Reduction of substituted phenyl 2-chloroacetates at silver cathodes: Electrosynthesis of coumarins

Article abstract of DOI:10.1149/2.0551412jes

To explore the electrosynthesis of coumarins, cyclic voltammetry and controlled-potential (bulk) electrolysis have been employed to investigate the reduction of the carbon-chlorine bond of five substituted phenyl 2-chloroacetates at silver cathodes in dimethylformamide (DMF) containing 0.10 M tetra-n-butylammonium tetrafluoroborate (TBABF₄) as supporting electrolyte; the five substrates are 2-formylphenyl 2-chloroacetate (1a), 2-acetylphenyl 2-chloroacetate (2a), methyl 2-(2-chloroacetoxy)benzoate (3a), 2-formyl-5-methoxyphenyl 2-chloroacetate (4a), and 2-formyl-3,5-dimethoxyphenyl 2-chloroacetate (5a). We have examined (a) the effects of substituents on the benzene ring of the substrate as well as the nature of the aryl carbonyl moiety on the formation of the coumarin product and (b) the effect of solvent - namely, DMF, acetonitrile (CH₃CN), benzonitrile (PhCN), and propylene carbonate (PC) - and substrate concentration on the yield of the coumarin. It was found that the most unsubstituted substrate (1a) afforded the highest yield (41%) of the desired coumarin in a DMF-TBABF₄ medium. A mechanistic scheme is proposed to account for the formation of the coumarin. Furthermore, the only other products seen in these reductions are 2-substituted phenols, which are precursors for synthesis of the various substrates.

Full text of DOI:10.1149/2.0551412jes

G98
Journal of The Electrochemical Society, 161 (12) G98-G102 (2014)
0013-4651/2014/161(12)/G98/5/$31.00 © The Electrochemical Society
Reduction of Substituted Phenyl 2-Chloroacetates at Silver
Cathodes: Electrosynthesis of Coumarins
Erick M. Pasciak∗ and Dennis G. Peters∗∗,z
Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA
To explore the electrosynthesis of coumarins, cyclic voltammetry and controlled-potential (bulk) electrolysis have been employed to
investigate the reduction of the carbon–chlorine bond of five substituted phenyl 2-chloroacetates at silver cathodes in dimethylform-
amide (DMF) containing 0.10 M tetra-n-butylammonium tetrafluoroborate (TBABF4) as supporting electrolyte; the five substrates
are 2-formylphenyl 2-chloroacetate (1a), 2-acetylphenyl 2-chloroacetate (2a), methyl 2-(2-chloroacetoxy)benzoate (3a), 2-formyl-
5-methoxyphenyl 2-chloroacetate (4a), and 2-formyl-3,5-dimethoxyphenyl 2-chloroacetate (5a). We have examined (a) the effects
of substituents on the benzene ring of the substrate as well as the nature of the aryl carbonyl moiety on the formation of the coumarin
product and (b) the effect of solvent—namely, DMF, acetonitrile (CH3CN), benzonitrile (PhCN), and propylene carbonate (PC)—and
substrate concentration on the yield of the coumarin. It was found that the most unsubstituted substrate (1a) afforded the highest
yield (41%) of the desired coumarin in a DMF–TBABF4 medium. A mechanistic scheme is proposed to account for the formation
of the coumarin. Furthermore, the only other products seen in these reductions are 2-substituted phenols, which are precursors for
synthesis of the various substrates.
© 2014 The Electrochemical Society. [DOI: 10.1149/2.0551412jes] All rights reserved.
Manuscript submitted July 14, 2014; revised manuscript received August 18, 2014. Published August 28, 2014. This was Paper 824
presented at the Orlando, Florida, Meeting of the Society, May 11–15, 2014
Coumarins have become important in many fields such as bi-
references pertaining to the use of silver cathodes for the reduction of
halogenated organic compounds appears in a recent publication.24 In
other work,25 our laboratory has investigated the direct and nickel(I)
salen-catalyzed reductions of chloroacetamides at carbon and silver
electrodes; it was discovered (a) that direct reduction of the carbon–
chlorine bond occurs at potentials as much as 600 mV more positive
when a silver cathode is used and (b) that direct reduction at silver is
100–200 mV more facile than the nickel(I) salen-promoted reaction.
