A practical and benign synthesis of amines through Pd@mpg-C 3N4 catalyzed reduction of nitriles

Article abstract of DOI:10.1016/j.catcom.2012.08.005

Liquid phase hydrogenation of nitriles is an important method for the production of amines, which find a variety of applications as intermediates in chemical and pharmaceutical industry. In the present work, a highly efficient Pd@mpg-C₃N₄ catalytic system has been developed for chemoselective reduction of nitriles providing good to excellent conversion with remarkable chemoselectivity (up to 99%) without additives. Compared with homogeneous catalyst systems, the developed protocol is more advantageous due to the use of ambient hydrogen, solvent free and effective catalyst recyclability.

Full text of DOI:10.1016/j.catcom.2012.08.005

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Catalysis Communications 28 (2012) 9–12
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
A practical and benign synthesis of amines through Pd@mpg-C3N4 catalyzed
reduction of nitriles
⁎
Yi Li, Yutong Gong, Xuan Xu, Pengfei Zhang, Haoran Li, Yong Wang
Key Lab of Applied Chemistry of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou 310028, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2012
Received in revised form 2 August 2012
Accepted 8 August 2012
Available online 21 August 2012
Liquid phase hydrogenation of nitriles is an important method for the production of amines, which find a
variety of applications as intermediates in chemical and pharmaceutical industry. In the present work, a
highly efficient Pd@mpg-C3N4 catalytic system has been developed for chemoselective reduction of nitriles
providing good to excellent conversion with remarkable chemoselectivity (up to 99%) without additives.
Compared with homogeneous catalyst systems, the developed protocol is more advantageous due to the use
of ambient hydrogen, solvent free and effective catalyst recyclability.
Keywords:
Nitriles
© 2012 Elsevier B.V. All rights reserved.
Amines
Pd@mpg-C3N4
Heterogeneous catalysis
1. Introduction
Although these catalytic systems are effective, the critical process for
the synthesis of the catalyst and the use of large amount of base such
Amines are very important industrial organic compounds in a wide-
spread range of applications, including intermediates for pharma-
ceuticals, raw materials for resins and plastics, reagents for organic
synthesis, and textile additives [1,2]. During the recent decades, several
novel catalytic methods have been established for the synthesis of
amines, such as the reductive amination of carbonyl compounds [3–5],
hydroaminomethylation or hydroamination of olefins and alkynes [6,7],
and palladium catalyzed amination of aryl halides [8,9]. Among the
different methods used, hydrogenation of nitriles is one of the most
common methods to prepare amines due to the high atom efficiency
[2,10–14].
as tBuOK, NaOH and KOH strongly limit the usefulness of these
catalysts. Separation of the products from solvents and the catalysts is
usually diffcult, which is also a typical problem associated with ho-
mogeneous catalysts.
Due to the high reactivity of the reaction intermediates (generally
imine), the liquid hydrogenation of nitriles occur as a set of consecutive
and parallel reactions (Scheme 1), resulting in a mixture of primary,
secondary and tertiary amines [10]. Separation of the reaction products
is usually difficult, due to small differences in boiling point. For this
reason, one of the most important issues in the hydrogenation of nitriles
is the control of the selectivity.
In organic synthesis, nitriles are commonly reduced with stoi-
chiometric amounts of metal hydrides, which is expensive and not
environmentally benign [15]. Raney Ni, Raney Co, Pd@C, Pt@C, Ru@C,
and Rh@C are suitable catalysts and rank among the most commonly
used for this process [16–19]. The same metals but supported on SiO2
or Al2O3 are often employed as well [20,21]. Notably, all these
catalysts reveal the formation of side products, which lower the
selectivity. In additon, excess of base is usually needed for high
chemoselectivity [22]. Recently, homogeneous reduction of nitriles in
the presence of ruthenium complexes has been reported [11–13,23].
Although there are many factors that affect the selectivity to some
degree, the nature of the catalyst is the most important parameter to
control the selectivity, therefore, developing of new catalyst for the
efficient and selective hydrogenation of nitriles continues to be a
challenging goal.
Our group and others have recently shown that an abundant and
easily accessible polymeric semiconductor, polymeric mesoporous
graphitic carbon nitride (mpg-C3N4), exhibits extreme chemical and
thermal stability, can be chemically shaped to a variety of nanostruc-
tures, and can be directly used in heterogeneous catalysis or as
catalyst support [24–33]. As part of our ongoing effort to develop new
strategies for chemoselective hydrogenation, we report the results of
our preliminary investigation of chemoselective hydrogenation of
nitriles with H2 under mild reaction conditions.
⁎
Corresponding author. Fax: +86 571 87951895.
E-mail address: chemwy@zju.edu.cn (Y. Wang).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2012.08.005

