Amination of aliphatic alcohols catalyzed by CuO-NiO/γ-Al 2O3

Article abstract of DOI:10.1007/s00706-013-0941-7

The amination of aliphatic alcohols in the gas-solid phase was investigated in a fixed-bed reactor in the presence of CuO-NiO/γ-Al₂O ₃ as the catalyst. This catalytic system was successfully applied for both the N-methylation of aliphatic amines and N-alkylation of piperidine with primary or secondary alcohols. N-Alkylation of piperidine with low-carbon alcohols resulted in high conversions and selectivities, and the conversion of piperidine and the selectivities toward the desired products declined gradually with the increase of the carbon number of aliphatic alcohols. The influence of varied conditions on the N-cyclohexylation of piperidine was also evaluated, including liquid hourly space velocity (LHSV), temperature and the catalyst; especially the catalyst had the greatest impact. Finally, the test of the catalyst's stability was performed.

Full text of DOI:10.1007/s00706-013-0941-7

Monatsh Chem (2013) 144:1187–1190
DOI 10.1007/s00706-013-0941-7
ORIGINAL PAPER
Amination of aliphatic alcohols catalyzed by CuO–NiO/c–Al O
2
3
Jia-min Huang
Yun-bin Chen
•
Chao Qian
Xin-zhi Chen
•
Lie Feng
•
•
Received: 28 September 2012 / Accepted: 1 February 2013 / Published online: 5 March 2013
Ó Springer-Verlag Wien 2013
Abstract The amination of aliphatic alcohols in the gas–
solid phase was investigated in a fixed-bed reactor in the
presence of CuO–NiO/c–Al O as the catalyst. This catalytic
synthetic organic chemistry [1], because a large number of
amines have been utilized as synthetic intermediates for
pharmaceuticals, agricultural chemicals and bioactive
compounds [2]. With the applications widening, the reac-
tions of amines are still an active area of research.
2
3
system was successfully applied for both the N-methylation
of aliphatic amines and N-alkylation of piperidine with pri-
mary or secondary alcohols. N-Alkylation of piperidine with
low-carbon alcohols resulted in high conversions and
selectivities, and the conversion of piperidine and the
selectivities toward the desired products declined gradually
with the increase of the carbon number of aliphatic alcohols.
The influence of varied conditions on the N-cyclohexylation
of piperidine was also evaluated, including liquid hourly
space velocity (LHSV), temperature and the catalyst; espe-
cially the catalyst had the greatest impact. Finally, the test of
the catalyst’s stability was performed.
The alkylation with aryl/alkyl halides is a well-known
procedure, and an article about this procedure has reported
a chemoselective protocol for the mono-N-alkylation of
primary amines [3]. However, the procedure is limited
because of the use of the toxic aryl/alkyl halides and the
generation of undesired waste salts [4]. With the rise of
green chemistry, the atom efficiency of the process has
become particularly important [5]. There are only a few
methods for the synthesis of amines that take into account
the atom efficiency factor. One of them is the hydroam-
ination of olefins and alkynes [6, 7], although the procedure
cannot generate the products of the methylation, benzyla-
tion, etc., and the regioselectivity of the addition is also a
difficult problem. Another attractive protocol is the cata-
lytic amination of alcohols, the so-called ‘‘hydrogen
autotransfer process,’’ in which the by-product is only
water, and alcohols are friendlier to the environment than
the corresponding halides [8, 9].
Keywords Fix-bed reactor Á Piperidine Á N-Alkylation Á
Catalyst
Introduction
The development of general and efficient methods for
the synthesis of amines is of fundamental importance in
The catalytic systems for the amination of alcohols can
be divided into heterogeneous and homogeneous catalysts
[
10]. Many homogeneous transition metal catalysts, espe-
cially ruthenium complexes [11] and iridium complexes
12], have been extensively used in the catalytic amination
J. Huang Á C. Qian Á X. Chen (&)
State Key Laboratory of Chemical Engineering,
Zhejiang University, Hangzhou,
People’s Republic of China
[
of alcohols. However, the disadvantages of these systems
lie in their non-recoverability and high cost. Compared
with the reactions catalyzed by the homogeneous catalysts,
the catalytic amination of alcohols with the heterogeneous
one allows the separation of catalysts and products easily
e-mail: chemtec@163.com
J. Huang
e-mail: gavinhjm@163.com
L. Feng Á Y. Chen
[
13, 14]. There are many different heterogeneous catalysts
Zhejiang Jianye Chemical Co., Ltd, Hangzhou,
People’s Republic of China
that have been reported, such as silicon and aluminum
123

