Chemoselective electrochemical reduction of nitroarenes with gaseous ammonia

Article abstract of DOI:10.1039/d1ob00077b

Valuable aromatic nitrogen compounds can be synthesized by reduction of nitroarenes. Herein, we report electrochemical reduction of nitroarenes by a protocol that uses inert graphite felt as electrodes and ammonia as a reductant. Depending on the cell voltage and the solvent, the protocol can be used to obtain aromatic azoxy, azo, and hydrazo compounds, as well as aniline derivatives with high chemoselectivities. The protocol can be readily scaled up to >10 g with no decrease in yield, demonstrating its potential synthetic utility. A stepwise cathodic reduction pathway was proposed to account for the generations of products in turn.

Full text of DOI:10.1039/d1ob00077b

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Biomolecular Chemistry
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Chemoselective electrochemical reduction of
nitroarenes with gaseous ammonia†
Cite this: Org. Biomol. Chem., 2021,
19, 2468
Liu Chang,‡a Jin Li,‡b Na Wua and Xu Cheng
*
a
Valuable aromatic nitrogen compounds can be synthesized by reduction of nitroarenes. Herein, we report
electrochemical reduction of nitroarenes by a protocol that uses inert graphite felt as electrodes and
ammonia as a reductant. Depending on the cell voltage and the solvent, the protocol can be used to
obtain aromatic azoxy, azo, and hydrazo compounds, as well as aniline derivatives with high chemoselec-
tivities. The protocol can be readily scaled up to >10 g with no decrease in yield, demonstrating its poten-
tial synthetic utility. A stepwise cathodic reduction pathway was proposed to account for the generations
of products in turn.
Received 14th January 2021,
Accepted 23rd February 2021
DOI: 10.1039/d1ob00077b
rsc.li/obc
The reduction of nitroarenes can provide a variety of useful gated, and research to date has focused on the development of
nitrogen compounds, such as anilines, azobenzenes and azox- novel electrode materials with improved electrocatalytic activity
ybenzenes. Azobenzenes also have applications as energy in reactions involving inert hydrogen sources.7,13 For example,
storage materials,1 molecular switches,2 monomers for azoxy Cyr and co-workers reported the electrolytic reduction of nitro-
polyesters,3 as building blocks for liquid crystals,4 and as benzene at polycrystalline copper and nickel electrodes with
directing groups in transition-metal-catalyzed C–H functionali- water as the hydrogen source.14 Recently, cathodes made of
zation reactions.5 Reduction of nitroarenes to anilines is defect-engineered TiO2−x single crystals,15 Sm,16 nitrogen-
usually accomplished by heterogeneous catalytic hydrogen- doped carbon-supported non-noble metals,17 and a CoP/Co3S4
ation or by transfer hydrogenation mediated by elemental nanosheet18 have been used for electrochemical conversion of
reagents (Scheme 1a).6 In comparison, the protocols reducing nitroarenes to azoxybenzenes, azobenzenes, hydroazoben-
nitroarenes to azobenzene and azoxybenzenes were less devel- zenes, hydrazobenzenes, or anilines (Scheme 1a). Although
oped as explicit controls of reaction conditions were required these methods are safe and environmentally friendly, engin-
to achieve the chemoselectivities at different levels of eered electrodes are usually costly and difficult to prepare,
reduction.7 The development of mild, atom-economical and which limits their utility for large-scale applications.
highly selective methods for reduction of nitroarenes is highly
desirable.
We speculated that an electrochemical method might be
useful for this purpose. Research on electrochemical synthesis
has resulted in new transformations,8 better understanding of
reaction mechanisms,9 the development of combinations with
other synthetic protocols10 and new instruments,11 and
exploration
of
potential
industrial
applications.12
Electrochemical reduction of nitroarenes has been investi-
aInstitute of Chemistry and Biomedical Sciences, Jiangsu Key Laboratory of Advanced
Organic Materials, School of Chemistry and Chemical Engineering, National
Demonstration Center for Experimental Chemistry Education, Nanjing University,
Nanjing, 210023, China. E-mail: chengxu@nju.edu.cn; Tel: +86-25-89689037;
Fax: +86-25-89689037
bJiangsu Provincial Engineering Laboratory of Advanced Materials for Salt Chemical
Industry, College of Chemical Engineering, Huaiyin Institute of Technology, Huaian
223003, China
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1ob00077b
Scheme 1 Synthesis of aromatic azoxy, azo, hydrazo, and aniline
derivatives via reduction of nitroarenes.
‡These two authors contribute equally to this work.
