An experimentalist's guide to electrosynthesis: The Shono oxidation

Article abstract of DOI:10.1016/j.tetlet.2015.10.090

Electrosynthesis is a powerful method to functionalise organic molecules without the need to use chemical reagents or protecting groups, yet it is not widely used in synthesis. In this study, we investigated the Shono oxidation of a tertiary amide (electrochemical functionalisation of a C-H bond adjacent to an amide nitrogen atom), demonstrating the value of performing cyclic voltammetry, varying voltage and charge per mole, selection of electrolyte and electrode material. We demystify the process to demonstrate a simple relationship between oxidation potential, and charge transfer required, which affords a high conversion to the desired alpha-methoxylated product using an undivided experimental cell.

Full text of DOI:10.1016/j.tetlet.2015.10.090

Tetrahedron Letters 56 (2015) 6863–6867
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An experimentalist’s guide to electrosynthesis: the Shono oxidation
⇑
⇑
Paulino Alfonso-Súarez, Athanasios V. Kolliopoulos, Jamie P. Smith, Craig E. Banks , Alan M. Jones
Manchester Metropolitan University, Faculty of Science and Engineering, School of Science and the Environment, Division of Chemistry and Environmental Science, John
Dalton Building, Chester Street, Manchester M1 5GD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Electrosynthesis is a powerful method to functionalise organic molecules without the need to use
chemical reagents or protecting groups, yet it is not widely used in synthesis. In this study, we investi-
gated the Shono oxidation of a tertiary amide (electrochemical functionalisation of a C–H bond adjacent
to an amide nitrogen atom), demonstrating the value of performing cyclic voltammetry, varying voltage
and charge per mole, selection of electrolyte and electrode material. We demystify the process to demon-
strate a simple relationship between oxidation potential, and charge transfer required, which affords a
high conversion to the desired alpha-methoxylated product using an undivided experimental cell.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 20 August 2015
Revised 21 October 2015
Accepted 27 October 2015
Available online 29 October 2015
Keywords:
Electrochemistry
Electrosynthesis
Shono oxidation
Anodic methoxylation
Potentiometry
Cyclic voltammetry
Introduction
Results and discussion
Electrochemistry meets all the criteria of green, sustainable
chemistry for organic synthesis1 and can be used for protecting
group-free synthesis, CH activation chemistry and umpolung reac-
tion centres, generating complex reaction products from simple
We selected a simple tertiary amide 1 that meets the criteria of
the Shono oxidation, yet has not been systematically investigated
as far as we know in electrosynthesis. Although Eberson et al.
6
reported a one-off galvanostatic route to 2 in 1979, no spectra
2
starting materials. In our laboratory, our interest has focused on
or characterisation was reported. This method required a high sur-
3
2
the Shono oxidation, which has the remarkable ability to trans-
face area graphitic rod (800 cm ) and a stainless steel cathode
form C–H groups adjacent to tertiary amides via an N-acyl iminium
intermediate, to C–X bonds, for example, C–O, C–C bonds. In light
of the current interest in C–H activation chemistry,4 we sought
to demonstrate how this seminal reaction can be performed in a
standard University laboratory set-up. In our recent review of the
placed 1 mm apart to reduce resistance. An applied voltage of
between 20 and 26 V and a current of 50 A was passed through a
solution of 1 in methanol with 0.01 M Bu NBF as the electrolyte
4 4
to afford 2 in a current yield of 63% and material yield of 76%.
Clearly, this high voltage and current is not attainable in most
chemical laboratories and the choice of reaction conditions was
not understood nor justified.
5
Shono reaction we identified a paucity of literature on how to
get the best results from this reaction. This can be off-putting to
those organic chemists considering performing reactions using
electrochemistry. The goal of this article is to demonstrate how a
simple screen of three parameters can increase the likelihood of
success in electrosynthesis, and make this exciting, emerging and
enabling branch of synthesis more widely used by the organic
community.
