The synthesis of asymmetric ethylenediamine derivatives catalyzed by ion-exchange resins

Article abstract of DOI:10.1007/s11164-014-1547-3

The ring-opening reaction of aziridine with alkylamines over a series of ion-exchange resins was investigated. Among these catalysts, D001-CC exhibited excellent catalytic performance. The catalysts were characterized by SEM and N₂ adsorption-desorption. The results indicated that the selectivity of N,N-diethylethylenediamine mainly depended on the acidity and S _BET of the resins. Strong Br?nsted acid sites played an important role on the conversion of aziridine, and the distribution of acid sites on catalyst had a significant effect on the selectivity of N,N-diethylethylenediamine. The reaction parameters, such as reaction time, molar ratio, reaction temperature, and catalyst loading, were also optimized and N,N-diethylethylenediamine was obtained in an excellent yield of 97 %. Furthermore, D001-CC was efficiently recycled five times by simple treatment with large amounts of deionized water and mineral acid. Finally, a series of asymmetric ethylenediamine derivatives were successfully synthesized with this method. Therefore, a simple and versatile process for the synthesis of asymmetric ethylenediamine derivatives has been established over ion-exchange resins.

Full text of DOI:10.1007/s11164-014-1547-3

Res Chem Intermed
DOI 10.1007/s11164-014-1547-3
The synthesis of asymmetric ethylenediamine
derivatives catalyzed by ion-exchange resins
Wenwen Wang
Jun Tian Yifan Duan
•
•
Ruisong Wei
•
•
Guohui Yin
•
•
Ligong Chen
Yang Li
Received: 18 November 2013 / Accepted: 20 January 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract The ring-opening reaction of aziridine with alkylamines over a series of
ion-exchange resins was investigated. Among these catalysts, D001-CC exhibited
excellent catalytic performance. The catalysts were characterized by SEM and N2
adsorption–desorption. The results indicated that the selectivity of N,N-diethyleth-
ylenediamine mainly depended on the acidity and SBET of the resins. Strong
Br o¨ nsted acid sites played an important role on the conversion of aziridine, and the
distribution of acid sites on catalyst had a significant effect on the selectivity of N,N-
diethylethylenediamine. The reaction parameters, such as reaction time, molar ratio,
reaction temperature, and catalyst loading, were also optimized and N,N-diethyl-
ethylenediamine was obtained in an excellent yield of 97 %. Furthermore, D001-CC
was efficiently recycled five times by simple treatment with large amounts of
deionized water and mineral acid. Finally, a series of asymmetric ethylenediamine
derivatives were successfully synthesized with this method. Therefore, a simple and
versatile process for the synthesis of asymmetric ethylenediamine derivatives has
been established over ion-exchange resins.
Keywords Asymmetric ethylenediamine derivatives ꢀ Aziridine ꢀ
Heterogeneous catalysis ꢀ Ion-exchange resins ꢀ Nucleophilic addition
ring-opening reaction
W. Wang ꢀ G. Yin ꢀ J. Tian ꢀ Y. Duan ꢀ L. Chen ꢀ Y. Li (&)
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072,
People’s Republic of China
e-mail: liyang777@tju.edu.cn
W. Wang ꢀ G. Yin ꢀ J. Tian ꢀ Y. Duan ꢀ L. Chen ꢀ Y. Li
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072,
People’s Republic of China
R. Wei
Department of Chemistry and Life Science, Hechi University, Guangxi 546300,
People’s Republic of China
123

