A novel electrochemical conversion of CO2 with aryl hydrazines and paraformaldehyde into 1,3,4-oxadiazol-2(3H)-one derivatives in one step

Article abstract of DOI:10.1016/j.elecom.2016.09.016

Using CO₂ to replace phosgene or CO as the C1 synthon, we successfully achieved the one-pot electrochemical synthesis of 1,3,4-oxadiazol-2(3H)-one derivatives via a three-component coupling reaction of CO₂ with aryl hydrazines and pa

Full text of DOI:10.1016/j.elecom.2016.09.016

A novel electrochemical conversion of CO2 with aryl hydrazines and
paraformaldehyde into 1,3,4-oxadiazol-2(3H)-one derivatives in one step
Na Yang, Qiang Lai, Huanfeng Jiang, Gaoqing Yuan
PII:
DOI:
Reference:
S1388-2481(16)30226-0
doi:10.1016/j.elecom.2016.09.016
ELECOM 5786
To appear in:
Electrochemistry Communications
Received date:
Revised date:
Accepted date:
9 August 2016
2 September 2016
15 September 2016
Please cite this article as: Na Yang, Qiang Lai, Huanfeng Jiang, Gaoqing Yuan, A
novel electrochemical conversion of CO2 with aryl hydrazines and paraformaldehyde into
1,3,4-oxadiazol-2(3H)-one derivatives in one step, Electrochemistry Communications (2016),
doi:10.1016/j.elecom.2016.09.016
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ACCEPTED MANUSCRIPT
A novel electrochemical conversion of CO2 with aryl hydrazines
and
paraformaldehyde
into
1,3,4-oxadiazol-2(3H)-one
derivatives in one step
Na Yang, Qiang Lai, Huanfeng Jiang, Gaoqing Yuan*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou,
China
Abstract
Using CO2 to replace phosgene or CO as the C1 synthon, we successfully achieved the
one-pot electrochemical synthesis of 1,3,4-oxadiazol-2(3H)-one derivatives via
a
three-component coupling reaction of CO2 with aryl hydrazines and paraformaldehyde in an
undivided cell. With NaI as the electro-catalyst and t-BuOK as the base, this electrochemical
process could be smoothly performed to afford the target products in good to high yields at
room temperature.
Keywords: CO2 conversion, Electrosynthesis, 1,3,4-Oxadiazol-2(3H)-one derivatives, Iodine
catalysis.
* Corresponding author. E-mail: gqyuan@scut.edu.cn (G. Yuan)
1. Introduction
Carbon dioxide is a green, abundant and ideal one-carbon source and shows a great
potential in organic synthesis. Using carbon dioxide as C1 raw material to synthesize useful
chemicals has drawn more and more attention. Various kinds of organic chemicals have been
synthesized by the use of CO2. For example, Riduan et al. completed the hydrocarboxylation
of alkenes or alkynes with CO2 [1]. Yu and coworkers synthesized 2-quinoliones with CO2 as
the carbon source [2]. Zhang et al. realized the carboxylative cyclization of substituted
propenyl ketones with CO2 [3]. Jiang and co-workers successfully synthesized carbamates via
the coupling reaction of CO2 with amines and N-tosyldrazones [4]. Dinsmore et al. obtained
oxazolidinone from aminoethanol and CO2 [5]. Duñach’s group developed an electrochemical

