An Electrochemical Beckmann Rearrangement: Traditional Reaction via Modern Radical Mechanism

Article abstract of DOI:10.1002/cssc.202001553

Abstract: Electrosynthesis as a potential means of introducing heteroatoms into the carbon framework is rarely studied. Herein, the electrochemical Beckmann rearrangement, i. e. the direct electrolysis of ketoximes to amides, is presented for the first time. Using a constant current as the driving force, the reaction can be easily carried out under neutral conditions at room temperature. Based on a series of mechanistic studies, a novel radical Beckmann rearrangement mechanism is proposed. This electrochemical Beckmann rearrangement does not follow the trans-migration rule of the classical Beckmann rearrangement.

Full text of DOI:10.1002/cssc.202001553

Chemistry–Sustainability–Energy–Materials
Accepted Article
Title: An Electrochemical Beckmann Rearrangement: Traditional
Reaction via Modern Radical Mechanism
Authors: Li Tang, Zhi-Lv Wang, Yan-Hong He, and Zhi Guan
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemSusChem 10.1002/cssc.202001553
Link to VoR: https://doi.org/10.1002/cssc.202001553
0
1/2020

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
An Electrochemical Beckmann Rearrangement: Traditional
Reaction via Modern Radical Mechanism
*
*
Li Tang, Zhi-Lv Wang, Yan-Hong He , and Zhi Guan
Dr. Tang; Dr. Wang; Prof. He*, and Prof. Guan*
School of Chemistry and Chemical Engineering
Southwest University
Chongqing 400715, China
E-mail: heyh@swu.edu.cn; guanzhi@swu.edu.cn.
Supporting information for this article is given via a link at the end of the document.
Abstract: Electrosynthesis as a potential means of introducing
heteroatoms into the carbon framework is rarely studied. Herein, the
electrochemical Beckmann rearrangement, i.e. the direct electrolysis
of ketoximes to amides, is presented for the first time. Using a
constant current as the driving force, the reaction can be easily
carried out under neutral conditions at room temperature. Based on
aldoximes to nitriles using halogen ions as mediators (Scheme 1,
b).[17] In 2015, Waldvogel’s group reported the same
transformation using a Pb cathode as a sacrificial reductant
(Scheme 1, b).[ In 2018, Xu’s group reported that by using
different cathode materials, biaryl ketoximes can be converted to
polycyclic N-heteroaromatics and their corresponding N-oxides,
respectively (Scheme 1, c).[19]
18]
a
series of mechanistic studies, a novel radical Beckmann
rearrangement mechanism was proposed. This electrochemical
Beckmann rearrangement does not follow the trans-migration rule of
the classical Beckmann rearrangement.
The C-N bond is ubiquitous in natural compounds, materials and
pharmaceuticals.[1] Therefore, the development of synthetic
methods for the formation of a C-N bond or a C-N-C bond
directly from a C-H bond or a C-C bond is of great significance
to academia and industry.[2] The amide bond is one of the most
important C-N bonds. It is not only the most essential backbone
for proteins or peptides, but also widely found in a variety of
pharmaceuticals and pesticides.[3] One of the high atom
economy methods for amide formation is the insertion of
nitrogen into ketones or aldehydes. The most well-known of this
[4]
type of reactions are Schmidt rearrangement and Beckmann
[
5]
rearrangement . Schmidt rearrangement requires hazardous
and explosive hydrazoic acid as the nitrogen source. Hence
Beckmann rearrangement has a wider range of applications in
amide synthesis.[6] Conventional Beckmann rearrangements are
Scheme 1. Electrolysis of oximes.
usually prompted by excessive amounts of strong acids and
dehydrating media at elevated temperatures.[7] These harsh
conditions still limit the application of Beckmann rearrangement.
In recent years, some improved approaches of Beckmann
rearrangement have been reported, such as organic initiator
promoted reaction,[8] metal complex[9] or boronic acid[10]
catalyzed rearrangement, pre-activation of oximes by equal or
excess equivalent stoichiometric reagents,[11] the rearrangement
Herein, we report the first electrochemical Beckmann
rearrangement, that is, the direct electrolysis of ketoximes to
amides (Scheme 1, d). Unlike the classical Beckmann
rearrangement, this reaction involves a free radical process and
does not follow the trans-migration rule of the classical
Beckmann rearrangement (substituent "trans" migration to
nitrogen). To the best of our knowledge, free radical Beckmann
rearrangement has not been reported so far. This
electrochemical reaction does not require any catalysts,
additives or elevated temperatures to achieve good yields in
short reaction time. In other words, the reaction is efficient,
environmentally friendly and easy to operate.
executed by visible-light-driven generation of Vilsmeier–Haack
[
12]
and the use of vapor phase[13] or supercritical
reagent,
water.[
14]
Although these strategies are efficient, most of them
require additional chemical reagents or special equipments.
