Continuous N-Hydroxyphthalimide (NHPI)-Mediated Electrochemical Aerobic Oxidation of Benzylic C?H Bonds

Article abstract of DOI:10.1002/chem.201802588

Electroorganic chemistry has emerged as an environmentally benign tool for synthetic chemists to achieve efficient transformations that are challenging with traditional reagent-based methods. Continuous flow chemistry brings pharmaceutical industry numerous advantages, but implementing electroorganic synthesis in flow is challenging, especially for electroorganic reactions with coupled electrode reactions and slow chemical reactions. We present a continuous electrolysis system engineered for N-hydroxyphthalimide (NHPI) mediated electrochemical aerobic oxidation of benzylic C?H bonds. First, a cation-exchange membrane prevents the crossover of the NHPI anion from anolyte to catholyte avoiding reductive decomposition of NHPI at the cathode, and enables the usage of a cost-effective reticulated vitreous carbon (RVC) cathode instead of a platinum electrode. Second, running the electrochemical flow cell with recycle streams accommodates the inherently slow kinetics of the chemical reaction without phthalimide-N-oxyl (PINO) radical self-decomposition at the anode, and allows the usage of gaseous oxygen as co-oxidant.

Full text of DOI:10.1002/chem.201802588

A Journal of
Accepted Article
Title: Continuous NHPI-Mediated Electrochemical Aerobic Oxidation of
Benzylic C-H Bonds
Authors: Yiming Mo and Klavs F. Jensen
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
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the VoR from the journal website shown below when it is published
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201802588
Link to VoR: http://dx.doi.org/10.1002/chem.201802588
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Chemistry - A European Journal
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Continuous NHPI-Mediated Electrochemical Aerobic Oxidation of
Benzylic C-H Bonds
Yiming Mo, and Klavs F. Jensen*
Abstract: Electroorganic chemistry has emerged as an
environmentally benign tool for synthetic chemists to achieve efficient
transformations that are challenging with traditional reagent-based
methods. Continuous flow chemistry brings pharmaceutical industry
numerous advantages, but implementing electroorganic synthesis in
flow is challenging, especially for electroorganic reactions with
coupled electrode reactions and slow chemical reactions. We present
continuous manufacturing will have additional benefits, such as
low cell resistance due to the reduced electrode distance,
improved throughput, and easy flow cell setup. Considering the
complexity of the organic electrochemical systems, the design of
a continuous electrochemical cell needs to accommodate the
coupled electrochemical reaction and chemical reaction, various
electrode materials, utilization of the gaseous reagents, and allow
for cost-effective scale-up.
a
continuous electrolysis system engineered for the N-
hydroxyphthalimide (NHPI) mediated electrochemical aerobic
oxidation of benzylic C-H bonds. First, a cation-exchange membrane
prevents the crossover of the NHPI anion from anolyte to catholyte
avoiding reductive decomposition of NHPI at the cathode, and
enables the usage of a cost-effective reticulated vitreous carbon
Researchers have already devoted efforts to developing
efficient continuous electroorganic synthesis.[ Yoshida’s group
used a divided-wall microfluidic cell under -72 °C to generate
cationic intermediates in situ, and subsequently mixed with
nucleophiles to obtain corresponding C-C formation products.[14]
Wirth’s group demonstrated an easy-to-machine electrochemical
microreactor for facile synthesis of amidyl radicals used in
intramolecular hydroaminations to produce isoindolinones.[
13]
(RVC) cathode instead of a platinum electrode. Second, running the
electrochemical flow cell with recycle streams accommodates the
inherently slow kinetics of the chemical reaction without phthalimide-
N-oxyl (PINO) radical self-decomposition at the anode, and allows the
usage of gaseous oxygen as co-oxidant.