As part of an effort to develop a strategy for the electrosyn-
thesis of coumarin and its derivatives, we have explored the di-
rect electrochemical reduction of five different substituted phenyl 2-
chloroacetates at silver cathodes in DMF as well as several other com-
mon organic solvents. Shown below are the compounds used for this
study. Cyclic voltammetry and controlled-potential (bulk) electroly-
sis have been employed to characterize the electrochemistry of these
substrates, and gas chromatography (GC) and gas chromatography–
mass spectrometry (GC–MS) have been utilized for the separa-
tion, identification, and quantitation of the electrolysis products.
ology, medicine, and organic chemistry; for example, coumarins
have been employed as polymers for industry.1 Coumarin and
its derivatives exhibit biological activity and could possibly be
used as anti-coagulant,2 antitumor,3 anti-inflammatory,4 antibiotic,5
anti-HIV-1,5 anti-diabetic,6 and anti-depressant drugs.6 Two of the
most well-known coumarin derivatives are (RS)-4-hydroxy-3-(3-oxo-
1-phenylbutyl)-2H-chromen-2-one (Warfarin) and its sodium salt
(Coumadin), both of which are prescribed as anti-coagulants. Ad-
ditionally, optical properties of coumarins allow them to be employed
in applications such as laser devices, light-emitting diodes, and flu-
orescent markers in biomedical imaging.7 There are many classic
processes for the synthesis of coumarins,8–12 including the use of
transition-metal catalysts;13–19 however, among all of these methods,
the most commonly employed is the Pechmann reaction.8 Classic ap-
proaches allow a large range of derivatives to be prepared, but these
methods usually require harsh conditions, such as addition of strong
acids, and can afford mixtures of products that are difficult to separate.
Despite the many applications of coumarins mentioned above, very
few publications can be found that deal with the electrosynthesis of
these compounds. In comparison with traditional methods, electrosyn-
thesis can provide many advantages, such as short reaction times, mild
reagents, low energy cost, and easily isolated products; and, in most
cases, the reaction can be conducted at room temperature. Batanero
and co-workers20–22 studied the electrochemical reduction of various
substituted phenyl 2,2,2-trichloroacetates at a mercury pool cathode
in acetonitrile containing lithium perchlorate as a route to the synthe-
sis of derivatives of 3-chlorocoumarins; product yields were as low as
33% and, in one case, as high as 97%. Earlier work23 in our laboratory
focused on both the direct and cobalt(I)-catalyzed reduction of 2-
acetylphenyl 2-chloroacetate and 2-acetylphenyl 2,2-dichloroacetate
at glassy carbon electrodes in dimethylformamide (DMF) containing
0.10 M tetra-n-butylammonium tetrafluoroborate (TBABF4); yields
of the desired product (4-methylcoumarin) ranged from 20–30% for
the direct reduction and 45–50% for the catalytic process.
Experimental
In the present research, we have utilized silver cathodes in an ef-
fort to develop a method for the electrosynthesis of coumarins that
requires neither the negative potentials used previously nor the pres-
ence of a solution-phase transition-metal catalyst. Previous work has
demonstrated that silver has electrocatalytic activity toward the cleav-
age of carbon–halogen bonds, as seen by a significant positive shift
in reduction potentials and by higher current efficiencies; a list of
Reagents.— Each of the following chemicals was employed,
as received, without further purification: anhydrous diethyl
ether (absolute, EMD Chemicals), n-hexadecane (99%, Sigma),
chloroacetyl chloride (98%, Aldrich), chloroform-d (99.8%, Aldrich),
coumarin (1b, ≥99%, Sigma), 4-methylcoumarin (2b, 98%,
Alfa Aesar), 4-methoxycoumarin (3b, 98%, Alfa Aesar), 7-
methoxycoumarin (4b, ≥98%, SAFC), 5,7-dimethoxycoumarin (5b,
98%, Alfa Aesar), 2-hydroxy-4-methoxybenzaldehyde (98%, Sigma
Aldrich), 4,6-dimethoxysalicylaldehyde (98%, Sigma-Aldrich), 2ꢀ-
hydroxyacetophenone (99%, Sigma-Aldrich), and potassium hydrox-
ide (97%, Alfa Aesar). Salicylaldehyde (Fisher Scientific) and methyl
∗Electrochemical Society Student Member.