Therefore, it is highly desirable to explore milder reaction
conditions and even new reaction pathways for Beckmann
rearrangement.
So far, some organic electrolysis of oximes has been reported.
In 1981, van de Mark’s group reported for the first time that
Our initial investigation focused on the Beckmann
rearrangement of acetophenone oxime (1a) in an undivided cell
equipped with a platinum anode, a platinum cathode, utilizing
0
.1 M nBu
4 4
NBF as the supporting electrolyte, and acetonitrile
(
MeCN) as the solvent at room temperature (rt) under a constant
aliphatic ketoximes can be converted to aliphatic ketones in a
compartment cell containing nitrile and water (Scheme 1, a).[15]
current of 10 mA. After consumption of 2.0 F/mol of charge, the
desired product N-phenylacetamide (2a) was not detected
(Table 1, entry 1). Then, three other common electrosynthetic
solvents, methanol (MeOH), dichloromethane (DCM), and
In 1997, Tallec and coworkers developed an electrochemical
deoximation of aromatic oximes (Scheme 1, a).[16] In 1989,
Shono’s group reported the electrochemical transformation of
1
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
1
1
,1,1,3,3,3-hexafluoroisopropanol (HFIP) were screened (Table
, entries 2 - 4). It was found that when HFIP was used as the
1 [
0
d]
e]
nBu
nBu
NBF
NBF
DCE/HFIP = 1:1
DCE/HFIP = 1:1
0.55
75
4
4
solvent, 2a was obtained in 50% isolated yield (Table 1, entry 4).
When the total charge consumption was reduced to 0.55 F/mol,
the reaction in HFIP gave the product in 74% yield (Table 1,
entry 5). During the solvent screening process, we found that
HFIP is crucial to the reaction (Table 1, entries 1 - 4). According
to the literature, HFIP, as a fluorinated alcohol, has the ability to
facilitate the formation of intermediates (radicals, radical cations
and cations) by the electro-oxidation of substrates and to
stabilize these intermediates.[20] Due to its protic and non-
nucleophilic character, HFIP has good electrochemical
1 [
1
-
n.r.
4
4
2
[
a] 1a (0.5 mmol), nBu
anode and cathode, undivided cell, J = 10.0 mA/cm , rt. [b] isolated yield. [c] J
5.0 mA/cm . [d] J = 15.0 mA/cm . [e] J = 0 mA/cm , 24 h.
4
NBF
4
(0.1 M), solvent (5.0 mL), Pt (1.0 × 1.0 cm )
2
2
2
2
=
With the optimized experimental protocol in hand (Table 1, entry
8), the scope and limitations of this electrochemical Beckmann
rearrangement were evaluated (Scheme 2). Firstly, the ortho-Me,
meta-Me, and para-Me substituted acetophenone oximes were
examined, and the corresponding N-phenylacetamides (2b - 2d)
were obtained. However, the ortho-substituted acetophenone
oxime only achieved moderate productivity, indicating that the
steric hindrance of substrates may have an impact on the
reaction. To verify the influence of the electronic effect on the
2
properties and produces H as the only byproduct at cathode to
maintain the charge balance of the cell.[21] HFIP is a strong
hydrogen-bonding donor also can stablize the the radical
intermediates.[22] As another fluorinated alcohol, 2,2,2-
trifluoroethanol (TFE) was also tested as a solvent for this
electrochemical reaction, which can give the product, but the
yield was much lower than that of HFIP (Table 1, entry 6). Next,
mixed solvents were examined (Table 1, entries 7 and 8) and it
was found that when dichloroethane (DCE)/HFIP = 1:1 (v/v) was
used, the yield was increased to 77% (Table 1, entry 8). The
yield barely changed when the current density was adjusted
reaction,
a
series of acetophenone oximes with para-
substituents of different electronic properties were tested, and
the corresponding N-phenylacetamides (2e - 2t) were obtained.