15]
Noël’s
group
employed
the
commercially
available
electrochemical flow cell, Asia Flux, to evaluate the effect of
applied electrolysis potential on the selectivity of thioethers and
thiols oxidation reactions, and also elucidate the mass-transfer
limitations under low-flowrate regimes.[16] In addition, over the
past two decades, research on flow batteries for large-scale
energy storage applications has advanced the knowledge of how
to design scalable and mass-transfer efficient flow cells. This
Introduction
Organic electrochemistry has emerged as an environmentally
friendly, atom-economic, and sustainable alternative to traditional
synthetic methods because of the use of the redox power from
clean electrons in place of stoichiometric amount of oxidants or
reductants.[1–3] In addition, electrochemical methods are able to
make certain complex molecular moieties easily accessible under
mild conditions. The advantages above drive synthetic chemists
to start embracing this technology, and many innovative
electrochemical transformations for fine chemical synthesis have
been developed recently. Moeller’s group extensively studied the
anodic cyclization reactions of electron-rich olefins.[4–6] Baran’s
group discovered various synthetic strategies to utilize
electrochemical reactions to generate reactive radical species to
accomplish challenging C-H functionalization, such as allylic C-H
progress could translate to improvement in electroorganic flow
[17,18]
cells.
However, it is particularly challenging to realize
scalable flow systems for electrochemical reactions with
inherently slow chemical reaction kinetics, possible side reactions
of mediators and intermediate radical species, and the usage of
gaseous reagents.
Liquid-phase radical-chain autoxidation reactions are among
the large-scale oxidation reactions performed in industry.[19] The
oxidation of the side chain of alkyl aromatics is an important
[20–23]
method for the preparation of aromatic carbonyl compounds.
Electrochemistry offers a pathway to conduct those oxidations
under mild conditions. In this work, we demonstrated an
electrochemical flow system specifically engineered for NHPI-
mediated electrochemical aerobic oxidations of benzylic C-H
bonds. This transformation is a metal-free and sustainable
[
7]
[8]
oxidation , trifluoromethylation , and functionalization of
[
9]
methylene and methine moieties .
Advantages of continuous manufacturing over the
conventional batch or semi-batch process, such as efficient heat
and mass transfer rates, reproducibility, and improved safety and
process reliability, drive the transformation of manufacturing
process from batch to continuous.[10–12] Incorporating newly
developed organic electrochemical synthetic methods into
synthetic pathway, and compatible with heterocycles, suggesting
the suitability for pharmaceutical applications.[7,24] With detailed
electrochemical analysis of the reaction system, we identified two
NHPI decomposition mechanisms that may lead to decreased
product yield. To avoid the reductive decomposition of NHPI at
the cathode and enable the usage of the cost-effective RVC
electrode, we incorporated a Nafion membrane to circumvent the
crossover of NHPI from anolyte to catholyte. To limit PINO radical
self-decomposition at the anode, the recycle operation mode of
the flow cell provided sufficiently small driving force for the
electron transfer step to accommodate the inherently slow
chemical reaction step, and thus limit the buildup of PINO radical.
Moreover, the recycle allowed the efficient usage of the gaseous
[a]
Y. Mo, and Prof. K. F. Jensen
Department of Chemical Engineering
Massachusetts Institute of Technology
77 Massachusetts Avenue, Cambridge, MA, 02139, USA
E-mail: kfjensen@mit.edu
Supporting information for this article is given via a link at the end of
the document.
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Chemistry - A European Journal
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+
molecular oxygen as a green co-oxidant instead of other oxidation
reagents.
a half-wave redox potential E1/2 = 0.47 V (vs. Fc/Fc ). PINO radical
subsequently mediates selective abstraction of benzylic hydrogen
atom to generate a benzyl radical. This radical can be trapped by
O
2
to form peroxy radical, which then decomposes to yield the
oxygenated carbonyl products.[
7,21]
The corresponding cathode
Results and Discussion
reaction is supposed to be the reduction of pyridinium cation to
evolve gaseous hydrogen and regenerate pyridine. The potential
of cathode reaction displays a dependence on the cathode
materials, where it is irreversible with a half-peak potential -1.79
We started the investigation with optimizing reaction
conditions in batch (Table 1). Considering the scalability and
mass transfer performance for future flow cell designs, we
selected RVC as electrode material, which offers large interfacial
areas (100 pores per inch) and is cost-effective ($1.50 per cubic
inch). Initial trial only offered 43% yield (Table 1, entry 1). The
variations of galvanostatic current, co-oxidants (air, t-BuOOH,
+
V (vs. Fc/Fc ) at RVC electrode, and reversible with a half-wave
+
potential -0.92 V (vs. Fc/Fc ) at Pt electrode. Interestingly, the
reduction potential of pyridinium at the RVC electrode overlaps
with the irreversible cathodic decomposition of NHPI, which
corresponds to the reduction of the amide group in NHPI[25]
.
