Chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot reductive acetylation of nitroarenes using carbon-supported palladium catalytic system in water

Article abstract of DOI:10.1007/s11164-021-04469-9

Developing and/or modifying fundamental chemical reactions using chemical industry-favorite heterogeneous recoverable catalytic systems in the water solvent is very important. In this paper, we developed convenient, green, and efficient approaches for the chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot reductive acetylation of nitroarenes in the presence of the recoverable heterogeneous carbon-supported palladium (Pd/C) catalytic system in water. The utilize of the simple, effective, and recoverable catalyst and also using of water as an entirely green solvent along with relatively short reaction times and good-to-excellent yields of the desired products are some of the noticeable features of the presented synthetic protocols. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-021-04469-9

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-021-04469-9
Chemoselective reduction of nitroarenes, N‑acetylation
of arylamines, and one‑pot reductive acetylation of nitroarenes
using carbon‑supported palladium catalytic system in water
Behzad Zeynizadeh1 · Farkhondeh Mohammad Aminzadeh1 ·
Hossein Mousavi1
Received: 9 December 2020 / Accepted: 10 April 2021
© The Author(s), under exclusive licence to Springer Nature B.V. 2021
Abstract
Developing and/or modifying fundamental chemical reactions using chemical indus-
try-favorite heterogeneous recoverable catalytic systems in the water solvent is very
important. In this paper, we developed convenient, green, and efcient approaches for
the chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot
reductive acetylation of nitroarenes in the presence of the recoverable heterogeneous
carbon-supported palladium (Pd/C) catalytic system in water. The utilize of the simple,
efective, and recoverable catalyst and also using of water as an entirely green solvent
along with relatively short reaction times and good-to-excellent yields of the desired
products are some of the noticeable features of the presented synthetic protocols.
Graphic abstract
Keywords Nitro reduction · Amine · Amine N-acetylation · One-pot · Nitro
reductive acetylation · N-Arylacetamide · Heterogeneous catalyst · Carbon-
supported palladium catalytic system · Pd/C
*
Hossein Mousavi
1hossein.mousavi@gmail.com
1
Department of Organic Chemistry, Faculty of Chemistry, Urmia University, Urmia, Iran
Vol.:(0123456789)
1 3