1
188
J. Huang et al.
oxides [15–17], nickel catalysts [18–20], copper catalysts
21–23] and platinum catalysts [24]. The catalytic activity
Table 1 Amination of methanol with different amines
[
a
Entry
Amine
Product
Conversion/% Selectivity/%
of silicon and aluminum oxides is low and requires a high
reaction temperature. Although nickel catalysts have high
catalytic activity, the catalytic selectivity is not good. Due
to the short lifetime of the copper catalysts and the high
cost of the platinum catalysts, their applications are limited.
Until now, there have been no reports on the CuO-NiO/
1
HN
N
>99
96
>99
92
2
3
4
5
HN
O
N
O
81
97
99
90
83
98
N
H
N
c-Al O catalyst for the N-methylation of aliphatic amines
2
3
and N-alkylation of piperidine with different alcohols,
which has the advantages of good selectivity, high activity,
a long lifetime and low cost.
N
NH2
In this article, we show that the CuO-NiO/c-Al O cat-
2
3
N
2
H N
alyst, prepared by the impregnation method, can act as an
efficient heterogeneous catalyst for the N-methylation of
aliphatic amines and N-alkylation of piperidine with dif-
ferent kinds of alcohols as alkylating agents in a fixed-bed
reactor. Furthermore, the influence of varied conditions,
especially the catalyst, on the N-alkylation of piperidine
was also studied.
Reaction conditions: Cu content of the catalyst 17.2 wt%; Ni content
of the catalyst 4.5 wt%; mole ratio of methanol/amine = 3:1,
T = 150 °C, LHSV = 0.18 h
P = 1.0 MPa
-1
a
Conversion of amines
Table 2 N-alkylation of piperidine with different alcohols
a
Entry
Alcohol
Product
Conversion/% Selectivity/%
Results and discussion
1
OH
N
99
99
92
99
99
94
Initially, methanol was treated as a substrate to give dif-
ferent amines in the presence of CuO-NiO/c-Al O as the
OH
2
3
2
3
N
N
catalyst. The reactions were carried out at a 3:1 mol ratio of
-
methanol to amine, 0.18 h liquid hourly space velocity
1
OH
(
LHSV), 150 °C temperature and 1.0 MPa. Results are
summarized in Table 1. Piperidine and morpholine reacted
with an excess of methanol to give methylated amines with
high conversions and selectivities (entries 1, 2). Diisopro-
pylamine gave a poor conversion, probably because of the
steric effect of the diisopropylamine molecule (entry 3).
The reaction using butylamine had a good conversion, but
the selectivity of the product was unsatisfactory. This might
be the self-disproportionation of butylamine (entry 4). Tert-
butylamine was also successfully applied under the same
conditions (entry 5).
4
5
6
7
OH
95
87
96
90
N
N
OH
89
90
OH
N
--------
----
----
HO
Results of N-alkylation of piperidine with different ali-
phatic alcohols are listed in Table 2. In general, the good
conversion of piperidine and high selectivities of products
were obtained, except for the reaction using tert-butyl
alcohol (entry 7). It is demonstrated in Table 2 that the
conversion of piperidine and the selectivities of the desired
products declined gradually with the increase of the carbon
number of aliphatic alcohols (entries 1, 2, 4, 8, 9). Nev-
ertheless, applications of ethanol and 1-propanol afforded
ideal results (entries 1, 2). When the reactions of piperidine
with secondary alcohols were carried out under the same
conditions, the results were slightly worse than those of the
reactions using primary alcohols, but the conversions and
selectivities were also considerably high (entries 2–5). This
8
9
OH
88
84
84
81
N
OH
N
Reaction conditions: Cu content of the catalyst 17.2 wt%; Ni content
of the catalyst 4.5 wt%; mole ratio of methanol/amine = 3:1,
T = 150 °C, LHSV = 0.18 h
P = 1.0 MPa
-1
a
Conversion of piperidine
indicates that both primary and secondary alcohols are
good alkylating reagents. Besides the kind of alcohol, the
molecular volume of the alcohol also influences the result,
1
23