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Therefore, it would be desirable to develop affordable, readily in 8 hours (ESI, section 6†) and the isolated yield was 82%
available electrode materials for reduction of nitroarenes with (entry 7). When tetrabutyl ammonium salts was used instead
various and economic-friendly hydrogen sources.
of LiClO4, the yield dropped more or less (entries 8–10). Next,
Recently, we demonstrated that graphite felt (GF), an in- the decrease of cell voltage to 4 V resulted in sluggish conver-
expensive carbon material, can be used for electrochemical sion (entry 11) and the increase to 8 V leaded to poor chemo-
reduction of alkenes with ammonia as a hydrogen source.19 In selectivity (entry 12). If NH3 was replaced by H2O, no reduction
these transformations, the GF act as both anode and cathode, took place (entry 13).
which facilitates scale up. In addition, ammonia is compatible
Using the optimized conditions for 2a (Table 1, entry 1), we
with various electrochemical reaction conditions owing to its explored the substrate scope with respect to the nitroarene
safety, solubility, and reactivity. In industry, the ammonia was (Scheme 2). Reduction of 1a on a 0.1 mol scale with enlarged
applied as the hydrogen source in the transitional-metal-cata- GF electrodes (8 cm × 5 cm × 1 cm) gave 2a in 66% isolated
lysed reduction of nitroarene.20 Inspired by these previous yield. Smaller-scale reactions of fluoro-substituted nitroben-
works, we have now reported the first electrochemical zenes afforded 2b and 2c in 57% and 72% yields, respectively;
reduction of nitroarenes on GF electrodes with ammonia as and para-CF3-substituted product 2d was obtained in 86%
the hydrogen source (Scheme 1b).
We began by carrying out reactions of a model substrate, in moderate to good yields; notably, dechlorination side reac-
nitrobenzene (1a), under an ammonia atmosphere at room tions did not take place. In a reaction of 1g at 0.08 mol L−1
yield. Chloro-substituted azoxybenzenes 2e–2g were prepared
,
temperature with variable parameters (Table 1). A series of the faradaic efficiency to 2g was measured to be 22% (ESI,
optimization experiments revealed that azoxybenzene 2a, azo- section 5†). In addition, even though styrene moieties are
benzene 3a, and hydrazobenzene 4a could be obtained respect- highly reactive in electrochemical transformations, we were
ively. When MeCN was used as the solvent in an undivided cell able to obtain azoxybenzene 2h, which has two vinyl groups, in
with a 6 V cell voltage and LiClO4 as a supporting electrolyte, 47% yield. Substrates with electron-donating methyl and
reaction of 4 hours could provide 2a in 68% NMR yield and methoxy groups were evaluated and found to give good yields
65% isolated yield (entry 1). If the reaction was allowed to run of the corresponding azoxybenzenes (2i–2l). A thioether group
till 7 hours, azobenzene 3a was observed as the major product was also well-tolerated (2m, 68% yield). 2,2′-Dinitro-1,1′-biphe-
in 76% NMR yield (entry 2). Further prolonged reaction time nyl (1n) underwent a reductive annulation reaction to afford
could afford 4a in almost quantitative yield (entry 3). Other sol- 2n in 40% yield. Finally, a reaction of nitrobenzene and
vents (DMF and DMSO) gave inferior results (entries 4 and 5). 4-nitroanisole gave a mixture of 2o and 2o′ in a combined yield
It was glad to observe by using MeOH as solvent, the yield of of 45%. Product 2p bearing ester groups was also achieved in
3a got improved slightly to 80% (entry 6). Changing the elec- 52% yield.
trolytic method to constant current protocol at 25 mA cm−3
,
As that revealed during the reaction optimization, electroly-
the yield of 3a was increased to 86% in a tracking experiment sis in MeOH under constant current conditions provided the
Table 1 Optimization of conditions for reduction of nitrobenzene to azoxybenzene, azobenzene, and hydrazobenzenea
Yieldb (%)
Entry
Solvent
Supporting electrolyte
Electrolytic method
Time (h)
2a
3a
4a
1
2
3
4
5
6
7
8
CH3CN
CH3CN
CH3CN
DMF
DMSO
MeOH
MeOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
LiClO4
nBu4NBF4
nBu4NBr
nBu4NClO4
LiClO4
LiClO4
LiClO4
6 V
6 V
6 V
6 V
6 V
6 V
25 mA
6 V
6 V
6 V
4 V
8 V
6 V
4
7
12
12.5
12
8
8
3.5
4
4
12
3
68(65)
Trace
ND
24
ND
Trace
Trace
Trace
Trace
10
66
10
Trace
76%
ND
Trace
ND
81
86(82)
59
65
57
12
47
ND
Trace
Trace
96(96)
Trace
ND
Trace
10
Trace
21
18
9
10
11
12
13c
Trace
33
12
ND
a Standard conditions: 1a (0.2 mmol), supporting electrolyte (0.1 mmol), solvent (5 mL), GF electrodes, undivided cell, ammonia atmosphere, rt.
b 1H NMR yields are provided. ND, not detected. c Use H2O (10 equiv.) instead of NH3.
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Scheme 3 Electrochemical reduction of nitroarenes 1 to azoarenes 3
with ammonia as a reductant. Reaction conditions: 1 (0.2 mmol), LiClO4
(0.1 mmol), MeOH (5 mL), GF electrodes, 25 mA, undivided cell,
ammonia atmosphere, rt, 3–14 h. Isolated yields are provided.