B. Zeynizadeh et al.
(a) Aromatic and heteroaromatic amine-containing drugs
(b) N-Arylacetamide-containing drugs
NH2
O
O
H3C
H3C
S
N
NH2
F
O
N
O
O
N
N
O
F
F
OH
H
N
H
N
H
N
O
N
CH3
H3C
HN
HO
N
O
O
O
I
H3C
CH3
O
CH3
Sparfloxacin
Trametinib
Amprenavir
O
N
CH3
N
N
NH2
N
CH3
O
O
N
F
H
N
H3C
CH3
CH3
O
H2N
N
N
O
O
H2N
H3C
HO
Acetaminophen
Lorlatinib
Iclaprim
Fig. 1 Examples of some drugs bearing aromatic and heteroaromatic amine and N-arylacetamide
Introduction
Aromatic and heteroaromatic amines, and also N-arylacetamides are existed in
the structure of various and valuable organic compounds, especially drugs such
as amprenavir (HIV-protease inhibitor) [1], sparfoxacin (antibiotic) [2], lorlatinib
(anti-cancer) [3], iclaprim (antibiotic) [4], trametinib (anti-cancer) [5], acetami-
nophen (analgesic) [6, 7], and many others (Fig. 1). In this regard, introducing novel,
simple, and efcient protocols for the preparation of diverse amines and N-arylaceta-
mides is of great and exceptional value.
The environment around us has been acutely afected by pollution caused by
harmful chemical processes (especially in the industrial scales) in recent decades.
Therefore, chemists have tried to minimize the detrimental consequences of chem-
ical reactions by designing a series of protocols, which now are known as green
chemistry principles. The reaction solvent is the most important decisive factor in
the safety of the chemical processes, greenness, and cost-efectiveness [8–14]. Water
has received signifcant attention as an entirely environmentally benign solvent con-
sidering it’s harmless in contrast to many common hazardous organic solvents. In
recent decades, water as a green, abundant, easily accessible, low-cost, and highly
efcient reaction solvent has been successfully applied in various organic transfor-
mations [15–29]. Therefore, developing new chemical reactions and/or optimization
of existing and classical synthetic methods based on water solvent are worthwhile.
In designing a new synthetic protocol, the catalyst has a fundamental role in
the industrial and green chemistry point of view [30–34]. Heterogeneous catalytic
systems, due to their respective and unique properties, especially for easy recover-
ability, are attractive in organic synthesis [35–39]. Among various heterogeneous
catalytic systems, supported palladium catalysts are signifcant, well-known, and
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
practical in numerous organic transformations, even on industrial scales. Supported
palladium on carbon (Pd/C) is one of the mentioned systems that has received a lot
of attention in recent years. Up to now, numerous catalytic applications of Pd/C have
been reported in various organic transformations, including selective reduction of
non-aromatic C=C bonds [40–42], hydrogenation of 1,2-cyclohexenedicarboxylates
to 1,2-cyclohexanedicarboxylates [43], one-step reduction of carbonyls to hydrocar-
bons [44], hydrogenation of nitriles [45, 46], chemoselective reductive amination
of carbonyl compounds [47], hydrogenation of carbon dioxide (CO2) (preparation
of formic acid) [48], N-methylation of nitroarenes and amines [49], amination of
phenols [50], synthesis of α-carbonyl-α′-amide sulfoxonium ylides [51], C‒H bond
functionalization of 1,2,3-triazoles [52], one-pot synthesis of 1,2-diaryl azaindoles
[53], direct arylations of heteroarenes [54], methoxycarbonylation of aryl chlorides
[55], stereospecifc hydrogenolysis of benzyl alcohols [56], synthesis of unsymmet-
rically substituted triarylamines through a dehydrogenative aromatization strategy
[57], and many others.
The literature survey shows that the reduction (or hydrogenation) of the nitro
functional group in the presence of the Pd/C catalytic system is a fateful step in the
multi-step synthesis of pharmaceutically interesting and agrochemical frameworks
(Fig. 2) such as SB-235349 that is a key intermediate compound in the preparation
of lotrafban (oral platelet glycoprotein IIb/IIIa blocker) [58], telmisartan (antihyper-
tensive medicine) [59], PF-4171455 (Toll-like receptor (TLR7) agonist) [60], and
brofanilide (insecticide) [61], even in the scales of multi-gram and multi-kilogram.
Due to the importance of developing the Pd/C catalytic system in organic syn-
thesis [62], and in continuation of our research program [63–70], we wish to report
convenient, efcient, and environmentally benign strategies for the chemoselective
reduction of aromatic nitro compounds (nitroarenes), N-acetylation of arylamines,
and one-pot reductive acetylation of nitroarenes using mentioned efcacious recov-
erable heterogeneous catalytic system (Pd/C) in water (Fig. 3).
Results and discussion
Reduction of nitroarenes
In the past decades, many protocols reported for the reduction of aromatic nitro
compounds in the presence of the Pd/C catalytic system that most of them have
some drawbacks [71–84]. To the best of our knowledge, the combination system of
NaBH4 and Pd/C for the reduction of an aromatic nitro compound was reported for
the frst time by Smith in 1987 (Fig. 4, section a) that carried out in methanol:water
(60:5) under argon atmosphere [85]. In the same year and only a few months later,
Petrini and co-workers described another strategy for the mentioned reaction in THF
(Fig. 4, section b) [86]. In the Smith method, some (6%) of the hydrodehalogen-
ated products were obtained, and also the protocol which was reported by Petrini
et al. was not controllable, and the hydrodehalogenation process was wholly done
along with nitro reduction. In this regard, we decided to introduce a new, efcient,
and chemoselective strategy based on green chemistry principles in the reduction of
1 3