2
and 1 atm O ), and NHPI loading (Table 1, entries 2-5) did not
Nevertheless, the cathodic pyridinium reduction on Pt electrode
avoids the NHPI decomposition potential range, leading to the
significantly improved reaction yield (Table 1, entry 6 vs. entry 8).
have an impact on the reaction yield. Increasing the temperature
from 40 ºC to 50 ºC led to an improved yield (Table 1, entry 6),
and further increasing the reaction temperature to 70 ºC with pure
MeCN as solvent (acetone has a boiling point of 56 ºC) did not
show further improvement (Table 1, entry 7). On the other hand,
changing the cathode to platinum foil gave an excellent yield
(
Table 1, entry 8), which can be rationalized in terms of the cyclic
voltammetry (CV) characteristics of the chemical species in the
system.
Table 1. Influence of batch reaction conditions on NHPI-mediated
electrochemical aerobic oxidation of benzylic C-H bondsa
Anode/
Cathode
T
(ºC)
Current
(mA)
Other
conditions
Entry
Yieldb
1
2
RVC/RVC
RVC/RVC
40
40
5
2
43%
41%
1
.5 equiv.
3
RVC/RVC
40
5
35%
t-BuOOH
4
5
6
RVC/RVC
RVC/RVC
RVC/RVC
40
40
50
5
5
5
44%
43%
54%
Bubble O
2
40% NHPI
Pure MeCN as
solvent
7
8
RVC/RVC
RVC/Ptc
70
50
5
2
50%
89%
Figure 1. (a) Cyclic voltammograms of 20 mM NHPI (red curve), and 50 mM
pyridinium perchlorate at RVC electrode (blue curve) and Pt electrode (purple
curve) scanned at 100 mV/s in 0.1 M solution of TBAP in 1:1 acetone and MeCN
mixture. (b) Reaction mechanism for NHPI-mediated electrochemical aerobic
oxidation of benzylic C-H bonds.
aReaction conditions: 0.4 mmol of 1a was electrolyzed under constant current
in presence of 0.2 equiv. NHPI and 0.2 equiv. pyridine in 4 mL of 0.1 M solution
of tetrabutylammonium perchlorate (TBAP) in 1:1 acetone and acetonitrile
b
(
MeCN) mixture. Yield was determined using gas chromatograph (GC) with
c
dodecane as the internal standard. Platinum foil electrode.
Thus, avoiding the reductive decomposition of NHPI at the
cathode becomes the key for the NHPI-mediated oxidation.
Noting that the major form of NHPI in the basic reaction mixture
Based on the reaction mechanism (Figure 1)[7,24]
deprotonation of NHPI by pyridine, followed by anodic electron
transfer, leads to PINO radical, and this reversible conversion has
,
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Figure 2. (a) Cyclic voltammograms for various reagent concentrations 1d, corresponding to 2 mM NHPI, 0.15 M pyridine, and 0.1 M TBAP in MeCN. Scan rate:
1
50 mV/s. (b) Linear regression of catalytic current versus half-order of reagent concentration. (c) Hammett plots of kinetic constants for para-substituted
ethylbenzenes.
is the NHPI anion, we rationalize that a cation-exchange Nafion
membrane would prevent the crossover of the NHPI anion from
the anolyte to the catholyte, and hence, circumvent the NHPI
deactivation of the catalyst)[28]
concentration increases the catalytic current, which is linearly
.
Increasing the reagent
dependent on the half-order of reagent concentration (1d), giving
value of 9.2 ± 1.70 L mol-1
s
-1
(Figure 2b).
decomposition. As a consequence, incorporating
a
Nafion
the k
c
membrane would allow the usage of RVC as the cathode material
and give a similar reaction yield as the expensive Pt cathode.
