Iron and palladium(II) phthalocyanines as recyclable catalysts for reduction of nitroarenes

Article abstract of DOI:10.1007/s10562-014-1269-6

Iron(II) and palladium(II) phthalocyanines have been established as recyclable heterogeneous catalysts for the reduction of aromatic nitro compounds to corresponding amines using diphenylsilane/sodium borohydride as hydrogen sources in ethanol. Various reducible functional groups, such as acetyl, ester, cyano, amide, sulphonamide and carboxylic acid etc. were well tolerated, and the methods were applicable up to gram scale. Mechanistic studies showed that reduction of nitro group proceed through direct (nitroso) pathway and possibly iron or palladium phthalocyanines activates nitro group for reduction. FePc and PdPc also catalyzed the generation of hydrogen from the combination of diphenylsilane/sodium borohydride and ethanol.

Full text of DOI:10.1007/s10562-014-1269-6

Catal Lett
DOI 10.1007/s10562-014-1269-6
Iron and Palladium(II) Phthalocyanines as Recyclable Catalysts
for Reduction of Nitroarenes
•
Praveen Kumar Verma Manju Bala
•
•
Kavita Thakur Upendra Sharma
•
•
Neeraj Kumar Bikram Singh
Received: 11 February 2014 / Accepted: 30 April 2014
Ó Springer Science+Business Media New York 2014
Abstract Iron(II) and palladium(II) phthalocyanines
have been established as recyclable heterogeneous cata-
lysts for the reduction of aromatic nitro compounds to
corresponding amines using diphenylsilane/sodium boro-
hydride as hydrogen sources in ethanol. Various reducible
functional groups, such as acetyl, ester, cyano, amide,
sulphonamide and carboxylic acid etc. were well tolerated,
and the methods were applicable up to gram scale.
Mechanistic studies showed that reduction of nitro group
proceed through direct (nitroso) pathway and possibly iron
or palladium phthalocyanines activates nitro group for
reduction. FePc and PdPc also catalyzed the generation of
hydrogen from the combination of diphenylsilane/sodium
borohydride and ethanol.
Keywords Iron(II) phthalocyanine Á Palladium(II)
phthalocyanine Á Diphenyl silane Á Sodium borohydride Á
Nitro compounds
1 Introduction
The hydrogenation of nitroarenes to amines is one of the
important reactions in synthetic organic chemistry [1–3]
and industrially applied for the synthesis of dyes, bioactive
compounds and agricultural chemicals [4]. Total synthesis
of numerous pharmaceuticals (Fig. S1, see supporting
information) such as sildenafil [5], antibiotic linezolid [6],
the HIV protease inhibitor amprenavir [7] and nimesulide
[8] involve reduction of nitro group as the key step. Apart
from the traditionally used non-catalytic processes like
Bechamp or sulphide reduction [9], currently, transition
metals are frequently used for the selective reduction of
nitroarenes [10]. Transition metals such as Ni [11], Sn [12,
13], Cu [14], Co [14, 15], Zn [16–20], Au [21–29], Pd [30–
33], Sm [34–36], Mo [37, 38], Re [39], Rh [40, 41] Ir [42]
etc. has been widely explored for the reduction of nitroa-
renes. In recent years, iron due to its abundant availability
has been extensively applied for various catalytic methods
[43–50] and palladium complexes showed remarkable
efficiency towards reduction reactions [51–55]. Moreover,
iron compounds are relatively non-toxic, and inexpensive.
Although, combination of iron [43–49] and palladium
[30–33] catalysts has been applied for this conversion,
however, use of phosphine ligand, low yield of amines and
lack of selectivity limit their scope.
CSIR-IHBT Communication No. 3564.
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1269-6) contains supplementary
material, which is available to authorized users.
P. K. Verma Á M. Bala Á K. Thakur Á U. Sharma Á N. Kumar Á
B. Singh (&)
Natural Plant Products Division, CSIR-Institute of Himalayan
Bioresource Technology, Palampur 176 061, Himachal Pradesh,
India
e-mail: bikramsingh@ihbt.res.in; bikram_npp@rediffmail.com
P. K. Verma Á M. Bala Á B. Singh
Academy of Scientific & Innovative Research, CSIR-Institute of
Himalayan Bioresource Technology,
Palampur 176 061, Himachal Pradesh, India
Recently, metal phthalocyanines (MPcs) have been
studied for their catalytic potential due to their cyclic tetra-
dentate framework, which helps in electron transport
mechanism for various redox reactions [56]. Additionally,
U. Sharma
Department of Chemistry, Korea Advanced Institute of Science
& Technology (KAIST), Daejeon 305-701, South Korea
123

P. K. Verma et al.
2 Experimental
Table 1 Screening of MPcs and their corresponding salts for the
reduction of 4-nitrotoluene
NO2
NH2
MPcs (1 mol%)
2.1 General Information
NaBH4 (2 mmol), ethanol (5 ml)
H3C
100oC, 12 h
H3C
Metal salts used were purchased from Merck, Germany.