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Y. Li et al. / Catalysis Communications 28 (2012) 9–12
[Pd]
H2
[Pd]
H2
was finally dried in a vacuum oven at 80 °C for 6 h. The catalyst was
then reused under the same reaction conditions.
R
C
A
N
R
R
NH2
NH
B
C
3. Results and discussion
C, -NH3
In the present work, hydrogenation of butyronitrile (BTN) was
choosed as a model reaction. Various reaction parameters such as
effect of time, temperature, hydrogen pressure were studied in detail.
In general, the hydrogenation of BTN yields primary amine, mono-n-
butylamine (MBA), secondary amine, di-n-butylamine (DBA), and
tertiary amine, tri-n-butylamine (TBA), respectively. According to von
Braun's mechanism for the hydrogenation of nitriles, as shown in
Scheme 1, primary amine (C) is formed via hydrogenation of BTN,
passing through the intermediate butylidenimine. The formation of
secondary amines (E) is caused by the reaction of the primary amine
with the imine intermediate. Subsequent elimination of ammonia
yields but-1-enyl-dibutylamine as the condensation products to be
finally hydrogenated to the tertiary amines (F). The conversion of BTN
(at 100 °C, ambient hydrogen pressure) and selectivities toward TBA
and MBA as a function of time is presented in Fig. 1. As shown in
Fig. 1, the hydrogenation of BTN over the Pd@mpg-C3N4 catalyst
yielded TBA as the majority product, as well as minor amounts of
MBA at the initial state. In solvent free conditionds, the reaction gave
100% conversion of BTN and 99% selectivity of TBA after 9 h. Nitriles
must adsorb weakly on an electron-enriched carbon nitride surface,
inhibiting the catalytic activity of the catalyst. Therefore the reaction
can only be conducted well under solvent free conditions, if solvents
such as water, ethanol or acetone were used, no products have been
detected. Once the BTA was reduced to MBA or DBA, depending on
the nature of the catalyst's active site, MBA or DBA must adsorb
strongly on the carbon nitride surface via the formation of N–H…N
strong hydrogen bonds, which favoring the catalytic activity of the
Pd@mpg-C3N4 catalyst, hence the as produced MBA and DBA were
converted to TBA on the surface of the catalyst immediately, which
leads to the high selectivity toward TBA.
In order to examine the effect of temperature on reaction outcome,
reactions were carried out at different temperatures ranging from 25 to
120 °C (Fig. 2). With increasing temperature the conversion of BTN
increased while the selectivity toward TBA kept at high level (up to
99%). It was observed that at 25 °C the conversion of BTN was 11%
whereas with the increase in temperature up to 120 °C, 99% conversion
of the desired product was obtained within 5 h (Fig. 2). In general, the
hydrogenation of BTN does not occur significantly at normal temper-
ature over the traditional catalyst [12]. However, the hydrogenation of
BTN proceeded well using Pd@mpg-C3N4 catalyst even at normal
temperature and ambient hydrogen pressure (hydrogen balloon). As
shown in Fig. 2, a conversion of 49% and selectivity above 99% was
yielded in 5 h at a mild reaction temperature of 40 °C.
H2 pressure influenced BTN conversion as shown in Fig. 3. The
conversion of BTN increased from 70 to 99% by increasing the pressure
from 0.1 MPa to 3 MPa at 70 °C for 2 h. Notably, no side product was
observed even under high temperature and high hydrogen pressure.
To test the reusability of the catalyst system, the used Pd@mpg-C3N4
was washed with acetone and ethanol, dried at 80 °C, and then re-
employed with a new reactant mixture. As shown in Fig. 4, the catalyst
exhibited remarkable activity for the first two consecutive recycles
while slight decrease in conversion was observed during third and
fourth recycle. It is important to highlight that no changes regarding the
selectivity to TBA were observed respect to the fresh catalyst. The
decrease in yield for third and forth cycle may be caused by the minor
leaching of the Pd nano-particles as revealed in our previous work [27].
Furthermore, the applicability of Pd@mpg-C3N4 catalyst on
different nitriles was also investigated. The acetonitrile furnished
99% conversion with 99% selectivity toward triethylamine (Table 1,
entry 1) at 70 °C in 6 h, whereas aromatic benzontrile provided 89%
conversion with 99% selectivity (Table 1, entry 3). The hydroxyl-
[Pd]
H2
R
N
H
R
R
N
R
D
E
B, -NH3
R
N
F
R
R
Scheme 1. Formation of primary, secondary, and tertiary amines in the catalytic
hydrogenation of nitriles.
2. Experimental
2.1. Catalyst preparation
All reagents were obtained from Sigma-Aldrich, Acros, or Merck
and were used as received. The catalyst Pd@mpg-C3N4 was synthe-
sized according to our previous published literature procedure [27].
Typically, to synthesize the catalyst, PdCl2 and mpg-C3N4 were dissolved
in distilled water and the mixture was heated to 80 °C and stirred for
12 h. 1 M NaOH was added to adjust the pH of the solution to about 10.
Then NaBH4 solution was added to this suspension. Finally, Pd@mpg-
C3N4 was separated by filtration, washed with distilled water for five
times and then dried at 80 °C overnight in a vacuum oven. Pd@C was
obtained from ThalesNano. Pd@TiO2, Pd@CeO2, and Pd@γ-Al2O3 were
synthesized according to the literatures [34].
2.2. Hydrogenation of nitriles
The reaction was conducted in a Schlenk flask (20 ml) with a
graham condenser. A typical procedure was as follows: nitriles
(10 mmol), catalyst Pd@mpg-C3N4 (0.02 mmol of Pd, 0.2% mol relative
to nitriles) were placed in a flask. The flask was purged with H2 to
remove the air for 3 times, the reaction was then stirred at 800 rpm
under H2 atmosphere (connected to a hydrogen balloon). For the
reaction conducted in compressed hydrogen pressure, the hydrogena-
tion was carried out in a Teflon-lined stainless stell batch reactor (50 ml
total volume) with a magnetic stirrer. In a typical experiment, nitriles
and catalyst were loaded into the reactor. The reactor was sealed and
purged with H2 to remove the air for 3 times, then increased to the
desired hydrogen pressure. The stirring was started after the desired
temperature was reached. After the reaction the reactor was placed in
ice water to quench the reaction and the products were analyzed on
GC–MS (Agilent Technologies, GC6890N, MS5970) using nitrobenzene
as internal standard. The GC–MS conditions for the product analysis
were: Injector Port Temperature: 250 °C; Column Temperature: Initial
temperature: 50 °C (1 min); Gradient Rate: 20 °C/min (10 min); Final
Temperature: 250 °C (3 min); Flow Rate: 80 ml/min.
The reusability of Pd@mpg-C3N4 was tested for butyronitrile
hydrogenation. The reaction was conducted at 100 °C for 10 h. After
reaction, the reaction mixture was centrifuged and the liquid layer
was siphoned out. The residual solid was washed with anhydrous
ethanol and acetone and then centrifuged twice. The recycled catalyst

