Chemoselective hydrogenation of substituted nitroaromatics using novel water-soluble iron complex catalysts

Article abstract of DOI:10.1021/jo035511t

Chemoselective hydrogenation of substituted nitroaromatic compounds by water-soluble iron complex catalysts with molecular hydrogen has been reported for the first time. This biphasic catalyst presents an opportunity for a solvent-free hydrogenation. This catalyst system provides a low-cost, efficient alternative to the selective but environmentally unacceptable stoichiometric reductions as well as the supported noble metal catalysts used for hydrogenation. An efficient recycling strategy has resulted in a cumulative turnover number above 6000.

Full text of DOI:10.1021/jo035511t

TABLE 1. Hyd r ogen a tion of Nitr oben zen e w ith Ir on
Com p ou n d sa
Ch em oselective Hyd r ogen a tion of
Su bstitu ted Nitr oa r om a tics Usin g Novel
Wa ter -Solu ble Ir on Com p lex Ca ta lysts
Raj. M. Deshpande, Avinash. N. Mahajan,
Makarand. M. Diwakar, Prakash. S. Ozarde, and
R. V. Chaudhari*
nitrobenzene
catalyst
solvent time (h) conversion (%) TOFb (h-1
)
Homogeneous Catalysis Division, National Chemical
Laboratory, Pune 411008, India
toluene
8.33
9.23
3.08
3.08
4.26
4.66
8.33
0
0
433
1297
1297
937
857
0
Fe(NO3)3‚9H2O methanol
98.7
99.1
98.5
98.7
99.4
0
FeSO4‚7H2O
FeSO4‚7H2O
FeSO4‚7H2O
methanol
water
rvc@ems.ncl.res.in
toluene
toluene
toluene
Received October 14, 2003
III
Fe (acac)3
ferrocene
Abstr a ct: Chemoselective hydrogenation of substituted
nitroaromatic compounds by water-soluble iron complex
catalysts with molecular hydrogen has been reported for the
first time. This biphasic catalyst presents an opportunity
for a solvent-free hydrogenation. This catalyst system
provides a low-cost, efficient alternative to the selective but
environmentally unacceptable stoichiometric reductions as
well as the supported noble metal catalysts used for hydro-
genation. An efficient recycling strategy has resulted in a
cumulative turnover number above 6000.
a
Nitrobenzene 96 mmol, solvent 90 mL, catalyst 0.072 mmol,
pH2 400 psi, T ) 150 °C; conversion and selectivity in all cases
were found to be >98.5%. b Based on hydrogen consumption (mol
of hydrogen consumed/mol of catalyst/h).
9
gen. For the reduction of nitroaromatics, the byproduct
being water, a catalyst tolerant of water or, better still,
applicable in a biphasic aqueous-organic solvent system
would be more desirable.
At the outset, the catalytic activity of the iron com-
pounds for the hydrogenation of nitrobenzene was evalu-
Selective hydrogenation of substituted nitro aromatic
compounds has been a major challenge for chemists.
1
ated. Reactions were carried out with Fe(NO
3
)
3
‚9H
2
O,
FeSO ‚7H O, Fe(acac) , and ferrocene in water, methanol,
4
2
3
Stoichiometric reagent-based processes are very selective
toward reduction of nitro functions but generally not eco-
and toluene solvents. The results in Table 1 indicate that
except for ferrocene, iron compounds efficiently catalyze
nitrobenzene hydrogenation to aniline. In all the ex-
amples reported, where hydrogenation occurred, complete
conversion of nitrobenzene (residual nitrobenzene less
than 10 ppm) to aniline was obtained with selectivities
greater than 98%. The turnover frequencies (TOF, mol
2
friendly. Catalytic hydrogenations using molecular hy-
drogen are less chemoselective than the stoichiometric
methods; therefore, the catalysts have to be poisoned or
3
-7
tailored to achieve the desired selectivity.
In this
report, a highly chemoselective catalytic hydrogenation
of nitrobenzenes has been demonstrated using homoge-
neous iron complex catalysts. The water-soluble catalyst
has also been applied to hydrogenation in a biphasic
aqueous-organic system to achieve selective, robust, and
recyclable catalysis.
of H
2
consumed/mol of iron/h) were in the range of 433-
-
1
1
297 h . Under identical conditions, in the absence of
iron compound, no hydrogenation was observed, thereby
confirming the catalytic role of iron.
To elucidate the reaction pathway intermediate, samples
were withdrawn during the reaction for analysis. The
formation of phenyl hydroxylamine (III), azoxybenzene-
The use of homogeneous iron complexes for the hydro-
genation of nitro compounds has been reported earlier
in a few cases. Iron carbonyl phosphine complexes are
reportedly active for hydrogenation of nitro benzene
(V), and azobenzene was observed. Although nitrosoben-
8
zene (II) was not detected, its formation was evident since
azobenzene and azoxybenzene were formed. Azobenzene-
under exclusively nonaqueous conditions. Nitrobenzene
has been reduced under triphasic conditions using Fe
3
-
(VI) and hydrazobenzene(VII) were also formed by the
(CO)12 in stoichiometric quantities, in absence of hydro-
hydrogenation of azoxy benzene. The major impurities
observed at the end of the reaction were mainly the azo
and hydrazobenzene. The probable reaction pathway as
illustrated in Scheme 1 is found to be similar to that of
Raney nickel-catalyzed hydrogenation.10
(
1) Vogt, P. F.; Gerulis, J . J . Ullmans Encyclopedia, 5th ed.; Verlag
Chemie: Weinheim, 1985; Vol. A2, pp 37-55.
2) B e´ champ, A. J . Ann. Chim. Phys. 1854, 42, 186. Blaser, H. U.;
Studer, M. Appl. Catal. 1999, 189, 191-204
3) Downing, R. S.; Kunkeler, P. J .; van Bekkum, H. Catal. Today
997, 37, 121-136.
4) Baumeister, P.; Studer, N.; Roessler, F. In Handbook of Hetero-
(
(
1
The major objective of this study was to develop an
aqueous-phase catalyst so as to avoid all problems related
(
geneous Catalysis; Ertl, G., Knozinger, H., Weitkamp, J ., Eds.; Wiley:
New York, 1997, Vol 5.
(
5) Beller, M.; Gerdau, T.; Strutz, H. Ger. Offen. DE4316923, 1994.
(6) Baumeister, P.; Blaser, H. U.; Scherer, W. Stud. Surf. Sci. Catal.
(9) J yothimony, K.; Vancheesan, S.; Kuriacose, J . C. J . Mol. Catal.
1989, 52 (2), 297-300.
(10) Burge, H. D.; Collins, D. J .; Davis, B. H. Ind. Eng. Chem. Prod.
Res. Dev. 1980, 19, 389-391
1
991, 59, 321-328.
(
(
7) Chang, Y. W.; Seagraves, R. L. Eur. Pat. Appl. EP398542, 1990.
8) Knifton, J . F. J . Org. Chem. 1976, 41, 1200-1206.
1
0.1021/jo035511t CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/10/2004
J . Org. Chem. 2004, 69, 4835-4838
4835

