Palladium on activated carbon catalyzed reductive amination of aldehydes and ketones by triethylsilane

Article abstract of DOI:10.1002/aoc.3090

Various aldehydes and ketones were efficiently transformed into the corresponding amines using amine derivatives in the presence of triethylsilane and a catalytic amount of palladium on activated carbon in ethanol. The proposed method provides a one-pot synthesis of various amines in excellent yields after short reaction times.

Full text of DOI:10.1002/aoc.3090

Full Paper
Received: 28 September 2013
Accepted: 11 October 2013
Published online in Wiley Online Library: 6 December 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.3090
Palladium on activated carbon catalyzed
reductive amination of aldehydes
and ketones by triethylsilane
Maryam Mirza-Aghayana*, Mahdieh Molaee Tavanaa,
Mahshid Rahimifarda and Rabah Boukherroubb
Various aldehydes and ketones were efficiently transformed into the corresponding amines using amine derivatives in the
presence of triethylsilane and a catalytic amount of palladium on activated carbon in ethanol. The proposed method provides
a one-pot synthesis of various amines in excellent yields after short reaction times. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: Pd/C; triethylsilane; aldehyde; ketone; reductive amination
Organosilicon reagents in the presence of a catalyst have been
Introduction
widely applied to the reduction of functional groups.[8] Recently,
Amines are important intermediates in the fine chemicals, drugs,
pesticides, dyes and pigment industries.[1] Therefore, the develop-
ment of general and efficient methods for the preparation of amine
compounds is required. Several methods are available in the litera-
ture for the synthesis of amines.[2] Reduction of nitroaromatic
compounds[3] and reductive amination of carbonyl compounds or
reductive alkylation of amines are important tools in the synthesis
of different kinds of amines.[4] Reductive amination of carbonyl
groups is performed in the presence of metals, metals on activated
charcoal and metal complexes.[5] For example, Allegretti et al.
reported on the reduction of ketones to primary amines by reaction
with ammonium formate in aqueous methanol using Pd/C
catalyst.[5a] Potassium formate in the presence of catalytic palla-
dium acetate has also been used for reductive amination.[5b,c]
Chiral palladium catalysts have been successfully applied to the
one-pot asymmetric reductive amination of ketones.[5d] Other
metal catalysts such as gold(I), Pt and Pd on different acid and base
supports were used for reductive amination reaction of carbonyl
compounds.[6a] For example, Srivani et al. reported on the direct
reductive amination of carbonyl compounds using palladium-
exchanged molybdophosphoric acid (20%) supported on silica as
direct reductive amination of aldehydes with a catalytic system
[9c]
such as PhSiH3/ReIO2(PPh3)2,[9a] silanes/Ga(OTf)3,[9b] Et3SiH/InCl3
and sodium tetrakis[3,5-di(trifluoromethyl)phenyl]borate/hydrio-
iridium(III) complex[9d] were reported. We have investigated the ef-
ficiency of Et3SiH/PdCl2 system for several chemical transforma-
tions such as the hydrogenation of 1-alkenes,[10] selective
hydrogenation of α,β-unsaturated ketones,[11] reduction of aro-
matic ketones and aldehydes,[12] benzyl alcohol derivatives,[13]
acetal, ketal and ether compounds[14] and nitroaromatic com-
pounds.[15] We have also demonstrated the high performance of
triethylsilane and other palladium-based catalysts for the synthesis
of various amine derivatives by the reduction of aromatic,
heteroaromatic and aliphatic imine compounds using a Et3SiH/Pd
(OAc)2 system in ethanol[16] and for the reduction of 1-alkenes to
the corresponding alkanes and olefin isomerization.[10b]
This paper is an extension of our previous work on the use of
Et3SiH/palladium catalyst for other chemical transformations. In
this work, the reductive amination of aldehydes and ketones with
amine derivatives was investigated using a catalytic amount of
Pd/C in a one-pot reaction in the presence of triethylsilane at
room temperature (Scheme 1).
a
catalyst.[6b]
A polymer-supported palladium–N-heterocyclic
carbene (PS-Pd–NHC) catalytic system has been developed for
the direct reductive amination of carbonyl compounds in aqueous
reaction medium.[6c] Iridium complexes were also applied to
the preparation of amine compounds.[7] For example,
triazole-derived iridium(I) carbene complexes showed good
activity for transfer hydrogenation of imines with K2CO3 for the
preparation of amine compounds from aldehydes.[7a] Wang
et al. demonstrated the high performance of cyclometalated
iridium complexes for the reductive amination of carbonyl
groups in the presence of formic acid[7b] or formate[7c] as the
hydrogen source. Other Ir-based catalysts such as Ir–f-binaphane
complex exhibited high activities and enantioselectivities (up to
96% ee) for asymmetric reductive amination of aryl ketones in
the presence of Ti(OiPr)4 and I2.[7d]
Results and Discussion
In a typical reaction, 10 mg of Pd/C is added at room temperature to
a stirred mixture of benzaldehyde (1.1 mmol), aniline (1 mmol) and
triethylsilane (1.5 mmol) in dry ethanol (5 ml) under argon atmo-
sphere. The resulting mixture is further kept under stirring for the
*
Correspondence to: Maryam Mirza-Aghayan, Chemistry and Chemical
Engineering Research Center of Iran (CCERCI), PO Box 14335-186, Tehran, Iran.
Email: m.mirzaaghayan@ccerci.ac.ir
a Chemistry and Chemical Engineering Research Center of Iran (CCERCI), PO
Box 14335-186, Tehran, Iran
b Institut de Recherche Interdisciplinaire (IRI, USR 3078), 59658 Villeneuve d’Ascq, France
Appl. Organometal. Chem. 2014, 28, 113–115
Copyright © 2013 John Wiley & Sons, Ltd.