B. Zeynizadeh et al.
(a) Multi-step synthesis of SB-235349 as a key intermediate compound in the preparation of lotrafiban (ref. [58])
O
O
O
O
H3
C
O
C
H3
C
O
C
CH3
O
N
Pd/C
Cyclohexene
Reflux
OH
NO2
N
O
CH3
N
O
CH3
CH3
CH3
O
NO2
NH2
N
H
Yield = 92%
O
C
H3
SB-235349
Overall yield = 50-55%
O
N
CH3
O
N
O
N
H
HN
OH
·HCl
Lotrafiban
(b) Multi-step synthesis of telmisartan (ref. [59])
CH3
CH3
CH3
CH3
H
H
NH2
N
CH3
N
CH3
CH3
O
N
N
Pd/C
OH
H2
O
O
O
O
O
N
H3C
H3C
NO2
H3
C
NH2
CH3OH
25-35 °C
3-4 h
O
O
O
N
CH3
Yield = not reported
Telmisartan
Overall yield ≈ 50%
(c) Multi-step synthesis of PF-4171455 (ref. [60])
O
O
NH2
NH2
NH2
H
N
Cl
O
CH3
CH3
NO2
NH2
N
N
N
Pd/C
H2
O
N
+
O
F3C
N
O
F3C
N
F3C
NH2
CH3CH2OH
40 °C
O
O
O
F3C
O
Over two steps
H3C
H3C
Yield = 63%
PF-4171455
Overall yield = 12%
(d) Multi-step synthesis of broflanilide (ref. [61])
F
F
F
F3
F3
C
C
F3C
F3C
F3C
F3C
Br
O
F
O
F
O
F
O
F
CH3
N
NO2
NO2
NH2
Pd/C
H2
HO
N
H
N
H
N
H
CF3
CF3
CF3
O
CH3OH
Autoclave
70 °C
Broflanilide
Overall yield = 60.3%
Yield = 97%
9 h
Fig. 2 Some examples of the application of the nitro functional group reduction using Pd/C catalytic sys-
tem in the multi-step synthesis of pharmaceutically interesting and agrochemical frameworks
diverse aromatic nitro compounds using NaBH4 as a mild reducing agent and recov-
erable Pd/C catalyst. For this purpose, in the optimization step that the reduction of
nitrobenzene (PhNO2) in the presence of NaBH4 (2 mmol) and diferent amounts
of Pd/C catalyst was under-investigated, we did our best to design the nitro reduc-
tion reaction in the water solvent (Table 1). On the other hand, we designed some
control experiments to the investigation of reducing agent efect on the reduction
of PhNO2 in the presence of the Pd/C catalytic system (30 mg) in the refux water
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Fig. 3 Chemoselective reduction of nitroarenes, N-acetylation of arylamines, and one-pot reductive acet-
ylation of nitroarenes using Pd/C catalytic system in water
(a)
24
W.B. Smith, J. Heterocyclic Chem. , 745 (1987)
NH2
NH2
8%
NO2
6%
NO2
Cl
H
Cl
Cl
(5 wt%) Pd/C (0.5 g)
+
+
NaBH4 (10 mmol)
CH3OH:H2O (60:5)
Reflux
Argon atmosphere
15 min
(10 mmol)
86%
(b)
M. Petrini, R. Ballini, G. Rosini, Synthesis 713 (1987)
NH2
NO2
(10 wt%) Pd/C (0.4 g)
NaBH4 (25 mmol)
THF
H
Br
1) Ice-bath (for 10 min)
2) Room temperature (for 20 min)
(10 mmol)
86%
Fig. 4 Previously reported protocols for the reduction of aromatic nitro compsounds with NaBH4 cata-
lyzed by Pd/C
(Fig. 5). For this purpose, we used ammonium formate (NH4HCO2), formic acid
(HCO2H), and hydrazine monohydrate (NH2NH2·H2O) as well-known and green
reducing (or hydrogenating) agents. As exposed in Fig. 5, sodium borohydride is
a perfectly efective reducer rather than others. After obtaining the optimal reac-
tion conditions, we expanded our new protocol with various aromatic nitro com-
pounds reduction. As shown in Table 2, all nitroarenes successfully converted to
corresponding arylamines in good-to-excellent yields within approximately short
1 3

B. Zeynizadeh et al.
Table 1 Optimization experiments for the reduction of PhNO2 to aniline with NaBH4 catalyzed by Pd/C
in water
Entry
(7 wt%) Pd/C
(mg)
Condition
Time (min)
Conversion (%)
1
2
3
4
24
30
30
40
Refux
Refux
Room temperature
Refux
14
7
60
100
100
100
100
4
Fig. 5 Control experiments
reaction times (4–15 min). On the other hand, in our method, hydrodehalogenation
process was not occurred on the reduction of 3-bromonitrobenzene and 2-chloro-
5-nitrobenzaldehyde (Table 2, entries 18 and 19). Also, the reduction of acetamide
and carboxylic acid moieties were not possible (Table 2, entries 27 and 28). Unfor-
tunately, molecules with the complexity of nitro and carbonyl functional groups did
not show any selectivity in the reduction process and both of the mentioned groups
were reduced (Table 2, entries 12, 14, 16, 19, 21, 23, and 25). As shown in Table 2
(entries 13, 15, 17, 20, 22, 24, and 26), in these cases, both of the aldehyde and
ketone groups reduced to corresponding alcohols easier and faster than reduction of
nitro functional group.
Based on our observation, experimental results, and the Pd/C catalytic behavior,
we demonstrated a plausible reaction mechanism for the reduction of aromatic nitro
compounds to corresponding arylamines using NaBH4 catalyzed by Pd/C in water
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Table 2 Reduction of nitroarenes using NaBH4 catalyzed by Pd/C in water
Molar
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
1
Substrate
Product
Ratioa
1:2
30
30
47
30
30
7
93
84
89
86
89
2
3
4
5
1:2
8
1:3.5
1:3.5
1:3.5
10
8
12
6c
1:2
1:2
30
30
9
7
90
87
7c
1 3

