Development of an electrolytic system for non-kolbe electrolysis based on the acid-base reaction between carboxylic acids as a substrate and solid-supported bases

Article abstract of DOI:10.1021/ja070283w

We have successfully developed a novel electrolytic system for non-Kolbe electrolysis based on the acid-base reaction between carboxylic acids as a substrate and solid-supported bases. It was found that the acid-base reaction between carboxylic acids and solid-supported basespreferentially takes place to reduce the cell voltage in MeOH. On the basis of the electrolytic system, non-Kolbe electrolysis of various carboxylic acids was carried out to provide the corresponding methoxylated products in excellent yields. Copyright

Full text of DOI:10.1021/ja070283w

Published on Web 05/04/2007
Development of an Electrolytic System for Non-Kolbe Electrolysis Based on
the Acid-Base Reaction between Carboxylic Acids as a Substrate and
Solid-Supported Bases
Toshiki Tajima,*,† Hitoshi Kurihara, and Toshio Fuchigami
‡
‡
Global Edge Institute, Tokyo Institute of Technology, Yokohama 226-8502, Japan, and Department of Electronic
Chemistry, Tokyo Institute of Technology, Yokohama 226-8502, Japan
Received January 14, 2007; E-mail: tajima.t.ac@m.titech.ac.jp
Anodic oxidation of amides, lactams, carbamates, and N-acylated
amino acids is one of the most synthetically useful electrochemical
reactions and has proven to be a unique and powerful tool for the
1
synthesis of biologically active compounds. It can provide an
oxidative alternative to the synthesis of N-acyliminium ion inter-
mediates. Furthermore, it can serve as an excellent method for
generating chiral building blocks for synthesis. However, the use
of supporting electrolytes in electroorganic synthesis causes their
separation and waste problems after the electrolysis to restrict the
synthetic advantages.
We have recently developed a novel electrolytic system for
2
3
anodic methoxylation and acetoxylation using easily separable
and reusable solid-supported bases. The system is based on the
acid-base reaction between protic solvents such as MeOH and
solid-supported bases (eq 1). The ions derived from the acid-base
reaction seem to play the role of supporting electrolytes. Therefore,
no additional supporting electrolytes are necessary in the system.
Figure 1. Cyclic voltammograms of (a) 0.1 M silica gel supported
piperidine/MeOH and (b) 1a (0.1 M) in 0.1 M silica gel supported piperidine/
MeOH, recorded at a Pt disk electrode (φ ) 0.8 mm). The scan rate was
-1
1
00 mV s .
However, low acidity of MeOH (pK
a
) 15.5) affords low
concentration of the corresponding ions to cause high cell voltage
-
1
(Vcell ) J C ), which is a unit of energy to drive charge between
the electrodes. On the other hand, carboxylic acids have much
higher acidity compared to that of MeOH. Thus, carboxylic acids
would serve as both a substrate and a supporting electrolyte based
on the acid-base reaction between carboxylic acids and solid-
supported bases in non-Kolbe electrolysis, and they would reduce
the cell voltage in MeOH (eq 2). Non-Kolbe electrolysis, which is
effective for anodic oxidation of amides, lactams, carbamates, and
N-acylated amino acids, is defined as the two-electron oxidation
of carboxylate ions with decarboxylation that leads to carbenium
ions which are trapped by nucleophiles. Herein, we report a novel
electrolytic system for non-Kolbe electrolysis based on the acid-
base reaction between carboxylic acids as a substrate and solid-
supported bases.
Figure 2. Experimental procedure for non-Kolbe electrolysis using solid-
supported bases.
Figure 1b, the oxidation current for MeOH was decreased because
of the adsorption of a carboxylate ion derived from 1a on the anode
surface,4 while the reduction current for H+ was remarkably
increased. These indicate that the acid-base reaction between 1a
and silica gel supported piperidine preferentially takes place
(eq 2), and the resulting ions seem to play the role of supporting
electrolytes.
5
We, in contrast, investigated non-Kolbe electrolysis of 1a and
anodic methoxylation of 1b using silica gel supported piperidine.
The overall experimental procedure for non-Kolbe electrolysis is
illustrated in Figure 2. As shown in Table 1, non-Kolbe electrolysis
of 1a proceeded smoothly to provide 2 in quantitative yield (entry
First, we measured the cyclic voltammogram of 0.1 M silica gel
supported piperidine/MeOH (based on the concentration of piperi-
dine). As shown in Figure 1a, the oxidation current for MeOH (over
+
1
.5 V vs SCE) and the reduction current for H were observed,
1
), while a large amount of 1b was recovered because of the high
respectively. Next, in order to confirm the acid-base reaction