∗∗Electrochemical Society Fellow.
zE-mail: peters@indiana.edu
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Journal of The Electrochemical Society, 161 (12) G98-G102 (2014)
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salicylate (Fisher Scientific) were purified by vacuum distillation
prior to use. Dimethylformamide (DMF, 99.9%, EMD Chemicals),
acetonitrile (CH3CN, 99.9%, EMD Chemicals), benzonitrile (PhCN,
99%, Sigma-Aldrich), and propylene carbonate (PC, 99.7%, Sigma-
Aldrich) were utilized without further purification as solvents for
electrochemical experiments. Tetra-n-butylammonium tetrafluorobo-
rate (TBABF4, >99%, GFS Chemicals), which served as the support-
ing electrolyte, was recrystallized from water–methanol and stored in
a vacuum oven at 70–80◦C prior to use. All deaeration procedures
were accomplished with zero-grade argon (Air Products).
aqueous suspension of 0.05-μm alumina on a polishing pad, followed
by a rinse with distilled water in an ultrasonic bath. All potentials
are reported with respect to a reference electrode that consisted of a
cadmium-saturated mercury amalgam in contact with DMF saturated
with both cadmium chloride and sodium chloride;28–30 this electrode
has a potential of –0.76 V versus an aqueous saturated calomel elec-
trode (SCE) at 25◦C. Cyclic voltammetry experiments were performed
as described in a previous paper.31
Information about the cell, instrumentation, and procedures used
for controlled-potential (bulk) electrolysis is provided elsewhere.32,33
Silver gauze working electrodes (approximate surface area of 20 cm2)
were constructed from commercially available material (Alfa Aesar,
99.9%, 20 mesh woven from 0.356-mm diameter wire). For bulk
electrolyses, the aforementioned cadmium-saturated mercury amal-
gam reference electrode was utilized, and the auxiliary anode was a
graphite rod immersed in a DMF–0.10 M TBABF4 solution separated
from the cathode compartment by a sintered-glass disk backed by a
methyl cellulose–DMF–0.10 M TBABF4 plug.
General procedure for synthesis of substituted phenyl 2-
chloroacetates (1a–5a).— Preparation and purification of 2-
formylphenyl 2-chloroacetate (1a), 2-acetylphenyl 2-chloroacetate
(2a), methyl 2-(2-chloroacetoxy)benzoate (3a), 2-formyl-
5-methoxyphenyl 2-chloroacetate (4a), and 2-formyl-3,5-
dimethoxyphenyl 2-chloroacetate (5a) were adapted from a procedure
outlined by Hennessy and Buchwald.26 This approach involved the
reaction of 1 equivalent of salicylaldehyde, 2ꢀ-hydroxyacetophenone,
methyl salicylate, 2-hydroxy-4-methoxybenzaldehyde, or 4,6-
dimethoxysalicylaldehyde with 1.5 equivalents of chloroacetyl
chloride in a 2:1 ethyl acetate–water mixture and in the presence
of 3 equivalents of potassium hydroxide in an ice–water bath. Each
reaction mixture was stirred for 1 h at 0◦C and then transferred to
a separatory funnel; the organic layer was separated, washed twice
with brine, dried over anhydrous sodium sulfate, and concentrated
with the aid of rotary evaporation. Products 2a–5a were purified by
recrystallization from ethanol and water, whereas 1a was obtained
as a yellow oil via vacuum distillation. Spectroscopic data were
acquired for each compound: (a) for 1a, 1H NMR (500 MHz, CDCl3)
δ 4.36 (s, 2H), 7.06 (d, J = 8.0 Hz, 1H), 7.24 (t, J = 7.5 Hz, 1H),
Separation, identification, and quantitation of electrolysis
products.— At the end of each controlled-potential (bulk) electrol-
ysis, the catholyte was partitioned three times between diethyl ether
and brine. Then the ether phase was dried over anhydrous sodium sul-
fate and concentrated with the aid of rotary evaporation. Products were
separated and identified by means of gas chromatography (GC) and
gas chromatography–mass spectrometry (GC–MS). Each chromato-
graph (Agilent 7890A) was equipped with a 30 m × 0.25 mm capillary
column (J & W Scientific) with a DB-5 stationary phase; the GC sys-
tem utilized a flame-ionization detector, whereas the GC–MS system
included an inert mass-selective detector operating in electron ioniza-
tion mode (70 eV). Gas chromatographic retention times and mass
spectral data for the electrolysis products were compared with those
for commercially available or chemically synthesized authentic sam-
ples. Identities of all synthesized materials were confirmed by means
of both 1H and 13C NMR spectrometry (500 MHz, Varian Inova) and
high-resolution GC–MS (Thermo Electron Corporation) coupled to a
MAT-95XP magnetic-sector mass spectrometer. Procedures used for
the quantitation of electrolysis products have been described in an
earlier paper.34 Peak areas for the various products were determined
with respect to an internal standard (n-hexadecane) added in known
amount to the electrolysis cell prior to the start of each controlled-
potential reduction. All yields are reported as the absolute percentage
of starting material incorporated in the desired product (1b–5b).