The goal of this study will be to show how model compound 1
can be anodically (electrochemical oxidation) methoxylated to give
2 (Scheme 1) using a simple parameter screen and enabling this
sustainable chemistry to be used in synthetic labs, more generally.
For comparison, Weinreb and co-workers reported an alternative
7
synthetic route for the preparation of 2 from 3 using a chemical
oxidant and transition metal co-additive (Scheme 1). Of note,
Weinreb’s route suffered from a dealkylation side reaction due to
adventitious water.
⇑
Corresponding authors. Tel.: +44 (0) 161 247 1196 (C.E.B.), +44 (0) 161 247
195 (A.M.J.).
E-mail addresses: c.banks@mmu.ac.uk (C.E. Banks), a.m.jones@mmu.ac.uk
Amide 1 was prepared in 85% yield using previously reported
6
8
chemistry. Prior to performing electrosynthesis we wished to
(
A.M. Jones).
determine the oxidation potential of 1 in methanol using cyclic
voltammetry, however the oxidation peak for 1 to 2 was masked
URLs: http://www.craigbanksresearch.com (C.E. Banks), http://www.jonesgroup
research.wordpress.com (A.M. Jones).
http://dx.doi.org/10.1016/j.tetlet.2015.10.090
0
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

6
864
P. Alfonso-Súarez et al. / Tetrahedron Letters 56 (2015) 6863–6867
This
Weinreb's
voltammetric scan rate, the diffusion coefficient and concentration
of the analyte under investigation and the electrode area all
work
route
anodic
NaNO2, HCl
CuCl (5%)
O
O
OMe
H2N
O
p
significantly affect the observed voltammetric signal (I ). Note that
oxidation
2
N
N
N
current density (A/m ) is frequently mentioned in various publica-
tions, which from inspection of the units is simply the current (A)
MeOH
MeOH
1
2
rt, 86%
3
2
divided by the electrode area (m ), and allows a comparison
Scheme 1. Anodic oxidative methoxylation of 1 to 2 and Weinreb’s route to 2 from
between experimentalists and represents the current density of
the active electrode surface.
3.
In an electrosynthetic experiment, the potential needs to be
fixed at a suitable value chosen by the experimentalist. In the liter-
ature, we sometimes find cyclic voltammetry exhibits a useful
voltammetric signal at +1.5V but then the electrosynthesis is held
by the oxidation of the solvent beginning at +1.6 V (cyclic
voltammograms are located in ESI S1–S4). Therefore, we switched
to a solvent with a wider potential window, namely, acetonitrile
containing 10% methanol as the co-solvent. Using the relatively
cheap electrode material with a large electrode surface area, retic-
ulated vitreous carbon (RVC), as both the working electrode and
counter electrode and a silver wire as the reference (see ESI S5
for an example electrode set-up) we obtained typical cyclic
voltammograms that exhibited a distinct oxidation peak for 1
which was well resolved prior to the onset of solvent breakdown
1
0
at an extreme potential of +4.5 V or not using the oxidation
1
1
potential to enhance selectivity. The question is why? In addition,
how was this value deduced and what are the implications? If we
return to our exemplar Shono electrosynthesis, a key experiment
to undertake is a blank voltammogram (Fig. 1a). This is required
to understand the exact solvent window (the point in which there
is no solvent breakdown) and to ensure that the voltammetric peak
of interest is not located in this region, since in addition to the
main desired electrochemical process underway; the degradation
of the solvent will also occur thus convoluting the electrochemical
and electrosynthetic processes (see later). Note the second peak in
the voltammogram presented in Figure 1b was due to the electro-
chemical oxidation of the electrolyte as was evident from compar-
ison of the blank voltammogram (Fig. 1a). With the knowledge that
1 cleanly oxidises at +1.65 V based on the cyclic voltammetry
shown in Figure 1b with no interference from solvent degradation,
we considered the effect of increasing the potential at which the
electrosynthesis was conducted.
(Fig. 1).