Amination of aliphatic alcohols
1189
for example, the result of N-alkylation of piperidine with
isobutanol was worse than that obtained using N-butyl
alcohol (entries 4, 6).
100
Conversion
Selectivity
9
9
9
9
8
6
4
2
To determine how the varied reaction conditions and the
catalyst influence the N-alkylation of piperidine, several
related experiments were done in the model reaction
between piperidine and cyclohexanol, and the results are
summarized in Table 3. The conversion and product
selectivity are strongly affected by the LHSV, because it
determines the contact time with the catalyst. Low LHSV
prolongs the contact time, promoting the piperidine con-
version, but lowering the product selectivity. On the
contrary, at high LHSV, the short contact time led to the
reduction of the piperidine conversion, but the desired
product selectivity slightly increased (entries 1–3). In
addition, the reaction temperature is also an important
factor. Low temperature lowered the piperidine conversion,
but the selectivity toward the formation of the desired
product was enhanced. On the other hand, raising the
temperature gave a sufficient conversion but a low selec-
tivity instead (entries 1, 4, 5). Moreover, the influence of
the catalyst was also explored. When the supported metal
content was reduced, decreases in both conversion and
selectivity were recorded (entry 6). The worse result was
obtained for the non-calcined carrier Al O before the
90
8
8
86
8
8
8
7
4
2
0
8
76
7
7
7
6
4
2
0
8
66
6
4
62
6
0
0
50
100
150
200
250
300
Time/h
Fig. 1 The test of the catalyst’s stability. Reaction conditions: 3:1 mol
ratio of cyclohexanol to piperidine; P = 1.0 MPa; T = 150 °C;
LHSV = 0.18 h ; Cu content of the catalyst 17.2 wt%; Ni content
-1
of the catalyst 4.5 wt%
over a period of 300 h through product analysis at irregular
time intervals, and the results are summarized in Fig. 1.
Only trivial turbulence could be found in the result so as to
conclude the constant stability of the catalyst.
2
3
preparation (entry 7). Raising the Ni content of the catalyst
led to an increase in conversion up to 88 %, but the
selectivity decreased (entry 8).
Experimental
The test of the catalyst’s stability was also performed in
the model reaction between piperidine and cyclohexanol
Catalyst preparation
The CuO-NiO/c-Al O catalyst was prepared using the
2
3
impregnation method at a fixed Cu/Ni ratio. A solution of
copper nitrate and nickel nitrate was prepared to obtain a
Cu and Ni concentration of 14.5 and 3.8 wt%, respectively.
The carrier c-Al O with particle radius 2–3 mm was cal-
Table 3 The influence of varied conditions on the N-cyclohexylation
of piperidine
Entry Cu
Ni
content/% content/%
LHSV/ Conversion/ Selectivity/
-
1
e
2
3
h
%
%
cined for 4 h at 400 °C and for 5 h at 800 °C in a muffle
furnace to get SBET = 200-230 m g . Then, the calcined
a
2
-1
1
2
3
4
5
6
7
8
17.2
17.2
17.2
17.2
17.2
11.5
17.2
17.2
4.5
4.5
4.5
4.5
4.5
3.0
4.5
9.0
0.18
0.3
78
72
81
65
83
56
26
88
87
89
82
88
75
72
54
62
a
c-Al O was impregnated with the above-mentioned solu-
2
3
a
0.12
0.18
0.18
0.18
0.18
0.18
tion for 36 h, filtrated and dried at 60 °C for 2 h, and the
filtrate was collected at the same time. The filtrated catalyst
was calcined at 350 °C for 6 h in a muffle furnace and then
cooled. The cooled catalyst was repeated as in the above-
described concrete steps including impregnation, filtration,
evaporation, calcination and cooling until the filtrate was
absorbed entirely.
b
c
a
a,d
e
The reactions were carried out at a 3:1 mol ratio of cyclohexanol to
piperidine, and the product was N-cyclohexylpiperidine
Catalyst characterization
P = 1.0 MPa
a
T = 150 °C
b
The XRD analysis of CuO-NiO/c-Al O catalyst after
T = 120 °C
T = 180 °C
2 3
c
catalyst preparation is shown in Fig. 2. The crystallite
diameters of the copper oxide and nickel oxide were esti-
mated by the Scherrer formula, and both diameters were
5–6 nm.
d
2 3
The carrier Al O of the catalyst was not calcined before the
impregnation
e
Conversion of piperidine
123

1
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J. Huang et al.
2
3
.
.
A scatter plot was made with a regression line, of
which the abscissa and ordinate were the concentration
of standard sample and the peak area, respectively.
Finally, the reaction mixture was analyzed by GC at
the same injection volume as the standard samples,
then based on the peak area, the expected product’s
concentration was obtained.
Acknowledgments The authors are grateful for the financial sup-
port from the Natural Science Foundation of the Zhejiang Province
(R4090358, Y4100147) and the Low Carbon Fatty Amine Engi-
neering Research Center of Zhejiang Province (2012E10033).
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Fig. 2 XRD patterns of CuO-NiO/c-Al O catalyst
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The reaction was performed in a stainless-steel reactor tube
filled with catalyst and surrounded by a jacket filled with
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1
1
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2
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1
23