The results indicated that the reaction is strongly influenced by
electronic effect. The aromatic ketoximes with electro-
withdrawing groups showed diminished reactivity, which
required more charge and only resulted in poor conversion.
Moreover, when more than 1.1 F/mol of charge was introduced
on them, their products began to be converted into by-products,
resulting in low yields of the corresponding amides. In contrast,
the aromatic ketoximes with electron-donating groups can be
completely converted with less electricity. Coming next, the
acetophenone oximes with chain or cyclic di-substituted groups
on the benzene rings can also be smoothly converted into the
corresponding amides (2u - 2y). Both 2-naphthalene ketoxime
and 1-naphthalene ketoxime were suitable for this reaction to
give the corresponding amides (2z and 2aa), but the latter gave
a lower yield than the former, possibly due to the steric
hindrance. Pharmaceutically relevant heteroaromatic amides
also can be formed by the reaction. The free pyrrole and indole
oximes were smoothly converted to the corresponding amides
2
2
from 5 mA/cm to 15 mA/cm (Table 1, entries 8 - 10), indicating
that this electrochemical Beckmann rearrangement can tolerate
current fluctuations. Finally, the control experiment showed that
electricity is necessary for this reaction (Table 1, entry 11). For
detailed condition optimization, see the Supporting Information
(
SI).
Table 1. Selected optimization experiments.a
(
2ab and 2ac). This indicated that the reaction is applicable to
unprotected substrates, providing significant synthetic
advantages in terms of steps and atomic economy compared to
the amidation methods requiring protected heterocycles. After
that, we investigated the variation in the other part (-R ) of the
substrate. It was found that a series of ketoximes wherein R2
Entry[a]
Electrolyte
Solvent
Charge (F/mol)
2.00
Yield (%)[b]
2
1
nBu
nBu
nBu
nBu
nBu
nBu
nBu
nBu
nBu
4
4
4
4
4
4
4
4
4
NBF
NBF
NBF
NBF
NBF
NBF
NBF
NBF
NBF
4
4
4
4
4
4
4
4
4
MeCN
n.d.
n.d.
n.d.
50
was phenyl (2ad), alkyl (2ae - 2ag) or benzyl (2ah and 2ai) were
also cleanly converted to the corresponding amides in good
yields. The benzalacetone oxime also can be transformed to
corresponding amide (2aj) by 2.5 F/mol total charge. Additionally,
the reaction was also applicable to the alkyl oximes, providing
the corresponding amides (2ak - 2am) in moderate yields. It is
worth mentioning that this electrochemical Beckman
rearrangement has good functional group tolerance. Oximes
with acid-sensitive or base-sensitive groups can be converted
into the corresponding amides in good yields (eg 2n, 2p, 2q and
2
MeOH
2.00
3
DCM
2.00
4
HFIP
2.00
5
HFIP
0.55
74
6
TFE
0.55
21
2
x); reactive groups such as free NH
can well tolerate reaction conditions (eg 2m, 2o, 2t, 2ag and
aj).
2
, OH, alkynyl and alkenyl
7
DCM/HFIP = 1:1
DCE/HFIP = 1:1
DCE/HFIP = 1:1
0.55
66
2
8
0.55
77
9[c]
0.55
77
2
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
Scheme 3. Substrate scope (electrolysis of E/Z mixture of oximes) and
unsuccessful substrates. Reaction conditions: 1 (0.5 mmol), nBu
4
NBF
4
(0.1 M),
2
DCE (2.5 mL), HFIP (2.5 mL), Pt (1.0 × 1.0 cm ) anode and cathode,
2
undivided cell, J = 10.0 mA/cm , rt.
In order to demonstrate the utility of this electrochemical
Beckmann rearrangement,
a scale-up experiment for the
synthesis of the amide-containing drug acetaminophen (2o) (one
of the top prescription drugs for analgesic and antipyretic) was
carried out. As shown in scheme 4, under standard conditions,
the readily available oxime 1o was electrolyzed by a total charge
of 0.30 F/mol (within 54 min) to afford acetaminophen (2o) in an
excellent yield of 90%. Since this electrochemical Beckmann
rearrangement is air compatible and a chain reaction for
aromatic ketoximes (see proposed mechanism in Scheme 8),
the scale-up synthesis of acetaminophen can be carried out in a
beaker with low energy consumption, which shows a great
industrial potential for amide synthesis.