A
scan rate study, as shown in Figure 1b, is
a useful
voltammetric approach to try and understand the process in hand.
In this case, the voltammetry is conducted over a range of scan
rates. A plot of peak current (I ) against scan rate t, and an addi-
p
tional plot of peak current against the square-root of the scan rate
allows one to determine if the process is diffusional (since
1
=2
I
p
ꢀ
t
) or adsorbed in nature (I
p
ꢀ
t) where the plot with the
9
most linear response indicates the dominant process. In our case,
analysis of the data presented in Figure 1 showed a linear response
ꢂ4
ꢂ1 1=2
ꢂ6
2
(
I
p
/A = 5.16 ꢁ 10
A=ðt
s
Þ
+ 4.34 ꢁ 10 A; N = 5; R = 0.999)
Once the voltammetric potential has been carefully chosen, the
electrosynthetic reaction (also known as bulk electrolysis) is con-
ducted by holding the reaction at the chosen potential. A common
approach is to use chronocoulometry where the total charge (Q)
that passes during the time following a potential step is measured
as a function of time. Q can be obtained by integrating the current
during the applied potential step. In order for the electrosynthetic
reaction to go to completion, the amount of charge (C) passed is
given by:
indicating a diffusional process. Therefore, due to the unique
voltammetric signature presented in Figure 1, the appropriate
equation for the case of a fully irreversible electron transfer process
(
not stirred) the Randles–Šev c´ ik equation is as follows:
n0ÞnFACðFD
1=2
I
p
¼ ꢃ0:496ð
a
t=RTÞ
where A is the geometric area of the electrode (cm2),
a
is the trans-
fer coefficient (usually assumed to be close to 0.5), n is the total
number of electrons transferred per molecule in the electrochemi-
cal process, n is the number of electrons transferred before the rate
Q ¼ ðm
A
=RMMÞnF
0
determining step, F is the Faraday constant, R is the universal gas
constant and T is the temperature at which the electrochemical pro-
cess is performed. This equation clearly shows that temperature,
where Q is the charge required to drive the reaction to completion,
m
A
is the mass (g) of the electroactive analyte, RMM is the relative
ꢂ1
molecular mass (g mol ), F is the Faraday constant and n is the
Figure 1. (a): Cyclic voltammetric profile for the blank in MeCN/MeOH (10:1) with 0.47 M TBAP as electrolyte at rates 5 mV/s, 10 mV/s, 25 mV/s, 50 mV/s, 100 mV/s and
50 mV/s at 0 °C. (b): Cyclic voltammograms for 1 in MeCN/MeOH (10:1) with 0.47 M TBAP as electrolyte and 4.7 mM of compound 1 at scan rates of 5 mV/s, 10 mV/s, 25 mV/
s, 50 mV/s, 100 mV/s and 250 mV/s at 0 °C.
2

P. Alfonso-Súarez et al. / Tetrahedron Letters 56 (2015) 6863–6867
6865
total number of electrons passed in the electrochemical reaction.
Table 2
The effect of varying F/mole. Potential held at +1.8 V in all cases
Once the amount of charge (C/mol) is known, the chronocoulometry
experiment can be performed. Through monitoring the charge, one
can determine how long the reaction will take to go to completion.
In order to decrease this time, large surface area electrodes and
mechanical stirring of the solution are typically employed.
Table 1 demonstrates the percentage conversions obtained for 1
to 2 using a range of voltages (+1.5 to +2.4 V) around the known
oxidation potential (+1.65 V). In all cases the temperature was
fixed at 0 °C, 4 F/mole was used and identical surface area elec-
trodes were used. All reactions were performed on the same scale
and upon reaction completion, the solvent was evaporated and the
Entry
F/mole
Time (min)
Normalised % conversion to 2
1
2
3
4
2
3
4
5
17
23
36
43
29
36
95
n.d.
a
a
Decomposition was observed in the 1H NMR spectrum, indicative of over-
reaction to 5 amongst other side products; n.d. = not determined.
