Electrochemical Deoxygenation of N-Heteroaromatic N -Oxides

Article abstract of DOI:10.1055/s-0037-1611541

An electrochemical method for the deoxygenation of N-heteroaromatic N -oxide to give the corresponding N-heteroaromatics has been developed. Several classes of N-heterocycles such as pyridine, quinoline, isoquinoline, and phenanthridine are tolerated. The electrochemical reactions proceed efficiently in aqueous solution without the need for transition-metal catalysts and waste-generating reducing reagents.

Full text of DOI:10.1055/s-0037-1611541

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Georg Thieme Verlag Stuttgart · New York
2019, 30, A–C
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P. X., H.-C. Xu
Cluster
Electrochemical Deoxygenation of N-Heteroaromatic N-Oxides
P. Xu
H.-C. Xu*
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8-5
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undivided cell
College of Chemistry and Chemical Engineering,
Xiamen University, 422 South Siming Road, Xia-
men 361005, P. R. of China
N
O
N
Et4NPF6 (0.2 equiv)
MeCN/H2O (4:1), 80 °C
14 examples
up to 86% yield
haichao.xu@xmu.edu.cn
Received: 19.04.2019
Accepted after revision: 25.04.2019
Published online: 10.05.2019
Pd/C + H2
or stoichiometric reagents
Zn, PCl3, H2NNH2
PPh3, (Bpin)2, etc.
DOI: 10.1055/s-0037-1611541; Art ID: st-2019-b0117-c
previous work
R
R
Abstract An electrochemical method for the deoxygenation of N-het-
eroaromatic N-oxide to give the corresponding N-heteroaromatics has
been developed. Several classes of N-heterocycles such as pyridine,
quinoline, isoquinoline, and phenanthridine are tolerated. The electro-
chemical reactions proceed efficiently in aqueous solution without the
need for transition-metal catalysts and waste-generating reducing re-
agents.
N
N
this work
O
electrochemical reduction
Scheme 1 Deoxygenation of N-heteroaromatic N-oxides
N-Oxide 1a was chosen as a model substrate for reaction
optimization (Table 1). The best conditions for the deoxy-
genation reaction involve running the electrolysis in
Key words reduction, organic electrosynthesis, deoxygenation, elec-
trolysis, heterocycles
MeCN/H O (4:1) at 80 °C employing reticulated vitreous
2
carbon (RVC) as anode, Pb as cathode, and a constant cur-
rent of 10 mA. Et NPF (0.2 equiv) was added as a support-
The N–O bond in aromatic N-oxides serves as an excel-
lent directing group in C–H activation reactions, conferring
enhanced reactivity and regioselectivity over their oxygen-
4
6
ing electrolyte to increase conductivity of the reaction mix-
ture. Under these conditions, the deoxygenated quinoline
2a was obtained in 76% yield after the consumption of 2 F
1
free counterparts. However, the deoxygenation of N-oxides
generally requires Pd-catalyzed hydrogenation or a stoi-
chiometric amount of a chemical reductant (Scheme 1,
mol–1 of charge. Control experiments showed that H O (en-
2
try 2) and heating (entry 3) were needed for optimal re-
sults. Replacing MeCN with MeOH also led to yield reduc-
tion (entry 4). Pb was the optimal material for cathode as
other materials such as Pt (entry 5), Fe (entry 6), graphite
(entry 7), red brass (entry 8), and Ni (entry 9) were all less
efficient for promoting the deoxygenation reaction. In addi-
tion, replacing RVC with graphite plate also reduced the
yield of 2a slightly.
1b,c,2
top),
the latter of which are not only uneconomical, but
also pose an environmental hazard. The development of
more sustainable synthetic methods requires the reduction
in use of sacrificial reagents. Organic electrosynthesis em-
ploys electricity to promote redox reactions and have been
3
attracting increasing attention among chemists. We have
been interested in electrochemical synthesis and function-
4
alization of N-heterocycles and recently developed an elec-
The scope of the electrochemical deoxygenation reac-
5
trochemical dehydrative cyclization reaction of oximes for
the synthesis of N-heteroaromatics.4 The reactions pro-
ceed through dehydrogenative cyclization to form an N-he-
teroaromatic N-oxide followed by deoxygenation to give the
final product. Herein we report the detailed studies on the
electrochemical deoxygenation of N-heteroaromatic N-ox-
ides (Scheme 1, bottom).
tion was explored (Scheme 2). 2-Methylquinoline N-oxide
a
(1b) and quinoline N-oxide (1c) reacted to give the corre-
6
7
sponding deoxygenated products (2b, 2c ) in good yields. A
brominated quinoline N-oxide (1d) underwent decomposi-
tion and failed to afford the desired product 2d. Pyridine N-
8
oxides bearing at the 4-position an OMe (2e ), tBu (2f), Ph
(2g), or CN (2h) group reacted smoothly. The relative low
yield of the electron-deficient 2h might be caused by its
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–C