Iron phthalocyanines, palladium phthalocyanine, nitro
compounds, sodium borohydride and silanes were pur-
chased from Sigma to Aldrich USA. Silica gel
(60–120 mesh) used for column chromatography was
purchased from Sisco Research Laboratories Pvt. Ltd. India
and all other chemicals were purchased from Spectrochem,
India, Merck, Germany, and Sigma-Aldrich, USA and were
used without further purification. NMR spectra were
recorded on a Bruker Avance-300 and Bruker Avance-600
spectrometer. Mass spectra were recorded on QTOF-Micro
of Waters Micromass. The GC and GC–MS analysis was
carried out on a Shimadzu (QP 2010) series Gas Chro-
matogram-Mass Spectrometers (Tokyo, Japan), AOC-20i
auto-sampler coupled, and a DB-5MS capillary column,
(30 m 9 0.25 mm i.d., 0.25 lm). The initial temperature
of column was 70 °C held for 4 min and was programmed
to 230 °C at 4 °C/min., then held for 15 min at 230 °C; the
sample injection volume was 2 lL in GC grade dichloro-
methane. Helium was used as carrier gas at a flow rate of
1.1 mL min-1 on split mode (1: 50). Melting points were
determined on a Barnstead Electrothermal 9100.
Entry
Catalyst
Conv.(%)a
Sel.(%)a
1
–
NR
66
28b
41b
46
99b
96b
20
–
2
Fe(II)Pc
Fe(OAc)2
Fe(III)Pc
FeCl3
61
51
33
[99
–
3
4
5
6
Co(II)Pc
Co(II)Pc(t-Bu)4
CoCl2
7
1
8
15
10
7
9
Ni(II)Pc
NiCl2
14
10
11
12
13
14
15
16
17
18
19
20
37b
22b
43
Cu(II)Pc
CuSO4
2
[98
95
–
Zn(II)Pc
ZnCl2
35
NR
65b
4
Mg(II)Pc
MgCl2
2
–
Al(III)PcOH
A1C13
95b
–
7
50
[99
–
Pd(II)Pc
Pd(OAc)2
98
[99b
2.2 General Experimental Procedure for FePc
Catalyzed Reduction of Nitro Compounds
Reaction conditions: 4-nitrotoluene (1 mmol), NaBH4 (2 mmol),
catalyst (1 mol%), EtOH (5 mL), and 100 °C temperature for 12 h
Determined by GC using n-hexadecane as internal standard; and
also confirmed by GC–MS
a
To a stirred suspension of FePc (1 mol%) and diphenyl
silane (3 mmol) in ethanol (5 mL) were added nitro com-
pounds (1.0 mmol) at room temperature and then temper-
ature was raised to 100 °C for 24 h. On completion of the
reaction (as monitored by TLC), reaction mixture was fil-
tered and passed through anhydrous Na2SO4 and dried
under vacuum. The GC conversions and yields were
determined by internal standard technique. The isolation of
anilines was carried out by column chromatography on
silica-gel (60–120) with appropriate mixture of n-hexane
and ethyl acetate as an eluent.
b
Intermediates were formed as major products (see Supporting
information Table S1)
they are highly stable towards heat, moisture, acidic and/or
basic conditions. More importantly MPcs works as hetero-
geneous recyclable catalysts without the need of any external
ligands as they itself acts as fabulous ligands.
In this context, recently, apart from the synthesis of
MPcs [57] we have reported their catalytic applications for
various important organic transformations [14, 57–63]. In
addition, during our studies, we observed iron and palla-
dium phthalocyanines (FePc and PdPc) in combination
with diphenylsilane and sodium borohydride, respectively,
provided the best results for the reduction of aromatic nitro
compounds to corresponding amines.
