N-alkylation of ethylenediamine with alcohols catalyzed by CuO-NiO/γ-Al2O3

Article abstract of DOI:10.2478/s11696-012-0140-8

A simple method for N-alkylation of 1, 2-diaminoethane with different alcohols in a fixed-bed reactor using cheap CuO-NiO/γ-Al₂O ₃ as the catalyst has been developed. The present catalytic system was applicable in the N-alkylation of 1, 2-diaminoethane with both primary and secondary alcohols. Mono-N-alkylation of 1, 2-diaminoethane with low-carbon alcohols resulted in high yields; the yields of tetra-N-alkylation of 1, 2-diaminoethane with low-carbon alcohols declined markedly with the increase of the molecular volume of alcohols.

Full text of DOI:10.2478/s11696-012-0140-8

Chemical Papers 66 (4) 304–307 (2012)
DOI: 10.2478/s11696-012-0140-8
SHORT COMMUNICATION
alkylation of ethylenediamine with alcohols catalyzed
by CuO–NiO/γ-Al O3
2
a
a,b
a
a
Jia-Min Huang, Lu-Feng Xu, Chao Qian, Xin-Zhi Chen*
aDepartment of Chemical and Biological Engineering, Zhejiang University, 310027 Hangzhou, China
bCollege of Chemical and Materials Engineering, Quzhou College, 324000 Quzhou, China
Received 1 September 2011; Revised 5 December 2011; Accepted 6 December 2011
A simple method for N-alkylation of 1,2-diaminoethane with different alcohols in a fixed-bed
reactor using cheap CuO–NiO/γ-Al O as the catalyst has been developed. The present catalytic
2 3
system was applicable in the N-alkylation of 1,2-diaminoethane with both primary and secondary
alcohols. Mono-N-alkylation of 1,2-diaminoethane with low-carbon alcohols resulted in high yields;
the yields of tetra-N-alkylation of 1,2-diaminoethane with low-carbon alcohols declined markedly
with the increase of the molecular volume of alcohols.
ꢀ
c 2012 Institute of Chemistry, Slovak Academy of Sciences
Keywords: N-alkylation, ethylenediamine, alcohols, catalyst
N-alkylation of 1,2-diaminoethane (ethylenedi-
amine) is of fundamental importance in synthetic or-
ganic chemistry granting access to valuable
N-alkylethylenediamine widely used as a synthetic
intermediate (Lawrence, 2004) for pharmaceuticals,
agrochemicals, bioactive compounds, polymers, and
dyes. With the field of applications widening, the de-
velopment of general and efficient methods for the
synthesis of N-alkylethylenediamine is still an ac-
tive area of research. N-alkylation of ethylenediamine
with aryl/alkyl halides is the most commonly used
method (Bernady, 1979). This procedure is very con-
venient; also, a chemoselective protocol for mono-
N-alkylation of ethylenediamine has been developed
as the by-product and alcohols are friendlier to the
environment than the corresponding halides. The re-
action pathway (Balcells et al., 2008; Dobereiner &
Crabtree, 2010) proceeds through the dehydrogena-
tion of alcohol to the corresponding carbonyl in-
termediate which reacts with an amine to generate
an imine. Then, imine is hydrogenated by the bor-
rowed hydrogen, so-called “borrowing hydrogen” ap-
proach (Hamid et al., 2007; Saidi et al., 2010), to
afford the expected N-alkylated amine. Some cat-
alytic systems for N-alkylation of amines with alco-
hols have been studied using homogeneous catalysts,
such as ruthenium (dichloro(p-cymene)ruthenium(II)
6
dimmer, ((η -cymene)RuCl2)2) (Hamid & Williams,
(Salvatore et al., 2000). However, the procedure em-
2007), iridium (di-µ-chloro-bis(chloro(pentamethylcy-
ploying aryl/alkyl halides is unfriendly to the environ-
ment and generates large amounts of inorganic salts as
by-products. Alkylation of ethylenediamine can also
be accomplished with different ethers using cheap
γ-Al O as the catalyst; this method was reported on
clopentadienyl)iridium(III)), (Cp*IrCl ) ) (Fujita et
2
2
al., 2003), rhodium (hydridotetrakis(triphenylphos-
phine)rhodium(I), RhH(PPh ) ) (Grigg et al., 1981),
3
4
and platinum (cis-bis(triphenylphosphine)platinum
(II) chloride, PtCl (PPh ) ) (Takeuchi et al., 1986).
2
3
2
3 2
in a preceding article (Chen et al., 2010).
N-alkylation of ethylenediamine with alcohols is
an attractive and environmentally-friendly approach
Although many homogeneous catalysts are active in
the N-alkylation of amines with alcohols, their dis-
advantages lie in their non-recoverability and high
cost (Guillena et al., 2010). Most important, com-
(Kim et al., 2009) because it produces only water
*Corresponding author, e-mail: xzchen@zju.edu.cn