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method to synthesize cyclic carbamates from aziridines and carbon dioxide for the first time
[6]. Feroci and co-workers achieved electrochemical synthesis of carbamates from CO2 and
amines in ionic liquid BMIm-BF4 [7]. In the past decade, great progress has been made in the
utilization of CO2 [8,9]. However, in order to extend application scope of carbon dioxide, it is
highly desirable to develop new routes for the conversion of CO2.
Some investigations have demonstrated that 1,3,4-oxadiazol-2(3H)-one derivatives can
inhibit HSL (Hormone-sensitive Lipase) [10–13] effectively and are used as an herbicide and
a fungicide [14]. Some commercial medicines, such as RF04958 [10], MmPPOX [12] and
CAY10499, could inhibit HSL and FAAH (Fatty Acid Amide Hydrolase) [15,16].
Conventional methods [12,17] for the synthesis of these compounds involved in toxic
phosgene or CO and a tedious multi-step synthetic process. From the viewpoints of simplicity,
cost effectiveness, nontoxicity and sustainability, using carbon dioxide to replace phosgene or
CO for the direct one-step synthesis of 1,3,4-oxadiazol-2(3H)-one derivatives seems to be
more attractive and more challenging. To the best of our knowledge, such a synthetic route
has not been explored to date.
Our group has been interested in exploring a new electrochemical route to convert CO2
into useful organic chemicals [18]. Based on our previous work, we attempted to search for a
new route to extend the utilization of CO2. We herein disclose an unprecedented strategy for
the one-pot synthesis of 1,3,4-oxadiazol-2(3H)-one derivatives by a three-component
coupling reaction of CO2 with aryl hydrazines and paraformaldehyde under electrochemical
conditions.
2. Experimental
The electrosynthesis was carried out in an undivided cell with a Ni foil (2 cm × 2.5 cm ×
0.02 cm) cathode and a graphite rod anode at room temperature. In a typical procedure,
MeOH (20 mL), n-Bu4NBF4 (2 mmol), phenylhydrazine (1.5 mmol), (HCHO)n (1.5 mmol),
NaI (0.45 mmol), and t-BuOK (1.5 mmol) were added to the cell, followed by charging CO2
into the desired pressure (1.5 MPa). Then, a constant current of 50 mA was passed through

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the electrolytic cell for 5 hours. During the electrolysis, the electrolyte solution was
continuously stirred by a magnetic stirrer. After the electrolysis was finished, the electrolyte
solution was washed with distilled water (10 mL), and then extracted with ethyl acetate (10
mL) for three times. The organic layer was collected and dried with anhydrous MgSO4. The
solvent was evaporated to give the crude product. The crude product was purified by silica gel
column chromatography with a mixture of petroleum and ether-ethyl acetate (100:1) as
eluent.
1
The obtained products were characterized by H NMR and 13C NMR spectra, which
were determined on a Bruker Advance 400 spectrometer in CDCl3 at 400 MHz and 100 MHz,
respectively. Mass spectra were recorded on a Shimadzu GC-MS-QP5050A spectrometer at
an ionization voltage of 70 eV. High resolution mass spectra (HRMS) analysis was performed
in a MAT95XP high resolution mass spectrometer. Fourier transform infrared spectrum
(FTIR) was measured by a TENSOR27 spectrometer.
The model product 3-phenyl-1,3,4-oxadiazol-2(3H)-one was characterized as follows.
3-Phenyl-1,3,4-oxadiazol-2(3H)-one (3a): IR (KBr): 3130, 1774 (C=O), 1596, 1497, 1376,
1
1190, 948, 729, 683 cm–1. H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 7.9 Hz, 2H), 7.71 (s,
1H), 7.45 (t, J = 7.7 Hz, 2H), 7.28 (t, J = 7.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 150.2
(C=O), 143.8 (C=N), 135.7, 129.2, 126.4, 118.3; HRMS (ESI) m/z: calcd for C8H6N2O2Na
[M+Na]+, 185.0321; found, 185.0316.
3. Result and discussion
The reaction of CO2 with phenylhydrazine (1a) and paraformaldehyde chosen as a model,
we initiate to study on the electrochemical synthesis of 3-phenyl-1,3,4-oxadiazol-2(3H)-one
(3a) in an undivided cell with graphite as an inert anode and Ni as a cathode. Using MeOH as
the solvent and n-Bu4NBF4 as the supporting electrolyte, the desired product was not obtained
at all (Table 1, entry 1). In the presence of base t-BuOK, 3a was obtained in 8% yield (entry
2). Despite of the yield being very low, this means that CO2 with phenylhydrazine (1a) and
paraformaldehyde could be converted to 3-phenyl-1,3,4-oxadiazol-2(3H)-one under
electrochemical conditions. We attempted to improve the yield of 3a via optimized
electrolytic conditions. Delightfully, the yield of 3a could be drastically raised to 49% and