2.3 General Experimental Procedure for PdPc
Catalyzed Reduction of Nitro Compounds
To a stirred suspension of PdPc (1 mol%) and NaBH4
(2 mmol) in ethanol (5 mL) were added nitro compounds
(1.0 mmol) at room temperature and then temperature was
raised to 100 °C for 12 h. On completion of the reaction (as
monitored by TLC), reaction mixture was filtered and
passed through anhydrous Na2SO4 and dried under vac-
uum. The GC conversions and yields were determined by
internal standard technique. The isolation of anilines was
Herein, we disclose two new methods, first, selective
reduction of nitro compounds using inexpensive, highly
stable and abundantly available FePc with Ph2SiH2 in
ethanol, and secondly, highly efficient PdPc with NaBH4
for the same reduction process. PdPc has been applied for
the first time for reduction process.
123

MPcs Catalyzed Nitro Reduction
Table 2 Screening of hydrogen sources with Pd(II)Pc and Fe(II)Pc for the reduction of 4-nitrotoluene
NO2
NH2
MPcs (1 mol%)
hydrogen Source(x mmol)
H3C
ethanol (5 ml), 100oC, 12 h
H3C
Entry
Hydrogen Source(mmol)
FePc
PdPc
Conv.(%)a
Sel.(%)a
Conv.(%)a
Sel.(%)a
1
–
NR
NR
10
66
86
59
NR
NR
NR
54
3
–
NR
NR
\1
98
–
2
CaH (2)
–
–
3
Na(CN)BH3 (2)
NaBH4 (2)
NaH (2)
64
traces
[99
6
4
61
5
37
57
6
NH2–NH2.H2O (2)
HCOOH (2)
HCOOK (2)
HCOONH4 (2)
DPS (2)
[99
–
\1
NR
27
traces
–
7
8
–
[99
–
9
–
NR
23
10
11
12
13
14
[99
[99
[99
[99
[99
78
TPS (2)
NR
\1
\1
NR
–
PMHS (2)
MDES (2)
TMDS (2)
7
traces
traces
–
12
4
CH3
CH3
Si
H
Si
H
Si
H
O
H3C
CH3
H
Si
TMDS
H
TPS
DPS
CH3
CH3
CH3
CH3
Si
Si
Si
O
O
Si CH3
CH3
H3C
n
CH3
CH3
O
O
CH3
H
H
PMHS
MDES
Reaction conditions: 4-nitrotoluene (1 mmol), hydrogen source (2 mmol), PdPc or FePc (1 mol%), EtOH (5 mL), and 100 °C temperature for 12 h
a
Determined by GC using n-hexadecane as internal standard; and also confirmed by GC–MS
carried out by column chromatography on silica-gel
(60–120) with appropriate mixture of n-hexane and ethyl
acetate as an eluent.
4-nitrotoluene to corresponding amine with NaBH4 in eth-
anol (Table 1). As expected reaction did not initiate without
catalyst (Table 1, entry 1). Fe(II)Pc showed some promising
results out of the tested iron catalysts (Table 1, entries 2–5).
Excellent conversion was observed with Co(II)Pc and
Co(II)Pc(t-Bu)4, however, reaction halted at intermediate
stage and did not provide the desired product (Table 1,
entries 6–7). The corresponding cobalt salt (CoCl2) was also
not found to be effective for the reaction (Table 1, entry 8).
Ni(II)Pc, Cu(II)Pc, Zn(II)Pc, Mg(II)Pc, Al(III)PcOH and
their corresponding metal salts did not give the satisfactory
conversions and selectivities for the desired product
(Table 1, entries 9–18). In case of Pd(II)Pc excellent con-
version and selectivity was observed (Table 1, entry 19).
The corresponding salt, Pd(OAc)2 of Pd(II)Pc also provided
the excellent conversion, albeit, reaction stopped at inter-
mediate stage without yielding the desired product (Table 1,
3 Results and Discussion
3.1 Optimization Studies
Various combinations of catalysts, hydrogen sources and
solvents were screened to access the best reaction condi-
tions for the reduction of 4-nitrotoluene.
3.1.1 Catalysts Screening
Different MPcs and their corresponding metal salts were
screened to find the best catalyst for the reduction of
123

P. K. Verma et al.
entry 20). Hence, out of the tested MPcs, Fe(II)Pc and
Pd(II)Pc afforded the satisfactory results for the reduction of
4-nitrotoluene to corresponding amine and selected for fur-
ther study.