Scheme 2. Substrate scope (electrolysis of E-isomers of oximes). Reaction
conditions: 1 (0.5 mmol), nBu
4
NBF
4
(0.1 M), DCE (2.5 mL), HFIP (2.5 mL), Pt
2
2
(1.0 × 1.0 cm ) anode and cathode, undivided cell, J = 10.0 mA/cm , rt. The
Faradaic yield was marked in parentheses after the reaction time.
It’s worthy to note that the electrolysis of the E/Z mixture of
oxime 1an (E / Z = 1.91:1.00) produced the only product 2an in
8
2% yield (Scheme 3). This result indicated that the phenyl
group in both the trans and cis positions can migrate. Similarly,
electrolysis of 1ao (E / Z = 1.70:1.00) and 1ap (E / Z =
1
.56:1.00) also showed that the migration was not limited to the
group at the trans position (Scheme 3). Therefore, it can be
concluded that this electrochemical Beckmann rearrangement
does not follow the trans-migration rule of the classical
Beckmann rearrangement (migration of "trans" substituent to
nitrogen). We speculate which group migrates may depend on
the migration trend rather than the position. From the substrates
we examined above (Schemes 2 and 3), it seems that the
aromatic group is more likely to migrate than the aliphatic group,
and the bulky group is more likely to migrate than the small
group.
Scheme 4. A scale-up reaction for the synthesis of acetaminophen (2m).
Reaction conditions: 1m (10.0 mmol), nBu
4
NBF
4
(0.1 M) in DCE (50.0 mL) and
2
HFIP (50.0 mL), Pt (1.0 × 1.0 cm ) anode and cathode, undivided cell, J = 10.0
2
mA/cm , 54 min (0.3 F/mol), rt.
Despite
the
success
of
electrochemical
Beckmann
rearrangement for most oximes, there were some particular
types of oximes that were not observed for rearrangement.
Oximes on the ring (1aq and 1au) were not working. The
corresponding formamide could not be detected when aldehyde
oxime (1av) was used as a substrate under standard conditions.
To gain insight into the reaction mechanism, a series of
mechanism studying experiments were conducted. First, in order
to confirm whether the reaction undergoes a radical process,
common radical scavengers, 2,2,6,6-tetramethylpiperidinooxy
(
TEMPO) and 2,6-di-tert-butyl-4-methylphenol (BHT), were
employed for the radical trapping and inhibition experiments. In
3
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
the presence of TEMPO (2.0 equivalents) or BHT (2.0
equivalents), no product was detected for the model reaction
under standard conditions even after 1.10 F/mol total charge,
suggesting that the reaction may go through a radical pathway
DCE/HFIP = 1:1 without 1a
-
4
4
4
.0x10
.0x10
0
0
.1 mM 1a in DCE
.1 mM 1a in DCE/HFIP = 1:1
(
Scheme 5, a). Then, we tried to capture the possible radical or
-
0.1 mM 1a in DCE/HFIP/H2O = 9:9:2
2
radical ion by radical clock trap experiments. The ketoxime (1ag)
containing the radical clock pentenyl[19,23] was electrolyzed in the
presence of the radical scavengers TEMPO and BHT separately,
leading to the generation of 2ag-T and 2ag-B, respectively
0
.0
-4
(
Scheme 5, b and c). The structure of 2ab-T was determined by
-2.0x10
single-crystal X-ray diffraction (CCDC 1944911). These results
showed that the electrochemical Beckmann rearrangement may
involve the iminoxyl radical as an intermediate. Interestingly,
TEMPO is coupled to the alkyl radical produced by the 5-exo-trig
cyclization of iminoxyl radical with the alkene moiety to give 2ag-
T, while BHT directly captured the iminoxyl radical to give 2ag-B.
We speculate that the iminoxyl radical is polarity-match with
BHT but not polarity-match with TEMPO, so it first undergoes
cyclization before captured by TEMPO.
-4.0x10-4
-4
-6.0x10
-2
-1
0
1
2
Potential (V)
Figure 1. Cyclic voltammetry experiments.
To further understand the electrochemical Beckmann
1
8
rearrangement process, a series of O-labeling experiments
were performed to obtain information on the source of oxygen in
the amide and the fate of oxygen in the oxime (Scheme 6).
