Organic Electrochemistry
S
S
2
+
S
S
- 2eCH3CN, NaClO4
,2ClO4
97%
Summer 2003
Historical perspective
Organic Electrochemistry is a multidisciplinary science overlapping
the vast fields of organic chemistry, biochemistry, physical chemistry
and electrochemistry.
The first electroorganic synthesis was performed by Michael Faraday
(1843). It was the anodic decarboxylation of acetic acid in aqueous
medium, and the formation of ethane via creation of a new carboncarbon bond:
2 CH3COO
-2ePt
CH3CH3
+
2CO2
Henry Kolbe (1849) electrolyzed fatty acids and half-esters of
dicarboxylic acids and established the practical basis of electroorganic
synthesis. Near the end of the 19th century various electrolytic
industrial processes emerged, mostly reductive, stimulated by
pioneering works of Kolbe, Haber, Fitcher, Tafel and other notable
contemporaries who expanded the foundation of organic
electrochemical technology.
Great progress in the understanding of fundamental mechanisms of
electrochemical reactions has been achieved during the last few
decades in parallel with the spectacular advances of electroanalytical
and spectroanalytical methodologies and the commercial availability
of the relevant instruments.
Electrochemical Techniques
Previous courses: Pr. D. Thomas, Pr. M. Baker, Pr. J. Lipkowski, Dr.
G. Szymanski and I. Burgos)
Cyclic Voltammetry:
Potential (mV)
Reversible System
E2
i
-E
E1
Time(s)
Irreversible System
workstation
CE
RE
WE
i
-E
Important characteristics:
- Peak Potential
- Number of electrons exchanged per molecule (n)
- Transfer coefficient 
Bulk electrolysis:
- Constant current
- Constant potential
Reaction Mechanisms, Kinetics and Thermodynamics
k1
A + e-
.
A-
k2
B +
C
k4
E
+e- k3
D
Initial electrochemical investigation is necessary to set up the electrosynthesis
- First step: Nature of Electron Transfer (Example: dissociative ET).
RX + e-
R + X
?
RX
R
eRH
SH
R
Nu
(SRN1)
.
RNu-
R-R
Dissociative Electron Transfer (Savéant’s Theory)
R + X
R-X + e
?
R-X
In electrochemical studies of organic compounds, a widely
investigated process is the Dissociative ET where a chemical bond is
broken as a result of a first ET. When the one electron-transfer product
is an intermediate, the ET follows a stepwise mechanism and can be
described by the Hush –Marcus theory when the initial electron
transfer step is the rate determining step.1 On the other hand, when the
ET and the bond breaking occur in a concerted manner, Savéant2
proposed a model based on Morse curve picture of bond breaking.
This model gives a similar quadratic activation-free energy
relationship (eq 1), the difference being the contribution of the bond
dissociation energy (BDE) of the fragmented bond to the activation
barrier, G ‡0 , which involves only the solvent ( 0 ) and the inner ( i )
reorganization energies for a stepwise mechanism (eq 2). G‡ (the
activation free energy), G 0 (the reaction free energy) and G‡0,s and
G‡0, c (i.e. the activation energy at zero driving force) represent the
intrinsic barriers for a stepwise and a concerted ET respectively.

G o 
‡
‡
G  G0 1 
 4G ‡ 
0 

G ‡0, s 
i  0
4
2
and
(1)
G ‡0, c 
0  BDER X
4
(2)
(1) See for example: (a) Marcus, R. A. Theory and Applications of Electron Transfers at Electrodes
and in Solution. In Special Topics in Electrochemistry; Rock, P. A., Ed.; Elsevier: New York,
1977; pp 161-179.
(2) (a) Savéant, J-M. J. Am. Chem. Soc. 1987, 109, 6788. (b) Savéant, J-M. Dissociative Electron
Transfer. In Advances in Electron Transfer Chemistry; Mariano, P. S., Ed.; JAI Press: New York,
1994; Vol. 4, p. 53-116.
How does the driving force affect the ET mechanism?
Potential Energy
RX.- Stepwise
E0
RX / RX .
Concerted
-E
RX + e-
.
R + X-
E0
RX / R.  X 
-E
RX + e-
Reaction Coordinate
Figure: Passage from the stepwise to the concerted mechanism upon decreasing
the driving force. Potential energy profiles. E: electrode potential.
Concerted vs stepwise ET mechanisms
How do know, in practice, whether one or the other mechanism is
followed?
1- Experimental detection of the radical anion intermediate:
- High scan rate cyclic voltammetry: using ultra microelectrodes, scan
rates as high as a few million V/s may be reached, corresponding to
lifetimes in the sub-s range.
- Homogeneous catalysis allows the extension of the lifetime range up
to the ns.
Example:
O2N
SCN
O2N
Figure: Cyclic Voltammetry in CH3CN/TBAF (0.1M) at a glassy carbon electrode, v = 0.2
V/s, temperature = 20 oC of 3,5-dinitroPhSCN (3) 2 mM at v = 0.2 V/s (c) and v = 2 V/s (d).
2- Transfer coefficient (), which is directly related to the intrinsic
barrier (eq 3), is a sensitive probe of the mechanistic nature of the first
ET in dissociative processes:
1 
G 0 