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Y. Li et al. / Catalysis Communications 28 (2012) 9–12
11
Pr
N
Pr
Pd@mpg/C3 N4
H2
Pr
NH2
Pr CN
BTN
Pr
MBA <1%
TBA >99%
Fig. 1. Effect of reaction time on the reduction of butyronitrile. Reactions were carried out at 100 °C with 10 mmol butyronitrile and Pd@mpg-C3N4 (0.2%mol Pd relative to
butyonitrile) under hydrogen (hydrogen balloon).
substituted 3-hydroxypropionitrile gave a moderate conversion (40%)
and selectivity (73%). However, no product was detected in the case of
the chloro-substituted 4-chlorobutyronitrile. Moreover, the catalyt
Pd@mpg-C3N4 was compared with the commercially available Pd@C,
and the home made Pd@TiO2, Pd@CeO2, and Pd@γ-Al2O3, for the
hydrogenation of benzontrile at 0.1 MPa of hydrogen and 80 °C for
12 h, and the results obtained are shown in Table 1. Results from
Table 1 clearly show that the Pd@mpg-C3N4 catalyst synthesized here
gives better activity and selectivity than the commercially prepared Pd
on carbon and other Pd@ support catalysts.
4. Conclusions
In conclusion, the present study reports a development of highly
efficient protocol for chemoselective reduction of nitriles in mild
reaction conditions using Pd@mpg-C3N4 as a heterogeneous recyclable
catalyst. The catalyst system was optimized with respect to various
parameters and affording good to excellent conversion with apprecia-
ble selectivity (up to 99%) of the desired products. The catalyst can be
Fig. 3. Effect of pressure on the reduction of butyronitrile. Reactions were carried out at
70 °C for 2 h with 10 mmol butyronitrile and Pd@mpg-C3N4 (0.2% mol Pd relative to
butyonitrile) under specified hydrogen pressure.
easily recycled by simple filtration process up to four consecutive
recycles. The developed protocol with solvent free reaction condition,
ambient hydrogen pressure and recyclable catalytic system introduces
a success towards green approach in organic synthesis. However, it
should be noted that the solvent free method may only be suitable for
the substrates with a low melt point and in most cases the reduction of
nitriles to primary amines is preferred. Work to improve the selectivity
toward primary amines is still ongoing, and we believe that adding
Fig. 2. Effect of temperature on the reduction of butyronitrile. Reactions were carried
out at the specified temperature for 5 h with 10 mmol butyronitrile and Pd@mpg-C3N4
(0.2% mol Pd relative to butyonitrile) under hydrogen (hydrogen balloon).
Fig. 4. Reusing of the Pd@mpg-C3N4 in hydrogenation of butyronitrile. Reactions were
carried out at 100 °C for 9 h with 10 mmol butyronitrile and Pd@mpg-C3N4 (0.2% mol
Pd relative to butyonitrile) under ambient hydrogen pressure.