Firstly, under standard conditions, the electrolysis of 1a in the
1
8
presence of 5.0 equivalent of H
was found to contain 18O [M : M+2 = 100.0 : 72.8) (Scheme 6, a).
This phenomenon indicated that H O is involved in the amide
2
O gave 2a in 32% yield, which
2
formation, and the oxygen in the amide can be derived from
water. The experiment also showed that excess water leads to a
decrease in reaction yield, probably because, as mentioned
above, HFIP is crucial to the reaction, but excess water can
competitively inhibit the interaction between HFIP and
substrates
or
intermediates.
Then,
the
18O-labeled
Scheme 5. Radical mechanism exploration experiments.
acetophenone oxime 1a (M : M+2 = 52.4 : 100.0) was
prepared[24] and electrolyzed under standard conditions to give
amide 2a (M : M+2 = 65.4 : 100.0) in 76% yield (Scheme 6, b),
indicating that 18O-labeled 2a can be obtained from O-labeled
Next,
a series of cyclic voltammetry (CV) studies were
18
performed. Based on preliminary measurements, the -2.0 - 2.0 V
potential window was tested for cyclic voltammetry (for details
see SI Figure S1). As showed in Figure 1, the oxidation potential
1
a. The experiment also showed that the abundance of 18O in 2a
was slightly lower than in 1a. This may be due to the following
factors: The solvent was only treated with molecular sieves, so it
was not absolutely anhydrous. Since this electrochemical
Beckmann rearrangement is compatible with air, the reaction
was not isolated from the air. Therefore, water remaining in the
solvent and water vapor in the air may become a source of
oxygen of the amide 2a during the reaction. Finally, 18O-labeled
acetophenone oxime 1a (M : M+2 = 52.4 : 100.0) and 16O
butyrophenone oxime 1af (M : M+2 = 100.0 : 0.7) were
electrolyzed together under standard conditions for the cross-
over experiment, which provided 2a (M : M+2 = 100.0 : 47.4) in
p
of the substrate 1a in the mixed solvent containing HFIP (E =
1
.42 V (vs. Ag/AgCl)) is slightly higher than that in DCE without
p
HFIP (E = 1.33 V (vs. Ag/AgCl)). We speculate that as a strong
hydrogen-bonding donor, HFIP may decrease the electron cloud
density of the oxime (as shown in SI Scheme S1). So that when
HFIP is used as a solvent, the oxidation potential of oxime
increases. The CV curve showed that in the mixed solvent of
DCE/HFIP/H O = 9:9:2 (v/v), the oxidation potential of 1a is
2
slightly reduced (Ep= +1.11 V (vs. Ag/AgCl)). This may be due
to the competitive effect of water on the hydrogen bond between
HFIP and oxime, thereby reducing the effect of HFIP on oxime.
At the same time, as an excellent hydrogen bond donor and
acceptor, water would also form hydrogen bonds with oxime and
affect the oxidation potential of oxime.
7
5% yield and 2af (M : M+2 = 100.0 : 31.7) in 78% yield
(
Scheme 6, c), indicating that the oxygen atom in the oxime can
leave its molecule and transfer to other intermediate as an
oxygen source of the amide. Therefore, it can be inferred from
the above labeling experiments that the oxygen in the amide
comes from water, including external water and water derived
from the hydroxyl group of the oxime.
4
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
Scheme 6. 18O-labeling experiments.
The previously reported organic agent-activated Beckmann
rearrangement involves a chain reaction mechanism8d, 8e in
which oxime is transferred to the amide by a self-propagating
Scheme 7. Chain reaction study.