7.45 (t, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 9.90 (s, 1H); 13
C
NMR (125 MHz, CDCl3) δ 41.0, 123.1, 127.0, 127.6, 132.2, 135.5,
150.3, 166.0, 189.3; HRMS (ESI) m/z: calcd. for C9H7O3Cl [M]+
198.0078, found 198.0096; (b) for 2a, 1H NMR (500 MHz, CDCl3) δ
2.53 (s, 1H), 4.39 (s, 2H), 7.13 (d, J = 8.5 Hz, 1H), 7.34 (t, J = 7.5
Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 29.0, 41.1, 123.7, 126.7, 129.6, 130.8, 133.9,
148.6, 166.1, 197.2; HRMS (ESI) m/z: calcd. for C10H9O3Cl [M]+
212.0235, found 212.0230; (c) for 3a, 1H NMR (500 MHz, CDCl3) δ
3.80 (s, 3H), 4.40 (s, 2H), 7.11 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 7.5
Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 8.01 (d, J = 7.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 41.1, 52.3, 122.6, 123.5, 126.6, 131.9, 134.2,
150.3, 164.5, 166.2; HRMS (ESI) m/z: calcd. for C10H9O4Cl [M]+
1
228.0184, found 228.0186; (d) for 4a, H NMR (500 MHz, CDCl3)
Results and Discussion
δ 3.86 (s, 3H), 4.43 (s, 2H), 6.71 (d, J = 2.1 Hz, 1H), 6.91–6.89 (m,
1H), 7.80 (d, J = 8.5 Hz, 1H), 9.90 (s, 1H); 13C NMR (125 MHz,
CDCl3) δ 40.9, 56.0, 108.9, 112.5, 121.2, 134.7, 152.0, 165.3, 165.8,
187.8; HRMS (ESI) m/z: calcd. for C10H9O4Cl [M]+ 228.0184,
Cyclic voltammetric behavior of substituted phenyl 2-
chloroacetates.— Shown in Figure 1 is a representative pair of cyclic
voltammograms recorded at a scan rate of 100 mV s−1 with glassy car-
bon (solid curve) and silver (dot-dashed curve) disk electrodes for a 3.0
mM solution of 2-formylphenyl 2-chloroacetate (1a) in oxygen-free
DMF containing 0.10 M TBABF4. For both electrodes, we observed
three irreversible cathodic peaks. We propose that the first peak is
due to reductive cleavage of the carbon–chlorine bond; note that the
potential for the first peak for a silver cathode is shifted positively by
280 mV in comparison with the glassy carbon electrode. Reduction
of coumarin or salicylaldehyde is responsible for the second cathodic
peak; both products are observed for controlled-potential (bulk) elec-
trolyses conducted at a potential corresponding to the first cathodic
peak (as will be discussed later), and their reduction potentials were
determined from cyclic voltammetric studies with authentic samples
of each product under the same conditions. We suggest that the third
peak is attributable to reduction of the conjugate base of salicylalde-
hyde, which is formed at potentials corresponding to the first cathodic
peak, as will be discussed later in the mechanistic section of this paper.
Because the main objective of this work was focused on the reduc-
tive electrochemical cyclization of substituted phenyl 2-chloroacetates
(1a–5a) at silver cathodes, we measured the cathodic peak potentials
for reduction of all five substrates. As shown in Table I, only two
1
found 228.0186; (e) for 5a, H NMR (500 MHz, CDCl3) δ 3.85 (s,
3H), 3.90 (s, 3H), 4.45 (s, 2H), 6.24 (d, J = 2.25 Hz, 1H), 6.38 (d, J
= 8.5 Hz, 1H), 10.21 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 41.2,
55.9, 56.2, 96.5, 101.0, 110.6, 152.0, 164.7, 165.8, 165.9, 186.6;
HRMS (ESI) m/z: calcd. for C11H11O5Cl [M]+ 258.0290, found
258.0290.