B
Synlett
P. X., H.-C. Xu
Cluster
Table 1 Optimization of Reaction Conditionsa
RVC
Pb
R
constant current = 10 mA
R
RVC
Pb
N
O
Et4NPF6 (0.2 equiv)
MeCN/H2O (4:1), 80 °C
N
Et4NPF6 (0.2 equiv)
N
O
Ph
CH3CN/H2O (4:1), 80 °C
N
Ph
1b−o
2b−o
"
standard conditions"
1
a
2a
R
N
OMe
Entry
Deviation from standard conditions
none
Yield (%)b
1
2
3
4
5
6
7
8
9
76c
N
N
N
no H
reaction at RT
MeOH/H O (4:1)
2
O
71
2
b, 70%
R = H, 2c, 65%
(2.2 F mol )
R = Br, 2d, 0%
2e, 77%
2f, 86%
(6.0 F mol–1)
(
2.4 F mol–1)
–1
(4.0 F mol–1)
55 (25)
60 (13)
35 (47)
37 (44)
69 (10)
65 (12)
58 (19)
70 (<5)
2
Ph
CN
Pt plate as cathode
Fe plate as cathode
graphite plate as cathode
red brass as cathode
Ni plate as cathode
N
Ph
N
OH
N
N
2g, 82%
2h, 46%
(2.5 F mol–1)
2i, 82%
(2.7 F mol–1)
2j, 63%
(4.5 F mol–1)
(
2.2 F mol–1)
10
graphite plate as anode
R
a
O
O
Reaction conditions: 1a (0.3 mmol), MeCN (8 mL), H
2
O (2 mL), Et
4 6
NPF
–1
(
0.06 mmol), argon, RVC anode, Pb cathode, 10 mA, 1.6 h (2.0 F mol ).
N
b
Yield determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as
N
N
an internal standard. Unreacted 1a is shown in parentheses.
N
c
Isolated yield.
R = H, 2k, 80%
2m, 75%
(2.5 F mol–1)
2n, 68%
(2.5 F mol–1)
2o, 28%
(3.1 F mol–1)
–
1
(3.5 F mol )
R = CO2Me, 2l, 34%
overreduction at the cathode. 2-Substitued pyridine N-ox-
ides were also suitable substrates (2i and 2j). The reaction
tolerated other N-heteroaromatic N-oxides derived from
isoquinoline (2k and 2l), phenanthridine (2m), and benzo-
phenanthridine (2n). Acridine N-oxide (1o) reacted to give
acridine (2o) in a low yield of 28%.
(5.2 F mol–1)
Scheme 2 Reaction scope
anode
e
cathode
A possible mechanism for the electrochemical deoxy-
genation process was illustrated in Scheme 3. The aromatic
N-oxide is reduced at the cathode through a 2e process
2
H O
–
H2O
with the assistance of H O to give the corresponding deoxy-
N
O
2
genated product. At the anode, H O is probably oxidized to
2e
2
2e
+
−
generate O . Since the same amount of H and OH are gen-
2
erated at the anode and cathode, respectively, H O is not
2
/2 O2 + 2H+
1
consumed, and the net results are that the N-oxide reacts to
give the deoxygenated product and O2.
N
2 HO
In summary, an electrochemical method for the deoxy-
genation of N-heteroaromatic N-oxide has been developed.
The reactions are compatible with several classes of N-het-
erocycles and proceed efficiently in aqueous solution in the
absence of transition-metal catalysts and waste-generating
reducing reagents.
Scheme 3 Proposed mechanism
China (NSFC, Grant No. 21672178) is acknowledged. We also ac-
knowledge the support of Fundamental Research Funds for the Cen-
tral Universities.
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Funding Information
Supporting Information
Financial support of this research from the Ministry of Science and
Technology of the People’s Republic of China (MOST, Grant No.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611541.
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2016YFA0204100) and the National Natural Science Foundation of
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P. X., H.-C. Xu
Cluster
References and Notes
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the N-heteroaromatic N-oxide (0.30 mmol, 1.0 equiv) and
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4
6
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2
(
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(
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3
(
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7.21 (m, 1 H), 2.72 (s, 3 H). C NMR (101 MHz, CDCl ):  = 159.1,
3
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(
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3
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
= 8.94–8.83 (m, 1 H), 8.10 (d, J = 8.2 Hz, 2 H), 7.82–7.63 (m, 2
13
H), 7.56–7.45 (m, 1 H), 7.35 (dq, J = 7.5, 3.8 Hz, 1 H). C NMR
(101 MHz, CDCl ):  = 150.5, 148.4, 136.1, 129.6, 129.5, 128.4,
3
1
27.9, 126.6, 121.2.
8) Spectral Data for 2e
Colorless oil; yield 77%; 4.0 F mol . H NMR (400 MHz, CDCl ):
–1
1
3
(
4) (a) Zhao, H.-B.; Xu, P.; Song, J.; Xu, H.-C. Angew. Chem. Int. Ed.
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
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(101 MHz, CDCl ):  = 165.7, 151.2, 110.0, 55.2.
3
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©
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–C