Electrochemical conversion of benzylamine to dibenzylamine using a microreactor: Analogous system of photocatalytic redox combined synthesis

Article abstract of DOI:10.1246/cl.2011.606

An electrochemical conversion of benzylamine to dibenzylamine using a microreactor has been investigated as an alternative of photocatalytic redox combined reaction. The use of the microreactor was clearly superior to the use of a more conventional batch type reactor.

Full text of DOI:10.1246/cl.2011.606

doi:10.1246/cl.2011.606
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Published on the web May 14, 2011
Electrochemical Conversion of Benzylamine to Dibenzylamine Using a Microreactor:
Analogous System of Photocatalytic Redox Combined Synthesis
1
1
1
1,2
Fumihiro Amemiya, Tsuneo Kashiwagi, Toshio Fuchigami, and Mahito Atobe*
1
Department of Electronic Chemistry, Tokyo Institute of Technology,
4
259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8502
Department of Environment and System Sciences, Yokohama National University,
9-7 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa 240-8501
2
7
(
Received March 8, 2011; CL-110197; E-mail: atobe@ynu.ac.jp)
An electrochemical conversion of benzylamine to dibenzyl-
amine using a microreactor has been investigated as an
alternative of photocatalytic redox combined reaction. The use
of the microreactor was clearly superior to the use of a more
conventional batch type reactor.
1
2
3
Redox combined synthesis is a very efficient method for the
preparation of desired compounds. In heterogeneous photo-
¹
catalysis, a reduction by electron (e ) and an oxidation by hole
+
(
h ) proceed separately at each site on the particle (Figure 1b).
Photocatalytic redox-combined synthesis purposely utilizes
both simultaneous reduction and oxidation for the synthesis
of desired compound(s).1 On the other hand, electrochemical
­3
redox combined synthesis, which is a type of paired electro-
synthesis, has also been proposed.4­6 In this case, a single
Figure 1. Schematic representations of the conversion of
benzylamine to dibenzylamine. (a) Model reaction scheme. (b)
The reaction by using a heterogeneous photocatalyst. (c) The
reaction by using an electrochemical microreactor.
starting substrate is oxidized or reduced at the electrode to give
an intermediate, which is further reduced or oxidized at the
counter electrode to give the corresponding single final product
(Figure 1c). Electrochemical methods generally afford a higher
productivity than photocatalytic methods. Redox-combined
synthesis can serve as a powerful tool for synthetic organic
chemistry, and therefore, further extensive studies would be
valuable.
microreactors over conventional batch-type reactors in an
electrochemical redox-combined reaction. This demonstration
will not only enhance the practical value of electrochemical
microreactors but also show a possibility of the electrochemical
microreactor system as an analog of photocatalytic redox-
combined reaction systems.
In photocatalytic redox-combined synthesis, the reduction
site and the oxidation site on the photocatalyst particle are
located nearby (nano- or micrometer order), enabling the desired
sequential reactions to proceed very smoothly. In contrast, in
electrochemical redox-combined synthesis, the distance between
the anode and cathode is on the order of centimeters when the
reaction is carried out in a conventional batch type reactor.
Consequently, electrochemically generated intermediates need
specific time to diffuse from the electrode surface to the counter
electrode surface, so that complete conversion of the intermedi-
ates would be difficult to achieve by passing only the theoretical
amount of electricity. This damages the efficiency of the
electrolysis reaction and hence the utility of the synthetic
process.
As a model reaction, an electrochemical conversion of
benzylamine (1) to dibenzylamine (3) via N-benzylidenebenzyl-
amine (2) as an intermediate was employed (Figure 1a). Oxida-
tive condensation of benzylamines to N-benzylidenebenzyl-
1
1,12
amines has been widely studied
are useful synthetic intermediates.
because benzylideneamines
1
3,14
Furthermore, N-alkylation
1
5,16
of primary amines has also been studied extensively.
At first, the electrochemical behaviors of the substrate and
intermediate were examined. As shown in Figure 2a, the linear
sweep voltammograms for benzylamine (1), which were
recorded at a Pt disk electrode, show specific wave changes.
Wave I (ca. 1.6 V vs. SCE) was decreased with increasing
the concentration of 1, while wave II (ca. 2.2 V vs. SCE) was
increased with increasing the concentration. The increase of
wave II with almost a linear relationship between the peak
current and the concentration of 1 indicates that this wave was
derived from the oxidation of 1. On the other hand, wave I may
be derived from the oxidation of ethoxide ion contained in the
electrolytic solution. The current of wave I decreased with
increasing the concentration of 1 and it was much lower than
that of wave II at a higher concentration of 1. Therefore, it can
be stated that the ethoxide oxidation is suppressed to some
In order to solve this problem, an electrochemical micro-
reactor7 was employed in this work. The short distance
between the electrodes in the microreactor would enable
fast molecular diffusion to the counter electrode, offering
similar circumstances of the surface of photocatalyst particles
­9
(Figures 1b and 1c). Hence, efficient sequential electrochemical
reactions would be achieved. In addition, an increase in
throughput in microreactors can be achieved by a numbering-
1
0
up approach. With this consideration in mind, the aim of this
work is to demonstrate a clear advantage of electrochemical
Chem. Lett. 2011, 40, 606­608
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

