Selective synthesis of secondary amines from nitriles using Pt nanowires as a catalyst

Article abstract of DOI:10.1039/c3cc48596j

A new one-pot method has been developed for the selective synthesis of secondary amines via reductive amination of the corresponding nitriles using Pt nanowires as a catalyst. This method allows for the synthesis of both unsymmetrical and symmetrical secondary amines in excellent yields (up to 95%) in the presence or absence of additional amines, respectively. Furthermore, the reaction proceeds under mild conditions and is environmentally benign.

Full text of DOI:10.1039/c3cc48596j

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Selective synthesis of secondary amines from
nitriles using Pt nanowires as a catalyst†
Cite this: Chem. Commun., 2014,
50, 3512
Shuanglong Lu, Jiaqing Wang, Xueqin Cao, Xinming Li and Hongwei Gu*
Received 11th November 2013,
Accepted 10th February 2014
DOI: 10.1039/c3cc48596j
www.rsc.org/chemcomm
A new one-pot method has been developed for the selective synthesis
We previously reported the development of a method for the
of secondary amines via reductive amination of the corresponding formation of C–N bonds via the coupling of aldehydes with an
nitriles using Pt nanowires as a catalyst. This method allows for the amine,7 as well as a method for the reductive amination of
synthesis of both unsymmetrical and symmetrical secondary amines in aldehydes and ketones in the presence of ammonia to give
excellent yields (up to 95%) in the presence or absence of additional secondary amines in a good yield.8 The direct use of nitriles as
amines, respectively. Furthermore, the reaction proceeds under mild alkylating agents for the preparation of secondary amines repre-
conditions and is environmentally benign.
sents a feasible alternative to the strategies commonly used for
amine alkylation, because of their bioavailability in nature and
Secondary amines are an important functional group in organic general commercial availability. Sabo-Etienne et al.9 investigated
chemistry and examples belonging to this group can be found the mechanism of the ruthenium-catalyzed hydrogenation of
in an extensive range of natural products, bioactive molecules nitriles for the preparation of primary amines, and Srimani
and industrial materials.1 Despite their numerous applications et al.10 selectively prepared a series of imines in high yields via
and presence in a wide variety of different materials, the develop- the hydrogenation of nitriles. Sajiki et al.11 reported the Pd/C
ment of methods allowing for the selective synthesis of secondary catalyzed synthesis of secondary and tertiary amines using
amines represents a long-standing problem in organic chemistry, simple aliphatic nitriles. It is worth mentioning that aromatic
and considerable research efforts have been focused2 on exploring and aliphatic primary amines could also be used as added
new synthetic methods in this particular area. Three conventional amines in this particular case. Sharma12 described the use of a
routes have been reported for the synthesis of these important continuous flow multichannel microreactor for the reductive
synthetic targets, including (1) direct base-promoted mono-N- amination of nitriles in the presence of a Pt/C catalyst.
alkylation,3 (2) reductive amination,4 and (3) alkylative amination.5
Herein, we report an entirely new Pt nanowire (Pt NW)
To date, however, there have been no reports in the literature synthesized from platinum bis(acetylacetonate)13 catalyzed reductive
describing the development of truly efficient and environmentally amination process for the preparation of both symmetric and
benign methods for the selective N-alkylation of primary amines unsymmetrical secondary amines from the corresponding nitriles.
to form secondary amines. With this in mind, considerable
At the beginning of this study, we evaluated the possibility of
opportunities therefore still exist to improve these methods, in hydrogenating nitriles as a method for accessing symmetrical
terms of avoiding the generation of wasteful salts6 and develop- secondary amines (Scheme 1). Under the optimized reaction
ing more facile processes to enhance the selectivity of these conditions (i.e., reaction temperature of 80 1C in methanol under
methods for the formation of secondary amines.
an atmosphere of H2, see the ESI†), benzonitrile was efficiently
hydrogenated to afford dibenzylamine in an isolated yield of 95.4%.