O
-e-
O
-
+
O
O
-e , -H
deprotonation
Ph
N
Ph
N
Ph
N
Ph
N
residue was dissolved in 0.60 mL d
.0 ppm internal reference).12
It was found that as the voltage of the electrosynthesis reaction
increased from +1.5 V to +2.4 V a clear maxima was observed at
1.9 V. However, discoloration of the electrodes (from black to grey
6
-DMSO (with TMS as the
1
4
5
0
+
-
MeOH
+
- MeOH
H
>
> V
O
OMe
or >> F/mol
or strongly
protic solvent
+
Ph
N
5 + decompostion
products
and then blue) suggested over reaction and deposition on the elec-
trode surface at this potential which would require replacement of
the electrode materials for every reaction, limiting the green
potential of this method. As the potential (V) was increased, the
potential approaches and becomes outside of the potential window
at which point solvent decomposition/degradation occurs. In this
instance, the electrosynthetic process becomes complicated by
solvent degradation products which affect the efficiency of the
formation of the desired product 2.
In conclusion, based on modification of the voltage parameter,
as shown above (Table 1) it is pertinent to hold the potential for
the electrosynthetic reaction at +1.9 V. Therefore, a simple formula
based on cyclic voltammetry can be proposed for this example:
Potentiostat voltage = CV oxidation potential (E/V) + a suitably
applied over potential voltage (E/V). However, for the following
experiments we decided to use +1.8 V for the following variation
of the F/mole to reduce electrode attrition and reduce the severity
of solvent degradation.
The Shono two-electron process should only necessitate the use
of 2 F/mole, however the use of an excess, often 4 F/mole is used.
We next investigated whether the reaction can indeed be per-
formed at a lower charge (Table 2).
It was evident from Table 2 that 4 F/mole was optimal to
achieve the highest conversion. The exact reason as to why this
experimental value was twice that required theoretically (see
Scheme 2 for the formation of the intermediate N-acyliminium
ion 4) is not fully understood but could possibly be due to the con-
comitant oxidation of solvent breakdown and/or over-reaction; the
exact reason will be considered in future reactions. Scheme 2
highlights this issue.
2
Scheme 2. Postulated mechanism to form 2 via N-acyliminium intermediate 4 and
possible routes to the side-reaction product, enamide 5 amongst others.
Removal of a single electron from the lone pair of the amide
nitrogen atom generates an unstable radical cation. Removal of
the second electron via the concomitant expulsion of a proton gen-
erates the N-acyliminium ion 4 which can be intercepted by
methanol to yield 2. As expected in an acidic environment it is pos-
2
sible for 2 to revert to 4 via an E mechanism. N-acyliminium 4
may also deprotonate to enamide 5 via either 2, 4 or 5 to give a
variety of other decomposition products. It was noted that the
presence of compounds other than amide 1 or the desired oxida-
tion product 2 could be influenced via increasing the protic
strength of the solvent and/or electrolyte (see later), increased
charge or the over-voltage applied to the reaction system.
We next considered whether the choice of electrolyte influ-
enced the outcome of the reaction (Table 3). Interestingly, the orig-
inally selected electrolyte, tetrabutylammonium perchlorate
1
3
(
TBAP), afforded the highest conversion and yield despite using
the same conditions of charge and voltage. Of note, it was found
that changing both the electrolyte and solvent resulted in a quan-
titative conversion to enamide 5 (comparison with Ref. 14) in 100%
MeOH. Enamide 5 was not isolated due to instability on silica gel
chromatography.
At this point, it was considered whether the perchlorate counter
ion accelerated or caused a background chemical oxidation event
independent of the electrical voltage applied. It could be seen both
from entry 1 in Table 1 and from a control experiment of 1 in TBAP
at 0 °C, that this caused no detectable change to 2. Therefore, we
next sought to optimise the concentration of TBAP employed
(
Table 4).