In addition to the reductive decomposition of NHPI, the PINO
radical, generated at the anode, is known to undergo a
A Hammett study was carried out for five different para-
substituted ethylbenzenes by measuring the kinetic constants
individually by cyclic voltammetry, providing additional insights
into the electronic effects on the reactivity. The Hammett plot
(Figure 2c) reveals a strong electronic trend with a slope ρ of -
1.09. The benzylic hydrogen abstraction of electron-donating
ethylbenzenes will proceed more rapidly with the PINO radical,
which may be rationalized as the stabilization of the partially
positive charged reaction center on the C-H abstraction transition
state.[26,29]
bimolecular self-decomposition with a kinetic constant on the
order 1 L mol-1 s . The benzylic hydrogen abstraction rate (k
-1 [26]
c
)
from the substrate must match with the PINO radical
electrochemical generation rate at the anode. Otherwise, if the
PINO radical generation rate is faster than its consumption rate,
the accumulation of PINO radical will lead to its bimolecular self-
decomposition. Thus, insights of the chemical reaction kinetics
c
The kinetic study shows the k value is comparable to PINO
(
k
c
) will provide in-depth understanding of how to precisely control
radical self-decomposition rate constant. Thus, controlling the
overpotential applied on the electrodes, which determines the
generation rate of PINO radical, is essential to limit the PINO
radical to a low concentration avoiding its self-decomposition.
However, the slow overall reaction rate associated with the small
overpotential applied will result in a prolonged residence time in a
continuous flow reactor, implying a large reactor volume, which is
unfavorable considering the electrode material cost associated
with large-volume electrochemical flow cell. To realize NHPI
aerobic electrochemical oxidation in flow, implementing recycle
stream offers the feasibility of controlling the PINO radical
the overpotential that governs the generation of the PINO radical.
We used CV to measure the reaction kinetics of the para-
substituted ethylbenzenes.[27,28] The catalytic current exhibits a
saturation dependence on the concentration of pyridine
(
Supplementary Figure S4). Hence, the pyridine concentration is
chosen in the concentration-independent regime (0.15 M) in order
to eliminate the kinetic effect of the NHPI and pyridine reaction on
the overall reaction rate. The S-shaped voltammograms (Figure
2
a) indicate that the electrocatalytic rate is independent on the
diffusion of base, substrate or NHPI to the electrode, and catalytic
current is limited only by first-order chemical step as shown in the
reaction mechanism (Figure 1b). The catalytic current can be
described as following[28]
ꢀꢁꢂꢃ = ꢄꢅꢆꢇꢈꢉꢊ�ꢋꢇꢈꢉꢊꢌꢁꢆꢍ
concentration at
a
low level without
a
large-volume
electrochemical flow cell.
:
Two NHPI decomposition mechanisms were identified as
discussed above: (1) NHPI irreversible reductive decomposition
at the cathode, and (2) PINO radical bimolecular self-
decomposition at the anode, competing with benzylic hydrogen
abstraction. To facilitate the transformation of NHPI aerobic
electrochemical oxidation from batch to flow, we engineered and
fabricated an electrochemical flow cell (Figure 3a) to incorporate
the cation-exchange membrane and operated the reactor in
recycle mode (Figure 3b) to circumvent two NHPI decomposition
pathways. The anodic and cathodic chambers are filled with
porous RVC electrodes providing uniform flow distribution and
( 1 )
where ꢄ is the Faraday constant, ꢅ is the working electrode area,
ꢆꢇꢈꢉꢊ is the NHPI concentration, ꢋꢇꢈꢉꢊ is the diffusion coefficient
of NHPI (determined by varying scan rate in cyclic voltammetry,
Supplementary Figure S5), and ꢆ is the concentration of reagent
with benzylic C-H bond.
The cyclic voltammograms of NHPI with 4-ethylanisole 1d of
various concentrations were measured (Figure 2a). The catalytic
current corresponds to the current plateau after the anodic peak,
and is averaged between 0.7 V – 0.8 V to minimize minor effects
of side-phenomena (e.g. consumption of the substrate and
ꢍ
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Figure 3. (a) Exploded-view CAD drawing of the electrochemical flow cell engineered for NHPI-mediated aerobic oxidation of benzylic C-H bonds. From top to
bottom, it sequentially contains aluminum holder (with cartridge heaters and thermal insulation layer), polyether ether ketone (PEEK) electrical insulator, copper
current collector, polytetrafluoroethylene (PTFE) electrolysis chamber, RVC electrode, and Nafion 117 membrane. The electrochemical flow cell is symmetric to
incorporate the divided-wall configuration. (See Supporting Information for the photos and detailed dimensions of the flow cell) (b) Schematics of the operation. Two
2
streams are driven by peristaltic pumps to cycle through the RVC electrodes. Anolyte gets saturated with O in a Teflon AF tube-in-tube device before entering
anodic chamber. FlowIR device monitors the species concentration in the anolyte.
enhanced interfacial areas for electron transfer[18]. A Nafion 117
membrane is sandwiched between two RVC electrodes to
selectively block the crossover of NHPI anion from anolyte to
catholyte. Considering the reaction requires molecular oxygen as
the co-oxidant and the oxygen solubility is limited in organic
solvent, the anolyte is saturated with oxygen (15 psi) using a
Teflon AF tube-in-tube device[30] to supply the required co-oxidant.