M. Mirza-Aghayan et al.
The reductive amination of aliphatic aldehyde such as hexanal with
aniline using the Pd/C/Et3SiH/EtOH system gave N-hexylaniline[22] in
89% yield after 30 min (Table 1, entry 8). Similarly, the reductive
amination of ketones was performed under the same conditions;
the reaction of cyclohexanone with aniline using 2 mmol Et3SiH in
the presence of 5 mg Pd/C gave N-cyclohexylaniline[19] in 56% yield.
It should be noted that increasing the amount of triethylsilane
to 4 mmol increases the yield to 73% (entry 9, Table 1).
We have investigated the reductive amination of aldehydes and
ketones with aliphatic amines under similar conditions. The
reaction of benzaldehyde or cyclohexanone with propylamine
gave 95% N-benzylpropan-1-amine[23] and 93% N-(n-propyl)
cyclohexanamine[24] after 30 min (Table 1, entries 10 and 11).
Finally, we have investigated the reaction of a secondary amine
such as pyrrolidine and morpholine with benzaldehyde under sim-
ilar conditions. 1-Benzylpyrrolidine[25] and 4-benzylmorpholine[6c,d]
were isolated in 94% and 89% yield, respectively, after 30 min
(Table 1, entries 12 and 13).
The reductive amination is initiated by a nucleophilic addition
of amine to the carbonyl group of an aldehyde or a ketone. The
resulting hemiaminal or imine derivative (in the case of primary
amine) is subsequently reduced by hydrogen to form the product
(Scheme 2).[9a–d] We have previously shown that oxidative
addition of Et3SiH to Pd(0) leads to the formation of Et3SiPdH
complex, which can be displaced by ethanol to generate molec-
ular hydrogen and ethoxytriethylsilane, accompanied by the re-
generation of the Pd catalyst (Scheme 3).[10b] The generated
molecular hydrogen may adsorb on the metallic palladium and
subsequently adds to the C¼N double bond of imine compound
or hemiaminal to yield the corresponding amine.
Scheme 1. Reductive amination of carbonyl compounds using
triethylsilane and Pd/C catalyst with amines.
time indicated in Table 1 prior to GC-MS analysis. The results show
that the corresponding N-phenylbenzylamine[17] was obtained in
high yield (92%) after 30 min. Decreasing the amount of Pd/C cata-
lyst to 5 mg gave N-phenylbenzylamine in 90% yield. However, un-
der the same conditions, we obtained N-(4-methyoxylbenzyl)
aniline[17] from the reaction of 4-methoxybenzaldehyde and aniline
in 73% yield. We then investigated the influence of Et3SiH concen-
tration on this chemical process. Using 2 mmol triethylsilane (in-
stead of 1.5 mmol) increased the yield of the reaction to 93% for
reductive amination of 4-methoxybenzaldehyde with aniline.
The optimal conditions were reached when the reaction of a
carbonyl compound (1.1 mmol), an amine derivative (1 mmol)
and triethylsilane (2 mmol) in dry ethanol (5 ml) in the presence
of 5 mg of Pd/C as catalyst was carried out at room temperature.
Under these conditions, the direct reaction of a broad range of
carbonyl compounds such as aldehydes and ketones with amine
derivatives afforded the corresponding amines in high yields. The
obtained results are summarized in Table 1.
For example, the reaction of benzaldehyde with aniline (Table 1,
entry 1) with
2 equiv. of Et3SiH in ethanol gave 90%
N-phenylbenzylamine[17] after 30 min. N-(4-methoxybenzyl)aniline[17]
(Table 1, entry 2) was obtained in 93% yield using the reaction of 4-
methoxybenzaldehyde and aniline under similar conditions. Similarly,
N-benzyl-2,5-dimethylaniline[18] and N-(4-methylbenzyl)aniline[19] were
isolated in 73% and 94% yields, respectively (Table 1, entries 3 and 4).
Next, we studied the performance of the Pd/C/Et3SiH/EtOH
system for the reductive amination of heteroaromatic alde-
hydes such as pyridin-4-carbaldehyde, furfural and thiophen-
2-carbaldehyde. The results showed that heteroaromatic
aldehydes can be readily converted to the corresponding amines
such as N-(pyridin-4-ylmethyl)aniline,[20] N-[(furan-2-yl)methyl]ani-
line[17] and N-(thiophen-2-ylmethyl)aniline[21] in 89%, 80% and 94
% yields, respectively, after 60 min (Table 1, entries 5–7).
Scheme 2. Reductive amination of carbonyl compounds with primary
and secondary amine derivatives.
Table 1. Reductive amination of carbonyl compounds using triethylsilane and Pd/C catalyst
Entry
Carbonyl compound
Amine
Producta
Time (min)
Yieldb,c (%)
1
Benzaldehyde
Aniline
Aniline
N-Phenylbenzylamine[17]
30
30
30
30
60
60
60
30
30
30
30
30
30
90
93
2
4-Methoxy Benzaldehyde
Benzaldehyde
N-(4-Methoxybenzyl)aniline[17]
N-Benzyl-2,5-dimethylaniline[18]
N-(4-Methylbenzyl)aniline[19]
N-(Pyridin-4-ylmethyl)aniline[20]
N-[(Furan-2-yl)methyl]aniline[17]
N-(Thiophen-2-ylmethyl)aniline[21]
N-Hexylaniline[22]
3
2,5-Dimethylaniline
Aniline
73
4
4-Methylbenzaldehyde
Pyridine-4-carbaldehyde
Furfural
94
5
Aniline
89
6
Aniline
80
7
Thiophen-2-carbaldehyde
Hexanal
Aniline
94
8
Aniline
89
56 (73d)
9
Cyclohexanone
Benzaldehyde
Aniline
N-Cyclohexylaniline[19]
10
11
12
13
Propylamine
Propylamine
Pyrrolidine
Morpholine
N-Benzylpropan-1-amine[23]
N-(n-Propyl)cyclohexanamine[24]
1-Benzylpyrrolidine[25]
95
Cyclohexanone
Benzaldehyde
93
94
Benzaldehyde
4-Benzylmorpholine[6]
89
aConditions: carbonyl compound (1.1 mmol), amine (1 mmol), 5 mg Pd/C, Et3SiH (2 mmol) at room temperature.
bIsolated yields.
1
cAll products were characterized by H NMR and mass spectrometry and compared with the literature.
dUsing 4 mmol Et3SiH.
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Appl. Organometal. Chem. 2014, 28, 113–115