Table 3 Screening of solvent for the reduction of nitro compounds
NO2
NH2
MPcs (1 mol%)
hydrogen Source(2 mmol)
H3C
solvent (5 ml), 100oC, 12 h
H3C
Conv./Sel.(%)a
FePc/DPSb
Conv./Sel.(%)a
PdPc/NaBH4
3.1.2 Screening of Hydrogen Source
Entry
Solvent
1
2
3
4
5
6
Water
NR
NR
After MPcs screening, different hydrogen sources were
tested for the reduction of 4-nitrotoluene with selected
Pd(II)Pc and Fe(II)Pc (Table 2). As expected, reaction did
not proceed without hydrogen source (Table 2, entry 1).
CaH2, HCOOH and HCOONH4 were completely ineffective
for the present reduction process (Table 2, entries 2, 7 and 9).
Traces to moderate yields were observed with Na(CN)BH3,
NaH, NH2-NH2.H2O, and HCOOK by both of the MPcs
(Table 2, entries 3, 5, 6 and 8). Good yield was observed with
NaBH4 by Pd(II)Pc and moderate by Pd(II)Pc (Table 2,
entry 4). Various silanes were also tested for the present
reaction by both of the selected MPcs. Very low yields were
observed with triphenyl silane (TPS), polymethylhydrosi-
loxane (PMHS), methyldiethoxysilane (MDES) and 1,1,3,3-
tetramethyldisiloxane (TMDS) by both of the MPcs
(Table 2, entries 11-14). Diphenyl silane (DPS) provided the
low yield with Pd(II)Pc, while, moderate yield was observed
with Fe(II)Pc for the present reaction (Table 2, entry 10).
Hence, on the basis of the results obtained by screening of
various MPcs and hydrogen sources it has been postulated
that two methods including Pd(II)Pc with NaBH4 and
Fe(II)Pc with DPS provided the best results for reduction of
4-nitrotoluene to corresponding amine.
Ethanol
Ethanol
PEG-400
EG
54/[ 99
84/[ 99b
80/38
98/[ 99
75/1
50/99
72/63
21/\ 1
1,4-Dioxane
75/70
Reaction condition: 4-nitrotoluene (1 mmol), NaBH4 or DPS
(2 mmol), FePc or PdPc (1 mol%), solvent (5 mL), and 100 °C
temperature for 12 h
PEG-400 polyethylene glycol-400, EG ethylene glycol
a
Determined by GC using n-hexadecane as internal standard; and
also confirmed by GC–MS
b
Reaction time 24 h
that 3 mmol of DPS and 2 mmol of NaBH4 were required
for the reduction of 4-nitrotoluene to corresponding amine
(Fig. S2, see supporting information).
3.2 Fe(II)Pc/DPS Catalyzed Reduction of Nitro
Compounds
After the screening of MPcs, hydrogen sources and solvents,
we also investigated the effect of other iron based catalysts
for their comparison with FePc under the optimized condi-
tions (Table 4). It was observed that various iron salts gave
3.1.3 Solvent Screening
Various green solvents were tested for the FePc and PdPc
catalyzed reduction of 4-nitrotoluene. Reaction did not
proceed in water with both the catalysts (Table 3, entry 1),
might be due to the insolubility of reactants. PEG-400, EG,
and 1,4-dioxane did not provide the satisfactory results for
the present reaction (Table 3, entries 4-6). Moderate con-
version and excellent selectivity was observed with ethanol
by FePc, while, PdPc provide the desired product with
excellent conversion and selectivity (Table 3, entry 2). In the
GC–MS analysis of FePc catalyzed reaction it was observed
that DPS remains unutilised, hence, we further increased the
reaction time up to 24 h that gave the desired product with
high conversion and excellent selectivity (Table 3, entry 3).
Table 4 Comparison of Fe(II)Pc with other iron based catalysts for
reduction of 4-nitrotoluene
NO2
NH2
catalyst (1 mol%)
Ph2SiH2 (3 mmol)
H3C
H3C
ethanol (5 ml), 100oC, 24 h
Entry
Catalyst
Yield (%)a
1
2
3
4
5
6
7
8
FeSO4
38
10
2
FeCI3
Fe metal
K3FeCN6
Fe2O3
5
7
Fe(OAc)2
Fe(ll)Pc
Fe(lll)Pc
36
91
8
3.1.4 Optimization of DPS and NaBH4 Quantity
In order to optimize the minimum amount of hydrogen
sources required for FePc and PdPc catalyzed nitro
reduction process, different amount of DPS and NaBH4
were examined with the respective MPcs. It was observed
Reaction conditions: 4-nitrotoluene (1 mmol), DPS (3 mmol), catalyst
(1 mol%), EtOH (5 mL), and 100 °C temperature for 24 h
Determined by GC using n-hexadecane as internal standard; and
also confirmed by GC–MS
a
123

MPcs Catalyzed Nitro Reduction
low yields of the desired product as compared to excellent
yield by Fe(II)Pc (Table 4, entries 1-7). Fe(III)Pc also pro-
vided the desired product in low yield (Table 4, entry 8).