During the recycle, the pyridinium cation is continuously
generated at the anode, is transported across the Nafion
membrane driven by the electric field, and gets reduced at the
cathode to form gaseous hydrogen and regenerate pyridine. The
hydrogen generated at the cathode can be released from the
catholyte in catholyte holding tank instead of accumulating in the
reactor and occupying the effective electrode surface area. Since
the cathodic side only involves the counter electrode reaction, the
catholyte will have a stable composition at steady state, allowing
continuous usage throughout the operation. And the process can
be transformed into fully continuous mode with continuous feed
and withdraw at the anolyte holding tank.
from anolyte to catholyte. GC analysis of two samples from each
side collected during the recycle (Figure 4b) shows negligible
crossover of NHPI from anolyte to catholyte, which validates the
function of the cation-exchange membrane. The overall yield was
94% (based on anodic side), significantly higher than the yield
(54%, Table 1, entry 6) in batch with the same electrode material.
To demonstrate the capability of producing the oxygenated
compounds continuously, we implemented the standard condition
with 1a, and added the continuous feed and withdraw streams as
shown in Figure 3b. The flowrates of continuous feed and
withdraw are identical, determined by the current and theoretical
electrons needed (2 F/mol):
ꢄꢎꢏꢐꢑꢒꢓꢔ = ꢀ/(2ꢄꢆꢍ)
( 2 )
where the ꢀ is the electrolysis current and ꢆ is the concentration
ꢍ
of 1a in the feed stream. The crossover of product from anolyte to
catholyte is not a concern since the product concentration in
catholyte will the same as anolyte during steady state. The system
is able to give 0.35 g of 2a in 74% yield continuously for 24 h. The
reduction in yield is primarily attributed to the reduction in reagent
concentration compensation from the catholyte during the steady
state as compared to the case without continuous feed and
withdraw.
The electrochemical flow cell was examined for oxygenation
of various substrates, giving good-to-excellent yields (Table 2, 1a-
1g). 2- and 3- substituted ethylpyridines (1a and 1b) give similar
yields, while 4-ethylpyrdine 1c is comparatively ineffective with
standard conditions, and requires adding more NHPI during the
recycle to obtain higher yield. The difference of yields for various
substituted ethylpyridines are consistent with results from
chemical oxidation methods[24]. Benzylpyridines 1e and 1f
requires 0.6 equiv. NHPI in order to reach good yields. Substituted
ethylbenzene 1d and benzimidazole 1g have good yields with the
standard conditions.
The evolution of oxygenated product concentration in the
anolyte during the recycle as an overall batch can provide further
insights into the behavior of the reaction in the electrochemical
flow cell. Thus, an in-line flow infrared spectroscopy apparatus[
31]
(
FlowIR), installed at the outlet of the anodic chamber,
continuously monitors 2-acetylpyridine 2a concentration during
the electrochemical oxygenation of 2-ethylprydine 1a. Figure 4a
shows the evolutions of product 2a concentration and electrolysis
current under potentiostatic conditions. The product concentration
keeps increasing with a steady current, and after around 8 h, the
current sharply decreases to a low value, with the product
concentration reaching the maximum value, indicating completion
of the reaction. The product concentration in the anolyte slowly
decreases over time afterwards, due to the crossover of product
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oxidation in this work offers a strategy to identify the essential
mediator decomposition mechanisms rationalizing reaction
conditions, and the flow system design provides insights enabling
electroorganic synthesis with inherently slow reaction kinetics and
gaseous reagents in flow.
Table 2. Substrate scope of NHPI-mediated electrochemical aerobic oxidation
of benzylic C-H bonds in the electrochemical flow cell with recyclea
aStandard conditions are the same as described in Figure 4. The optimized
reaction potentials are available in Supporting Information. Yield (based on the
anodic side) was determined using GC with dodecane as the internal standard.
b
c
Spike 0.2 equiv. more NHPI after current significantly reduces. 0.6 equiv.
NHPI.
