One-pot synthesis of cyclohexylamine and: N -aryl pyrroles via hydrogenation of nitroarenes over the Pd0.5Ru0.5-PVP catalyst

Article abstract of DOI:10.1039/d1nj00922b

The direct synthesis of cyclohexylamine via the hydrogenation of nitrobenzene over monometallic (Pd, Ru or Rh) and bimetallic (PdxRu1-x) catalysts was studied. The Pd0.5Ru0.5-PVP catalyst was the most effective catalyst for this reaction. The catalyst can be reused and applied for the synthesis of N-aryl pyrroles and quinoxalines from nitrobenzenes.

Full text of DOI:10.1039/d1nj00922b

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One-pot synthesis of cyclohexylamine and N-aryl
pyrroles via hydrogenation of nitroarenes over the
Pd0.5Ru0.5-PVP catalyst†
Cite this: New J. Chem., 2021,
45, 9743
Received 24th February 2021,
Accepted 26th April 2021
ab
Chandan Chaudhari,*a Katsutoshi Sato,
Yasuyuki Ikeda,c Kenji Terada,c
a
Naoya Abec and Katsutoshi Nagaoka
*
DOI: 10.1039/d1nj00922b
rsc.li/njc
The direct synthesis of cyclohexylamine via the hydrogenation of later, carbon-supported Ni- and Pd-based catalysts were
nitrobenzene over monometallic (Pd, Ru or Rh) and bimetallic reported to be effective for similar transformation under low
(PdxRu1ꢀx) catalysts was studied. The Pd0.5Ru0.5-PVP catalyst was pressure (3.5 MPa)21 and/or with an additive (LiOH).21,22 The
the most effective catalyst for this reaction. The catalyst can be basic additive (LiOH) was used to neutralize the surface acidic
reused and applied for the synthesis of N-aryl pyrroles and quinox- sites on the carbon support and, consequently, the selectivity
alines from nitrobenzenes.
for cyclohexylamine was enhanced. Additive-free conditions
were also investigated by using supported Ru catalysts.23,24
The development of effective and environmentally-friendly syn- However, these catalytic methods require the use of high
thetic methods is a great challenge. In this context, synthetic temperature (4150 1C) and high pressure (43 MPa).
methods that accomplish multi-step reactions in a single reaction
Recently, we have synthesized a Pd0.5Ru0.5-PVP solid solution
vessel are highly desirable to reduce energy consumption and alloy and applied it as a cheap alternative and pseudo-Rh catalyst
chemical waste. Cyclohexylamine is an important intermediate for for CO oxidation and automobile exhaust purification.25,26 Further-
the synthesis of artificial sweeteners, metal corrosion inhibitors, more, Pd0.5Ru0.5-PVP showed excellent activity for the chemoselec-
rubber vulcanizing additives, dyestuffs and plasticizers.1–3 Several tive hydrogenation of heteroarenes and arenes.27 In continuation of
catalytic methods have been reported for the synthesis of cyclo- the exploration of new applications of Pd0.5Ru0.5 catalyst, we report
hexylamine such as hydrogenation of aniline4–9 or flammable and herein the one-pot synthesis of cyclohexylamine and N-aryl pyrroles
hazardous nitrocyclohexane,10 amination of cyclohexanone or via the hydrogenation of nitrobenzene under mild reaction condi-
cyclohexanol,11 and amination of chlorocyclohexane.12 Among tions (Table S2, ESI†).
these, hydrogenation of aniline is a simple and atom-efficient
Initially, we studied the effect of pressure on the hydrogena-
route for the synthesis of cyclohexylamine. However, aniline is tion of nitrobenzene using Pd0.5Ru0.5-PVP. As shown in Table 1,
produced by the hydrogenation of nitrobenzene.13–19 Therefore, it clearly indicated that hydrogen pressure affected the selec-
the direct synthesis of cyclohexylamine via the hydrogenation of tivity of the products, while no change in conversion of nitro-
nitrobenzene is more practical.