W. Wang et al.
Introduction
Ethylenediamine and its derivatives have been extensively used in chemical
production, in particular, asymmetric ethylenediamine derivatives are important
intermediates in a variety of fields such as surfactant, pesticide, and pharmaceutical
[
1–3]. For example, N-ethylethylenediamine is an important intermediate for the
synthesis of piperacillin, cefbuperazone, and cefoperazone [4, 5]. N,N-dimethyl-
ethylenediamine can be used in the synthesis of thioxanthenone, procainamide, and
neohetramine [6, 7]. Consequently, much attention has been paid to the synthesis of
these compounds. Asymmetric ethylenediamines have been synthesized by
alkylation of ethylenediamine, catalytic amination of aldehyde, amine cyanome-
thylation, and ring-opening of aziridine [5, 8–11]. Among all these methods, the
ring-opening of aziridine with alkylamines attracted our attention because it is the
most direct method for the synthesis of asymmetric ethylenediamines.
Several kinds of catalysts have been reported to catalyze the ring-opening of
aziridine. Coleman and Callen [12] and Dong et al. [13] have reported anhydrous
aluminum chloride as a catalyst in the addition of amines such as diethylamine and
diisopropylamine to aziridine with yields ranging from 77 to 90 % at 90–180 °C.
However, the application of aluminum chloride will lead to tedious work-up
procedures and a large quantity of wastewater. Alekperov and Kostyanovskii [14]
and Nippon and Kagaku [15] prepared N,N-dimethylethylenediamine in the
presence of Me NHꢀHCl and HCl with 40 and 89 % yields, respectively. This
2
approach suffers from equipment corrosion and environmental pollution. Hohmann
et al. [16] patented the approach to synthesize asymmetric ethylenediamines
catalyzed by CO , and the yields of asymmetric ethylenediamines range from 50 %
2
(
N,N-diethylethylenediamine) to 78 % (N,N-dimethylethylenediamine). Neverthe-
less, the application of CO has limitations due to its low acidity.
2
As catalysts, ion-exchange resins have been reported to offer many advantages,
such as ease of handling and product separation, reduced equipment corrosion, and
minimized waste stream contamination, combined with catalyst reusability [17–21].
Therefore, their application fields have been greatly extended in recent years, such
as esterification, etherification, and dehydration [18, 22–24]. However, they have
not been applied in the synthesis of asymmetric ethylenediamines.
In this paper, we tried to establish a simple and versatile process for the synthesis
of N,N-diethylethylenediamine (3a) over acid ion-exchange resins. Meanwhile, the
catalysts were characterized to clarify the influence of acidity and acid sites
distribution on the catalytic performance. Finally, the process of the synthesis of
asymmetric ethylenediamines was established over the chosen catalyst.
Experimental
Materials
Acid ion-exchange resins (NKC-9, D072, D001-CC, D061, D001SS, 00194,
0
0197, 001914.5, D113), HY and c-Al O were obtained from the Chemical Plant
2
3
1
23

The synthesis of asymmetric ethylenediamine derivatives
of Nankai University (China). All chemicals were used directly without further
purification unless otherwise noted.
Catalytic reactions
Taking the reaction of aziridine with diethylamine as an example, D001-CC
(20 wt%) and 60 % aqueous diethylamine solution (18.28 g) were added into a
three-necked round flask equipped with a condenser and a magnetic stirrer, then the
temperature was rapidly increased to 40 °C. Next, 60 % aqueous aziridine solution
(
3.58 g) was added dropwise within 30 min. The mixture was stirred at 65 °C for a
further 10 h. The reaction mixture was analyzed without preliminary separation by
gas chromatography (SE-30 capillary column, 60 m 9 0.32 mm, 0.50 lm film
thickness). Moreover, the composition of samples was identified by GC/MS (HP-1
capillary column: 30 m 9 0.25 mm, 0.2 lm film thickness) equipped with an ion
trap MS detector and chemical database software. The conversion of aziridine, the
selectivity and yield of 3a, and the amount of catalyst loading were defined as
follows:
Maziridine;initial ꢁ Maziridine;final
Conversion ¼
ꢂ 100 %
ꢂ 100 %
ð1Þ
Maziridine;initial
Maziridine;targetproduct
Selectivity ¼ M
ð2Þ
ð3Þ
ð4Þ
aziridine;targetproduct
þ Maziridine;byproduct
Yield ¼ Conversion ꢂ Selectivity
Mcat
Wcat ¼
ꢂ 100 %
Maziridine;initial þ Mdiethylamine;initial
where Maziridine, initial and Maziridine, final are the mass of aziridine in the feedstock and
final reaction solution, respectively, Maziridine, target product and Maziridine, byproduct are
the mass of aziridine which yield to target product and byproduct, respectively, Mcat
is the mass of catalyst, and Mdiethylamine, initial is the mass of diethylamine in the
feedstock.
The recycling experiment of D001-CC was performed by separation of resins
from reaction media by filtration, washing with large amounts of deionized water
for removing adsorbed reactants or products. The recycled D001-CC was activated
by 0.1M HCl at room temperature before the next run.
Catalyst characterization
Textural properties of the catalysts were measured by N adsorption–desorption
2
on an ASAP 2405 apparatus and the specific surface areas were calculated by the
Brunauer–Emmett–Teller (BET) equation. The surface morphologies of the resins
were observed by a scanning electronic microscope (SEM; S4800; Hitachi,
Japan).
123

