophenol using supported noble
metal catalysis in the presence of an acid like H2SO4 (7%).
At present, Mallinckrodt Inc. (U.S.A.) is the only company
producing PAP by this route.4 The process involves initial
reduction of nitrobenzene to give â-phenylhydroxylamine
as an intermediate (Scheme 1) which then rearranges in situ
to p-aminophenol in the presence of an acid (Bamberger’s
rearrangement).5 Formation of aniline is the main competing
side reaction in this process.
The preparation of p-aminophenol (PAP) by hydrogena-
tion of nitrobenzene using Pt/C catalyst in the presence of a
mineral acid was originally discovered in 1940.6 Other
catalysts mentioned in the literature are PtO2, Pd, Mo,7-9
etc. The use of surfactants for increasing the rate of reaction
has been mentioned in some other patents.10 Attempts have
been made to replace mineral acid by other solid acids in
order to eliminate the corrosion problems. However, the yield
of PAP in such reactions was found to be very low.11 The
use of formic acid or acetic acid is mentioned in other
patents.12 Most of the information regarding this industrially
important reaction is available in the form of patents except
for a few reports in the open literature.13,14 In the present
work, effects of various process parameters such as catalyst
loading, substrate loading, hydrogen partial pressure, organic
phase hold up on the rate of the reaction and selectivity to
p-aminophenol were investigated. Also, the catalyst recycle
was successfully carried out in up to three experiments and
the catalyst turnover number (TON) was found to be much
higher than the literature value.
The present work describes the preparation of p-aminophenol
via single-step catalytic hydrogenation of nitrobenzene in acid
medium. A conventional method of synthesis of p-aminophenol
is a two-step reaction involving iron-acid reduction of p-
nitrophenol. This method causes serious effluent disposal
problems due to the stoichiometric use of iron-acid, which leads
to the formation of Fe-FeO sludge (=1.2 kg/kg of product) in
the process, which cannot be recycled. The single-step hydro-
genation of nitrobenzene was carried out using platinum
catalyst, and the process conditions were optimized. Complete
conversion of nitrobenzene was achieved with selectivity to
p-aminophenol as high as 75% under the best set of conditions.
Furthermore, the catalyst can be easily recovered and efficiently
recycled giving the TON as high as 1.38 × 10.5 This paper
presents studies on the effect of various process parameters such
as temperature, hydrogen pressure, and substrate and acid
concentration on the rate of reaction and selectivity to p-
aminophenol.
Introduction
p-Aminophenol is of great commercial importance as an
intermediate for the manufacture of paracetamol, acetanilide,
phenacetinsall analgesic and antipyretic drugs.1 It is also
used as a developer in photography under trade names activol
and azol and in chemical dye industries.2 Conventionally,
p-aminophenol is synthesized by the following methods:1
(i) From p-chloronitrobenzene: this is the most commonly
used multistep process starting from chlorobenzene.
(ii) From phenol: this is also a two-step process starting
from phenol.
Both of these multistep routes involve an important step
of reduction of p-nitrophenol using stoichiometric quantities
of Fe-HCl reagents. These routes have several drawbacks
and lead to a poor overall yield. The major disadvantages
of iron-acid reduction process are:1,3 (1) The quantity of
iron required is very large, and hence the subsequent
production of Fe-FeO sludge is large (1.2 kg/kg of product),
posing serious effluent problems. (2) Workup of reaction
crude for separation of p-aminophenol from Fe-FeO sludge
is cumbersome. (3) The rate of reduction varies in a single
batch, sometimes leading to a violent reaction. (4) Erosion
of the reactor takes place due to Fe particles. Now, with a
(4) Caskey, C. C.; Chapman, D. W. U.S. Patent 4,571,437, 1986.
(5) March, J. AdVanced Organic Chemistry, 3rd ed.; Wiley: New York, 1984;
p 606.
(6) Henke, C. O.; Vaughen, J. V. U.S. Patent 2,198,249, 1940.
(7) Derrenbacker, E. L. U.S. Patent 4,307,249, 1981.
(8) Rylander, P. N.; Karpenko, I. M.; Pond, G. R. U.S. Patent 3,715,397, 1970.