B. Zeynizadeh et al.
Table 2 (continued)
Molar
Ratioa
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
8
1:2
1:2
30
30
7
4
90
83
9c
10c
1:2
30
6
88
11c
1:2
30
4
89
12
13
1:3
30
12
5
3
85
88
1:0.5
14
1:3
30
11
86
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Table 2 (continued)
Molar
Ratioa
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
15
1:0.5
1:3
12
30
12
30
2
6
89
83
88
90
16c
17
18
1:0.5
1:2
2
12
19c
1:3
30
12
14
85
88
20
1:0.5
0.833
21c
1:3
30
5
85
1 3

B. Zeynizadeh et al.
Table 2 (continued)
Molar
Ratioa
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
22
1:1.5
24
30
24
1
85
87
80
23c
1:3
6
24
1.1.5
10
25c
1:3
30
15
88
26
1:1.5
24
1
85
27c
1:3
1:3
30
30
14
89
88
28
2
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Table 2 (continued)
Molar
Ratioa
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
29c
1:3
30
7
88
30
1:3
30
8
92
aSubstrate: NaBH4
bYields refer to isolated pure products
cIn these reactions, NaBH4 was added portion-wisely
(Scheme 1). Notably, by seeing the production of hydrogen gas (H2) inside the reac-
tion vessel, we believe that produced H2 difused in the reaction environment and
then activated on the Pd surface of the mentioned catalytic system to form H‒Pd‒H
species, which was one of the fundamental steps in the mentioned reduction reaction
process.
N‑Acetylation of arylamines
The N-acetylation of amines [87, 88], which is one of the famous reactions in
organic synthesis, has perpetually been employed as a straightforward and sturdy
tool for the protection of amine functional groups in multi-step syntheses and also
in the preparation of strategic acetamide-containing organic frameworks. It is wor-
thy to note that eforts to develop this relatively simple and basic chemical reaction
are still ongoing. In the past two decades, various N-acetylation methods based on
diverse catalytic systems such as niobiumV chloride (NbCl5) [89], bismuth ferrite
(BiFeO3) [90], P(4-VPH)ClO4 [91], ZnAl2O4@SiO2 [92], trimethylsilyl chloride-
potassium iodide (TMSCl-KI) [93], SiO2/PDA-SO3H [94], dialuminium nickel
tetraoxide (NiAl2O4) [95], Ni2(BDC)2(DABCO) [96], Fe3O4@PEG [97], Fe3O4@
Chitosan-TCT-Salen-CuII [98], and many others have been reported.
Given the importance of this transformation, we tried to introduce an efcient
and environmentally benign method for the N-acetylation of arylamines using
the Pd/C catalytic system. For the optimization process, which was investigated
on the N-acetylation of aniline (PhNH2), all the reactions were done in water as
a green solvent using one mmol of acetic anhydride (Ac2O) as an acetylating
agent in the presence of a various amount of the Pd/C catalyst (Table 3). After
the optimization process, the scope and limitations of the mentioned reaction
are explored by various arylamines. As shown in Table 4, all the N-acetylation
1 3