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74% when KBr or KI was used as the electrocatalyst (entries 3 and 4), respectively. However,
KCl as the catalyst did not give an unsatisfactory result (entry 5). Further investigations
demonstrated that n-Bu4NI (especially NaI) could more effectively electrocatalyze this
reaction (entries 6 and 7). In addition, the effect of solvents on the reaction was further
examined. DMF, MeCN, EtOH and IPA (isopropanol) solvents could give acceptable yields
(entries 9–12). However, the yield of 3a sharply declined to 13% in the DMSO solvent case
(entry 13). These results showed that the solvents had a significant impact on the
electrosynthesis of 3a. In the present system, the base is also a key factor. In the absence of
additional base, the yield of 3a was only 18% (entry 18), indicating that additional base is
necessary for the formation of 3a. Among the surveyed bases (t-BuOK, DBU, K2CO3,
Na2CO3 and Cs2CO3), the strong base t-BuOK seems to be more beneficial for this
transformation (entries 7 and 14–17). The amount of t-BuOK was further screened. Using 0.5
equiv. of t-BuOK as the base, 3a was obtained in only 47% yield (entry 19). This means that
base t-BuOK serves as a promoter rather than a catalyst in the present system.
Under the optimized electrolytic conditions (Table 1, entry 7), we further investigated the
application scope of this electrochemical route. As shown in Scheme 1, various hydrazines
with CO2 and paraformaldehyde could be smoothly converted to the corresponding
1,3,4-oxadiazol-2(3H)-one derivatives in good to high yields. Notably, this electrochemical
process could well tolerate various functional groups such as halogen (F, Cl and Br), –CN,
–CF3, –CH3, and –OCH3 (Scheme 1, 3b–3h), which provided the possibility for the further
functionalization. In addition, it should be noted that the hydrazine derivatives with
electron-withdrawing groups showed higher reactivity than those with electron-donating ones,
and the stronger the electron-withdrawing group is, the easier the reaction is. For instance, the
aryl hydrazine with –CF3 group could afford the target product in a high yield (81%, Scheme
1, 3f), while the hydrazine bearing –OCH3 one gave an unsatisfactory result (only 25%,
Scheme 1, 3h). The relevant discussion would be given later. Moreover, the substituted group
at different positions on the phenyl ring of hydrazines had also effect on the reaction (Scheme
1, 3d and 3j).

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To better gain insight into the reaction mechanism, several control experiments were
carried out. In the absence of CO2, 3a was not obtained at all (Eq. 1), indicating that CO2 was
indispensable for the formation of 1,3,4-oxadiazol-2(3H)-one derivatives. If the electrolysis
for 2.5 h, the yield of 3a declined to 42% and 1-methylene-2-phenylhydrazine (2a) with the
yield of 23% was detected (Eq. 2). When the electrolysis was carried out for 5 h,
1-methylene-2-phenylhydrazine (2a) was hardly observed (Table 1, entry 7). This means that
1-methylene-2-phenylhydrazine (2a) with CO2 could be fully converted to the target product
3a with prolonging the electrolytic time. In addition, phenylhydrazine could react with
paraformaldehyde in MeOH solvent at room temperature to easily form
1-methylene-2-phenylhydrazine (2a) under non-electrochemical conditions (Eq. 3). Therefore,
we deduce that 1-methylene-2-phenylhydrazine (2a) may be an intermediate product during
the formation of 3a. According to the investigation reported by Matsubara’s group [19],
N-(α-chloroalkylidene)-N´-phenylhydrazine
could
react
with
CO2
to
form
1,3,4-oxadiazolin-2-ones in the presence of base Et3N or DABCO. In the present system, the
reaction mechanism could involve the generation of an important intermediate
N-(α-iodomethylene)-N´-phenylhydrazine.
Based on our experimental results and analyses described above, the probable reaction
mechanism is depicted in Scheme 2. Phenylhydrazine first reacts with paraformaldehyde to
yield intermediate 1-methylene-2-phenylhydrazine (2a), followed by the reaction with I2
generated from the oxidation of I– ions (2I– → I2 + 2e–) at the anode to produce a key
intermediate N-(α-iodomethylene)-N´-phenylhydrazine A. Meanwhile, CH3OH is
electroreduced to produce base CH3O– (2CH3OH + 2e– → 2CH3O– + H2) at the cathode [20].
Being similar to the reaction of N-(α-chloroalkylidene)-N´-phenylhydrazines with CO2 [19],