(9) Shi, L.; Zhou, X. CN Patent 1,087,623, 1992; Chem. Abstr. 1995, 123:
111663w.
(10) Greco, N. P. U.S. Patent 3,953,509, 1976.
(11) Chaudhari, R. V.; Divekar, S. S.; Vaidya, M. J.; Rode, C. V. U.S. Patent
Appl. No. 09/257, 107, 1999.
(12) Lee, L.; Chen, M. H.; Yao, C. N. U.S. Patent 4,885,389, 1989.
(13) Juang, T. M.; Hwang, J. C.; Ho, H. O.; Chen, C. Y. J. Chin. Chem. Soc.
1988, 35 (2), 135.
(1) Mitchell, S. Kirk-Othmer Encyclopaedia of Chemical Technology, 4th ed.;
Wiley-Interscience: New York, 1992; Vol. 2, pp 481, 580.
(2) Venkatraman, K. The Chemistry of Synthetic Dyes; Academic Press: New
York, 1952; Vol. I, p 184.
(3) Lawrence, F. R. and Marshall, W. J, Ullamann’s Encyclopedia of Industrial
Chemistry, VCH Publishers: New York, 1985; Vol. A2, p 306.
(14) Rylander, P. N. Hydrogenation methods; Academic Press: New York, 1985;
p 107.
10.1021/op990040r CCC: $18.00 © 1999 American Chemical Society and The Royal Society of Chemistry
Published on Web 11/05/1999
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Scheme 1: Schematic of hydrogenation of nitrobenzene
Table 1: Range of operating conditions
1
2
3
4
5
6
7
8
hydrogen pressure
sulfuric acid concentration
substrate concentration
catalyst loading
speed of agitation
organic phase hold up
temperature
0.68-6.80 MPa
5-20% w/w
0.54-3.73 kmol/m3
0.175-0.70 kg/m3
500-1000 rpm
0.1-0.4
323-373 K
total reaction volume
1 × 10-4 m3
Experimental Section
Materials. Nitrobenzene, aniline, and H2SO4 (98%) were
procured from SD Fine Chemicals Ltd. (India). Catalyst
(3%Pt/C) and p-aminophenol were Aldrich products.
Experimental Setup. The reactions were carried out in
a 300 cm3 capacity high-pressure Hastelloy reactor supplied
by Parr Instruments Co., U.S.A. The reactor was connected
to a hydrogen reservoir held at a pressure higher than that
of the reactor, through a constant pressure regulator. Hy-
drogen gas was supplied from this reservoir to the reactor
through a nonreturn valve. The gas consumed during the
course of the reaction was monitored by pressure drop in
the reservoir vessel using a transducer.
A Hewlett-Packard model 1050 liquid chromatograph
equipped with an ultraviolet detector was employed for the
analysis. The analytical column, lichrospher RP 18 (125 ×
4 mm), supplied by Hewlett-Packard was used for analysis.
The separation of nitrobenzene hydrogenation products was
achieved with 30% acetonitrile-water as mobile phase at
25 °C and flow rate of 1 mL/minute. Samples of 10 µL were
injected into the column through the septum.
Procedure. In a typical hydrogenation experiment, 23 gm
(1.86 kmol/m3) of nitrobenzene, 35 mg of 3% Pt/C catalyst,
and 6 mL of sulfuric acid were charged, and the total reaction
volume was made to 1 × 10-4 m3 with water. The contents
were first flushed with nitrogen and then with hydrogen.
After the desired temperature was attained, the system was
pressurized with hydrogen to a level required for the
experiment, and the reaction was started by switching the
stirrer on. The progress of the reaction was monitored by
the observed pressure drop in the reservoir vessel as a
function of time. The contents were cooled to room tem-
perature and discharged after completion of the reaction. The
resultant reaction crude product was filtered to separate the
solid catalyst. The filtrate was extracted with toluene (2 ×
30 mL) to remove the byproduct aniline and traces (<0.1%)
of any unconverted nitrobenzene. The pH of the aqueous
layer after extraction was made to 8 by the addition of
aqueous ammonia leading to the complete precipitation of
solid PAP. The solid PAP was filtered under vacuum and
washed with toluene and distilled water twice, vacuum-dried,
Figure 1. Effect of hydrogen pressure on initial rate of
hydrogenation of nitrobenzene to p-aminophenol. Reaction
conditions: nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3;
water, 70 × 10-6 m3; acid, 10% w/w; temperature, 353 K;
agitation, 700 rpm; total reaction volume, 1 × 10-4 m3.
and weighed. The amount of p-aminophenol obtained was
11.8 gm (yield, 58.2%).