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123,
China. E-mail: hongwei@suda.edu.cn; Fax: +86-65880905; Tel: +86-65880905
† Electronic supplementary information (ESI) available: Experimental procedures
include a synthetic protocol for the construction of the Pt NWs, optimization of
the reaction conditions, catalytic activities with different Pt morphologies, and
upscaled results for this system. And also, real GC measurements for the
formation of asymmetrical secondary amine, catalytic stability of the Pt NW
and full spectroscopy data for all compounds (24 pages). See DOI: 10.1039/
c3cc48596j
Scheme 1 Symmetrical secondary amine formation from the hydrogen-
ation reaction of benzonitrile.
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Scheme 2 Asymmetrical secondary amine formation from the hydrogen-
ation reaction of benzonitrile with pentylamine.
and afforded relatively high yields of the corresponding sym-
metrical secondary amine products (Table 1, entries 5–7).
Given the highly efficient nature of this reaction for the
generation of symmetrical secondary amines via the hydrogena-
tion of nitriles,14 we proceeded to examine the catalytic capability
of our system for the preparation of unsymmetrical secondary
amines by conducting the reaction in the presence of an
additional amine (Scheme 2).
Fig. 1 Time-conversion plot for DBA formation from the hydrogenation
of benzonitrile using Pt NWs as the catalyst.
To begin with, the reaction was screened in seven different
solvents under 1 bar of hydrogen pressure. In ethanol, dioxane
and toluene, the Pt NW catalyst did not exhibit a strong
dependence on the polarity of the solvent and showed excellent
catalytic activity towards the reaction between benzonitrile and
pentylamine, with the N-benzylpentan-1-amine product being
formed in yields of up to 90%. However, when water and heptane
were used as the solvent, the desired secondary amine products
were formed in much lower yields, with significant quantities of the
imine being formed instead. Based on these results, toluene was
selected as the best solvent for further studies. The reaction
temperature also had a noticeable impact on the selectivity of the
reaction, and the reaction system was found to exhibit its highest
selectivity for the generation of unsymmetrical secondary amines at
80 1C in toluene. In addition, when the reaction was conducted in
the absence of the catalyst or hydrogen, the conversion of the
benzonitrile was relatively low, which indicated that the Pt NW and
hydrogen were critical to the success of this transformation.
With the optimal reaction conditions in hand, we proceeded
to investigate the scope of the reaction for the synthesis of
unsymmetrical secondary amines using a range of different nitriles
and amines (ESI†). In most of these cases, however, the reaction only
afforded a mixture of the secondary amine and the corresponding
imine. Pleasingly, the use of a higher reaction pressure led to an
increase in the selectivity. Thus, when 4 bars of H2 pressure were
used, the imine intermediates were readily converted to the desired
secondary amines. Further increases in the pressure, however, led to
self-coupling reactions in the aromatic nitriles and the formation of
the symmetrical secondary amines (ESI†).
Then we divided this process into two steps. Thus, the reaction
was initially conducted under an atmosphere of H2 for the first
10 h, and the whole system was then subjected to 4 bars of H2
pressure for another 10 h. Under these new conditions, all of the
different substrates were converted to the desired unsymmetrical
secondary amine products in yields of up to 90% (Table 2).
Furthermore, the substituents on the phenyl rings of the substrates
did not appear to have a significant influence on the outcome of
the reaction, and steric hindrance only exerted a minor influence
on the reaction yield. Overall, the current transformation is
both simple and effective, and satisfies the requirements of a
green chemical process. It is noteworthy that the reaction still
Furthermore, only a trace amount of the corresponding tribenzyl-
amine was detected during the reaction (Fig. 1).