With the optimized conditions in hand, the scope of the FePc
catalyzed method was investigated for the reduction of
various substituted nitro compounds (Table 5). 2- and
4-Nitrotoluenes was effectively reduced to corresponding
anilines with high yields (Table 5, entries 2a and 2b). Hal-
ogen substituted nitroarenes (F, Cl, Br, I) were efficiently
reduced to corresponding anilines in high yields (Table 5,
entries 2c–2 g). Importantly, no dehalogenation or decom-
position was observed in any case, often encountered with
several reduction methods [64–66]. Nitrobenzene was
hydrogenated to aniline in good yield (Table 5, entry 2 h).
The methoxy and hydroxyl substituted nitroarenes were
reduced to corresponding amines in high yields (Table 5,
entries 2i–2j). Interestingly, in contrast to some previous
reports, high yield [39, 43] and selectivity [67] of
4-cyanoaniline were observed under the present reaction
condition (Table 5, entry 2 k). In case of 4-nitrobenzalde-
hyde, both nitro and aldehyde functional groups were
reduced by present protocol (Table 5, entry 2 l). Notably, the
other reducible functionalities such as acid, ketone, ester,
amide and sulfonamide remain intact during the reduction
(Table 5, entries 2 m-2q). The reduction of m-phenylnitro-
benzene gave desired product in good yield (Table 5, entry
2r). The reduction of 1-nitronaphthalene, 2-nitrofluorene
[43] and 4-chloro-2-nitrophenol afforded the corresponding
amines in good yields (Table 5, entries 2s–2u). The present
protocol was also applicable for complex nitro compounds.
The reduction of 4-nitrobenzene-b-D-glucopyranoside pro-
vided the corresponding amine in good yield (Table 5, entry
2v). In case of 4-nitrochalcone, mixture of product was
observed corresponding to double bond reduction along with
nitro group (Table 5, entry 2w). Regioselective reduction of
dinitro compounds is one of the challenging tasks for the
development of reduction methodologies. Under present
reaction conditions, o-, m- and p-dinitrobenzenes were
regioselectively reduced to corresponding mono amines [20,
68–73] in good to high yields (Table 5, entries 2x–2z).
Interestingly, when reaction of dinitro compound was car-
ried out with the doubled of the optimized amount of DPS,
both nitro groups were reduced to corresponding diamines in
excellent yields (Table 5, entries 2xa and 2za). Unfortu-
nately, in case of aliphatic nitro compounds, promising
results were not observed for the reduction of nitro group
under present reaction conditions (Table S2, entries 1 and 2,
see supporting information).
Table 5 Fe(II)Pc catalyzed reduction of various aromatic nitro
compoundsa,b
NO2
NH2
Fe(II)Pc, Ph2 SiH2
ethanol, 100oC, 24 h
R1
R1
1
2
2a
2j, 82%, R 1 = 4-OH
2k, 89%, R1 = 4-CN
, 82%, R1 = 2-Me
2b, 90%, R 1 = 4-Me
2c
, 78%,R 1 = 4-CH2OHc
, 75%,R 1 = 2-Cl
2d, 89%, R 1 = 4-Cl
2e
2l
2m
NH2
, 75%, R 1 = 4-COCH3
,79%, R 1 = 3-COOCH3
R1
,92%, R 1 = 4-F
2f,91%, R 1 = 4-Br
2g
2n
2o,87%, R 1 = 4-COOH
2p,90%, R 1 = 4-CONH2
2q,81%, R 1 = 4-SO2NH2
Present reaction conditions are also applicable for the
reduction of nitro-substituted heteroaromatics (Table 6).
The reduction of 5-nitroisoquinoline and 5-nitroindole
gave the desired products in high yields (Table 6, entries 4a
and 4b). Also, high chemoselectivity was observed for nitro
group over carbonyl group in case of 5-nitrophthalide and
4-nitrophthalimide (Table 6, entries 4c and 4d). The
deoxygenation of 6-nitrobenzothiazole and 4-nitrobenzo-
thiadiazole was achieved in good yields (Table 6, entries
4e and 4f) to afford the biologically important precursors
[74–76] 6-aminobenzothiazole and 4-aminobenzothiadiaz-
oles. The reduction of 2-chloro-5-nitropyridine afforded
the desired product in high yield (Table 6, entry 4 g).