 1
G 0 2  4G0‡ 
G ‡
(3)
The transfer coefficient can be determined from the electrochemical
peak characteristics (peak width, Ep-Ep/2), or from the slop of the Ep vs
log(v) plot.
RT  Ep 


 
2 F   log( v) 

1
 Ep 

 29.6
  log( v) 
RT
1.85
1
 47.5
F Ep / 2  Ep
Ep / 2  Ep
1
at 25o C
at 25o C
E p is the peak potential and E p / 2 is the half peak potential
In a concerted mechanism, a value significantly lower than 0.5 is
expected, whereas an  value close to or higher than 0.5 is expected in
the case of a stepwise mechanism.
Example 1: Electrochemical reduction of alkylhalides (concerted ET)
Br
250
a
Ep-Ep/2 (mV)
200
Br
150
Ep = -2.30V
n = 2e- /molecule
 = 0.3
100
log(v)
50
Ep (V vs Fc)
-2
0
2
-2
b
-2.2
-2.4
-2.6
log(v)
-2.8
-2
Figure: CV of 1,3-dibromoadamantane (c=1.56
mM) in CH3CN + 0.1M NBu4ClO4 on a glassy
carbon electrode. v = 0.1 V/s.
0
2
Figure: variation of (a) the
peak with and (b) the peak
potential with the scan rate.
Alkylhalides are known to follow a concerted ET mechanism. Alkyl
radicals are generally easier to reduce than their parent halides, the
electrochemical reduction is usually a 2 electron process leading to the
corresponding anion.
R-X + eR
+ e-
R
+ X
R
One can Use this chemistry for an efficient electrosynthesis. Example:
The electrogenerated anion can be used as an intramolecular
nucleophile (the initial molecule containing a good leaving group) for
the electrosynthesis of alkenes, alkynes and cyclic compounds.
X (CH2)n Y + 2en = 2,
n = 3,
Product + X- + Yn = 4,
n = 5,
Ex: Electrochemical reduction of dihaloadamantanes
X
H
+ 2eY
+
Y
B
A
The yield of the intramolecular nucleophilic substitution depends on
the nature of the leaving group.
X
I
I
Y
Br
Cl
Br
F
H
Br
Cl
F
H
Ep (V/SCE) -1.50 -1.66 -1.84 -2.38 -2.23 -2.04 -2.36 -2.80 -2.74

0.31
0.32
0.31
0.30
0.30
0.30
0.31
0.32
0.32
A(%)
3
12
56
100
100
5
30
100
100
B(%)
96
75
44
0
0
94
70
0
0
Example 2: Electrochemical reduction of arylhalides (stepwise ET)
Aryl halides are reduced following a stepwise mechanism.
Ar-X
Ar-X + eAr-X
Ar
+ X
Here again one can target the aryl radical and uses it efficiently for the
synthesis of valuable aromatic compound. An example is the SRN1
reaction (see later).
How Molecular Structure Controls the ET Mechanism?
Both thermodynamic and kinetic factors are involved in the
competition between concerted and stepwise mechanisms. The
passage from the stepwise to the concerted situation is expected to
arise when the ion radical cleavage becomes faster and faster. Under
these conditions, the rate determining step of the stepwise process
tends to become the initial electron transfer. Then thermodynamics
will favor one or the other mechanism according to equation 4.
G
0
0
0
..  D R  X  E X . / X   E RX / RX .  TS
.
RX e R  X
RX e R  X .
(4)
Thus, one passes from the stepwise to the concerted mechanism as the
driving force for cleaving the ion radical becomes larger and larger.
0
A weak R-X bond, a negative value of ERX
/ RX and a positive value
E X0 / RX of will favor the concerted mechanism and vice versa. All
three factors may vary from one molecule (RX) to another. However,
there are families of compounds where the passage from one
mechanism to the other is mainly driven by one of them. Illustrating
examples are given in the Table 1.
.
.