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Y. Li et al. / Catalysis Communications 28 (2012) 9–12
Table 1
Scope and limitations of Pd@mpg-C3N4 and comparative catalytic performance of different palladium catalysts.a
Entry
Substrate
T (°C)
Conv.
(%)
Product
Sel. (%)
1
2
70
70
99
>99
>99
99
3
100
80
70
40
>99
73
4b
5c
6
80
80
–
–
–
89
>99
7d
80
80
80
80
80
35
25
32
16
15
>99
85
8e
9f
94
10g
11h
88
93
a
10 mmol substrate, Pd@mpg-C3N4 (0.2% mol Pd relative to substrate), 1.0 MPa H2, reaction time 6 h.
10 mmol 3-hydroxypropionitrile, Pd@mpg-C3N4 (0.2% mol Pd relative to substrate), 0.1 MPa H2, reaction time 12 h.
10 mmol 4-chlorobutyronitrile, other reaction conditions as in entry 4.
10 mmol benzonitrile, other reaction conditions as in entry 4.
commercial Pd/C as catalyt, other reaction conditions as in entry 4.
Pd/TiO2 as catalyt, other reaction conditions as in entry 4.
b
c
d
e
f
g
h
Pd/CeO2 as catalyt, other reaction conditions as in entry 4.
Pd/γ-Al2O3 as catalyt, other reaction conditions as in entry 4.
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Appendix A. Supplementary data
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.catcom.2012.08.005.
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