Hydrodehalogenation of Aryl Halides through Direct Electrolysis

Article abstract of DOI:10.1002/chem.201901082

A catalyst- and metal-free electrochemical hydrodehalogenation of aryl halides is disclosed. Our reaction by a flexible protocol is operated in an undivided cell equipped with an inexpensive graphite rod anode and cathode. Trialkylamines nBu₃N/Et₃N behave as effective reductants and hydrogen atom donors for this electrochemical reductive reaction. Various aryl and heteroaryl bromides worked effectively. The typically less reactive aryl chlorides and fluorides can also be smoothly converted. The utility of our method is demonstrated by detoxification of harmful pesticides and hydrodebromination of a dibrominated biphenyl (analogues of flame-retardants) in gram scale.

Full text of DOI:10.1002/chem.201901082

A Journal of
Accepted Article
Title: Catalyst- and Metal-Free Hydrodehalogenation of Aryl Halides
through Direct Electrolysis
Authors: Jie Ke, Hongling Wang, Liejin Zhou, Chengli Mou, Jingjie
Zhang, Lutai Pan, and Yonggui Robin Chi
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To be cited as: Chem. Eur. J. 10.1002/chem.201901082
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Hydrodehalogenation of Aryl Halides through Direct Electrolysis
†
†
Jie Ke, Hongling Wang, Liejin Zhou, Chengli Mou, Jingjie Zhang, Lutai Pan,* and Yonggui Robin Chi*
Abstract:
A
catalyst-
and
metal-free
electrochemical
reductants and hydrogen atom donors (Figure 1b). Our reaction
is performed in an undivided cell equipped with graphite rod
electrodes. Catalysts and metals are not required, and the
reductive processes are enabled by electric currents. It is worth
to note that in previous electrochemical hydrodehalogenation
hydrodehalogenation of aryl halides is disclosed. Our reaction via a
flexible protocol is operated in an undivided cell equipped with
n
inexpensive graphite rod anode and cathode. Trialkylamines Bu
3
N
3
or Et N behave as effective reductants and hydrogen atom donors
[8]
for this electrochemical reductive reaction. Various aryl and
heteroaryl bromides worked effectively. The typically less reactive
aryl chlorides and fluorides can also be smoothly converted. The
utility of our method is demonstrated via detoxification of harmful
methods with undivided cells, metals were used as scarified
[
9]
anodes and separate hydrogen atom providers were needed.
pesticides and hydrodebromination of
a dibrominated biphenyl
(analogs of flame-retardants) in gram scale.
Hydrodehalogenation of organic halides is an important strategy
[
1]
in functional molecule synthesis. It also allows for detoxification
of environmentally hazardous chemicals containing halogen
[
2]
atoms. Numerous methods have been developed for this
reductive process that replaces halogens with hydrogen
[
3]
atoms. Representative reductants employed in this process
[
3a]
[3b-d]
include metals or low-valent metal compounds,
hydrides,
[
3e]
[3f]
hydrogen,
electron-rich
organic
molecules,
and
[
3g]
alcoholate.
These methods, with their own merits and
limitations with respects to key measures such as chemo-
selectivities and operational costs, are complimentary to each
other. There are continuous needs to develop new methods for
dehalogenation of organic halides under mild, operationally
simple, and cost-effective conditions. Trialkylamines are
inexpensive reagents and may behave as effective reductants
Figure 1. Hydrodehalogenation of Aryl Halides.
[
4]
The 4-phenoxylbromobenzene 1a was chosen as the model
substrate to evaluate the reaction conditions for this
hydrodehalogenative process (Table 1). We first examined the
reaction in an undivided cell equipped with a reticulated vitreous
carbon (RVC) anode and cathode. The proposed product 2a
under suitable activation conditions. For example, Stephenson