Cells, electrodes, procedures, and instrumentation.— A descrip-
tion of the cell used for cyclic voltammetry can be found in a previous
publication.27 We constructed planar, circular glassy carbon and sil-
ver working cathodes (each with a geometric area of 0.071 cm2)
by press-fitting a short piece of either a glassy carbon rod (Grade
GC-20, 3.0-mm-diameter, Tokai Electrode Manufacturing Company,
Tokyo, Japan) or a silver rod (3.0-mm-diameter, 99.9% purity, Alfa
Aesar) into the end of a machined Teflon tube. Electrical connection
to each of these working electrodes was made via a 3.0-mm-diameter
stainless-steel pole that contacted the cathode material and extended
upward through the tube. A coil of platinum wire served as the aux-
iliary (counter) electrode for cyclic voltammetry. Prior to each scan,
the glassy carbon and silver working electrodes were cleaned with an
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Journal of The Electrochemical Society, 161 (12) G98-G102 (2014)
Table II. Coulometric data and product yields for direct reductions
of 1a–5a at silver gauze cathodes.
Substrate
(concentration)
Coumarin;
yield (%)d
Solventa
Potential (V)b
nc
1a (5.0 mM)
1a (5.0 mM)
1a (5.0 mM)
1a (5.0 mM)
DMF
CH3CN
PhCN
PC
–0.72
–0.63
–0.69
–0.63
1.3
1.3
1.2
1.1
1b; 41
1b: 37
1b; trace
1b: trace
2a (5.0 mM)
2a (10.0 mM)
2a (20.0 mM)
2a (50.0 mM)
DMF
DMF
DMF
DMF
–0.80
–0.80
–0.80
–0.80
1.1
1.2
1.2
1.1
2b; 21
2b: 28
2b: 36
2b: 31
3a (5.0 mM)
4a (5.0 mM)
5a (5.0 mM)
DMF
DMF
DMF
–0.72
–0.73
–0.79
1.3
1.3
1.2
3b; trace
4b; 34
5b: 35
aAll solutions contained 0.10 M TBABF4 as the supporting electrolyte.
bPotentials are given with respect to a cadmium-saturated mercury
amalgam reference electrode in contact with DMF saturated with both
cadmium chloride and sodium chloride; this electrode has a potential
of –0.76 V versus SCE at 25◦C.
Figure 1. Cyclic voltammograms for a 3.0 mM solution of 1a recorded with a
glassy carbon (solid curve) and silver (dot-dashed curve) disk electrode at 100
mV s−1 in oxygen-free DMF containing 0.10 M TBABF4. Potentials are given
with respect to a cadmium-saturated mercury amalgam reference electrode in
contact with DMF saturated with both cadmium chloride and sodium chloride;
this electrode has a potential of –0.76 V versus SCE at 25◦C. For the cyclic
voltammogram recorded with glassy carbon, the potential was scanned from 0
to –2.0 to 0 V; for the cyclic voltammogram recorded with silver, the potential
was scanned from 0 to –1.8 to 0 V.
cAverage number of electrons per molecule of substrate.
dYield expressed as the percentage of substrate converted into the
coumarin.
we observed a decrease in the amount of coumarin as the carbonyl
functionality changed from an aldehyde (41% of 1b) to a ketone (21%
of 2b) to a methyl ester (trace of 3b), respectively. It is unclear how
stereochemical and electronic effects dictate this phenomenon, but
it is clear that the identity of the carbonyl group plays an important
role in the cyclization to form the coumarin. Substrates 1a, 4a, and
5a, all of which are aldehydes, led to the production of coumarins
in comparable yields (34–41%), which demonstrates the tolerance of
the electrochemical process to substituents on the benzene ring. For
the electrolysis of 2a at a silver cathode, the observed yield of 2b
is reasonably close to that found in earlier work23 dealing with ei-
ther direct reduction of 2a at reticulated vitreous carbon or cobalt(I)
salen-catalyzed reduction of 2a. However the use of silver as a cath-
ode permits a more positive electrolysis potential (compared to a bare
carbon electrode) and eliminates the need for an expensive and non-
reusable procatalyst.