J. M. Huang et al./Chemical Papers 66 (4) 304–307 (2012)
305
pared with the homogeneous system, the heteroge-
neous one can be easily recovered. There are dif-
ferent types of heterogeneous catalysts, such as sili-
con, aluminum, nickel, copper, platinum, and, among
them, Cu–Ni catalysts show the best performance
(
Martínez-Asencio et al., 2010; He et al., 2010; Valot
et al., 1999).
A report on the use of CuO–NiO/γ-Al2O3 cata-
lyst, prepared using the coprecipitation method at the
Cu/Ni mass ratio of 37 : 36, for the N-methylation of
ethylenediamine, while the yield of N-methylethane-
1
%
,2-diamine (N-methylethylenediamine) was only 1.3
can be found in literature (Yamakawa et al., 2004).
Fig. 1. Effect of reaction temperature on N-ethylation of
ethylenediamine.
In this paper, the CuO–NiO/γ-Al2O3 catalyst, pre-
pared using the impregnation method at the Cu/Ni
mass ratio of 128 : 37, is reported to be able to
act as an efficient heterogeneous catalysts for the
N-alkylation of ethylenediamine with different alco-
hols in a fixed-bed reactor. According to the one-
pot method for the alkylation of amines with non-
activated alcohols (Guérin et al., 2011), representa-
tive primary, secondary and tertiary alcohols were
selected. Furthermore, both mono-N-alkylation and
poly-N-alkylation of the ethylenediamine were also
studied.
◦
lyst was reduced at 240 C for 7 h before the reaction.
Ethylenediamine and alcohol were introduced at the
top of the reaction tube via an injection pump. The
reaction mixtures passed through the catalyst in the
fixed-bed, and the gas products were cooled down af-
ter passing through the cooler at the bottom.
The reaction mixtures were analyzed by gas chro-
matography (Agilent 1790F and SE-30 column; Nan-
jing Xuxi Apparatus Co., Ltd., China) and GC-MS
(TRACE GC2000/TRACE MS; ThermoQuest, USA).
The yields were determined by an external standard
method as follows: (i) based on the probable concen-
tration of the analyte, standard samples of seven dif-
ferent concentrations were prepared and analyzed by
GC at the same injection volume; (ii) a scatter plot
with the regression line was drawn and its abscissa
and ordinate represented the concentration of stan-
dard sample and the peak area, respectively; (iii) the
reaction mixture was detected by GC at the same in-
jection volume as the standard samples and the con-
centration of the expected product was determined on
basis of the peak area.
Initially, the reaction of ethylenediamine with
ethanol to generate N-ethylethylenediamine in a fixed-
bed reactor was studied as a model reaction. The re-
action was carried out at an 1 : 3 mole ratio of ethanol
to ethylenediamine, 0.15 h liquid hourly space ve-
locity (LHSV), and 1.0 MPa, in the presence of CuO–
NiO/γ-Al2O3 as the catalyst. To explore the influ-
ence of the temperature on the reaction, the temper-
ature was varied from 120 C to 200 C to reach the
yield of N-ethylethylenediamine. Results are shown in
Fig. 1. The yield of N-ethylethylenediamine increased
obviously as the temperature increased, while it de-
creased at over 160 C because the polysubstituted re-
action of ethylenediamine was enhanced. In this re-
search, the maximum yield of N-ethylethylenediamine
was recorded at 160 C. The reaction is also strongly
affected by the LHSV, because low LHSV prolongs the
contact time with the catalyst, promoting further re-
actions, and generating polysubstituted products. On
the other hand, at high LHSV, the contact time is too
The CuO–NiO/γ-Al2O3 catalyst was prepared us-
ing the impregnation method at a fixed Cu/Ni ratio,
and concrete steps followed: (i) the carrier, γ-Al2O3
2
−1
(
solid’s total surface area = 220–250 m g , diame-
◦
ter = 2–3 mm), was calcined at 450 C for 3 h and at
50 C for 5 h in a muffle furnace; (ii) calcined γ-Al2O3
◦
7
was impregnated with water for 36 h, the decrement of
water volume was measured to determine the pore vol-
ume; (iii) solution of copper(II) nitrate and nickel(II)
nitrate was prepared to obtain Cu and Ni concentra-
tions of 12.8 mass % and 3.7 mass %, respectively, and
the volume of the solution was two times the total pore
volume; (iv) calcined γ-Al2O3 was impregnated with
the above-mentioned solution for 36 h, filtered and
◦
dried at 60 C for 2 h, and the filtrate was collected at
the same time; (v) the filtered catalyst was calcined
◦
at 280 C for 6 h in a muffle furnace, and cooled down;
−
1
(
vi) the catalyst was then impregnated with the fil-
◦
trate from (iv) for 24 h, filtered and dried at 80 C;
(
◦
vii) at last, the catalyst was calcined at 450 C for
6
h, and then cooled to the room temperature.
◦
◦
All other raw materials were all provided by
Hangzhou Chemical Reagent Co., Ltd. (China). Alky-
lation of amines was done in a stainless reactor tube
filled with the catalyst and surrounded by a jacket
filled with salt bath to control the temperature of the
fixed-bed. Total height of the reactor was 60 cm while
the effective length was 40 cm; there were ceramic
rings on the top and at the bottom of the reactor.
Effective radius of the reactor was 15 mm.
◦
◦
All reactions were carried out under the atmo-
sphere of hydrogen in a fixed-bed reactor which was
3
filled with 95 cm of the calcined catalyst; the cata-

