Electrochemical Hydrogenation with Gaseous Ammonia

Article abstract of DOI:10.1002/anie.201813464

As a carbon-free and sustainable fuel, ammonia serves as high-energy-density hydrogen-storage material. It is important to develop new reactions able to utilize ammonia as a hydrogen source directly. Herein, we report an electrochemical hydrogenation of alkenes, alkynes, and ketones using ammonia as the hydrogen source and carbon electrodes. A variety of heterocycles and functional groups, including for example sulfide, benzyl, benzyl carbamate, and allyl carbamate were well tolerated. Fast stepwise electron transfer and proton transfer processes were proposed to account for the transformation.

Full text of DOI:10.1002/anie.201813464

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Accepted Article
Title: Electrochemical hydrogenation with gaseous ammonia
Authors: Jin Li, Linfeng He, Xu Liu, Xu Cheng, and Guigen Li
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201813464
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10.1002/anie.201813464
Angewandte Chemie International Edition
COMMUNICATION
Electrochemical hydrogenation with gaseous ammonia
Jin Li,[a,d] Lingfeng He,[a] Xu Liu,[a] Xu Cheng,*[a,b] Guigen Li[a,c]
Abstract: As a carbon-free and sustainable fuel, ammonia serves as
high energy density hydrogen storage material. It is important to
develop new reactions able to utilize ammonia as hydrogen source
directly. Herein, we report an electrochemical hydrogenation of
alkenes, alkynes, and ketones using ammonia as the hydrogen
source and carbon electrodes. A variety of heterocycles and
functional groups, including for example sulfide, benzyl, benzyl
carbamate and allyl carbamate were well tolerated. A fast stepwise
electron transfer and proton transfer process were proposed to
account for the transformation.
Herein, we report the first electrochemical hydrogenation of
alkenes, alkynes, and ketones using gaseous ammonia as the
proton source. This transformation was carried out at balloon
pressure at room temperature with carbon anode and cathode. In
contrast to established Birch reduction, arenes, such as phenyl
and heterocycles, were well tolerated and a number of functional
goups labile in transition-metal-catalyzed hydrogenation reaction
were compatible in this reaction.
As one of the most highly produced industrial chemicals in the
world, ammonia was used as fertilizer for one century. Most
recently, ammonia was found to be one efficient and renewable
energy storage material.[1] In terms of energy density, safety in
storage and transportation, ammonia acts as an ideal hydrogen
source with nitrogen as the only side product and found
applications in hydrogen-powered fuel cell devices.[2] In the trends
of sustainable chemistry, direct utilization of ammonia in organic
synthesis is, therefore, desirable.[3] One prominent protocol was
Birch reduction, employing liquid ammonia solution with cryogenic
or pressurized conditions and converting aromatic compounds to
dearomatized products.[4]
Electrochemical reactions are a fundamental tool for building
molecules with efficient utilization of energy. Recently,
electrochemical reactions have received a great deal of attention,
and new reactivity and mechanisms have been reported.[5] In
particular, electrochemistry has been shown to be a powerful
strategy for activating substrates in innovative ways.[6]
Tremendous progress has been achieved in various reactions to
construct C–C,[7] C–N,[8] C–O,[9] and C–halogen bonds,[10] as well
as multiple bonds.[11] Ammonia showed fundamental compatibility
with electrochemical conditions. Pioneering study by Thiebault[12]
and Bard[13] achieved electrochemical Birch reduction of arenes
in liquid ammonia. Most recently, Xu reported an novel example
utilizing ammonia directly in build nitrogen-containing compounds,
exhibiting the tremendous potential of ammonia in
electrochemical synthesis.[14]
Scheme 1 Direct application of ammonia in electrochemical reactions
We began by investigating the hydrogenation of substrate 1a in
an undivided cell with two electrodes made of graphite felt (Table
1). Substrate 1a was chosen in part because transition-metal-
catalyzed hydrogenation of this compound is challenging. For
example, in the presence of Wilkinson’s catalyst (entry 1) or
Crabtree’s catalyst (entry 2), hydrogenation of 1a under pressure
did not occur, possibly because of the coordination ability of the
pyridinyl group of the substrate. When Pd/C was the catalyst, the
reaction was not regioselective, and a mixture of hydrogenated
products was obtained (entry 3). In contrast, reaction of 1a in
acetonitrile at room temperature under gaseous ammonia in a
balloon at a cell potential of 5 V (cathode potential of -4.5 V vs
SCE) and a Faraday efficiency of 54% afforded 2a as the sole
product in 73% yield (entry 4). When ammonia was replaced with
water as the hydrogen source, only a trace of 2a was detected
(entry 5). In a protonic solvent (MeOH) instead of acetonitrile, an
inferior yield of 61% was obtained (entry 6).