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N-(α-iodomethylene)-N´-phenylhydrazine A is converted into B anion under the co-operation
of the electrogenerated base CH3O– and additional base t-BuOK, followed by the reaction
with CO2 via the intermolecular nucleophilic attack to generate the target product 3a, together
with the elimination of I– ions. The I – ions can enter the next electrolytic circulation.
According to the proposed mechanism (Scheme 2), the hydrazines with
electron-withdrawing groups are more favorable for the formation of the intermediate B anion
than those with electron-donating ones. This mechanism could well explain that the
hydrazines bearing electron-withdrawing groups could give better results than those bearing
electron-donating ones, such as 3f and 3h (Scheme 1).
4. Conclusions
In
summary,
we
developed
a
novel
route
to
electrosynthesize
1,3,4-oxadiazol-2(3H)-one derivatives from CO2, aryl hydrazines and paraformaldehyde in
one step. This electrochemical route could effectively avoid the use of toxic phosgene or CO
which usually was used in traditional methods, and transform CO2 into useful organic
chemicals. In addition, the one-pot synthesis greatly simplifies a synthetic process of
1,3,4-oxadiazol-2(3H)-one derivatives. The present work provides a new, environmentally
friendly and effective alternative route for the synthesis of 1,3,4-oxadiazol-2(3H)-one
derivatives and the utilization of CO2.
Acknowledgements
This work was supported by the National Natural Science Foundation of China
(21572070 and 21172079), and Ministry of Science and Technology of the People’s Republic
of China (2016YFA0602900).
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Table 1
Optimization of electrolytic conditions a
Entry
Base
Catalyst
Solvent
Yield (%)b
1
–
–
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
DMF
0
2
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
–
8
3
KBr
KI
49
74
15
82
87
57
52
80
60
4
5
KCl
n-Bu4NI
NaI
NH4I
NaI
NaI
NaI
6
7
8
9
10
11
MeCN
EtOH
t-BuOK
t-BuOK
DBU
12
13
14
NaI
NaI
NaI
IPA
52
13
70
DMSO
MeOH
15
16
17
18
19c
K2CO3
Na2CO3
Cs2CO3
–
NaI
NaI
NaI
NaI
NaI
MeOH
MeOH
MeOH
MeOH
MeOH
69
54
79
18
47
t-BuOK
a
Electrolytic conditions: phenylhydrazine 1a (1.5 mmol), (HCHO)n (1.5 mmol), n-Bu4NBF4 (2 mmol), catalyst (0.3 equiv.), base
(1 equiv.), solvent (20 mL), CO2 (1.5 MPa), undivided cell, the separation distance 2.5 cm between Ni cathode and graphite
anode, and the two electrodes paralleling with each other, current 50 mA and 5 h. b Isolated yields. c 0.5 equiv. of t-BuOK.

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Scheme 1. Electrosynthesis of 1,3,4-oxadiazol-2(3H)-one derivatives from a variety of aryl
hydrazines (electrolytic conditions as shown in Table 1 (entry 7))

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Scheme 2. Proposed reaction mechanism.

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A novel electrochemical conversion of CO2 with aryl hydrazines
and
paraformaldehyde
into
1,3,4-oxadiazol-2(3H)-one
derivatives in one step
Na Yang, Qiang Lai, Huanfeng Jiang, Gaoqing Yuan*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou,
China
Graphical abstract

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Highlights


Using CO2 to replace toxic phosgene or CO as the C1 synthon.
The electrochemical conversion of CO2 with aryl hydrazines and paraformaldehyde
into 1,3,4-oxadiazol-2(3H)-one derivatives in one step.


The present work provides a new route to synthesize 1,3,4-oxadiazol-2(3H)-one
derivatives and utilize CO2.
I2 and base electrogenerated in situ play a significant role in the transformation.