W. Wang et al.
Results and discussion
Catalyst selection
The reaction of aziridine with diethylamine is a typical nucleophilic ring-opening
reaction. All the factors that could be prone to increasing the nucleophilicity of
diethylamine or the electrophilicity of aziridine are conducive to the reaction [25].
However, Milstein [26] reported that aziridines, unlike epoxides, cannot open under
alkaline conditions, and it is well known that a proton donor acid catalyst is crucial
for the activation of aziridine. Therefore, a series of solid acid catalysts, such as acid
ion-exchange resins, HY and c-Al O , were selected for the reaction of aziridine
2
3
and diethylamine, and the results are shown in Table 1.
As Table 1 indicates, strong acid ion-exchange resins had a distinct advantage
over other types of solid acid catalysts and about 100 % conversion of aziridine was
observed. Accordingly, a conclusion can be made that strong Br o¨ nsted acid sites
may be more effective for the ring-opening of aziridine. In addition, different strong
acid ion-exchange resins exhibited different selectivity of 3a. Macroporous resins
exhibited higher selectivity of 3a than gel resins. Among these macroporous resins,
the highest selectivity was obtained with D001-CC. The reason may be attributed to
the effect of textural property of resins. In order to investigate the relationship
Table 1 Reaction of aziridine with diethylamine over solid acid catalysts
a
b
b
b
Entry
Catalyst
Time (h)
Conversion (%)
Selectivity (%)
Yield (%)
c
1
2
3
4
5
6
7
8
9
–
10
7
6
5
9
7
6
7
6
7
6
9
37
100
99
22
85
87
91
83
87
81
81
80
74
72
65
8
85
86
91
82
86
81
81
80
54
61
45
NKC-9
D072
D001-CC
D061
100
99
D001SS
00194
00197
001914.5
D113
99
100
100
100
73
1
1
1
a
0
1
2
HY
85
c-Al
2
O
3
69
2
0 wt% catalyst loading
b
Directly determined by GC
Pseudo-catalyzed reaction
c
1
23

The synthesis of asymmetric ethylenediamine derivatives
between catalytic performance and textural property, strong acid ion-exchange
resins were characterized by N adsorption–desorption and SEM.
2
Catalyst characterization
BET
The N adsorption–desorption isotherms of D001-CC, D072, NKC-9, and D061 are
2
shown in Fig. 1. All the resins exhibited a type II isotherm with a steep increase in
adsorption volume at P/P = 0.8–0.95. The steep increase was due to the multilayer
0
adsorption of macropores. Acidity and SBET of the resins are shown in Table 2, and
the distribution of acid sites can be calculated by the ratio of acidity and SBET. The
distribution of acid sites followed the trend of D061[NKC-9[D072[D001-CC.
Combined with the selectivity of 3a, it can be concluded that, with the decrease of
acid sites per unit specific surface area, the selectivity of 3a increased. In the resins,
aziridine and diethylamine are protonated by free hydrogen proton and then
protonated aziridine and diethylamine are adsorbed on the surface of the resins by
electrostatic adsorption. As shown in Fig. 2 and Scheme 1, 3a is obtained by free
diethylamine reacting with protonated aziridine. With the decrease of acid sites per
unit specific surface area, the probability of 3a reacting with protonated aziridine
decreases [21]. Accordingly, the lower distribution of acid sites on catalyst was
beneficial to restrain the formation of byproducts.
SEM
The morphologies of D001-CC and 00194 were evaluated by SEM. The SEM images
show that commercial beads are nearly spherical (Figs. 3a, 4a) and 00194 has a more
5
4
3
2
1
0
0
0
0
0
0
D001-CC
D061
D072
NKC-9
0
.0
0.2
0.4
0.6
0.8
1.0
P/P0
Fig. 1 N
2
adsorption–desorption isotherms at 77 K of D001-CC, D072, NKC-9, and D061
123