[a]
Jin Li, Lingfeng He, Xu Liu, Xu Cheng, Guigen Li
Institute of Chemistry and Biomedical Sciences, Jiangsu Key
Laboratory of Advanced Organic Materials, National Demonstration
Center for Experimental Chemistry Education, School of Chemistry
and Chemical Engineering, Nanjing University
Address Xianlin Rd. 163, , Nanjing, 210023, China
E-mail: chengxu@nju.edu.cn
[b]
[c]
[d]
Xu Cheng
State Key Laboratory Cultivation Base for TCM Quality and Efficacy,
Nanjing University of Chinese Medicine, Nanjing, China.
Guigen Li
Department of Chemistry and Biochemistry, Texas Tech University,
Lubbock, Texas, United States
Jiangsu Provincial Engineering Laboratory of Advanced Materials
for Salt Chemical Industry, College of Chemical Engineering,
Huaiyin Institute of Technology, Jiangsu Province, Huaian 223003,
China
Using the optimum conditions (Table 1, entry 4), we explored
the substrate scope of this hydrogenation reaction by evaluating
a
variety of compounds with C–C double and triple
bonds.(Scheme 2) We found that trisubstituted alkenes gave
better yields than disubstituted alkenes, regardless of whether the
pendant chain was para to the pyridine nitrogen (2b and 2c vs 2d)
or meta or ortho to it (2e and 2f, respectively). That we were able
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10.1002/anie.201813464
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COMMUNICATION
to obtained 2g (52% yield) showed that this protocol was
compatible with a sulfide group. A steroid moiety remained intact
under the reaction conditions: 2h was obtained in 51% yield.
Esters 2i–2n, which contained other aryl groups (i.e., quinoline,
indole, thiophene, or phenyl), were obtained in moderate to good
yields. A product without a conjugated aryl group (2o) was
prepared in 36% yield. Next, we subjected a variety of
corresponding alkyne precursors, and diphenyl acetylene could
be converted to fully saturated product 2ag in 88% yield. Product
2al bearing a bromo atom could be prepared with 43% yield.
unsaturated amides to the protocol (Figure 3). When
Table 1. Hydrogenation and hydrogenation of alkene 1a.[a]
Entry
1
Conditions
Product/Yield
No reaction
RhCl(PPh3)3 (1 mol %),
MeOH, H2 (10 bar), rt, 30
min
[Ir(cod)(PCy3)(py)]PF6 (1
mol %), H2 (10 bar), rt, 30
min
2
3
No reaction
Pd/C (5 mol %), H2
balloon, rt, 25 min
1a (0.2 mmol), NH3
balloon, LiClO4 (0.1
mmol), MeCN (5 mL),
graphite felt electrodes,
undivided cell, 5 V, rt, 80
min
4
Variation from entry 4:
H2O (3 mmol) instead of
NH3 balloon
2a, trace
2a, 61%
5
6
Variation from entry 4:
MeOH (5 mL) instead of
MeCN
[a] GC-MS yields are provided. [b] Isolated yield.
cinnamide was used as the substrate, corresponding product 2p
was obtained in 93% yield on a 0.2 mmol scale and in 87% yield
on a 2.6 g scale. Amides 2q, 2r, and 2s could also be prepared,
in yields ranging from 33% to 77%. Subsequently, we determined
whether Boc, Cbz, and Aloc protecting groups could survive the
reaction conditions. To our delight, desired products 2t, 2u, and
2v were obtained with their carbamate moieties intact. A substrate
with a free hydroxyl group (2w) was also amenable to this
transformation, and amino acid derivatives 2x and 2y could be
obtained as well. An -unsaturated nitrile substrate gave 2z in
92% yield. Compound 2aa, which is derived from a styrenyl
pinacol borate, was generated in 37% yield. Subsequently, we
found that tri- and diaryl-substituted alkenes were converted to
corresponding saturated products 2ab–2ai in good to excellent
yields. -Methyl styrene underwent hydrogenation as well,
affording 2aj in 60% GC yield and 46% isolated yield. Completely
hydrogenated products 2ak and 2l could be obtained from the
Scheme 2. Hydrogenation of alkenes and alkynes. Conditions: 1 (0.2 mmol),
NH3 in balloon, LiClO4 (0.1 mmol), MeCN (5 mL), graphite felt electrodes, 5 V,
rt, 1.5 – 7 h; isolated yields are given.