,84%, R 1 = 4-I
2h,90%, R 1 = H
2i
,88%, R 1 = 4-OCH3
2r
,87%, R 1 = 3-Ph
NH2
OH
NH2
NH2
2v
OH
, 83%
NH2
O
HO
HO
O
Cl
, 86%
2s
,89%
2t
, 87%
O
2u
OH
NH2
2x, 86%, 2-NO2
2y
2z, 91%, 4-NO2
Ph
, 88%, 3-NO2
O2N
2w, 32 %d,e
H2N
NH2
NH2
NH2
2xa, 91%f
H2N
2za, 92%f
3.3 Pd(II)Pc/NaBH4 Catalyzed Reduction of Nitro
Compounds
a
Reaction condition: nitro compound (1 mmol), Ph2SiH2 (3 mmol),
Fe(II)Pc (1 mol%), EtOH (5 mL), and 100 °C temperature for 24 h
b
Isolated yields
Various palladium salts and complexes were screened to
compare their catalytic activity with Pd(II)Pc catalyzed
nitro reduction process (Table 7). Excellent conversion and
selectivity was observed with PdCl2 (Table 7, entry 2),
however, Pd(OAc)2 from which PdPc was prepared
c
Both aldehyde and nitro group were reduced
d
Both carbon-carbon double bond and nitro group were reduced
e
61 % Only carbon-carbon double bond reduced product obtained
f
Both nitro groups were reduced using 6 equiv. of DPS
123

P. K. Verma et al.
Table 7 Screening of palladium catalysts for the reduction of nitro
compoundsa
Table 6 Fe(II)Pc catalyzed reduction of various heteroaromatic nitro
compounds
NH2
NO2
Fe(II)Pc, Ph2SiH2
catalyst (1 mol%), NaBH4(2 mmol)
ethanol, 100oC, 12 h
R
NO2
R
NH2
ethanol, 100oC, 24 h
3
H3C
Entry
H3C
4
Conv.[%]b
Sel.[%]b
Catalyst (mol %)
Pd(II)Pc
PdCl2
Pd(OAc)2
Pd(OAc)2/A
Pd(OAc)2/B
Pd(OAc)2/C
NH2
O
O
>99
86
-
88
74
84
77
9
70
25
H2N
H2N
1
2
3
4
98
H2N
>99
>99c
>99
>99
>99c
NH
O
N
N
H
O
4b, 88%
4c, 86%
4a, 92%
4d, 75%
5
H2N
S
N
S
N
6
7
8
98
Pd(OAc)2/D
E
F
93c
97c
N
N
Cl
H2N
9
10
NH2
4f, 71%
82c
G
4e, 74%
4g, 88%
Reaction conditions: nitro compound (1 mmol), Ph2SiH2 (3 mmol),
Fe(II)Pc (1 mol%), EtOH (5 mL), and 100 °C temperature for 24 h.
Isolated yields
N
N
N
N
N
NH
N
A
B
N
N
P
HN
N
N
C
D
Cl
afforded the reaction intermediates as major products
(Table 7, entry 3). Excellent conversion and selectivity
were observed with PdPc (Table 7, entry 1). The combi-
nation of Pd(OAc)2 with other ligands (A–D) provided the
excellent conversion and high selectivity for the desired
product (Table 7, entries 4–7). Reaction was also carried
out with three palladium complexes (E–G) to compare with
PdPc, however, acceptable results were not observed
(Table 7, entries 8–10). Hence, PdPc was selected for the
further study.