3
06
J. M. Huang et al./Chemical Papers 66 (4) 304–307 (2012)
Table 1. Effect of catalyst on N-ethylation of ethylenediamine
Yield/%
di-
Catalyst
Ethylenediamine conversion/%
mono-
poly-
γ-Al2O3
0.5
4.5
31.6
39.8
1.2
10.4
82.3
3.6
–
–
–
1.9
–
CuO/γ-Al2O3
CuO–NiO/γ-Al2O3
NiO/γ-Al2O3
1.6
5.1
0.9
Table 2. Mono-N-alkylation of ethylenediamine with different alcohols
Yield/%
di-
◦
−1
Productc
Entry
Alcohol
T/ C
LHSV/h
mono-
poly-
a
1
Methanol
Ethanol
Propan-1-ol
Butan-1-ol
Propan-2-ol
Butan-2-ol
160
160
160
160
160
160
170
180
0.15
0.15
0.15
0.15
0.15
0.15
0.14
0.12
Methyl
Ethyl
Propyl
Butyl
Isopropyl
2-butyl
Cyclohexyl
–
80.2
82.3
83.7
85.2
82.8
80.8
76.1
–
4.7
5.1
3.8
3.5
3.6
3.5
1.8
–
2.8
1.9
1.5
1.3
0.8
0.6
0.0
–
a
2
a
3
a
4
a
5
a
6
7b
Cyclohexanol
2-Methylpropan-2-ol
a
8
a) Reactions were carried out at 1 : 3 mole ratio of alcohol to ethylenediamine and 1.0 MPa; b) reaction was carried out at 1 : 2
mole ratio of alcohol to ethylenediamine and 1.1 MPa; c) N-alkylethylenediamine.
short to convert raw materials to the desired product.
entry 7), such as higher temperature, longer contact
time, higher hydrogen pressure, and higher amount
of cyclohexanol, to obtain high yields of the product.
This might be due to the steric effect of the cyclohex-
anol moelcule.
−
1
LHSV of 0.15 h resulted in the formation of mono-
alkylated ethylenediamine in a high yield. Moreover,
influence of the catalyst was also explored and the
results are summarized in Table 1. Catalytic activity
of alumina and CuO–alumina were low, NiO–alumina
had very high catalytic activity. However, catalytic se-
lectivity of NiO–alumina was not good, and the main
process was the disproportionation of amines. There-
fore, CuO–NiO/γ-Al2O3 was selected as the catalyst.
On basis of the optimization of reaction condi-
tions, mono-N-alkylation of ethylenediamine with dif-
ferent alcohols was performed. Results are summa-
rized in Table 2. The reactions of ethylenediamine
with primary alcohols resulted in high yields of the
main products (Table 2, entries 1–4). Yields of the
N-alkylation of ethylenediamine with methanol and
ethanol were a little lower than those obtained using
propan-1-ol and butan-1-ol. This was probably caused
by the small size of methanol and ethanol molecules;
further reactions can take place more easily than with
other primary alcohols. When the reaction of ethylene-
diamine with secondary alcohols was performed un-
der the same conditions (Table 2, entries 5–7), yields
of the desired products were also considerably high
and close to the yields of N-alkylation of ethylenedi-
amine with primary alcohols. This indicates that sec-
ondary alcohols are also good alkylating reagents. The
reaction using 2-methylpropan-2-ol was also studied.
However, tertiary alcohols cannot act as alkylating
reagents (Table 2, entry 8). The reaction using cyclo-
hexanol required more stringent conditions (Table 2,
Ethylenediamine contains two primary amines, so
it can react with four times the amount of alco-
hol at the most. The reaction of ethylenediamine
with different alcohols generating tetra-N-alkylated
ethylethylenediamines in a fixed-bed reactor in the
presence of CuO–NiO/γ-Al2O3 as the catalyst was
studied. The results are summarized in Table 3. For-
mation of tetra-N-alkylated ethylenediamines required
more drastic conditions than that of mono-alkylated
ethylenediamines. It is demonstrated in Table 3 that
the yields of tetra-N-alkylated ethylenediamines de-
clined markedly with the increase of steric hindrance
(Table 2, entries 1–6). Moreover, the reaction us-
ing cyclohexanol cannot provide tetra-cyclohexyl-N-
ꢀ
ethylenediamine and the main product was N,N -
dicyclohexyl-ethylenediamine (Table 2, entry 7). The
reactions using methanol and ethanol had satisfactory
results, and the mole ratio of alcohol and ethylene-
diamine was close to the stoichiometric one. On the
other hand, the yields of ethylenediamine N-alkylation
with propan-2-ol and butan-2-ol decreased signifi-
cantly, which was probably due to propan-2-ol and
butan-2-ol, secondary alcohols, whose volume is larger
than that in Table 2, entries 1–4.
In conclusion, N-alkylation of ethylenediamine
with different alcohols in the gas-solid phase was ex-
amined in a fixed-bed reactor in the presence of CuO–