and König have recently shown that hydrodehalogenation of
organic halides can be realized by using trialkylamines as the
[
5]
terminal reductants and hydrogen atom donors (Figure 1a). In
[
5a]
[5b]
their approaches, metal complexes
or organic sensitizers
was not detected when using LiClO
CH
entry 1). Replacing LiClO
4
as the electrolyte and
are used as the photocatalysts and the radical processes are
enabled by visible lights.
Organic electrosynthesis has been recognized as a versatile
3
CN as the solvent under 10 mA constant current for 3.3 h
n
(
4
with Me
4
4 4 4
NBF or Bu NBF led to 2a
with about 10% or 29% yield respectively (entries 2-3). Further
optimizations did not lead to obvious improvements on the
reaction yields. We suspected that the trace trialkyl amines
and
environmentally
friendly
approach
for
redox
[6]
transformations. It has also been well-documented that amines
can undergo single-electron-transfer processes and oxidations
under electrolysis conditions. This electrochemical oxidation
process has been mainly explored to convert amines to iminium
intermediates for further addition reactions. Here we disclose a
method for dehalogenation of organic halides under
electrochemical conditions with amines as the terminal
[
10]
generated from the ammonium electrolytes under electrolysis
might behave as reductants and hydrogen atom providers for
the formation of 2a. We then added Et N as a potential reductant
to the reaction mixture and found that 2a was formed in 13%
yield with LiClO used as the electrolyte (entry 4). In the
presence of Et N, switching the electrolyte from LiClO to
Me NBF led to 2a with a significantly improved yield (31% yield,
entry 5). The combination of Et N as the reductant and
as the electrolyte led to 2a with 83% yield (entry 6).
[7]
3
4
3
4
4
4
3
[
+]
[+]
n
[*]
Dr. J. Ke, H. Wang, Dr. L. Zhou, Prof. Dr. Y. R. Chi, Division of
Chemistry & Biological Chemistry, School of Physical &
Mathematical Sciences, Nanyang Technological University,
Singapore 637371 (Singapore)
4 4
Bu NBF
Other electrolytes containing different anion have little effect on
the formation of the product 2a (entries 7-8). The yield was
decreased to 70% when using platinum plate as the anode and
cathode (entry 9), but it could be slightly increased when using
E-mail: robinchi@ntu.edu.sg
C. Mou, J. Zhang, Prof. Dr. L. Pan, Guiyang College of Traditional
Chinese Medicine, Guizhou (P.R.China).
the cheap graphite rod as the anode and cathode (entry 10).
E-mail: ltpan@sina.cn
These authors contributed equally to this work.
n
+
3 3
Bu N showed a similar reactivity as that of Et N (entry 11), and
[
]
a slightly increased yield could be obtained under 15 mA
constant current for 1.8 h (entry 12). It is worth to note that no
Supporting information for this article is available on the WWW
under http://www.angewandte.org.
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COMMUNICATION
product 2a could be detected without an external current applied
substrates. To our delight, substituted benzyl bromides could
also undergo the hydrodehalogenative process through this
protocol, with the corresponding products afforded in moderate
isolated yields (2p, 2q).
(
entry 13).
[
a]
Table 1. Optimization of the Reaction Conditions.
[
a]
Table 2. Substrate Scope of the Debromination.
[
b]
Entry
amine
none
none
none
electrolyte
LiClO
Me NBF
NBF
anode \ cathode 2a Yield [%]
1
2
3
4
5
6
7
8
9
4
RVC \ RVC
RVC \ RVC
RVC \ RVC
RVC \ RVC
RVC \ RVC
RVC \ RVC
RVC \ RVC
RVC \ RVC
Pt \ Pt
n.d.
~10
29
4
4
n
Bu
LiClO
Me NBF
4
4
3
Et N
3
Et N
3
Et N
3
Et N
3
Et N
3
Et N
3
Et N
4
13
4
4
31
n
Bu
4
NBF
4
6
83
n
Bu
4
NPF
83
n
Bu
4
NClO
4
75
n
Bu
Bu
Bu
Bu
Bu
4
NBF
NBF
NBF
NBF
NBF
4
70
n
1
0
1
4
4
4
4
4
C \ C
85
n
n
n
n
1
Bu
Bu
Bu
3
N
3
N
3
N
4
4
4
C \ C
86
[
c]
n
n
12
C \ C
90
[
d]
13