Cl
HO
Cl
Cl
N
Cl
Pd
Cl
Pd
N
Pd
P
P
OH
Cl
Cl
E = PdCl2(PPh3)2
F = Najera Catalyst I
N
N
N
N
N
P
Pd
Pd
N
N
N
The scope of PdPc catalyzed method was investigated by
the reaction of various substituted nitro compounds
(Table 8). Excellent yields were observed for the reduction
of nitrobenzene and 4-nitrotoluene (Table 8, entries 6a and
6b). In case of nitro benzaldehydes, both carbaldehyde and
nitro groups were reduced to corresponding amino alcohols
(Table 8, entries 6c and 6d). The high yields for amino
alcohols proposed the present method to be well suited for
the one step double reduction of nitro benzaldehydes. The
methoxy, cyano and amide substituted nitro benzenes
afforded the desired products in good to excellent yields
(Table 8, entries 6e–6g). Good yield of corresponding
product was observed for tri-substituted chloronitrophenol
(Table 8, entry 6h). The reduction of 2-nitrofullerene gave
the desired product in moderate yield (Table 8, entry 6i). In
case of 4-nitrochalcone, the reduction of nitro as well as
carbon–carbon double bond occurred in excellent yield
(Table 8, entry 6j). High selectivity was observed for the
reduction of nitro group in case of 7-nitro-3,4-benzocoum-
arin, however, product was obtained in moderate yield
(Table 8, entry 6 k). Transesterified amino product was
observed for the reduction of methyl-3-nitrobenzoate
4
G = Pd(PPh3)4
Reaction condition: 4-nitrotoluene (1 mmol), NaBH4 (2 mmol),
catalyst (1 mol%), EtOH (5 mL), and 100 °C temperature for 12 h
Determined by GC using n-hexadecane as internal standard; and
also confirmed by GC–MS
PdPc
a
b
c
Intermediates were formed as other products
(Table 8, entry 6l). High regioselectivity was observed for
the reduction of 1,3- and 1,4-dinitrobenzenes along with
good to excellent yields (Table 8, entries 6m and 6n). In case
of 1,3-dinitrobenzene 25 % of 1,3-diaminobenzene was also
observed (Table 8, entry 6m). When reaction of dinitro
compounds was carried out with doubled of the optimized
amount of NaBH4 (4 equiv.), the reduction of both nitro
compounds was observed (Table 8, entries 6ma and 6na).
Hence, present method can efficiently be utilized for the
synthesis of diamines which are the precursors for the syn-
thesis of various heterocyclic compounds. Present method
123

MPcs Catalyzed Nitro Reduction
Table 8 Scope for the PdPc catalyzed reduction of nitro
compoundsa,b
NO2
NH2
NH2
NH2
Pd(II)Pc, NaBH4
ethanol, 100 oC, 12 h
R1
R1
6
5
NH2
NH2
HOH2C
6c, 74%c
H3C
6a, >98% (93%)
6b, >99% (92%)
NH2
HOH2C
NH2
NC
H3CO
6e, 91% (86%)
6d, 98%c
Fig. 1 Recycling of catalyst FePc (dahsed line) and PdPc (hyphen-
ated line)
6f, 95% (90%)
OH
NH2
NH2
NH2
H2NOC
Cl
6i, 57% (52%)
6g, >99% (94%)
6h, 89% (80%)
O
O
OC2H5
Ph
NH
2 H2N
O
O
NH2
6j, >99%d
6l, >83%e (72%)
6k, 55% (50%)
NH2
NH2
O2N
NH2
Scheme 1 FePc and PdPc catalyzed reduction of 4-nitrotoluene on
gram scale
O2N
6n, >99% (94%)
N
6m, 74%f (70%)
6ma, 91%g
6o, >99% (91%)
3.4 Recyclability of Catalysts
6na, 98% (90%)g
NH2
The recyclability of FePc and PdPc catalysts was evaluated
by successive addition of 4-nitrotoluene and respective
hydrogen sources (DPS or NaBH4) and solvent to the
residue (see supporting information). FePc was recycled up
to four times, while, PdPc was recycled up to five times
without any significant loss of activity (Fig. 1).
N
S
N
S
N
OH
O
O
H2N
NH2
HO
HO
OH
6p, (91%)
6q, >99% (92%)
6r, (87%)
a
Reaction conditions: nitro compound (1 mmol), NaBH4 (2 mmol),
Pd(II)Pc (1 mol%), EtOH (5 mL), and 100 °C temperature for 12 h
Determined by GC using n-hexadecane as internal standard; and
also confirmed by GC–MS. Isolated yields given in parentheses
3.5 Gram Scale Reactions
b
Further, the two methods were successfully scaled-up to
1.0 g with 4-nitrotoluene (Scheme 1, FePc method; yield
87 % for 1.0 g vs 90 % for 1 mmol scale and PdPc method,
yield 90 % for 1.0 g vs 92 % for 1 mmol scale). Although,
3 mmol of NaBH4 was taken for 1.0 g scale reaction by
PdPc catalyzed method.
c
Both aldehyde and nitro group were reduced
d
Both carbon–carbon double bond in side chain and nitro group were
reduced
e
Transesterification of nitro reduced product was also occurred
f
25 % of diaminobenzene was observed
g
Both nitro group were reduced using 4 equiv. of NaBH4
3.6 Mechanistic Study
was also applicable for the chemoselective reduction of
heterocyclic nitro compounds such as 5-nitroisoquinoline,
5-nitrobenzothiazole and 4-nitrobenzothiadiazole in high
yields (Table 8, entries 6o–6q). The reduction of 4-nitro-
benzene-b-D-glucopyranoside afforded the corresponding
amine in good yield (Table 8, entry 6r). The reduction of
aliphatic nitro compounds was not observed under the
present reaction conditions (Table S2, entries 1 and 2).