Results and Discussion
The effects of various process parameters were studied
on the hydrogenation of nitrobenzene to p-aminophenol using
3% Pt/C catalyst and sulfuric acid (aqueous) medium. In each
experiment, a final sample was analyzed by HPLC to
calculate the conversion of nitrobenzene and selectivity to
p-aminophenol, which agreed well with the hydrogen
absorption data and recovered PAP. In each experiment,
complete conversion of nitrobenzene was observed. Initial
rates of hydrogenation were also calculated from the slope
of hydrogen absorbed vs time plots, essentially under low
conversion (<20%) conditions. Table 1 presents the range
of various process parameters studied in this work.
Effect of Hydrogen Pressure. The effect of hydrogen
partial pressure on the initial rate of hydrogenation was
studied in the range of 0.68-6.80 MPa at 353 K. The initial
rate of reaction increased linearly with increase in pressure
up to 2.72 MPa, beyond which the rate was constant as
shown in Figure 1. The selectivity to p-aminophenol showed
maxima at 2.72 MPa, and it decreased on further increase
in hydrogen pressure. The results are shown in Figure 2.
The increase in hydrogen pressure retards the desorption of
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Figure 2. Effect of hydrogen pressure on selectivity to
p-aminophenol by hydrogenation of nitrobenzene. Reaction
conditions: nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3;
water, 70 × 10-6 m3; acid, 10% w/w; temperature, 353 K;
agitation, 700 rpm; total reaction volume, 1 × 10-4 m3.
Figure 4. Effect of substrate concentration on initial rate of
hydrogenation of nitrobenzene to p-aminophenol. Reaction
conditions: catalyst, 0.35 kg/m3; acid, 10% w/w; temperature,
353 K; pressure, 2.72 MPa; agitation, 700 rpm. total reaction
volume, 1 × 10-4 m3.
Table 2: Effect of substrate concentration on selectivity to
p-aminophenol
substrate concn
(kmol/m3)
selectivity
(%)
0.54
0.90
1.86
3.73
70.66
70.06
58.20
42.19
Reaction conditions: catalyst, 0.35 kg/m3 acid, 10% w/w; temperature, 353
K; pressure, 2.72 MPa; agitation, 700 rpm; total volume, 1 × 10-4 m.3
aminophenol first increased with increase in acid concentra-
tion up to 15% w/w beyond which it was almost constant.
This may be due to the fact that the mobility of protons is
more at lower concentration than at higher acid concentration.
The results also suggest that the optimum acid strength of
sulfuric acid to be about 15% (w/w). However, the initial
rate of hydrogenation remained unaffected with change in
acid concentration. This observation supports the assumption
that the second step, that is, the rearrangement step, in the
mechanism is not a rate-determining step. This is also in
agreement with the observation made by Juang et al.13
Effect of Substrate Concentration. Typical results of
the effect of initial concentration of substrate in the range
from 0.548 to 3.73 kmol/m3 at 353 K are shown in Figure
4. It was found that the initial rate of reaction increased up
to 1.86 kmol/m3, beyond which the rate increased only
marginally with further increase in substrate concentration.
The results indicate a first-order tending to zero-order
dependence at higher concentration of nitrobenzene. The
selectivity to p-aminophenol was found to be almost constant
at lower substrate concentration up to 0.90 kmol/m3 (Table
2) but decreased with further increase in substrate concentra-
tion.
Figure 3. Effect of acid concentration on selectivity to
p-aminophenol by hydrogenation of nitrobenzene. Reaction
conditions: nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3;
water, 70 × 10-6 m3; temperature, 353 K; agitation, 700 rpm
total reaction volume, 1 × 10-4 m3.
the intermediate phenylhydroxylamine from the catalyst
surface, facilitating further hydrogenation of phenylhydroxy-
lamine and leading to the formation of aniline and decrease
in selectivity to p-aminophenol.