Scheme 2 Electrochemical reductions of nitroarenes 1 with ammonia
to afford azoxyarenes. Reaction conditions:
1 (0.2 mmol), LiClO4
(0.1 mmol), MeCN (5 mL), GF electrodes, 6 V cell voltage, undivided cell,
ammonia atmosphere, rt, 3–12 h. Isolated yields are provided.
be obtained, although the yields were reduced by oxidation
during workup and purification. As expected, methyl groups
did not interfere with the electrochemical process: 4h and 4i
optimal yield for 3a. Using these conditions (Table 1, entry 7), were obtained in good yields. A product 4k in 73% yield
we investigated transformations of other nitroarenes showed ester was also tolerated under this conditions. Finally,
(Scheme 3). Electron-withdrawing groups were acceptable sub- we found that substrates bearing strongly electron-donating
stituents, and desired products 3b–3g were obtained in groups afforded aniline derivatives (5a–5c) as the major pro-
44–68% yields. The vinyl groups of 3h remained intact during ducts. Along with the product 4k, compound 5d was also iso-
the reduction, and methyl-, methoxy-, and thioether-substi- lated in 24% yield.
tuted products 3i–3m could also be prepared. However, the
Next, cyclic voltammetry experiments was carried out to
reduction of 4-OMe-nitrobenzene (1k) was slower than that of study the property of reactant species. In MeCN, the cathodic
other substrate because of the effect of the para-methoxy reduction took place at about −0.7 V (vs. SCE) for 2a and 3a.
group; however, when the reaction time was prolonged, The anodic properties of 2a, 3a, 4a, and ammonia were exam-
product 3k partially decomposed, which reduced the yield to ined respectively, and ammonia was the most reductive species
33%. Benzo[c]cinnoline 3n was generated in 69% yield by reac- (Scheme 5a). Next, as that observed during the reaction con-
tion of 2,2′-dinitrobiphenyl. Azoarenes bearing CN (3o) and dition optimization (Table 1) and in the tracking of conversion
ester group (3p) were also prepared with this protocol in 61% of 2a and 3a (ESI, section 6†), the reduction of nitroarenes pro-
and 48% yields respectively.
ceeded stepwise to 2a, 3a, and 4a. In addition, by measuring
After synthesizing the azobenzenes, we explored the the chronoamperogram, it was found the reduction current
product scope of the protocol with further reduction from 1a dropped in stages at the point of about 3.0 and
(Scheme 4). Under the optimized conditions (Table 1, entry 3), 7.5 hours, suggesting the intermediate products, for example
electrochemical reduction of 1a for 12 h afforded hydrazoben- 2a and 3a, could be isolated, especially in MeOH (ESI, section
zene 4a in 96% yield. A similarly good yield of 4b (90%) was 6†). So a reaction pathway was proposed in Scheme 5b. The
also obtained. However, the yield of 4-CF3-substituted product nitroarene 1 get electrons from cathode coupled with protona-
4c was only 31%, owing to sluggish conversion of the starting tion by ammonium ion and underwent stepwise reduction
material. The yields of 4d and 4e were low for the same reason. from A to D. The dimerization of D provided E that dehydrated
Brominated and iodinated hydrazoarenes 4f and 4g could also to azoxyarene 2. Product 2 could further be reduced via
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Scheme 4 Electrochemical reductions of nitroarenes 1 to hydrazoar-
enes 4 or anilines 5 with ammonia as a reductant. Reaction conditions: 1
(0.2 mmol), LiClO4 (0.1 mmol), MeCN (5 mL), GF electrodes, 6 V cell
voltage, undivided cell, ammonia atmosphere, rt, 3–12 h. Isolated yields
are provided.
Scheme 5 Proposed reaction pathway with related analysis.
Author contributions
Chang Liu and Jin Li contribute equally to this work.
proton-coupled electron transfer at cathode to azoarene 3 and
hydrazoarenes 4. At anode, the ammonia was oxidized to cat-
ionic radical that reacted with ammonia to give ammonium
ion and neutral radical. The dimerization of nitrogen radical
would give hydrazine that in situ underwent further oxidation/
deprotonation and finally nitrogen was released (ESI, section
7.2†). This N2 evolution could provide a strong driving force
for reaction, making ammonia a potential and safe hydrogen
source in electrochemical reduction reactions. It was noted
that the aniline products 5 might be the result of further
reduction of D, other than dimerization.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was supported by the National Science Foundation
of China (no. 22071105 and 22031008) and QingLan Project of
Jiangsu Education Department. J. L. appreciates the funding
support from National Science Foundation of China (no.
22001089) and the Natural Science Foundation of Jiangsu
Province (no. BK20191046).
Conclusions
In summary, electrochemical reduction of nitroarenes with
ammonia as a hydrogen source was achieved for the first time.
Inert GF was used as both anode and cathode, and by tuning
the solvent and the reaction time, we could obtain azoxy, azo,
hydrazo, and aniline derivatives selectively. The reaction could
easily be scaled up to 10 g, and substituents such as bromo or
iodo atoms and vinyl groups were well-tolerated. Our findings
demonstrate the potential of ammonia as a hydrogen source
in electrochemical reduction reactions.
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