TABLE 2. Hyd r ogen a tion of Nitr oben zen e to An ilin e in Bip h a sic Med iu m a
conversion
(%)
selectivity to aniline
(%)
no.
catalyst
metal-to-ligand ratio
time (h)
1b
2
FeSO4
1:0
1:1
1:5
1:5
7.38
7.75
9.83
13.3
66.28
99.96
88.2
98.1
98.1
97.3
97.4
II
Fe /EDTANa2
II
3
Fe /EDTANa2
c
II
4
Fe /EDTANa2
99.9
a
Nitrobenzene 96 mmol, toluene 50 mL, water 50 mL, catalyst FeSO4‚7H2O 0.072 mmol, pH2 400 psi, T ) 150 °C. Procedure for
reaction: A Parr T316 SS autoclave of 300 mL capacity was charged with the requisite amount of water. The catalyst, FeSO4‚7H2O, and
the Na2EDTA were added to the water and dissolved. A toluene solution of nitrobenzene was added to the reactor, following which the
reactor was closed and flushed with nitrogen and hydrogen. The autoclave and its contents were heated to the requisite temperature,
under slow stirring. On attainment of the correct temperature [150 °C], the autoclave was pressurized with hydrogen to the desired
pressure [400 psig], through a constant pressure regulator, and connected to a hydrogen reservoir; the time was noted, and the stirrer
was increased to 900 rpm. The consumption of gas in the reactor was measured by monitoring the pressure in the reservoir. The pressure
in the reactor was held constant [at 400 psig] by a continuous feed of hydrogen from the reservoir. This ensured a constant pressure for
the entire duration of the reaction. After the stoichiometric consumption of hydrogen was achieved, the reactor was cooled and discharged.
A liquid sample was taken for analysis, and the mass balance of reactants and products was calculated. b Considerable amount (>80%)
of iron leaching to organic phase was observed in the absence of a coordinating ligand. In the presence of EDTA, the Fe content of the
c
organic phase was <5 ppm. Organic phase was pure nitrobenzene 50 mL (480 mmol).
SCHEME 1. Rea ction P a th w a y for Hyd r ogen a tion
of Nitr oben zen e to An ilin e w ith Ir on Ca ta lysts
to product separation and catalyst recovery.11 We there-
fore investigated iron ethylenediaminetetraaceticacid
II
disodium salt (Fe /EDTANa
2
) as a catalyst for the
F IGURE 1. Hydrogenation of nitrobenzene to aniline in a
biphasic medium. Reaction conditions: nitrobenzene 96 mmol,
hydrogenation of nitro-aromatics in a two-phase system.
In this reaction, Fe /EDTANa complex remains exclu-
2
sively in the aqueous phase, while the solvent, substrate
II
toluene 50 mL, water 50 mL, catalyst FeSO
4
2
‚7H O 0.072 mmol,
Fe:EDTANa2 ) 1:5, pH2 400 psi, T ) 150 °C. For recycling,
the excess water generated in the previous reaction was
removed under vacuum at room temperature to maintain the
aqueous phase volume at 50 mL.
nitrobenzene, and products form an immiscible organic
phase. With this catalyst, a TOF of 136 h-1 and a
turnover number (TON, mol of product formed per mol
of catalyst) of 1333 for nitrobenzene were achieved with
complete conversion of nitrobenzene and a selectivity to
aniline greater than 98% (Table 2). The activity of the
was found to be in the organic phase. Hence, the presence
of a strongly coordinating hydrophilic ligand such as
2
Fe(II) system in the presence of EDTANa is reduced due
EDTANa
2
is essential to retain iron catalyst in the
to coordination, which can restrict the access of nitroben-
zene, and also due to the fact that the catalyst is retained
in the aqueous phase. In the absence of the ligand, the
catalyst is predominantly in the organic phase where the
reaction takes place with no constraints on solubility
phenomena.
To examine the stability and recyclability of the
catalyst, the aqueous phase was successively recycled five
times with fresh organic phase to obtain a cumulative
TON of 6665 without loss of either the hydrogenation
activity or the selectivity to aniline (see Figure 1). In the
aqueous phase.
To establish the generality of the catalyst system, we
further investigated hydrogenation of numerous substi-
tuted nitrobenzenes in the absence of organic solvents.
In all cases, almost complete conversion of the nitro
compound could be obtained with a high selectivity to
the corresponding amine (Table 3). The Fe / EDTANa
catalyst system was assessed for its chemoselectivity in
the hydrogenation of the nitro group in preference to
other reducible functional groups.
As seen from Table 3, hydrogenation of 4-nitroac-
etophenone, 4-nitrophenyl acetonitrile, and 4-nitroben-
zoic acid gave the corresponding amino derivatives
without affecting the other reducible groups. Even the
hydrogenation of chloronitrobenzenes showed high se-
lectivity for chloroanilines without any dehalogenation
of chloronitrobenzenes, which is normally observed with
heterogeneous catalysts.1 The reduced selectivity to
II
2
absence of EDTANa
2 4
, the FeSO catalyst hydrogenated
nitrobenzene in a toluene-water biphasic system (TOF
-1
1
20 h ). However, at the end of the reaction the catalyst
(11) Claus, P.; Berns, M. Catalysis in Water as a Special Unit
Operation. In Aqueous-Phase Organometallic Catalysis: Concepts and
Applications. Cornils, B., Herrmann, W. A., Eds.; Wiley-VCH: Wein-
heim, 1998; pp 151-162.
4
836 J . Org. Chem., Vol. 69, No. 14, 2004