benzene was observed (entries 1–5). Under low H2 pressure
In 1972, direct synthesis of cyclohexylamine from nitroben- (0.5–1 MPa), aniline was the major product but it was not
zene cyclohexylamine was reported by using a supported Rh sufficient for the hydrogenation of benzene ring. When the
catalyst.20 This was the first example of the direct synthesis of hydrogen pressure was increased to 2 MPa, a high yield (95%)
cyclohexyl amine under high H2 pressure (6.8 MPa). Decades of cyclohexylamine was obtained. Increasing the pressure
further (42 MPa) decreased the yield of cyclohexylamine. Next,
we explored if the composition of the Pd1Ru1ꢀx-PVP catalyst
influenced the catalytic activity (entries 6 and 7). Pd0.7Ru0.3
catalyst was less active for the ring hydrogenation step, and
41% yield of aniline was obtained, along with 43% yield of
cyclohexylamine. By contrast, Pd0.3Ru0.7 catalyst gave higher
yield (83%) of cyclohexylamine but the yield was lower than that
of Pd0.5Ru0.5-PVP. The Pd–Ru site might be responsible for the
high selectivity. Finally, monometallic Pd and Ru catalysts
delivered aniline as the major product (entries 8 and 9), and
a Department of Chemical Systems Engineering, Graduate School of Engineering,
Nagoya university, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
E-mail: nagaoka.katsutoshi@material.nagoya-u.ac.jp,
chaudhari.chandan.subhash@d.mbox.nagoya-u.ac.jp
b Elements Strategy Initiative for Catalysts and Batteries (ESCIB), Kyoto University,
Katsura, Kyoto 615-8520, Japan
c Furuya Metal Co., Ltd, Higashitsukuba Niihari Kogyodanchi, 57-4, Sawabe,
Tsuchiura, Ibaraki 300-4104, Japan
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1nj00922b
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Table 1 One-pot synthesis of cyclohexylamine using metal catalystsa
Entry
Catalyst
Particle size (nm)
H2 (MPa)
Conv. (%)
Yield2b (%)
Yield3b (%)
Yield4b (%)
1
2
3
4
5
6
7
8
9
10
Pd0.5Ru0.5-PVP
Pd0.5Ru0.5-PVP
Pd0.5Ru0.5-PVP
Pd0.5Ru0.5-PVP
Pd0.5Ru0.5-PVP
Pd0.3Ru0.7-PVP
Pd0.7Ru0.3-PVP
Ru-PVP
5.6 ꢁ 1.6
5.6 ꢁ 1.6
5.6 ꢁ 1.6
5.6 ꢁ 1.6
5.6 ꢁ 1.6
2.4 ꢁ 0.8
4.2 ꢁ 2.8
8.4 ꢁ 2.4
4.8 ꢁ 0.8
5.4 ꢁ 1.0c
0.5
1
2
3
4
2
2
2
2
99
99
99
99
99
99
99
99
99
95
3
92
37
2
0
0
0
6
1
1
1
2
10
2
1
44
95
90
87
83
43
30
10
64
0
41
60
88
4
Pd-PVP
Rh-PVP
2
5
a
b
c
Reaction conditions: nitrobenzene (1 mmol), catalyst (1.4 mol%), cyclohexane (1 mL), 2 MPa H2, 100 1C, and 6 h. GC yield. Ref. 37
Table 2 Hydrogenation of substituted nitrobenzene using Pd0.5Ru0.5
-
monometallic Rh catalyst produced 64% yield of cyclohexyla-
mine (entry 10).
PVPa
It is well-known that solvent always plays a crucial role in
Entry Nitroarenes
Time (h) Conv. (%) GC Yield (%)
hydrogenation reactions by enhancing the activity and control-
ling byproduct formation. Therefore, we tested four alternative
solvents for the nitrobenzene hydrogenation reaction: THF, 1,
4-dioxane, toluene, and water (Fig. 1). In all these solvents, full
conversion of nitrobenzene was achieved, but the yield of
cyclohexylamine was highest in cyclohexane. The reaction in
water delivered substantial amounts of N-dicyclohexylamine
and cyclohexanol as byproducts.
To study the versatility of the Pd0.5Ru0.5-PVP catalyst, we
carried out the hydrogenation reaction of substituted nitro
benzene (Table 2). Hydrogenation of nitrobenzene bearing
an electron donating group (–CH3) showed high yield of
4-methylcyclohexylamine (entry 2). Nitrobenzene with an elec-
tron withdrawing group (–Cl) proceeded to dechlorination reac-
tion, and 92% cyclohexylamine was obtained (entry 3).
The chemo-selectivity of Pd0.5Ru0.5-PVP was investigated using
4-nitroacetophenone substrate. The acetyl group was completely
hydrogenated to hydroxyl and 1-(4-aminocyclohexyl)-ethanol
1
2
6
99
99
99
92
12
12
89
3
92b
4
24
99
60c
5d
48
48
99
99
76e
95
6f
a
Reaction conditions: nitroarene (1 mmol), Pd0.5Ru0.5-PVP (1.4 mol%
b
c
metal), cyclohexane (1 mL), and 100 1C. Cyclohexylamine. 4-Ethyl-
cyclohe-xylamine. 5 MPa H2. MDA was obtained. 3 MPa.
d
e
f
was obtained (60%). Furthermore, the hydrodeoxygenation of 1-(4-aminocyclohexyl)-ethanol gave 40% yield of 4-ethylcyclo-
hexylamine. Next, we applied our protocol for the synthesis of
industrially important chemical 4,40-diaminodicyclohexylmethane
(H12MDA) which is an important intermediate for the synthesis of
polyurethanes via the 4,40-diisocyanatodicyclohexylmethane routes.28
H12MDA is generally produced using the following two step proce-
dure, (i) synthesis of 4,40-diaminodiphenylmethane (MDA) from
aniline and formaldehyde29–31 and (ii) hydrogenation of MDA to
H12MDA.7,32,33 The use of Pd0.5Ru0.5-PVP catalyst resulted in a
moderate yield (76%) of H12MDA by the hydrogenation of MDA.