B. Zeynizadeh et al.
Scheme 1 Plausible mechanisn for the reduction of nitroarenes to arylamines using NaBH4 catalyzed by
Pd/C in water
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Table 3 Optimization experiments for the N-acetylation of aniline in the presence of the Pd/C catalytic
system in water
Entry
(7 wt%) Pd/C (mg)
Condition
Time (min)
Conversion (%)
1
2
3
4
59
30
24
6
Refux
Refux
Refux
Refux
1
2
2
10
100
100
100
40
reactions were performed in relatively short reaction times along with good-to-
excellent yields of the desired products. On the other hand, under optimized reac-
tion conditions, the benzylic alcohol group was not converted to the correspond-
ing benzyl acetate, which shows the chemoselectivity of the presented method
(Table 4, entries 13 and 14). Furthermore, an acceptable mechanism for this
transformation is depicted in Scheme 2.
One‑pot reductive acetylation of nitroarenes
In organic synthesis and green chemistry, omitting one or more of the synthetic
steps in preparing target compound(s) is extremely important. One-pot synthetic
approaches are an excellent choice for this purpose due to their several extraor-
dinary benefts, especially reduction in the number of tedious work-up, extrac-
tion, and purifcation steps [99–105]. On the other hand, the transformation of
toxic, waste, and cheap substances into strategic molecules is more desirable.
Not only aromatic nitro compounds are toxic [106–110], but also are low-price
than arylamines. Based on stated reasons, introducing novel, efcient, and envi-
ronmentally benign protocols for the straightforward one-pot reductive acetyla-
tion of nitroarenes in order to the preparation of the substituted N-arylacetamides
are valuable. In this research work, we successfully developed a novel, green,
efcient, and convenient strategy for the mentioned one-pot reaction by merely
combining the reaction conditions that have been obtained from the reduction
of nitroarenes (Table 3) and N-acetylation of arylamines (Table 4). As shown in
Table 5, the mentioned chemoselective one-pot reductive acetylation protocol
performed upon diverse aromatic nitro compounds in satisfactory yields of the
desired N-arylacetamide.
1 3

B. Zeynizadeh et al.
Table 4 N-Acetylation of arylamines using Ac2O catalyzed by Pd/C in water
Molar
Time
Yieldb
(%)
Entry
1
Substrate
Product
Ratioa
(min)
1:1
2
88
82
84
2
3
1:1
1:1
13
10
4
5
6
1:1
1:2
1:2
10
84
87
86
7
10
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Table 4 (continued)
Molar
Ratioa
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
7
1:1.5
15
87
8
9
1:1
1:1.5
1:1
15
85
85
85
88
5
10
11
10
1:1
5
12
1:1
8
85
1 3

B. Zeynizadeh et al.
Table 4 (continued)
Molar
Ratioa
Time
Yieldb
(%)
Entry
Substrate
Product
(min)
13
1:1.5
1:1.5
1:2
8
82
84
80
86
87
85
14
15
16
17
18
8
15
9
1:2
1:2
7
1:3
5
aSubstrate: Ac2O
bYields refer to isolated pure products
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Ar
N
H
H
H3C
O
CH3
O
O
Acetic anhydride
(Ac2O )
Pd
Pd
Pd
Pd
Ar
N
Pd
Ar
N
Pd
Pd
H
H
H
H
Arylamine
H3C
O
CH3
O
O
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Ar
N
H
H
O
Pd/C
H3C
CH3
O
O
Ar
Pd
Pd
HN
CH3
Pd
Pd
Pd
Pd
Pd
O
N-Arylacetamide
as the desired product
H
O
CH3
O
Acetic acid
as the side product
Scheme 2 Acceptable mechanism for the N-acetylation of arylamines using Ac2O catalyzed by Pd/C in
water
Experimental
Reagents, samples, and apparatus
Chemicals were purchased from the Merck, Fluka, and Sigma-Aldrich chemical
companies and directly used without any purifcation step. Melting points were
determined on an Electrothermal 9200 apparatus. Infrared spectra were recorded on
a Nexus 670 Thermo Nicolet Fourier transform infrared spectrometer and measured
1
as KBr discs. H NMR spectra were recorded on a Bruker Avance spectrometer at
300 MHz in CDCl3 with tetramethylsilane (TMS) as an internal standard.
General procedure for the reduction of nitroarenes to arylamines catalyzed
by Pd/C
For example, in a round-bottom fask (15 mL) equipped with a magnetic stirrer,
a mixture of PhNO2 (1 mmol, 0.123 g) and H2O (2 mL) was prepared. Then, (7
wt%) Pd/C (30 mg) was added, and the mixture was stirred. At the next step,
NaBH4 (2 mmol, 0.076 g) was added, and the resulting mixture continued to stir
at refux for 7 min. After completion of the reaction (monitored by thin-layer
1 3