Effect of Sulfuric Acid Concentration. In situ rear-
rangement of an intermediate phenylhydroxylamine to p-
aminophenol is acid-catalyzed, and hence it is necessary to
study the effect of acid concentration on the selectivity of
p-aminophenol. The effect of acid concentration on selectiv-
ity of PAP was studied in the range of 5-20% w/w, keeping
other reaction conditions constant, and the results are shown
in Figure 3. It was observed that the selectivity to p-
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467

Figure 6. Effect of catalyst loading on selectivity to p-
aminophenol by hydrogenation of nitrobenzene. Reaction
conditions: nitrobenzene, 1.86 kmol/m3; acid, 10% w/w; water,
70 × 10-6 m3; temperature, 353 K; pressure, 2.72 MPa;
agitation, 700 rpm; total volume, 1 × 10-4 m3.
Figure 5. Effect of catalyst loading on initial rate of hydro-
genation of nitrobenzene to p-aminophenol. Reaction condi-
tions: nitrobenzene, 1.86 kmol/m3; acid, 10% w/w; water, 70
× 10-6 m3; temperature, 353 K; pressure, 2.72 MPa; agitation,
700 rpm; total volume, 1 × 10-4 m3.
Effect of Catalyst Loading. The effect of catalyst loading
on the initial rate of reaction was studied in the range of
0.175-0.70 kg/m3 at 353 K and 2.72 MPa of hydrogen
pressure and the results are presented in Figure 5. The initial
rate was found to increase by 4.5 times when catalyst loading
was increased from 0.175 to 0.70 kg/m.3 A linear dependence
with respect to the catalyst loading indicates that the external
gas-liquid mass transfer resistance may not be significant.15
A plot of selectivity of p-aminophenol vs catalyst loading
for the same range of conditions is also shown in Figure 6.
It can be seen from this figure that the selectivity increased
up to a catalyst loading of 0.35 kg/m3 beyond which it
decreased. This may be due to the fact that increase in
catalyst loading mainly increases the rate of hydrogenation
of the intermediate, phenylhydroxylamine, leading to the
formation of more of aniline, which is a major byproduct in
this reaction.
Effect of Speed of Agitation. The effect of speed of
agitation on the selectivity and rate of reaction was studied
between 500 and 1000 rpm at 353 K and at hydrogen
pressure of 2.72 MPa, and the results on the selectivity
pattern are presented in Figure 7. The selectivity of PAP
was found to increase with increase in speed of agitation
from 500 to 1000 rpm. This indicates that the phase-transfer
catalysis may be an important aspect, since the present
system involves two immiscible liquids. More work needs
to be done to understand this phenomenon. However, as
shown in Figure 8, it was observed that the initial rate of
reaction remained unchanged beyond 700 rpm speed of
agitation.
Figure 7. Effect of speed of agitation on selectivity to
p-aminophenol by hydrogenation of nitrobenzene. Reaction
conditions: nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3;
water, 70 × 10-6 m3; acid, 10% w/w; temperature, 353 K;
pressure, 2.72 MPa; total volume, 1 × 10-4 m3.
essential to study the effect of organic phase hold up on the
rate of reaction and selectivity to p-aminophenol. The organic
phase hold up is the ratio of the weight of organic phase to
the total weight of charge. In these experiments, ratios of
concentration of substrate to that of catalyst and acid were
kept constant. The total reaction volume, that is, 1 × 10-4
m3, was kept constant in each experiment. It can be seen
from Figure 9 that selectivity to p-aminophenol increased
with increase in organic phase hold up. Initial rate of
hydrogenation was also found to increase with increase in
organic phase hold up. The increase in organic phase hold
up causes an increase in interfacial area and subsequently
Effect of Organic Phase Hold Up. Since the present
system involved two immiscible phases, aqueous and organic
and the catalyst mainly stays in the organic phase, it was
(15) Rode, C. V.; Chaudhari, R. V. Ind. Eng. Chem. Res. 1994, 33, 3 (7), 1645.