n.d.
[
a] Reaction conditions: 1a (0.3 mmol), amine (0.6 mmol, 2.0 equiv),
electrolyte (0.3 mmol, 1.0 equiv), CH CN (7.0 mL), room temperature, N , 3.3
3
2
h (4.1 F). [b] Isolated yields. [c] constant current = 15 mA, 1.8 h (3.3 F). [d] No
externally applied current. RVC = Reticulated Vitreous Carbon (1.0 cm × 1.0
cm × 1.0 cm), Pt = Platinum Plate (1.0 cm × 1.0 cm × 0.1 cm), C = Graphite
Rod (Φ = 6 mm), n.d. = no detected.
[
a] Reaction conditions: Method A: graphite rod anode (Φ = 6 mm), graphite rod
With the optimized electrochemical reaction conditions at
hand (Table 1, entry 12), we then examined the substrate scope
for this transformation using various substituted aryl- or alkyl-
bromides (Table 2). Substituents could be installed on each
position of the benzene mono-bromides, with all the products
afforded in moderate to good isolated yields (2b-2g, 2l). Strong
electron donating substituents generally give the products in
lower yields, but this obstacle could be overcome through a
slight modification of the reaction conditions (2e, 2f, 2l, 2m).
Unfortunately, aryl bromides with electron-deficient substituents
cathode (Φ = 6 mm), undivided cell, constant current = 15 mA, 1 (0.3 mmol),
n
n
3 4 4 3
Bu N (0.6 mmol, 2.0 equiv), Bu NBF (0.3 mmol, 1.0 equiv), CH CN (7.0 mL),
room temperature, N , 1.8 h (3.3 F). [b] Method B: RVC anode (1.0 cm × 1.0 cm
× 1.0 cm), RVC cathode (1.0 cm × 1.0 cm × 1.0 cm), undivided cell, constant
2
n
current = 15 mA, 1 (0.3 mmol), Et
.0 equiv), CH
3
N (0.6 mmol, 2.0 equiv), Bu
4 4
NBF (0.3 mmol,
1
3
CN/THF (6.0 mL/1.0 mL), room temperature, N
2
, 4.4 h (8.1 F).
Aryl chlorides and aryl fluorides have been challenging
substrates in the hydrodehalogenative reactions. To date, few
successful examples have been reported.
[
3i,5b,11]
(
-COOEt, -CN, -NO
2
) were not compatible in this electrochemical
We were
condition. Only trace products can be detected by GC-MS,
without any other by-products and remaining substrates. Multi-
cyclic fused (hetero-) aromatic bromides also work well in this
process (2h-2k). Notably, both of bromine atoms could be
replaced with hydrogen atoms when aryl dibromides were used
as the reactants (2m). The debromination product could undergo
further reductions when using 9-bromophenanthrene (product
delighted to find that with aryl chlorides or fluorides used as the
reaction substrates, this hydrodechlorination process occurred
smoothly under the current optimized reaction conditions (Table
3). For example, electron-rich chlorobenzenes bearing various
substituents could be effectively reduced to give the substituted
benzenes in moderate to good yields (4a-4b, 4d-4e). Chloro-
and fluoro- naphthalenes could also be reduced through this
2n and 2n') and 9-bromoanthracene (product 2o and 2o') as the
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electrochemical transformation, with the naphthalenes (4c, 4f)
afforded as the final products in moderate yields.
harmful to human health and the ecosystem, and are very
[
13]
difficult to degradate. Dehalogenation of these molecules can
reduce their toxicity and accelerate their degradation process.
To further demonstrate the potential utilities of this method, we
performed the hydrodehylogenation reactions with several
pesticides and analogues of flame-retardant materials (Scheme
[
a]
Table 3. Substrate Scope of the Dechlorination and Defluorination.
1). For example, Propachlor (herbicide, 5) and Benodanil
(
fungicide, 7) could be smoothly converted to corresponding
non-halogen-containing products through this newly developed
electrochemical protocol (Scheme 1a). 4,4'-Dibromo-1,1'-
biphenyl (9), an anologue of the polybrominated biphenyls
(
PBBs) that have been widely used as flame-retardant
[14]
materials,
could also be smoothly reduced through this
electrochemical transformation in gram scales, with the fully
debrominative product 10 and the single debrominative product
11 afforded in 50% yield and 33% yield respectively (Scheme
1b).
This catalyst- and metal-free hydrodehalogenative reaction is
proposed to go through a two-electron transfer process (Figure
2). A two-electron anodic oxidation of Et
3
N provides the iminium
I
that may upon hydrolysis lead to diethylamine and
[
a] Reaction conditions: graphite rod anode (Φ = 6 mm), graphite rod cathode
n
acetaldehyde. On the other hand, a two-electron cathodic
reduction of aryl halide substrate Ar-X provides the aryl anion II
which is then protonated by acetonitrile or trialkylamine to give
the desired hydrodehalogenative aryl product (Ar-H).
(
Φ = 6 mm), undivided cell, constant current = 15 mA, 3 (0.3 mmol), Bu
3
N (0.6
n
mmol, 2.0 equiv), Bu
4
NBF
4
(0.3 mmol, 1.0 equiv), CH
3
CN (7.0 mL), room
2
temperature, N , 1.8 h (3.3 F). [b] Constant current = 20 mA, 3.3 h (8.1 F).
Figure 2. Proposed Pathway.
In summary, we have developed an electrochemical approach
for the hydrodehalogenation of organic halides. Our reaction
used trialkylamine as the reductant and hydrogen atom provider
under electrochemical conditions. The reaction was carried out
in an undivided cell equipped with the inexpensive graphite rod
anode and cathode. No catalysts or metals are needed for this
transformation. Substituted aryl or alkyl halides bearing different
halogen atoms worked well in this hydrodehalogenation process.
This method could be used for the detoxification and
degradation of harmful organic halides existed in pesticides and
flame-retardant materials. The development of efficient and
inexpensive electrochemical reactions, including catalytic
asymmetric reactions and post synthetic modification of
medicines and pesticides, are currently in progress in our
laboratories.
Scheme 1. Applications of Our Hydrodehalogenation Methods.
Halogen atoms are widely present in pesticides and chemical
[12]
materials. These organic halide-containing residuals are toxic,
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hydrodehalogenation
•
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Layout 2:
COMMUNICATION
Jie Ke, Hongling Wang, Liejin Zhou,
Chengli Mou, Jingjie Zhang, Lutai Pan,*
and Yonggui Robin Chi*
Page No. – Page No.
Eelectrochemical reduction: A catalyst- and metal-free electrochemical
hydrodehalogenation of aryl halides is disclosed. Aryl halides with bearing different
halogen atoms or different substituents were well tolerated.
Hydrodehalogenation of Aryl Halides
through Direct Electrolysis
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