Table 1
It was found, that in all cases, conversion of 1 to 2 was achieved
Variation of potential at a fixed F/mole on the percentage conversion of 1 to 2
but halving the concentration resulted in doubling the time
Entry
Voltage (V)
F/mole
Time (h)
Normalised % conversion to 2a
1
2
3
3
4
5
6
7
8
+1.5
+1.6
+1.7
+1.8
+1.9
+2.0
+2.1
+2.2
+2.4
4
4
4
4
4
4
4
4
4
2.6
2.0
3.2
2.2
2.3
1.7
0.9
1.4
0.2
0
26
93
95
100
99
77
75
Table 3
Changing the electrolyte based on the optimal +1.8 V and 4 F/mole conditions using
MeCN/MeOH; (10:1) unless otherwise stated to convert 1 to 2
Entry
Electrolyte
Time (min)
Normalised % conversion to 2
1
2
3a
Bu
Me
4
NClO
NClO
4
(TBAP)
36
—
60
218
—
99%
Not soluble
20%
0% (99% 5)
Limited solubility
Not soluble
Not soluble
4
4
(TMAP)
b
n.d.
Et
Et
4
NOTs
NOTs
a
3
4
5
6
b
4
a
The maximal integration of the diagnostic proton at 4.78 ppm is ca. 0.75H due
to the existence of rotamers around the amide bond accentuated by unsymmetrical
NaBF
NaOSO
Bu NI (TBAI)
4
2
Ph
—
—
methoxylation of one of the ethyl chains.
4
b
New aromatic protons were observed in the 1H NMR spectrum suggesting
a
formation of enamide 5 amongst other side products; n.d. = not determined.
Using 100% MeOH as solvent.

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866
P. Alfonso-Súarez et al. / Tetrahedron Letters 56 (2015) 6863–6867
Table 4
or 5 from amide 1. It was also found that increased charge or
potential led to degradation products from over-reaction, solvent
breakdown and tautomerisation of intermediate 4.
Effect of changing the concentration of TBAP using the optimised V and F conditions
for the conversion of 1 to 2
Entry
Electrolyte concentration (M)
Charge (C)
Time (min)
1
2
3
0.47
0.24
0.12
11
11.25
3.3
36
67
188
Acknowledgements
A.M.J. thanks the Royal Society (United Kingdom) for the award
of a research grant (RG150135). A.M.J. and C.E.B. thank Manchester
Metropolitan University for seed funding (Research Accelerator
Grant D-80005.5.B) and the Dalton Research Institute. P.A.S. thanks
O
H
1.8 V, RVC electrodes
F/mol, TBAP
O
N
OMe
4
N
+
MeCN/MeOH
10:1), 0 o
9% conversion
1% isolated
Erasmus and the University de La Laguna, Tenerife, Spain, for a
(
C
research traineeship at MMU. The authors thank the analytical
facilities team at Manchester Metropolitan University for NMR
and MS analysis time.
1
2
9
(
1:1 mix of rotamers)
(3:1 mix of rotamers)
5
Scheme 3. Optimised electrosynthesis of 2.
Supplementary data
Table 5
Re-interpretation of the rotamers produced by alpha-methoxylation of 1 to 2 as
Supplementary data (spectroscopic and analytical data includ-
ing 1H and C NMR spectra and cyclic voltammetry of all com-
pounds) associated with this article can be found, in the online
version, at http://dx.doi.org/10.1016/j.tetlet.2015.10.090.
measured by 1H NMR spectroscopy
13
Original assignment7 of 2 in CDCl
Our assignment of 2 in CDCl
3
3
7
4
.38–7.27 (m, 5H)
.82 and 3.65 (rotamers, 2 bs, 1H)
7.36–7.28 (m, 5H)
4.78 (s, 0.75H)
—
3.58 (s, 0.75H)
3.32–3.26 (m, 1.5H)
3.00 (s, 2.5H)
1.35 (d, J = 6.0 Hz, 3H)
1.28–1.23 (m, 3H)
References and notes
3
3
1
1
.35–3.26 (m, 2H)
.04 (br s, 3H)
.40–1.38 (d, J = 6.0 Hz, 3H)
.32–1.27 (m, 3H)
1.