B. Zeynizadeh et al.
Table 5 One-pot reductive acetylation of nitroarenes catalyzed by Pd/C in water
Molar
Ratioa
Pd/C
(mg)
Time
Yieldb
(%)
Entry
Substrate
Product
(min)
1
1:2:1
30
30
30
9
88
88
85
2
1:2:1
15
3
1:3.5:2
13
4
1:3.5:2
1:2:1
30
30
18
15
88
87
5c
6c
1:2:1
1:2:1
30
30
12
12
86
87
7
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
Table 5 (continued)
Molar
Ratioa
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
8c
1:2:2
30
12
80
9c
1:2:2
30
10
81
10c
11c
12
1:2:2
1:3:1
1:3:1
1:3:1
1:3:2
30
30
30
30
30
8
89
86
85
89
89
12
13
10
20
13c
14c
1 3

B. Zeynizadeh et al.
Table 5 (continued)
Molar
Ratioa
Pd/C
(mg)
Time
(min)
Yieldb
(%)
Entry
Substrate
Product
15c
1:3:2
1:3.25:2
1:3:2
30
47
30
40
30
14
79
79
80
87
85
16c
17c
18c
19
14
18
12
12
1:3:3
1:2:2
aSubstrate: NaBH4:Ac2O
bYields refer to isolated pure products
cIn these reactions, NaBH4 was added portion-wisely
chromatography (TLC) using CCl4:ether (5:2) as an eluent), the mixture was
cooled to room temperature, and the mentioned catalytic system was separated
by fltration. The reaction mixture was extracted with dichloromethane (DCM)
(3 × 5 mL) and then dried over anhydrous sodium sulfate (Na2SO4). Finally, the
solvent was evaporated under reduced pressure to aford the pure liquid aniline
in 93% yield.
1 3

Chemoselective reduction of nitroarenes, N-acetylation…
General procedure for the N‑acetylation of arylamines catalyzed by Pd/C
To the synthesis of N-phenylacetamide (acetanilide) as a representative exam-
ple, a mixture of aniline (1 mmol, 0.093 g) and H2O (2 mL) was prepared in a
round-bottom fask (15 mL), which equipped with a magnetic stirrer. Then, Pd/C
(24 mg) was added into the reaction environment, and the resulting mixture was
stirred at refux. Next, Ac2O (1 mmol, 0.102 g) was added to the prepared mixture
followed by stirring for 2 min at refux. After completion of the acetylation reac-
tion (monitored by TLC using n-hexane:EtOAc (5:1) as an eluent), the mixture
was cooled to room temperature, and the Pd/C catalyst was separated by fltration.
Then, the reaction mixture was extracted with DCM (3 × 5 mL) and then dried
over Na2SO4. Finally, evaporation of the solvent under reduced pressure aforded
the pure acetanilide in 88% yield.
General procedure for the one‑pot reductive acetylation of nitroarenes catalyzed
by Pd/C
As an example, PhNO2 (1 mmol, 0.123 g) was mixed with 2 mL of H2O in a
15 mL round-bottom fask equipped with a magnetic stirrer. Then, Pd/C (30 mg)
was added, and the mixture was stirred. Next, NaBH4 (2 mmol, 0.075 g) was
added, and the resulting mixture was stirred under refux conditions for 7 min.
After completion of the reduction reaction, acetic anhydride (1 mmol, 0.102 g)
was added to the reaction mixture, followed by stirring for an additional 2 min
at refux. Afterward, the mixture was cooled to room temperature, and the Pd/C
catalyst was separated by fltration. Then, the reaction mixture was extracted with
DCM (3 × 5 mL) and then dried over Na2SO4. Finally, evaporation of the solvent
under reduced pressure aforded the pure acetanilide in 88% yield.
Conclusion
In summary, we have tried to develop convenient, environmentally benign, and
efcient methodologies for the chemoselective reduction of nitroarenes, N-acety-
lation of arylamines, and one-pot reductive acetylation of nitroarenes in the pres-
ence of the recoverable heterogeneous carbon-supported palladium (Pd/C) cata-
lytic system in water. Due to the utilizing of the simple, capable, and recoverable
catalyst, along with using water as a green solvent, relatively short reaction times,
good-to-excellent yields of the desired products, all three introduced synthetic
strategies can apply to the chemical industry.
Acknowledgements We are thankful to the Research Council of Urmia University for the partial support
of this work.
Declarations
1 3

B. Zeynizadeh et al.
Confict of interest The authors declare no confict of interest.
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