We then proceeded to explore the scope of this catalytic
transformation using a range of para, meta, and ortho-substituted
aromatic nitrile substrates. The results of these scoping experi-
ments are summarized in the ESI† and Table 1. It is noteworthy
that the use of higher pressures led to increases in the yield and
shorter reaction times. Steric hindrance from the substituents
of the phenyl ring of the nitrile also had a noticeable impact on
the reaction (Table 1, entry 2). For example, the yields of
the symmetrical secondary amines decreased from 96.6% to
91.8% on going from the para-methylbenzonitrile to the ortho-
methylbenzonitrile (Table 1, entries 2 and 4). In addition, the
optimized reaction conditions were found to be highly compatible
with several other functional groups on the aromatic nitriles.
For example, electron-deficient substrates were well tolerated,
Table 1 Formation of symmetrical secondary amines from different nitrilesa
Entry Substrate
Product
Yieldb (%) Yieldc (%)
1
2
3
4
95.4
78.2
88.9
93
499
91.8
95.6
96.6
5
6
70.8
87.6
84.1
76
89.9
91.3
7
a
Reaction conditions: 80 1C, ethanol (2.0 mL), 1 bar of H2 pressure for
b
c
24 h. GC yield. 4 bars of H2.
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Table 2 The formation of unsymmetrical secondary amines from different
nitrilesa
Entry
Substrate
Product
Yieldb (%)
93.3
1
2
96.3
3
95.2
Scheme 3 Proposed mechanism for the synthesis of symmetrical and
unsymmetrical secondary amines.
4
5
6
7
8
77.4
91.8
88.6
90.9
A (either through the unsymmetrical imine or direct interaction
with the Pt NW catalyst) would lead to the formation of the
unsymmetrical secondary amine product. This mechanism also
accounts for the trace amount of dibenzyl amine observed
during the reaction, which would be formed from the side
reaction between benzyl amine and the benzyl imine.
In conclusion, we have successfully developed a one-pot
method for the synthesis of both symmetrical and unsymme-
trical secondary amines from nitriles using a Pt NW catalyst
with excellent yields of up to 96.6%. This method is attractive
because it does not involve alkyl halides or carbonyl compounds
and consequently avoids the harsh reaction conditions, poor yields
and low levels of chemical selectivity associated with these conven-
tional N-alkylation procedures. Further studies of this catalytic
system are currently underway in our laboratory to investigate its
wider applications.
89.2
91.8
9c
a
Reaction conditions: 80 1C, toluene (2.0 mL), nitrile:amine ratio of
1 : 2, 10 h in 1 bar of H2 pressure, and then 10 h in 4 bars of H2 pressure.
b
c
GC yield. 100 1C.
H.W.G. acknowledges financial support from the National
Natural Science Foundation of China (No. 21003092, 21373006),
the Key Project of the Chinese Ministry of Education (No. 211064),
and a project funded by the Priority Academic Program Develop-
ment of Jiangsu Higher Education Institutions.
afforded a satisfactory yield of the desired secondary amine product
when the substrate was changed to 2-phenylacetonitrile and the
temperature was increased to 100 1C. This result therefore demon-
strated that the system was valid for aliphatic nitriles.
Real time GC measurements were carried out during the
course of the model reaction between benzonitrile and pentyl-
amine in the presence of the Pt NW catalyst to develop a deeper
understanding of the mechanism of this catalytic process. The
results of these measurements suggested that the intermediate
N-benzylidenepentan-1-amine was formed quickly with the
consumption of benzonitrile. The amount of this intermediate
increased steadily up to its highest point around 7 h, and then
decreased sharply. During this decrease, there was a steady increase
in the amount of N-benzylpentan-1-amine. The reaction required a
total of 12 h to reach completion, and a small amount of dibenzyl
amine could also be detected.
Based on the kinetics, which is mentioned above, we have
proposed a plausible mechanism for the reaction shown in
Scheme 3. Thus, the partial hydrogenation of benzonitrile
would give the corresponding benzyl imine, which would react
with the added pentylamine to give intermediate A instead
of being further hydrogenated to form the corresponding
benzyl amine. The subsequent elimination of ammonia from
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