(a) Frontana-Uribe, B. A.; Little, R. D.; Ibanez, J. G.; Palma, A.; Vaquez-Medrano,
R. Green Chem. 2010, 12, 2099–2119; (b) Schäfer, H. J. C. R. Chimie 2011, 14, 745–
7
2
65; (c) Yoshida, J.-I.; Kataoka, K.; Horcajada, R.; Nagaki, N. Chem. Rev. 2008, 108,
265–2299; (d) Waldvogel, S. R. Beilstein J. Org. Chem. 2015, 11, 949–950.
2
3
4
.
.
.
For a comprehensive review see: Moeller, K. D. Tetrahedron 2000, 56, 9527–
554.
(a) Shono, T.; Hamaguchi, H.; Matsumura, Y. J. Am. Chem. Soc. 1975, 97, 4264–
4268; (b) Shono, T. Tetrahedron 1984, 40, 811–850.
(a) Chen, M. S.; White, M. C. Science 2007, 318, 783–787; (b) Chen, M. S.; White,
M. C. Science 2010, 327, 566–571; (c) Girard, S. A.; Knauber, T.; Li, C.-J. Angew.
Chem., Int. Ed. 2014, 53, 74–100.
9
required. Entry 3 was stopped early due to the excessive time
required and a spike in the observed resistivity. It appears due to
the fact that high levels of resistance encountered in organic media
necessitate the use of a high concentration of electrolyte to achieve
the reaction in a reasonable time frame.
5. For a recent review see: Banks, C. E.; Jones, A. M. Beilstein J. Org. Chem. 2014, 10,
Taken together, the optimal conditions1 of electrolyte choice,
electrolyte concentration, voltage and Faradays used yielded a
preparative conversion of 1 to 2 on a reasonable timescale, without
resorting to very large currents and voltages that are only
achievable in specialised labs.
5
3056–3072.
6.
Eberson, L.; Hlavaty, J.; Jönsson, L.; Nyberg, K.; Servin, R.; Sternerup, H.;
Wistrand, L.-G. Acta Chem. Scand. B 1979, 33, 113–115.
7. (a) Chao, W.; Weinreb, S. M. Tetrahedron Lett. 2000, 41, 9199–9204; (b) Han, G.;
LaPorte, M. G.; McIntosh, M. C.; Weinreb, S. M. J. Org. Chem. 1996, 61, 9483–
9493.
8. Du, Y.; Hyster, T. K.; Rovis, T. Chem. Commun. 2011, 12074–12076.
The previously optimised conditions were used to convert 1 to 2
in 99% conversion relative to the reference and after extraction and
purification by silica gel column chromatography afforded 2 (51%
yield) without the need to use transition metals, chemical oxidants
or harsh reaction conditions (Scheme 3).
9. (a) Brownson, D. A. C.; Banks, C. E. The Handbook of Graphene Electrochemistry;
Springer, 2014; (b) Compton, R. G.; Banks, C. E. Understanding Voltammetry, 2nd
ed.; Imperial College Press: London, 2011.
1
0. Saravanan, K. R.; Selvamani, V.; Kulangiappar, K.; Velayutham, D.;
Suryanarayanan, V. Electrochem. Commun. 2013, 28, 31–33.
11. Frankowski, K. J.; Liu, R.; Milligan, G. L.; Moeller, K. D.; Aubé, J. Angew. Chem.,
Int. Ed. 2015, 54, 10555–10558.
During the course of our analysis of the 1H NMR spectra
1
2. It was envisioned to monitor the diagnostic 4.78 ppm peak for 2 using CDCl
but due to overlap of the CHCl un-deuterated reference proton with the
phenyl ring in 1 and 2, d -DMSO was used for all the other reactions. The data
obtained for all the reactions compared favourably either in CDCl3 or d -DMSO
3
7
associated with 2 and in comparison to Weinreb’s spectral data, a
3
different rotameric ratio of 2 was observed ranging from a 1:1
6
7
6
mix (generated via a 1,5-H atom radical transfer route) to a ca. 3:1
(ESI S6).
mixture of rotamers using the alpha-methoxylation route (Table 5).