This result demonstrates the first successful attempt of the direct
synthesis of H12MDA from 4,40-dinitrodiphenylmethane (entry 5).
Furthermore, we hydrogenated 3-nitropyridine to 3-aminopiperidine
which is an essential ingredient for the synthesis of alogliptin, a
dipeptidyl peptidase-4 inhibitor (entry 6).34
The recyclability of the Pd0.5Ru0.5-PVP catalyst was examined
for the hydrogenation of nitrobenzene to cyclohexylamine
Fig. 1 The effect of solvent on the hydrogenation of nitrobenzene to
cyclohexylamine.
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under optimized reaction conditions. After the completion of nitrobenzene did not affect the heterocyclization of pyrrole
the reaction, the catalyst was washed with acetone multiple and excellent yields were obtained when nitrobenzene bearing
times, separated by centrifugation, and dried at 80 1C under an electron-donating group and an electron-withdrawing group
vacuum for 12 h.
Pd0.5Ru0.5-PVP catalyst was reused three times without any functional groups (–COCH3), Pd0.5Ru0.5-PVP catalyst showed
loss in its catalytic activity (Fig. S1, ESI†). chemo-selectivity for the hydrogenation of nitro group and
was used (entries 1–5). In the presence of other reducible
In recent years, one-pot synthesis of heterocycles such as formed the corresponding pyrrole (entry 6). 3-Nitropyridine
pyrroles from nitroarenes has attracted the attention of was converted to the corresponding pyrroles but heterocycliza-
researchers due to the high atom-economy of this strategy. tion step was partially retarded in this reaction (entry 7).
Pyrroles are important motifs in various natural products and Considering the activity for pyrrole synthesis, the scope of
synthetic medicinal agents. Pyrrole derivatives show a wide Pd0.5Ru0.5-PVP was expanded for the synthesis of N-containing
range of biological activities such as antibacterial, antiviral, heterocycle such as quinoxalines from 1,2-dinitrobenzene or
anti-inflammatory, antitumor, and anti-oxidant activities.35–38 2-nitroaniline and benzil. When 2-nitroaniline was used, a high
Heterogeneous (Pd, Pt, Rh, and Co) catalyst based and indium- yield of quinoxalines was obtained in 48 h (eqn (1)) and dinitro-
mediated methods have been developed for the synthesis of benzene gave a moderate yield (eqn (2)).
pyrrole from nitrobenzene and 2,5-hexanedione.39–45 However,
these methods require additives43–45 and toxic gas (CO)40,42,43
(1)
and have limited scope.39
Encouraged by the results of the hydrogenation of nitro-
benzene, we carried out one-pot synthesis of pyrroles from
substituted nitrobenzene and 2,5-hexanedione under low H2
(2)
pressure (0.5 MPa). As shown in Table 3, the substituted
Table 3 One-pot synthesis of N-aryl pyrroles from nitroarenes and 2,
5-hexanedione using Pd0.5Ru0.5-PVPa
Conclusions
We have developed an effective method using Pd0.5Ru0.5-PVP
for the direct synthesis of cyclohexylamine via the hydrogenation
of nitrobenzene under mild reaction conditions. By using this
catalyst, one-pot synthesis of N-aryl pyrroles and quinoxalines
was achieved from nitrobenzene. The catalyst can be reused and
is tolerant to different functional groups of nitrobenzene.
Entry Nitroarenes
1
Product
Conv. (%) GC Yield (%)
99
99
99
99
99
97
99
99
82
91
Author contributions
2
3
4
5
Chandan Chaudhari: designing of research, data collection-
analysis and writing-editing. Katsutoshi Sato: data curation and
validation. Katsutoshi Nagaoka: designing of research, data
collection-analysis and writing-editing. Yasuyuki Ikeda, Kenji
Terada and Naoya Abe: catalyst preparation.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This research was supported by the ACCEL program, Japan
Science and Technology Agency (JST, JPMJAC1501).
6
82
99
70
Notes and references
7
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Pd0.5Ru0.5-PVP (1.4 mol% metal), methanol (1 mL), 0.5 MPa H2, 100 1C,
and 24 h. 3-Aminopyridine was obtained as by product.
b
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