W. Wang et al.
Table 2 Characteristics of ion-exchange resins
a
Catalyst
Structure Acidity
(
S
BET
2
The ratio of
(m /g) acidity and SBET (cm /g)
Pore volume Average pore
3
T
max
b
mmol/g)
diameter (nm) (°C)
NKC-9
D072
MR
MR
4.8
4.4
4.1
4.2
4.2
4.5
4.5
3.8
11.94
15.79
22.86
4.89
0.40
0.28
0.18
0.86
0.030
0.044
0.073
0.013
10.09
11.03
12.82
10.62
100
120
120
120
120
120
120
120
D001-CC MR
D061
MR
MR
G
D001SS
0
0
0
0194
0197
G
01914.5
G
MR macroreticular structure, G gel type polymer
a
The particle size of ion-exchange resins is 0.3–1.25 mm
b
The acidity of dry ion-exchange resins was detected
Fig. 2 Scheme of the heterogeneous acid catalytic mechanism for 3a synthesis
Scheme 1 The synthesis of 3a
and side reaction
smooth surface than D001-CC (Figs. 3b, 4b). Obviously, the specific surface area of
D001-CC is larger than 00194. Combined with the acidity, we can speculate that the
acid sites per unit specific surface area have a significant effect on the catalytic
performance. The assumption was in accordance with the conclusion of BET.
Optimization of reaction conditions
As mentioned above, D001-CC was found to be the most effective catalyst for the
synthesis of 3a, so reaction conditions including reaction time, molar ratio, reaction
temperature, and catalyst loading were optimized for D001-CC.
1
23

The synthesis of asymmetric ethylenediamine derivatives
Fig. 3 SEM photomicrographs of D001-CC. a General view of beads (magnification 950). b Surface
detail of a bead (magnification 940,000 and 9150,000)
Fig. 4 SEM photomicrographs of 00194. a General view of beads (magnification 950). b Surface detail
of a bead (magnification 940,000 and 9150,000)
Effect of reaction time
The effects of reaction time on the aziridine conversion and the 3a selectivity are
illustrated in Fig. 5. It was noted that the conversion of aziridine increased from 53
to 100 % with the prolongation of reaction time. However, the selectivity of 3a
decreased slightly from 100 to 91 %. Considering both the aziridine conversion and
the 3a selectivity, 5 h was chosen as the optimum reaction time.
Effect of diethylamine/aziridine molar ratio
It is well known that the ring-opening of aziridine is a tandem reaction and that 3a
has a stronger nucleophilicity than diethylamine, so the molar ratio of diethylamine
to aziridine plays an important role in the selectivity of 3a. The effect of the molar
ratio was studied as demonstrated in Fig. 6. It was revealed that, as the molar ratio
increased, the conversion of aziridine was always maintained around 100 %.
However, the selectivity of 3a increased from 58 to 97 % as the molar ratio rose
from 1:1 to 4:1, and then remained unchanged. Therefore, the optimal molar ratio
was 4:1.
123

W. Wang et al.
100
9
9
8
8
7
7
6
6
5
5
5
0
5
0
5
0
5
0
5
0
Conversion
Selectivity
1
2
3
4
5
6
7
Reaction time (h)
Fig. 5 Effect of reaction time on aziridine conversion and 3a selectivity. D001-CC, 65 °C, diethylamine/
aziridine molar ratio = 3:1, 20 wt% catalyst loading
1
00
9
8
7
6
0
0
0
0
Conversion
Selectivity
1
:1
2:1
3:1
4:1
5:1
6:1
Molar ratio
Fig. 6 Effect of diethylamine/aziridine molar ratio on aziridine conversion and 3a selectivity. D001-CC,
5 °C, t = 5 h, 20 wt% catalyst loading
6
Effect of reaction temperature
The influence of reaction temperature on the catalytic performance of D001-CC was
then investigated and the results are shown in Fig. 7. It can be seen that the
conversion of aziridine increased from 85 to 100 % with the increase of temperature
from 55 to 65 °C, and then remained unchanged. However, the selectivity of 3a
1
23