cycle. The self-propagating cycle involves
a
nitrilium
intermediate rather than a radical chain reaction. As we all know,
at least 1.0 F charge is required for the conversion of 1 mol
substrate, but most of our products were produced with less
than 1 F/mol of charge, indicating that the reaction may involve a
chain reaction mechanism. In order to further confirm the
existence of a chain reaction in the electrochemical Beckmann
rearrangement, an electricity on/off reaction was designed and
implemented (Scheme 7). Firstly, after the reaction was carried
out under standard conditions for 20 min (0.25 F/mol), it was
quenched immediately and the product was isolated to give
amide 2a in 11% yield (Scheme 7, a). Secondly, after 20
minutes under standard conditions, the reaction was stirred for
another 20 min without charge to give amide 2a in 29% isolated
yield, indicating that after the reaction is initiated, it can continue
without charge (Scheme 7, b). Finally, after the reaction was
carried out under standard conditions for 20 min, the charge was
turned off, 1 equivalent of TEMPO was immediately added, and
the reaction was stirred for further 20 min. As expected, only
Based on above experiments, a plausible mechanism was
proposed (Scheme 8). Ketoxime 1 undergoes single-electron
oxidation on the anode to form radical cation 3. Then, the radical
cation 3 is nucleophilically attacked by water (a small amount of
water from the reaction system can initiate the reaction) to form
18
2
intermediate 4. The experiment with H O (Scheme 6, a)
proved that H O is involved in the amide formation. 4 is
2
converted to a more stable tertiary carbon radical 5 via a 1,2-
rearrangement (the lone pairs of -N and -O can stabilize the
1
2
[25]
carbon radical in 5). Both the R and R groups can migrate,
which explains the electrolysis results of 1ao and 1ap (Scheme
3
). In this mechanism scheme, for simplicity, we assume that the
1
rearrangement group is R . Reduction of 5 by discharge at the
cathode or by reaction with another ketoxime
1 (chain
propagation) closes the catalytic cycle to give the intermediate 6,
which is protonated to form intermediate 7. Finally, intermediate
7
loses one molecule of water to produce 2-I, which
tautomerizes to form product amide 2. The lost water can act as
a nucleophile to attack 3 in the next catalytic cycle, which
explains the 18O-labeled cross-over experiment (Scheme 6, c),
The control experiment (Table S5, entry 3) of adding molecular
sieve to the reaction system also showed that the water
circulation is important to the reaction. In this electrochemical
Beckmann rearmament, the conversion of most aromatic
ketoximes consume less than 1 F/mol of charge, while aliphatic
ketoximes require more than 1 F/mol of charge, which may be
due to the former being more inclined to the chain reaction
pathway. At the same time, in this process, the HFIP as a proton
1
2 % yield of amide 2a was obtained (Scheme 7, c), which was
almost identical to the first case. From the results of electricity
on/off experiments, it can be concluded that the electrochemical
Beckmann rearrangement may involve a radical chain reaction
mechanism.
2
donor is cathodically reduced to generate H to close the
electron cycle. In addition, the oximes on the ring (1aq and 1au)
did not work in this reaction, probably because the cyclic
intermediate 4 is difficult to rearrange to form the intermediate 5.
Aldehyde oxime (1av) failed to provide the corresponding
formamide, probably because the intermediate 5 formed by
aldehyde oxime is a secondary carbon radical which is not as
stable as the tertiary carbon radical intermediate formed by
ketoxime.
5
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
and the Natural Science Foundation of Chongqing (No.
cstc2019jcyj-msxmX0297).
Keywords: amides •electrosynthesis • Beckmann
rearrangement
[
[
1]
2]
a) R. Hili, A. K. Yudin, Nat Chem Biol 2006, 2, 284-287; b) S. Z. Zard,
Chem. Soc. Rev. 2008, 37, 1603-1618; c) J. L. Roizen, M. E. Harvey, J.
Du Bois, Acc Chem Res 2012, 45, 911-922; d) J. Bariwal, E. Van der
Eycken, Chem. Soc. Rev. 2013, 42, 9283-9303.
a) F. Collet, R. H. Dodd, P. Dauban, Chem. Commun. 2009, 5061-
5074; b) F. Chen, T. Wang, N. Jiao, Chem. Rev. 2014, 114, 8613-8661;
c) L. Souillart, N. Cramer, Chem. Rev. 2015, 115, 9410-9464; d) G.
Fumagalli, S. Stanton, J. F. Bower, Chem. Rev. 2017, 117, 9404-9432;
e) D. S. Kim, W. J. Park, C. H. Jun, Chem. Rev. 2017, 117, 8977-9015;
f) Y. Qin, L. Zhu, S. Luo, Chem. Rev. 2017, 117, 9433-9520; g) H. Yi, G.
Zhang, H. Wang, Z. Huang, J. Wang, A. K. Singh, A. Lei, Chem. Rev.