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Table 1. Preparative electrolysis results using microreactora
Electrode
Entry distance
Flow
rate
/mL min /mA cm
Current Total yield Product
b
b
density
/%
2 + 3
ratio
2:3
¹
1
¹2
/
¯m
1
2
3
4
5
6
7
80
50
0.1
0.1
0.1
0.16
0.05
0.1
5.0
5.0
5.0
5.0
5.0
97
61
88
76
28
18
74
58:42
67:33
56:44
66:34
71:29
67:33
66:34
130
80
80
80
80
10
3.2
0.1
a
The structure of the electrochemical microreactor was
described in the Supporting Information.17 The reaction
solution containing 30 mM of benzylamine, 250 mM of
n-Bu4NClO4 as supporting electrolyte, 30 mM of sodium
ethoxide, and ethanol as solvent was flowed through the
electrochemical microreactor at 25 °C by using a syringe
b
pump. Reactions were conducted galvanostatically. Deter-
mined by HPLC.
Table 2. Preparative electrolysis results under several condi-
tions
Starting Total yield/% Product ratioc
c
Entry Reactor
material
2 + 3
2:3
1a microreactor
1
1
3
2
97
96
91
58:42
97:3
29:71
26:74
b
2
3
4
a
batch-type reactor
microreactor
microreactor
a
a
Figure 2. Linear sweep voltammograms of (a) benzylamine
1) and (b) N-benzylidenebenzylamine (2) in 250 mM
100
(
n-Bu4NClO4 + 30 mM EtONa/EtOH. (a) Recorded at a Pt disk
electrode (3 mm diameter). (b) Recorded at a graphite disk
The electrode distance was set to 80 ¯m. The flow rate was
¹1
fixed at 0.1 mL min . The current density was set at 5.0
¹1
electrode (3 mm diameter). The scan rate was 50 mV s
.
¹2
¹1
b
mA cm . 3.1 F mol of charge was passed. A beaker cell
2
2
(50 mL) equipped with a 6 cm Pt plate anode and a 6 cm
extent while the desired amine oxidation occurs dominantly at a
higher concentration of 1.
Figure 2b shows the linear sweep voltammograms of 2
recorded at a graphite disk electrode. The reduction peak current
of 2 was clearly observed in ca. ¹2.1 V vs. SCE in the case of
graphite plate cathode was used. The electrode distance was ca.
1.5 cm. The electrolyte volume was 40 mL and the reaction
was carried out under vigorous stirring. The current density
¹2
¹1
was set to 5.0 mA cm . 3.1 F mol of charge was passed.
c
Determined by HPLC.
10 mM of 2.
Next, preparative electrolysis for the conversion of 1 to
case, it can be presumed that the overoxidation of 3 at the anode
would occurs to give by-products. Moreover, intermediate 2
would be reproduced by the overoxidation of 3. As shown in
Entry 6, the selectivity of the anodic oxidation of 1 to 2
decreased by applying higher current density. Overoxidation of
3 would be also enhanced. On the other hand, the lower current
density also resulted in a decrease in the total product yield due
to an insufficient bulk conversion of 1, as shown in Entry 7.
Subsequently, a comparison with a conventional batch-type
reactor was carried out. The electrode distance was set to
approximately 1.5 cm while that of the microreactor was fixed at
80 ¯m. As shown in Entry 2 of Table 2, using the batch reactor
product 3 was obtained in low yield. Instead, the reaction
proceeded to give predominately intermediate imine 2. This
comparative experiment clearly shows that the more narrow
spacing of the electrodes in the microreactor enables a highly
efficient sequential redox reaction that dramatically increases the
yield of the desired product 3.
dibenzylamine (3) was carried out using a microreactor with Pt
anode and graphite cathode combination. For the operation of
our electrochemical microreactor, there are too many parameters,
and hence these parameters should be investigated systemati-
cally for system optimization. It was expected that the narrower
electrode distance enhanced the desired redox reaction efficien-
cy. However, as shown in Entries 1­3 of Table 1, the narrower
electrode distance (50 ¯m) decreased the total product yield,
while the broader electrode distance (130 ¯m) also resulted in
a decrease in the product yield compared to the case with
the 80 ¯m electrode distance. Therefore, an extremely narrow
or broad electrode distance should be avoided to suppress
unfavorable effects. As shown in Entry 4, when the faster flow
rate was used, the yield of desired amine 3 was significantly
decreased while the yield of intermediate imine 2 was slightly
decreased. This was thought to result from the cathodic
reduction of 2 being not enough to follow the anodic production
of 2 under these conditions. On the other hand, the slower flow
rate also gave unfavorable results, as shown in Entry 5. In this
Finally, in order to improve the reaction yield of 3, a
possible side-reaction was confirmed. As shown in Entry 3 of
Chem. Lett. 2011, 40, 606­608
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