The synthesis of asymmetric ethylenediamine derivatives
decreased from 100 to 70 % with the increase of temperature from 55 to 75 °C. As a
result, a conclusion can be made that the increase of temperature was in favor of the
formation of N,N-diethyl-diethylenetriamine (4a), which resulted in the decrease of
the 3a selectivity. However, the increase of temperature improved the conversion of
aziridine. Therefore, it was very important to determine an appropriate temperature,
and 65 °C was chosen to be the optimum reaction temperature.
Effect of catalyst loading
Figure 8 indicates the effect of catalyst loading on the conversion of aziridine and
selectivity of 3a. With the increase of catalyst loading, the conversion of aziridine
increased while the selectivity of 3a decreased slightly. It was obvious that the
optimal amount of catalyst loading was 15 wt%.
The regeneration and reusability of catalyst
The recyclability of the resins is another very important aspect that one must
consider for large-scale production. Therefore, the regeneration and reusability of
D001-CC was investigated. As evident from the recyclability study (Table 3), it can
be seen that the conversion of aziridine and the selectivity of 3a decreased gradually
as the number of cycles increased. After the catalyst had been used for five cycles,
the conversion of aziridine and the selectivity of 3a dropped to 95 and 76 %,
respectively. When D001-CC was regenerated by pickling, the catalytic perfor-
mance recovered almost to the level of the fresh resins. We can speculate that the
possible reason leading to the decrease of catalytic performance was the adsorption
of products of high boiling point which prevented the contact of reactants with the
acid sites of D001-CC.
100
95
90
85
80
75
70
65
Conversion
Selectivity
55
60
65
70
75
o
Reaction temperature ( C)
Fig. 7 Effect of reaction temperature on aziridine conversion and 3a selectivity. D001-CC, t = 5 h,
diethylamine/aziridine molar ratio = 4:1, 20 wt% catalyst loading
123

W. Wang et al.
1
00
9
8
7
6
0
0
0
0
Conversion
Selectivity
0
5
10
15
20
25
Catalyst loading (wt %)
Fig. 8 Effect of catalyst loading on aziridine conversion and 3a selectivity. D001-CC, t = 5 h, 65 °C,
diethylamine/aziridine molar ratio = 4:1
Table 3 Reusability of D001-CC
a
a
Cycle Activated catalyst
Unactivated catalyst
b
b
b
Time (h) Conversion (%) Selectivity (%) Time (h) Conversion (%) Selectivity (%)
b
1
2
3
4
5
a
5
5
6
6
7
100
100
100
100
100
97
96
96
94
94
5
7
100
100
99
97
93
90
81
76
10
12
14
98
95
1
5 wt% catalyst loading
b
Directly determined by GC
Synthesis of asymmetric ethylenediamines
As mentioned above, D001-CC was the most effective catalyst for the synthesis of
a from aziridine and diethylamine. Accordingly, the generality of this method was
3
investigated with a series of substrates under the optimized conditions (Table 4).
The desirable results were also observed for the reaction of aziridine with primary
and secondary amines, except for diisopropylamine and di-n-butylamine. The
reason may be due to the steric hindrance of the two substrates.
1
23

The synthesis of asymmetric ethylenediamine derivatives
Table 4 The synthesis of asymmetric ethylenediamines over D001-CC
a
Entry
1
Product
Reaction time (h)
5
Yield (%)
3a
97
2
3
4
3b
3c
3d
4.5
5
98
95
95
5
5
6
3e
3f
5.5
4.5
96
98
7
8
3g
3h
4
–
98
–
9
3i
–
–
a
Directly determined by GC
Conclusions
In summary, a simple and versatile process for the synthesis of asymmetric
ethylenediamines via ring-opening of aziridine over ion-exchange resins was
123

W. Wang et al.
established. The results showed that strong Br o¨ nsted acid sites played an important
role on the conversion of aziridine. In addition, the influence of textural property of
catalysts on the catalytic performance was also investigated, and the results
indicated that the distribution of acid sites on catalyst also has a significant effect on
the selectivity of 3a, and that the lower distribution would inhibit the formation of
4
a, which improves the selectivity of 3a.
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