2017, 117, 9016-9085; h) Y. Adeli, K. Huang, Y. Liang, Y. Jiang, J. Liu,
S. Song, C.-C. Zeng, N. Jiao, ACS Catal. 2019, 9, 2063-2067.
[
3]
a) R. M. de Figueiredo, J. S. Suppo, J. M. Campagne, Chem. Rev.
2016, 116, 12029-12122; b) A. Ojeda-Porras, D. Gamba-Sanchez, J.
Org. Chem. 2016, 81, 11548-11555; c) L. Tang, X. M. Li, J. H. Matuska,
Y. H. He, Z. Guan, Org. Lett. 2018, 20, 5618-5621; d) L. Tang, J. H.
Matuska, Y. H. Huang, Y. H. He, Z. Guan, ChemSusChem 2019, 12,
2570-2575.
[
[
[
4]
5]
6]
H. Wolff, in Organic Reactions, 2011, pp. 307-336.
E. Beckmann, Ber. Dtsch. Chem. Ges. 1886, 19, 988-993.
a) R. E. Gawley, in Organic Reactions, 2004, pp. 1-420; b) S.
Chandrasekhar, in Comprehensive Organic Synthesis II (Ed.: P.
Knochel), Elsevier, Amsterdam, 2014, pp. 770-800.
Scheme 8. Plausible mechanism of electrochemical Beckmann rearrangement
[
[
7]
8]
L. Guy Donaruma, W. Z. Heldt, in Organic Reactions, 2011, pp. 1-156.
a) Y. Furuya, K. Ishihara, H. Yamamoto, J. Am. Chem. Soc. 2005, 127,
In summary, we have demonstrated that Beckmann
rearrangement can be carried out in a galvanostatic electrolysis
by electrolyzing ketoximes at ambient temperature without using
catalysts. Based on a series of experiments, a new radical
mechanism of electrochemical Beckmann rearrangement is
proposed. The reaction has the advantages of mild reaction
conditions, broad substrate scope, insensitivity to air, short
reaction time, and easy scale-up, making it an effective strategy
for introducing nitrogen into the C-C bond to synthesize amides.
11240-11241; b) M. Z. Zhu, C. T. Cha, W. P. Deng, X. X. Shi,
Tetrahedron Lett. 2006, 47, 4861-4863; c) M. Hashimoto, Y. Obora, S.
Sakaguchi, Y. Ishii, J. Org. Chem. 2008, 73, 2894-2897; d) H. J. Pi, J.
D. Dong, N. An, W. T. Du, W. P. Deng, Tetrahedron 2009, 65, 7790-
7793; e) V. P. Srivastava, R. Patel, Garima, L. D. Yadav, Chem.
Commun. 2010, 46, 5808-5810; f) C. M. Vanos, T. H. Lambert, Chem.
Sci. 2010, 1, 705-708; g) Y. Gao, J. Liu, Z. Li, T. Guo, S. Xu, H. Zhu, F.
Wei, S. Chen, H. Gebru, K. Guo, J. Org. Chem. 2018, 83, 2040-2049.
a) M. Arisawa, M. Yamaguchi, Org. Lett. 2001, 3, 311-312; b) S. Cook,
L. Jefferies, S. Weber, Synlett 2014, 26, 331-334; c) H. J. Kiely-Collins,
I. Sechi, P. E. Brennan, M. G. McLaughlin, Chem. Commun. 2018, 54,
[
9]
6
54-657.
10] X. Mo, T. D. R. Morgan, H. T. Ang, D. G. Hall, J. Am. Chem. Soc. 2018,
40, 5264-5271.
11] a) N. C. Ganguly, P. Mondal, Synthesis-Stuttgart 2010, 2010, 3705-
709; b) R. G. Kalkhambkar, H. M. Savanur, RSC Adv. 2015, 5, 60106-
Experimental Section
[
[
1
4 4
Ketoxime 1 (0.50 mmol), nBu NBF (0.1 M), DCE (2.5 mL) and
HFIP (2.5 mL) were combined and added into an undivided
beaker-type electrolysis cell equipped with a magnetic stirring
bar, a platinum plate (1.0ꢀcmꢀ×ꢀ1.0ꢀcm) anode and a platinum
plate (1.0ꢀcmꢀ×ꢀ1.0ꢀcm) cathode. A constant current electrolysis
with a current density of 10.0 mA/cm2 was performed at rt.