For all of the electrolyses, the only other product observed
is a substituted phenol: (a) for 1a, 4a, and 5a, this prod-
uct is salicylaldehyde, 2-hydroxy-4-methoxybenzaldehyde, and 4,6-
dimethoxysalicylaldehyde, respectively; (b) for 2a, this product is
2ꢀ-hydroxyacetophenone; and (c) for 3a, this product is methyl salicy-
late. Each of these additional products could be formed via a one- or
two-electron process, as discussed below; however, these compounds
are not of interest and were not quantitated. It should be noted that
these side products need not necessarily be wasted, as they are building
blocks (which can be recovered and reused) to synthesize the starting
materials (1a–5a) employed in this work.
A reviewer expressed concern about the stability of the various
starting materials (1a–5a) before and during an electrolysis, arguing
that the substrates might undergo hydrolysis, perhaps due to the pres-
ence of residual water in the solvent–electrolyte. To test this point, we
prepared a 10.0 mM solution of 2a in DMF–0.10 M TBABF4. A small
aliquot of this solution was immediately subjected to GC and GC–MS
analysis, and only 2a was seen. After a waiting period of 60 min, the
solution was reexamined, and no evidence for decomposition of 2a
was found. We conclude that, under the conditions of our experiments,
there was no hydrolytic loss of the starting material (which would have
led to a diminution in the yield of the desired coumarin). Moreover,
reductive consumption of 1a–5a occurs to the greatest extent at the
beginning of an electrolysis, which is another argument against loss
of starting material via hydrolysis.
cathodic peaks are observed when silver is employed as an electrode
for compounds 2a–5a; we believe that these two peaks correspond to
the first two stages for the reduction of 1a. For the first and second
cathodic peaks for 1a–5a, the tabulated results are similar; the notable
exception is that the second cathodic peak potential for reduction of
3a is at least 360 mV more negative than that for any of the other com-
pounds. Interestingly, on the basis of the controlled–potential (bulk)
electrolyses discussed below, we know that 3a behaves differently.
Controlled-potential (bulk) electrolyses of 1a–5a at silver gauze
electrodes in DMF.— A series of controlled-potential electrolyses of
compounds 1a–5a at a silver gauze cathode was carried out in DMF
containing 0.10 M TBABF4. Coulometric n values and yields of the
desired coumarins (1b–5b) are compiled in Table II; each entry cor-
responds to the average of at least duplicate experiments. Tabulated
n values (the number of electrons transferred per molecule of sub-
strate) were accurate to 0.10. For all substrates, the coulometric
n value was slightly higher than 1, supporting a mechanism where
the carbon–chlorine bond is mainly cleaved in a one-electron process
to give a radical intermediate that cyclizes intramolecularly to form
a coumarin. It is interesting that the nature of the carbonyl moiety
influences the yield of the coumarin; for substrates 1a, 2a, and 3a,
Table I. Cathodic peak potentials (Epc) for reduction of 3.0 mM
solutions of 1a–5a obtained from cyclic voltammograms recorded
with a silver cathode at 100 mV s−1 in oxygen-free DMF containing
0.10 M TBABF4.
Substrate
(Epc)1 (V)a
(Epc)2 (V)a
(Epc)3 (V)a
1a
2a
3a
4a
5a
–0.52
–0.62
–0.59
–0.53
–0.57
–0.97
–1.07
–1.44
–1.08
–1.05
–1.67
b
–
b
–
–
b
b
–
aPotentials are given with respect to a cadmium-saturated mercury
amalgam reference electrode in contact with DMF saturated with both
cadmium chloride and sodium chloride; this electrode has a potential
of –0.76 V versus SCE at 25◦C.
bA third cathodic peak was not observed for this substrate.
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Journal of The Electrochemical Society, 161 (12) G98-G102 (2014)
Electrochemical behavior of 1a in different solvents.— Acetoni-
G101
trile (CH3CN), benzonitrile (PhCN), and propylene carbonate (PC)
were employed to study their effects as solvents on the yield of
coumarin formed by reduction of 1a at a silver cathode. As shown
above, reduction of 1a, the least-substituted substrate, was found to
produce coumarin in the highest yield (41%) in DMF; therefore, it
was chosen for the study of solvent effects. Figure 2 is a set of cyclic
voltammograms recorded at 100 mV s−1 for reduction of a 3.0 mM
solution of 1a at a silver cathode in DMF, CH3CN, PhCN, and PC
containing 0.10 M TBABF4. Two key differences are seen in these
cyclic voltammograms. First, the peak potential for the first electron-
transfer process is essentially the same for DMF, CH3CN, and PhCN,
whereas that for PC is shifted to a more positive value. Second, the
current for the first peak is more than twice as large in CH3CN (in
comparison with the other solvents), which is most likely due to its
much lower viscosity.35–37
Compound 1a was subjected to controlled–potential (bulk) elec-
trolyses at a silver cathode in CH3CN, PhCN, and PC containing 0.10
M TBABF4 at a potential approximately 200 mV more negative than
each of its respective first-peak potentials; the coulometric n values
and the yields of 1b are included in Table II. Electrolyses in PhCN
and PC led only to the desired product (1b) in trace quantities. On
the other hand, CH3CN proved to be a suitable alternative solvent for
the formation of coumarin (1b) in 37% yield, which is similar to the
results found with DMF (41%).