Experimental Section
Procedure for batch electrolysis. The RVC electrode (ERG Aerospace
Corp) were cut into a semi-cylindrical shape, and soldered on a 316
stainless steel wire for electrical contact. Similarly, the platinum foil (Alfa
Aesar) was soldered on the stainless steel wire. (Supplementary Figure
S1) The solution as described in Table 1 was electrolyzed under constant
current condition with oil bath controlling the reaction temperature. After
the reaction, an aliquot of the reaction mixture was washed with 0.1 M
Figure 4. (a) FlowIR monitoring of product concentration in the anolyte during
the recycle, and the corresponding electrolysis current. (b) Gas chromatograph
analysis of two samples from each side during the electrolysis. Anolyte recycles
at 1 ml/min: 0.1 M 1a, 0.02 M NHPI, 0.04 M pyridine, 0.1 M TBAP, 0.05 M
pyridinium perchlorate, and 4 mM dodecane as internal standard in 16 mL of
2 3 2 4
Na CO solution, extracted with ethyl acetate, and dried over Na SO
1
:1 acetone and MeCN. Catholyte recycles at 1 ml/min: 0.1 M 1a, 0.04 M
before GC analysis.
pyridine, 0.1 M TBAP, 0.1 M pyridinium perchlorate, and 4 mM dodecane as
internal standard in 8 mL of 1:1 acetone and MeCN. Reaction temperature:
Procedure for operating electrochemical flow cell with recycle. The
anolyte and catholyte were prepared as described in Figure 4. Peristaltic
pumps (Masterflex L/S) with chemically resistant GORE Style 500 tubing
were used to recycle both streams at 1 mL/min. Anolyte was saturated with
5
0 °C.
Conclusion
15 psi oxygen using Teflon AF tube-in-tube device. The electrochemical
flow cell temperature was controlled by cartridge heaters and
thermocouple. In-line FlowIR recorded the infrared spectrum of anodic
stream every 1.5 min. The electrolysis was carried out under constant
potential condition. The electrolysis process without continuous feed and
withdraw was stopped when current dropped to a negligible value. When
there were continuous feed and withdraw, their flowrates were controlled
by LabView determined by the electrolysis current and theoretical electron
needed (Equation ( 2 )).
This work demonstrated an electrochemical flow system for
NHPI-mediated electrochemical aerobic oxidation of benzylic C-
H bonds. The use of a cation-exchange membrane avoided the
reductive decomposition NHPI at the cathode, which in turn
allowed the usage of the RVC as the electrodes instead of Pt to
achieve a high yield. The use of porous RVC significantly reduced
the cost of the electrochemical flow cell and increased the
interfacial areas to enhance mass transfer, enabling process for
further scaling-up. Operating the electrochemical flow cell with
recycle avoided the PINO radical self-decomposition, and
enabled use of green molecular oxygen as the co-oxidant. The
electrochemical analysis of the NHPI-mediated electrochemical
Cyclic voltammetry procedure. Working electrode: glassy carbon or
platinum (BASi). Counter electrode: platinum wire (Pine Instrument).
Reference electrode: silver wire in the solution of 0.01 M AgNO
3
and 0.1
M TBAP in MeCN (Pine Instrument). The setup is shown in Supporting
Information (Supplementary Figure S2). The potential measured vs.
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Chemistry - A European Journal
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Ag/Ag+ was transformed into potential vs. Fc/Fc+ for reproducibility. The
glassy carbon working electrode was polished with 0.05 µm alumina on a
Texmet/alumina pad, and rinsed and sonicated with deionized (DI) water
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This work was supported by Novartis-MIT Center for Continuous
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Keywords: Flow chemistry • Electrochemistry • NHPI oxidation •
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This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201802588
FULL PAPER
FULL PAPER
Y. Mo, K.F. Jensen*
Page No. – Page No.
Continuous NHPI-Mediated
Electrochemical Aerobic Oxidation of
Benzylic C-H Bonds
Electrochemical analysis identified two N-hydroxyphthalimide (NHPI) decomposition
mechanisms, and a continuous electrochemical system was engineered accordingly
for the NHPI-mediated electrochemical aerobic oxidation of benzylic C-H bonds,
which offers a cost-effective and efficient strategy to handle electrochemical organic
synthesis with inherently slow reaction kinetics and gaseous reagents in flow.
This article is protected by copyright. All rights reserved.