TABLE 3. Hyd r ogen a tion of Su bstitu ted Ar om a tics in Bip h a sic Med iu m a
a
Reaction conditions: pressure 400 psi; temperature 150 °C; aqueous phase 90 mL; organic phase consists of neat substrate; catalyst
FeSO4‚7H2O 0.072 mmol; Fe EDTANa2 1:5; conversion in all cases was complete. Based on GC analysis. c TOF calculated as mol of
nitro compound converted per mol of Fe per hour. Monoamino product was 11.5%.
b
d
J . Org. Chem, Vol. 69, No. 14, 2004 4837

products as observed for the hydrogenation of p-nitroben-
zoic acid, 4-nitrobenzyl nitrile, and 4-nitro anisole is due
to formation of other products, mainly the azo and
hydrazo derivatives and high boilers. In these reactions,
too, no aniline was formed and no hydrogenation of the
nitrile, keto, or carboxylic acid group was observed, which
shows the chemoselective nature of the catalyst. The
variation in the activity observed for the hydrogenation
of the different compounds could be attributed to the
influence of the substituents on the ring as well as the
solubilty of the substrate in water. In this reduction
process, water, apart from being a green solvent, ef-
fectively controls the rate of the reaction and hence
exothermicity. The limited solubility of the substrate in
water maintains sufficient productivity and also prevents
reaction runaway. This is an additional advantage since
hydrogenation of nitro aromatics is highly exothermic.
Due to the use of the aqueous-phase catalyst, organic
solvents can be totally avoided, thereby making the
process more eco-friendly.
The high chemoselectivity of the biphasic iron catalysts
for nitro-group hydrogenation, shown for the first time,
is similar to that observed in Bechamp reduction. The
simplicity of the catalyst preparation and recycling and
the low cost, coupled with the prospect of solvent-free
operations, are likely to form the basis for application of
such a catalyst in commercial practice in the future.
J O035511T
4
838 J . Org. Chem., Vol. 69, No. 14, 2004