Figure 2. Cyclic voltammograms for a 3.0 mM solution of 1a recorded with
a silver disk electrode at 100 mV s−1 in oxygen-free DMF (solid curve), PC
(dashed curve), PhCN (dotted curve), and CH3CN (dot–dash curve) containing
0.10 M TBABF4. Potentials are given with respect to a cadmium-saturated
mercury amalgam reference electrode in contact with DMF saturated with
both cadmium chloride and sodium chloride; this electrode has a potential
of –0.76 V versus SCE at 25◦C. For each solvent, the potential scan was as
follows: (a) DMF: 0 to –1.8 to 0 V; (b) PC: 0 to –1.4 to 0 V; (c) PhCN: 0 to
–1.0 to 0 V; (d) CH3CN: 0 to –1.5 to 0 V.
Effect of concentration of 2a on controlled-potential (bulk) elec-
trolyses in DMF.— To explore the effect of changing the concentra-
tion of substrate on the yield of the coumarin, a series of electroly-
R3
O
R3
O
O
_
e
R1
R1
(1)
_
_
Cl
R2
O
R2
Cl
O
a
.
O
i1
R3
O
O
R3
R3
.
R1
O
R1 OH
H
H
H
cyclization
R1
H
H
(2)
R2
R2
R2
O
O
O
O
.
O
i2
i1
R3
R1
_
H2O
(3)
(4)
Scheme 1. Mechanism for reduction of substituted phenyl 2-
chloroacetates.
i2
R2
O
O
b
R3
O
R3
O
O
R3
O
H
R1
R1
R1
H2C
C
O
+
R2
O
.
R2
R2
OH
.
O
c
i3
i1
+
H
R3
O
O
R3
O
O
_
e
R1
R1
(5)
i1
H2C
C
O
+
_
R2
R2
_
O
i5
i4
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G102
Journal of The Electrochemical Society, 161 (12) G98-G102 (2014)
ses of 2a was conducted. Presented in Table II are the yields of 4-
methylcoumarin (2b) produced from the reduction of concentrations
of 2a ranging from 5.0 to 50.0 mM. As we increased the concentra-
tion of 2a, the yield of 2b reached a plateau between approximately
30–35%, which is commensurate with the results seen when 5.0 mM
1a, 4a, and 5a were electrolyzed. In comparison with previously re-
ported results,23 we find that silver performs as well as a bare carbon
electrode for a concentration of 2a of 10 mM.
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Proposed mechanism for electrochemical reduction of substi-
tuted phenyl 2-chloroacetates.— Scheme 1 represents a plausible se-
quence of mechanistic steps for the reduction of substituted phenyl
2-chloroacetates. Reduction of the chloroacetate (a) occurs via one-
electron reductive cleavage of the carbon–chlorine bond to form a
radical intermediate (i1) and a chloride ion (Reaction 1). Cyclization
takes place when radical i1 attacks the carbonyl carbon, a process
followed by hydrogen atom abstraction from the solvent to form i2
(Reaction 2). Rapid loss of a water molecule then takes place to afford
the coumarin (b) (Reaction 3). A substituted phenol (c) can arise via
two possible routes. After the first electron-transfer event to form i1,
the latter radical can expel a ketene, leaving behind the oxy-radical i3,
which can abstract a hydrogen atom from solvent to yield c (Reaction
4). On the other hand, as seen in Reaction 5, further one-electron
reduction of radical i1 could take place at potentials corresponding to
the first cathodic peak to give carbanion i4, which loses ketene to pro-
duce phenolate i5, and the latter species is protonated (probably from
residual water in the solvent) to produce the final product (c). This
last electrochemical process might account for the somewhat elevated
coulometric n values, which range from 1.1–1.3 (Table II).
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