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Figure 10. Effect of catalyst recycle on conversion of nitroben-
zene and selectivity to p-aminophenol. Reaction conditions:
nitrobenzene, 1.86 kmol/m3; acid, 10% w/w; water, 70 × 10-6
m3; temperature, 353 K; pressure, 2.72 MPa; total volume, 1
× 10-4 m3.
Figure 8. Effect of speed of agitation on initial rate of
hydrogenation of nitrobenzene to p-aminophenol. Reaction
conditions: nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3;
water, 70 × 10-6 m3; acid, 10% w/w; temperature, 353 K;
pressure, 2.72 MPa; total volume, 1 × 10-4 m3.
Figure 11. Effect of temperature on selectivity to p-aminophe-
nol by hydrdogenation of nitrobenzene. Reaction conditions:
nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3; water, 70 ×
10-6 m3; acid, 10% w/w; temperature, 353 K; pressure, 2.72
MPa; total volume, 1 × 10-4 m3.
Figure 9. Effect of organic phase hold up on selectivity to
p-aminophenol. Reaction Conditions: pressure, 2.72 MPa;
temperature, 353 K; agitation, 700 rpm; total volume, 1 × 10-4
m3.
higher hydrogenation rates under the mass-transfer control-
ling conditions.
selectivity for PAP decreased by 5-7%. This lowering of
selectivity could be due to the handling losses of catalyst
transfer in the subsequent recycle runs. The overall turnover
number (TON) for the catalyst was found to be 1.38 × 105
which is more than the literature value4 of 1.34 × 10.3
Effect of Temperature. The effect of temperature on both
selectivity of PAP and the rate of reaction was studied in
the temperature range of 323-373 K and the results are
presented in Figures 11 and 12, respectively. The selectivity
to PAP was found to increase from 40 to 58% with an
increase in temperature up to 353 K, while it remained
constant with further increase in temperature from 353 to
Catalyst Recycle. Since the catalyst used in this reaction
was a noble metal catalyst, it was important to study the
recycle of this catalyst. In these experiments, the catalyst
charged for the first reaction was filtered out and again
recharged to the reactor for subsequent runs. The catalyst
recycle experiments were performed at 353 K and hydrogen
partial pressure of 2.72 MPa with acid concentration of 10%
w/w and the results are shown in Figure 10. The catalyst
was found to retain its activity even after fourth recycle
without affecting the conversion of nitrobenzene; however,
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469

Conclusion
Hydrogenation of nitrobenzene was carried out using 3%
Pt/C as a catalyst in the presence of sulfuric acid medium to
give p-aminophenol as a major product and aniline as a
byproduct. Under suitable reaction conditions (nitroben-
zene: 3.73 kmol/m3; 3% Pt/C catalyst: 0.70 kg/m3; sulfuric
acid: 15% w/w; water: 0.4 × 10-4 m3; total reaction
volume: 1 × 10-4 m3; temperature: 353 K; hydrogen
pressure: 2.72 MPa; speed of agitation: 1000 rpm) complete
conversion of nitrobenzene was achieved with 75% selectiv-
ity to p-aminophenol. Both the initial rate of hydrogenation
and selectivity of p-aminophenol increased linearly with the
increase in the hydrogen pressure up to 2.72 MPa, beyond
which the rate of reaction was constant, while selectivity of
PAP decreased with further increase in hydrogen pressure.
The selectivity of PAP was found to be strongly dependent
on acid concentration, catalyst loading, organic phase hold
up, and speed of agitation. The catalyst was successfully used
for three recycle experiments giving a total TON of 1.38 ×
105, which is 2 orders of magnitude higher than the literature
value.
Figure 12. Effect of temperature on hydrogenation of ni-
trobenzene to p-aminophenol (Arrhenius plot). Reaction condi-
tions: nitrobenzene, 1.86 kmol/m3; catalyst, 0.35 kg/m3; water,
70 × 10-6 m3; acid, 10% w/w; pressure, 2.72 MPa; agitation,
700 rpm; total volume, 1 × 10-4 m3.
373 K. The initial rate of reaction increased with increase
in temperature and the activation energy evaluated from the
Arrhenius plot (Figure 12) was found to be 10.3 kcal/mol.
Received for review May 4, 1999.
OP990040R
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