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10.1002/anie.201813464
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After exploring the reactivity of C–C double and triple bonds,
we then explored substrates bearing C–O multiple bonds
(Scheme 3), which are polarized. At a working voltage of 4 V in
the presence of 0.5 mmol of LiClO4 as a supporting electrolyte in
DMF (method A), diphenyl ketone 3a could be reduced to
diphenyl methanol (4a) in 73% yield. Several ketones that are
unable to tautomerize were successfully converted to the
corresponding alcohols (4b–4j) in yields ranging from poor to
good. In contrast, when the voltage was increased to 6 V (method
B), 3a was directly converted to diphenyl methane (5a). Other
diaryl ketones gave corresponding diaryl methanes 5b–5e in
moderate yields under the same conditions.
interrupted reaction using alkynes 1ap and 1aq as substrate. In
both cases, alkene 1l or 1ag with E configuration was detected as
the only isomer. In another reaction, by treating an interrupted
reaction mixture with 4-bromobenzaldehyde, we were able to
confirm the formation of hydrazine (as indicated by the formation
of product 6, Scheme 4c). A controlled reaction showed the
hydrazine could serve as a hydrogen source under standard
reaction condition, giving hydrogenation product 2ah from 1ah as
well. Next, alkyne 1aq was subject to the hydrogenation reaction
in CD3CN, a 15% D incorporation in product 2ag was observed.
Scheme 3. hydrogenation of carbonyl compounds.a Method A conditions: 3
(0.2 mmol), NH3 balloon, LiClO4 (0.5 mmol), DMF (5 mL), graphite felt
electrodes, 4 V, rt, 4 – 10 h; isolated yields are given. Method B conditions:
same as method A except that the working voltage was 6 V.
We then turned to investigate if the reaction only proceeds as
an room temperature version of Birch reaction (Scheme 4). As the
electrode material was important in electrochemical reactions, we
compared the electrode used in this work and previous
electrochemical Birch reaction. As that noted by Thiebault, the Mg
anode and Al cathode were crucial in achieving the desired Birch
reduction of arenes. If carbon electrodes were applied in a
controlled reaction, the corresponding transformation did not
occurr.[12] In Bard’s electrochemical Birch reduction of C60, Pt
electrodes were adopted.[13] A standard reaction (Table 1, entry
4) employing Pt cathode was carried out and desired
hydrogenation did not take place (Scheme 4a). Subsequently,
radical clock substrates 1am and 1an were evaluated and 2am
and 2an were detected as the only products, respectively,
suggesting a radical intermediate might be too transient to trigger
a ring opening of cycloproyl group in this electrochemical process
(Scheme 4b). In addition, (E)-1ao gave 2ao as a 1.0:1.9 syn/anti
mixture, and an almost identical result was obtained when (Z)-1ao
was used as the starting material, suggesting the hydrogenation
process was stepwise. This assumption was confirmed with two
Scheme 4. Control experiments and trapping of intermediate
On the basis of the above-described results, a plausible
pathway of hydrogenation of alkene via a fast stepwise process
was proposed in Scheme 5. At first, an electron transfer from
cathode to substrate is coupled with a proton transfer from
ammonia. The resulting intermediate A then undergoes the
second electron transfer from cathode and proton transfer from
ammonia to furnish hydrogenation product. The amide anion side
products undergo oxidation at the anode, forming hydrazine
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Scheme 5. A plausible pathway of electrochemical hydrogenation reaction
In summary, we have developed a convenient, transition-metal-
free electrochemical protocol for hydrogenation of alkenes,
alkynes and ketones with gaseous ammonia as hydrogen source.
This protocol was compatible with a variety of functional groups,
including unconjugated alkenes; benzyl, Boc, Cbz, Alloc, sulfide,
silyl, and borate groups, and heterocycles. The ammonia, which
is safe to use in an electrochemical setting, organic-solvent-
compatible, and an environmentally friendly bulk chemical,
provides a new and complementary approach for hydrogenation
reactions employing hydrogen.
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Acknowledgements
This work was supported by the National Science Foundation of
China (nos. 21572099 and 21332005) and the Natural Science
Foundation of Jiangsu Province (no. BK20151379). This study
was supported by the Open Project of State Key Laboratory Cul-
tivation Base for TCM Quality and Efficacy, Nanjing University of
Chinese Medicine (No. TCMQ & E 201702).
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Keywords: sustainable • hydrogen storage material • ammonia •
electrochemistry • hydrogenation
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COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Ammonia was used as a renewable
and carbon-free fuel and applied as a
high density hydrogen storage
material. A room temperature
electrochemical hydrogenation of
alkene, alkyne and ketones was
achieved with ammonia gas at balloon
pressure at room temperature with
carbon electrodes.
Jin Li, Lingfeng He, Xu Liu, Xu Cheng,*
Guigen Li
Page No. – Page No.
Electrochemical hydrogenation with
gaseous ammonia
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