Pd/C-catalyzed amination of aldehydes and ketones
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Scheme 3. Generation of hydrogen from Pd/C/Et3SiH/EtOH system.
In conclusion, we have developed an efficient, simple and conve-
nient method for the synthesis of various amine derivatives by the
reductive amination of aldehydes and ketones. The reductive
amination of aromatic, heteroaromatic and aliphatic aldehydes, and
ketones with aromatic or aliphatic amines in the presence of
triethylsilane and a catalytic amount of Pd/C in ethanol, afforded the
corresponding amines in excellent yields. The utility of this methodol-
ogy will make this simple technique an attractive addition to the
range of procedures already known for this general transformation.
Experimental
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All manipulations were carried out under an argon atmosphere.
Ethanol was distilled and stored under argon. GC-MS analysis
was performed on a FISON GC 8000 series TRIO 1000 gas chro-
matograph equipped with a capillary column CP Sil.5 CB, 60 m
× 0.25 mm i.d. H NMR spectra were recorded on a Bruker 80 or
500 spectrometer using tetramethylsilane as internal standard.
1
General Procedure for the Reductive Amination of Carbonyl
Compounds with Amine Derivatives
To a solution of a carbonyl compound (1.1 mmol), an amine de-
rivative (1 mmol) and triethylsilane (2 mmol) in 5 ml ethanol
was added 5 mg palladium on activated carbon (10 wt% loading)
under an argon atmosphere. The resulting mixture was kept un-
der stirring for the time indicated in Table 1 prior to GC-MS anal-
ysis. The mixture was filtered and evaporated under reduced
pressure. Pure products were isolated by column chromatogra-
phy using hexane–ethyl acetate (10:1) as eluent. The products
1
were characterized by H NMR and mass spectrometry.
Acknowledgment
[11] M. Mirza-Aghayan, R. Boukherroub, M. Bolourtchian, M. Rahimifard,
J. Organomet. Chem. 2007, 692, 5113.
[12] M. Mirza-Aghayan, R. Boukherroub, M. Rahimifard, J. Organomet.
The authors would like to thank the Iran National Science Foun-
dation (INSF-91004421) for financial support of this work.
Chem. 2008, 693, 3567.
[13] M. Mirza-Aghayan, R. Boukherroub, M. Rahimifard, Tetrahedron Lett.
2009, 50, 5930.
[14] M. Mirza-Aghayan, R. Boukherroub, M. Rahimifard, R. Zadmard,
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