between carboxylic acids and solid-supported bases, the cyclic
voltammogram of DL-pyroglutamic acid (1a, 0.1 M) in 0.1 M silica
gel supported piperidine/MeOH was also measured. As shown in
ox
oxidation potential of 1b (E
p
) 2.5 V vs SCE; entry 2). The cell
voltage in entry 1 (5-10 V) was much lower compared to that in
entry 2 (20-25 V). In these cases, the cell voltages would depend
mainly on the resistance of the solutions, which is closely related
to the concentration of ions. Therefore, the acid-base reaction
between 1a and silica gel supported piperidine seems to preferen-
†
Global Edge Institute.
‡
Department of Electronic Chemistry.
6680
9
J. AM. CHEM. SOC. 2007, 129, 6680-6681
10.1021/ja070283w CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Non-Kolbe Electrolysis of 1a and Anodic Methoxylation
of 1b Using Silica Gel Supported Piperidine
Table 3. Non-Kolbe Electrolysis of Various Carboxylic Acids
Using Silica Gel Supported Piperidine
supporting
electrolyte
(0.1 M)
current
density
(mA/cm2)
electricity
(F/mol)
yielda
(%)
entry substrate
anode
b
Si-piperidinec Pt
Si-piperidine Pt
Si-piperidine graphite
Si-piperidine graphite
d
1
2
3
4
5
6
7
1a
1b
1a
1b
1a
1a
1a
10
10
10
10
75
75
75
7
7
7
7
25
5
quant (29)
19 [81]
e
f
g
97 (28)
f
14 [84]
f
NaClO4
NaOMe
Pt
Pt
23
95 (38)
quant (44)
Si-piperidine Pt
4.5
a
b
c
Isolated yield. The cell voltage was 5-10 V. Silica gel supported
d
e
piperidine. Current efficiency in parentheses. The cell voltage was 20-
5 V. H NMR yield based on the NH group using nitromethane as an
internal standard. Recovery of 1b in brackets.
f
1
2
g
Table 2. Reusability of Silica Gel Supported Piperidine
cycle
1st
2nd
3rd
4th
5th
a
yield (%) of 2
quant
quant
92
quant
91
a
Isolated yield.
tially take place in entry 1 to realize the lower cell voltage compared
to that in entry 2. The influence of the anode materials on the non-
Kolbe electrolysis of 1a was not observed at all because the
generated carbenium ion is stabilized by the nitrogen atom to form
the iminium ion (entries 1 and 3). From the comparisons of entries
a
Isolated yield.
reaction between carboxylic acids as a substrate and solid-supported
bases. It was found that the acid-base reaction between carboxylic
acids and solid-supported bases preferentially takes place to reduce
the cell voltage in MeOH. It is hoped that this will make a
significant contribution to green chemistry and open a new aspect
of electroorganic synthesis.
1
and 2, and entries 3 and 4, non-Kolbe electrolysis of 1a is superior
to anodic methoxylation of 1b from the viewpoints of not only
cell voltage but also current efficiency. Entries 5 and 6 indicate
that a base was effective for the promotion of the non-Kolbe
electrolysis of 1a. Then, silica gel supported piperidine also worked
well as a base (entry 7). Therefore, silica gel supported piperidine
seems to promote the dissociation of 1a to enhance not only the
adsorption of the corresponding carboxylate ion on the anode
surface but also the oxidation of it. It is notable that 2 was easily
isolated by only evaporation of the filtrate after the filtration of
silica gel supported piperidine (Figure 2). Furthermore, as shown
in Table 2, non-Kolbe electrolysis of 1a was successfully carried
out five times under the conditions of entry 7 in Table 1 by the
reuse of silica gel supported piperidine.
Acknowledgment. This work was financially supported by a
Grant-in-Aid for Young Scientists (B) (No. 17750144) from The
Ministry of Education, Culture, Sports, Science and Technology,
Japan. We also thank Nissan Motor Co., Mizuho Foundation for
the Promotion of Sciences, The Foundation “Hattori-Hokokai”, and
Venture Business Laboratory of Tokyo Institute of Technology for
their financial support.
Supporting Information Available: Experimental procedures. This
material is available free of charge via the Internet at http://pubs.acs.org.
On the basis of the electrolytic system based on the acid-base
reaction between carboxylic acids and silica gel supported piperi-
dine, we investigated non-Kolbe electrolysis of various carboxylic
acids. As shown in Table 3, non-Kolbe electrolysis of a N-acylated
proline 3, a carbamate 5, N-acylated alanines 7 and 9, and
p-methoxyphenylacetic acid (11) was carried out to provide the
corresponding methoxylated products in excellent yields. From these
results, it was demonstrated that the system based on the acid-
base reaction between carboxylic acids and solid-supported bases
is available for the wide range of non-Kolbe electrolysis.
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1
In conclusion, we have successfully developed a novel electro-
lytic system for non-Kolbe electrolysis based on the acid-base
JA070283W
J. AM. CHEM. SOC.
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