In order to get insight, which pathway (direct route and
condensation route) [77] is going under present condition,
reduction of the possible reaction intermediates i.e., nitro-
sobenzene (direct route intermediate) and azobenzene
(condensation route intermediate), was carried out under
the standard reaction condition for two methods. For FePc
catalyzed method, nitrosobenzene provided aniline in 87 %
123

P. K. Verma et al.
Table 9 Hydrogenation of probable reaction intermediates
Entry
1
Substrate
Time (h) FePc/PdPc
6/4
Yield of anilinea FePc/PdPc
87 %/92 %
N
N
6/4
1
87 %/92 %
18 %/59 %
Ph
Ph
O
N
2
12/8
18 %/59 %
Ph
12/8
2
Reaction condition: substrate (1 mmol), Ph2SiH2 (3 mmol) or NaBH4 (2 mmol), Fe(II)Pc or Pd(II)Pc (1 mol%), EtOH (5 mL), and 100 °C
a
Yield determined by GC using n-hexadecane as internal standard
yield in 6 h, whereas, azobenzene yielded only 18 % ani-
line even after 12 h. The same reduction pattern was
observed for PdPc catalyzed method for the same reactions
(Table 9, entries 1 and 2). These results indicated the
possibility of direct route.
Furthermore, the role of MPcs (FePc and PdPc) was also
investigated. Transition metal complexes are well known to
catalyzed generation of hydrogen from silanes/borohy-
drides and alcohols combination, leading to the formation
of silyl ethers/borates as by-product [78–84]. Diphenyl
silyl ethyl ether was observed in most of the FePc catalyzed
reactions under present conditions.
Since, MPcsareknownforthe electrontransportprocesses,
based on these experimental observations and literature
reports it can be postulated that FePc and PdPc helps in
hydrogen generation from Ph2SiH2/ethanol with the forma-
tion of diphenyl silyl ethyl ether (Scheme S1a, see supporting
information)andNaBH4/ethanolwiththe evolutionofsodium
tetraethoxyborate (Scheme S1b, see supporting information),
respectively. To prove this, the model reaction was carried out
with some aprotic solvents (Table S3, entries 1–3, see sup-
porting information). The inhibition of the reactions under
aprotic solvent conditions proves the given hypothesis. Also,
reaction proceeded with H2 instead of using other hydrogen
source, which implies the usage of hydrogen for the reduction
(Table S4, see supporting information). These observations
are also supported by the fact that reaction did not occur
without catalysts (Table 1, entry 1). The partial electron
transfer from the phthalocyanine macrocycle through two
nitrogen atoms to the iron or palladium atom promoted the
coordination of electron-deficient nitrogen atom and the
electron enriched oxygen atom of the nitro group [85]. It was
supported by the absence of nitro compound in mass spectra
recorded after the five minutes of reaction time. When the
nitro group is reduced to the electron-enriched amine group it
tends to leave the MPcs (FePc or PdPc). This coordination of
nitro compounds with MPcs is probably responsible for the
chemo-and regio-selectivity ofthe present methods. Thus, the
electronic character of MPcs possibly promotes the reduction
of nitro compounds to the corresponding amines (Scheme 2).
Scheme 2 Plausible reaction mechanism
4 Conclusions
In conclusion, iron and palladium phthalocyanines has
been established as the excellent catalysts for the chemo-
and regio-selective reduction of functionalized nitro
123

MPcs Catalyzed Nitro Reduction
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Notably, the two methods are applicable to various aro-
matic and heteroaromatic nitro compounds tolerating a
large number of functional groups such as halo, cyano,
acetyl, amide, sulphonamide, hydroxyl, methoxy, ester,
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synthesis of large complex molecules. Furthermore, present
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dinitrobenzenes. The other remarkable advantages of the
methods include recyclability of catalysts, no use of base or
ligands like phosphines, gram scale applicability, high
stability of catalysts, easy workup, high isolated yields and
green solvent system.
Acknowledgments Authors are grateful to Director of the institute
for providing necessary facilities. Financial support received from
CSIR-India (fellowship to P. K. V) and DST under Fast Track
Scheme (U. S.) is gratefully acknowledged.
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