J. M. Huang et al./Chemical Papers 66 (4) 304–307 (2012)
Table 3. Tetra-N-alkylation of ethylenediamine with different alcohols
307
◦
−1
Mole ratioa
Entry
Alcohol
T/ C
LHSV/h
Hydrogen pressure/MPa
Yield/%
1
2
3
4
5
6
7
Methanol
Ethanol
180
180
180
180
200
200
220
0.12
0.12
0.12
0.12
0.12
0.12
0.10
5 : 1
6 : 1
1.0
1.0
1.0
1.0
1.1
1.1
1.2
91.6
76.3
56.8
47.9
27.3
18.2
56.7b
Propan-1-ol
Butan-1-ol
Propan-2-ol
Butan-2-ol
Cyclohexanol
10 : 1
10 : 1
12 : 1
12 : 1
16 : 1
ꢀ
a) Mole ratio was alcohol to ethylenediamine, b) yield of N,N -dicyclohexyl-ethylenediamine.
NiO/γ-Al2O3 as the catalyst. This catalyst allows se-
lective mono-N-alkylation of ethylenediamine by pri-
mary and secondary alcohols. However, the process
using tertiary alcohol resulted in no reaction. Tetra-
N-alkylation of ethylenediamine with low-carbon alco-
hols was also studied and the yields declined markedly
with the increase of the molecular volume of alcohols.
Hamid, M. H. S. A., Slatford, P. A., & Williams, J. M.
J. (2007). Borrowing hydrogen in the activation of alco-
hols. Advanced Synthesis & Catalysis, 349, 1555–1575. DOI:
10.1002/adsc.200600638.
Hamid, M. H. S. A., & Williams, J. M. J. (2007). Ruthenium
catalysed N-alkylation of amines with alcohols. Chemical
Communications, 7, 725–727. DOI: 10.1039/b616859k.
He, J. L., Yamaguchi, K., & Mizuno, N. (2010). Selective
synthesis of secondary amines via N-alkylation of primary
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Acknowledgements. This work was supported by the Na-
tional Natural Science Foundation of China (No. 21006087),
the Natural Science Foundation of the Zhejiang Province
10.1246/cl.2010.1182.
(Y4100147), and the Fundamental Research Funds for the Cen-
Kim, J. W., Yamaguchi, K., & Mizuno, N. (2009). Hetero-
geneously catalyzed selective N-alkylation of aromatic and
heteroaromatic amines with alcohols by a supported ruthe-
nium hydroxide. Journal of Catalysis, 263, 205–208. DOI:
tral Universities (2011QNA4018).
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