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ed using a microreactor. The key feature of the method is the
extremely narrow separation between the electrodes in the
microreactor. This sequential redox reaction hardly proceeded in
the conventional batch type reactor. These results clearly show a
significant advantage of the electrochemical microreactor for
redox combined synthesis. It can be also concluded that the
microreactor structure, which has the two electrode plates
facing each other is effective. The use of this microreactor
offers an alternative to photocatalytic redox combined reaction
systems.
Our system would be applicable to the redox combined
conversion of other substrates. To demonstrate this, further
application of this new methodology is now under investigation.
This work was financially supported by a Grant-in-Aid for
JSPS Fellows and Scientific Research from the Japanese
Ministry of Education, Culture, Sports, Science and Technology.
Figure 3. Schematic illustration of the newly designed micro-
reactor. The first segment of the microreactor was a Pt plate
anode and Pt plate cathode combination. The second segment of
the microreactor was a Pt plate anode and graphite plate cathode
combination. The first segment and second segment, which were
separated by spacer tape, were connected to different galvano-
stats, respectively, and the electrolyses were conducted inde-
pendently.
References and Notes
1
2
3
4
5
S. Nishimoto, B. Ohtani, T. Yoshikawa, T. Kagiya, J. Am.
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B. Ohtani, S. Tsuru, S. Nishimoto, T. Kagiya, K. Izawa,
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Table 2, when the electrolyte solution with 3 was introduced
into the reactor instead of the solution with starting material 1,
26% of intermediate imine 2 was obtained and 65% of 3 was
H. Maekawa, K. Nakano, T. Hirashima, I. Nishiguchi, Chem.
Lett. 1991, 1661.
recovered. This indicates that oxidation of the product can
regenerate intermediate 2 as a side reaction. In addition, when
the electrolyte solution with 2 was introduced into the reactor,
6
7
W. Li, T. Nonaka, T.-C. Chou, Electrochemistry 1999, 67, 4.
D. Horii, M. Atobe, T. Fuchigami, F. Marken, Electrochem.
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74% of 2 was converted into 3 (Entry 4). This suggests that it is
possible to improve the yield of 3 by further optimization such
as reactor structure modification.
8
9
F. Amemiya, D. Horii, T. Fuchigami, M. Atobe, J. Electro-
chem. Soc. 2008, 155, E162.
F. Amemiya, K. Fuse, T. Fuchigami, M. Atobe, Chem.
Commun. 2010, 46, 2730.
Thus, a new microreactor was designed. As shown in
Figure 3, in this new reactor, two separate reaction segments
were utilized. In the first, a Pt plate anode and Pt plate cathode
were employed, and in the second a Pt plate anode and graphite
plate cathode were used. In this special microreactor, it was
expected that intermediate imine 2 was generated and accumu-
lated at the first segment, and promptly transported to the second
segment without being reduced to 3 (Hydrogen evolution
occurred dominantly at the Pt cathode of the first segment.).
Consequently, a reaction condition similar to Entry 4 in Table 2
would be realized at the second segment. The transported 2
would be efficiently reduced at the second segment, and the
yield of 3 would be improved. Actually, the use of this new
reactor did lead to some improvement. An 80% yield of total
product was obtained, 51% of which was the desired product 3.
This suggests that we are moving in the correct direction.
In summary, the electrochemical redox combined reaction
of benzylamine to dibenzylamine was successfully accomplish-
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11 M. Largeron, A. Chiaroni, M.-B. Fleury, Chem.®Eur. J.
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17 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2011, 40, 606­608
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/