1
3. (a) Caution: Tetrabutylammonium perchlorate (TBAP) may intensify fire and is
an oxidiser (EU hazard code: H272). Although the safety data sheet for this
perchlorate indicates incompatibility with organic materials, sensible
precautions allow for the safe use of this material on a preparative scale. For
instance, heating may cause an explosion, therefore reactions and work-up are
performed at room temperature or below;
Conclusions
In conclusion, we have demonstrated that from a rapid cyclic
voltammogram measurement, an electrosynthetic experiment
can be undertaken which generates quantitative conversion and
isolable amounts of the desired product. This reaction mitigates
the use of chemical oxidants and transition group metals to
achieve the selective reaction of a C–H bond to give a C–O bond
using ‘traceless’ electrons. This work highlights the various factors
that the electrosynthetic chemist needs to take into consideration.
The selection and nature of electrolyte and counter ion are cur-
rently under study in our laboratory and will be reported in due
course. Together, these results should encourage those wishing to
quickly determine whether an electrosynthetic reaction may work
in their organic synthesis and not be a method of last resort. Simply
tuning the oxidation potential allows the dial-up of compounds 2
(
4
b) We thank reviewer 1 for suggesting a control experiment with TBABF (as
in Ref. 6) as a safer electrolyte, however due to limited solubility in acetonitrile
a reproducible comparison was not achievable;
(c) Organic Electrochemistry: 4th ed., Revised and Expanded, Lund, H.; Ham-
merich, O., Eds.; Marcel Dekker: New York, 2001.
1
1
4. Golding, B. T.; Wong, A. K. Angew. Chem. 1981, 93.
5. Representative experimental procedure for the electrosynthesis of
1 to
generate N-ethyl-N-(1-methoxyethyl)benzamide 2: To an undivided glass
cell (20 cm ) equipped with a magnetic stirrer along with a rectangular
reticulated vitreous carbon (RVC) anode (11 cm ) and rectangular RVC cathode
3
2
2
(
11 cm ), arranged opposite to one another at a distance of 3.0 mm with a
silver wire reference electrode placed 1.0 mm from the working electrode was
added 1 (20 mg, 4.73 mM) in acetonitrile (21.6 mL), methanol (2.2 mL) and
tetrabutylammonium perchlorate (3.84 g, 0.47 M). The electrolysis was carried
out with stirring at a potential of 1.8 V (producing a current density of 7.3
lA/
mm3 at 0 °C) until a charge of 4.0 F mol had passed. An average current of
ꢂ1
5.05 mA passed through the electrodes. The solvent was evaporated under

P. Alfonso-Súarez et al. / Tetrahedron Letters 56 (2015) 6863–6867
6867
reduced pressure, and the product was isolated by column chromatography
3.58 (s, 0.75 H), 3.32–3.26 (m, 1.5H), 3.00 (s, 2.5H), 1.35 (d, J = 6.0 Hz, 3H),
1.28–1.23 (m, 3H); 13C NMR (100 MHz, CDCl
) d = 171.9, 136.9, 129.5, 128.6,
126.7, 86.5, 54.7, 34.3, 20.2, 14.4; m/z (ESI) 208 (M+H); Hi-Res LC–MS (ESI) m/z
calcd for C12 18NO (M+H) 208.1338, found 208.1325.
(
ethyl acetate/petroleum ether, 10:90 to 15:85) to afford the title compound 2
3
ꢂ1
as a yellow oil, (9.3 mg, 51%).
m
max/cm 2963, 2913, 2859, 1763, 1738, 1646
and 1550; 1H NMR (400 MHz, CDCl
H
3
) d = 7.36–7.28 (m, 5H), 4.78 (s, 0.75H),
2