These conditions were applied until the substrate was consumed
up or the product began to transform (monitored by TLC), and
then the electrolysis was stopped. The reaction mixture was
concentrated in vacuo, and the residue was purified by flash
chromatography on silica gel with petroleum ether/ethyl acetate
3
60113; c) P. S. Mahajan, V. T. Humne, S. D. Tanpure, S. B. Mhaske,
Org. Lett. 2016, 18, 3450-3453.
[
12] V. P. Srivastava, A. K. Yadav, L. D. S. Yadav, Synlett 2014, 25, 665-
670.
[
[
13] S. Sato, H. Sakurai, K. Urabe, Y. Izumi, Chem. Lett. 1985, 14, 277-278.
14] a) O. Sato, Y. Ikushima, T. Yokoyama, Journal of Organic Chemistry
1998, 63, 9100-9102; b) Y. Ikushima, K. Hatakeda, O. Sato, T.
Yokoyama, M. Arai, J. Am. Chem. Soc. 2000, 122, 1908-1918.
[15] M. R. van de Mark, A. M. Scornavacca, Org. Prep. Proced. Int. 2009,
13, 395-399.
[
[
[
[
16] L. Bencharif, A. Tallec, R. Tardivel, Electrochim. Acta 1997, 42, 3509-
(
9:1 to 1:1) as the eluent to give the desired amide 2.
3512.
17] T. Shono, Y. Matsumura, K. Tsubata, T. Kamada, K. Kishi, Journal of
Organic Chemistry 1989, 54, 2249-2251.
Acknowledgements
18] M. F. Hartmer, S. R. Waldvogel, Chem. Commun. 2015, 51, 16346-
1
6348.
19] H. B. Zhao, P. Xu, J. Song, H. C. Xu, Angew. Chem. Int. Ed. 2018, 57,
5153-15156.
This work was financially supported by the National Natural
Science Foundation of China (Nos. 21672174 and 21977084)
1
6
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
[
20] a) R. Francke, D. Cericola, R. Kotz, D. Weingarth, S. R. Waldvogel,
Electrochim. Acta 2012, 62, 372-380; b) L. Eberson, M. P. Hartshorn, O.
Persson, J. Chem. Soc., Perkin Trans. 2 1995, 1735-1744; c) T. Broese,
R. Francke, Org. Lett. 2016, 18, 5896-5899.
[
21] a) I. Colomer, A. E. R. Chamberlain, M. B. Haughey, T. J. Donohoe,
Nat. Rev. Chem. 2017, 1, 0088; b) J. P. Begue, D. Bonnet-Delpon, B.
Crousse, Synlett 2004, 2004, 18-29.
[22] a) S. P. de Visser, J. Kaneti, R. Neumann, S. Shaik, J. Org. Chem.
2003, 68, 2903-2912; b) I. Colomer, C. Batchelor-McAuley, B. Odell, T.
J. Donohoe, R. G. Compton, J. Am. Chem. Soc. 2016, 138, 8855-8861;
c) A. Berkessel, J. A. Adrio, D. Huttenhain, J. M. Neudorfl, J. Am. Chem.
Soc. 2006, 128, 8421-8426; d) A. Berkessel, J. A. Adrio, Adv. Synth.
Catal. 2004, 346, 275-280.
[23] a) X.-X. Peng, D. Wei, W.-J. Han, F. Chen, W. Yu, B. Han, ACS Catal.
2017, 7, 7830-7834; b) X. X. Peng, Y. J. Deng, X. L. Yang, L. Zhang, W.
Yu, B. Han, Org. Lett. 2014, 16, 4650-4653; c) B. Han, X. L. Yang, R.
Fang, W. Yu, C. Wang, X. Y. Duan, S. Liu, Angew. Chem. Int. Ed. 2012,
51, 8816-8820.
[
24] I. Pusterla, J. W. Bode, Angew. Chem. Int. Ed. 2012, 51, 513-516.
25] H. Togo, Advanced free radical reactions for organic synthesis, Elsevier,
[
2004.
7
This article is protected by copyright. All rights reserved.

ChemSusChem
10.1002/cssc.202001553
COMMUNICATION
Entry for the Table of Contents
The first constant current driven Beckmann rearrangement via radical mechanism has been developed. With the radical
rearrangement process, only one type of amide was formed in good yield when E/Z mixture of cyclopropyl(phenyl)methanone oxime
was treated under standard conditions.
8
This article is protected by copyright. All rights reserved.