Table 1: Molecular factors governing the dichotomy between concerted
and stepwise mechanisms.
Transition between ET Mechanisms upon Changing the Driving
Force
A few experimental systems have shown a transition between
concerted and stepwise mechanisms as a function of the driving force
which could easily be controlled in electrochemistry by varying the
electrode potential. Similar mechanism transitions have been also
reported in homogeneous thermal and photochemical electron
transfer.3 This behavior demonstrates that the nature of the ET process
is dictated by the energetic advantage of one process over another.
Analyses of the variation of the transfer coefficient with either the
scan rate4 or the potential5 are the main criteria for such a mechanistic
transition. In this particular case, besides the conventional
voltammetric analysis, the convolution approach is a powerful tool for
studying intricate details of electrode processes.
Convolution analysis had been initially reported many years ago 6 but
has only recently been used rigorously to explore reaction
mechanisms and to provide valuable kinetic and thermodynamic data
for several systems.5,7 The great advantage with the convolution
analysis is that all data points of the voltammetric curve are used in
the kinetic analysis and that no assumptions on the ET rate law are
made in the analysis of the experimental data. This differs from the
conventional voltammetric method where a linear activation-driving
force relationship is implicitly assumed.8
(3) J. Am. Chem. Soc. 2000, 122, 5623; 2001, 123, 4886.
(4) (a) Andrieux, C. P.; Robert, M.; Saeva, F. D.; Savéant, J-M. J. Am. Chem. Soc. 1994, 116, 7864.
(b) Pause, L.; Robert, M.; Savéant, J-M. J. Am. Chem. Soc. 1999, 121, 7158.
(5) Antonello, S.; Maran, F. J. Am. Chem. Soc. 1997, 119, 12595.
(6) (a) Imbeaux, J. C; Savéant, J-M. J. Electroanal. Chem. 1973, 44, 169. (b) Savéant, J-M.; Tessier,
D. J. Electroanal. Chem. 1975, 65, 57.
(7) (a) Antonello, S.; Maran, F. J. Am. Chem. Soc. 1999, 121, 9668. (b) Antonello, S.; Musumeci, M.;
Wayner, D. D. M.; Maran, F. J. Am. Chem. Soc. 1997, 119, 9541. (c) Donkers, R. L.; Workentin, M. J.
Phys. Chem. B 1998, 102, 401. (d) Donkers, R. L.; Maran, F.; Wayner, D. D. M.; Workentin, M. J.
Am. Chem. Soc. 1999, 121, 7239. (e) Antonella, S.; Frmaggio, F.; Moretto, A.; Toniolo, C.; Maran, F.
J. Am. Chem. Soc. 2001, 123, 9577.
(8) (a) Nicholson, R. S.; Shain, I. Anal. Chem. 1964, 36, 706. (b) Nadjo, L.; Savéant, J-M. J.
Electroanal. Chem. 1973, 48, 113. (c) Bard, A. J.; Faulkner, L. R. Electrochemical Methods,
Fundamentals and Applications; Wiley: New York, 1980.
Convolution Analysis
The background-subtracted
voltammograms
are
convoluted
to
yield
convoluted current I vs E
plots. I is related to the
voltammetric
current
i
through the convolution
integral (eq 5).
I   1 / 2 0
t
i (u )
(t  u )1 / 2
The limiting current Il is
defined as Il = nFAD1/2C0,
where n is the overall
electron consumption per
molecule, A the electrode
area,
D
the
diffusion
coefficient, and C the bulk
substrate concentration. Il is
independent of scan rate and
is used to calculate D.
du
(5)
For a totally irreversible system
(when the dissociative electron
transfer is concerted or when the
dissociation of the reduction product
is fast) I can be related to the rate
constant of the heterogeneous
electron transfer khet through eq 6.
ln k het  ln D1/ 2  ln
I l  I (t )
i(t )
(6)
Systems following a single ET mechanism show either a linear or a
parabolic pattern. In mixed mechanisms neither a linear nor a
parabolic pattern is obtained. Values of ln khet indicate whether the
electron transfer is fast or slow.
Apparent
values
of
transfer
coefficient (app) can be obtained
from the ln khet vs E data by using eq
7.Derivatization is accomplished by
linear regression of the experimental
data within small E intervals (18 to
24 mV).
 app  
RT  ln k
F E
(7)
The app vs E plot shows that the electrode process is not ruled by a
simple ET mechanism. The app vs E plot is characterized by a
maximum at ca. –2.14 V, corresponding to an average  value of 0.31.
*app is related to  through the double-layer correction whose properties are yet unknown
for the glassy carbon electrode. However, it has been previously showed that uncorrected
transfer coefficient values provide a reasonable representation of the process, as these values
do not differ much from the true ones.
Example 1: Electrochemical reduction of aryl thiocyanates*
Convolution analysis was performed for scan rates ranging from 7.2 to
80 V/s for p-methyl (1) and p-methoxy (2) phenyl thiocyanates.
Both compounds show a non linear variation of the coefficient transfer
() with the driving force. Such nonlinear behavior reflects clearly a
change of the electrode mechanism as a function of the potential.
ArSCN + e
ArS + CN
ArSCN
It is important to notice that the same maximum was obtained within
only 20 mV at any of the scan rates providing  data in the
appropriate range. This ensures that the observed behavior reflects a
real dependence of , beyond experimental error or the effect of
artifacts (mainly IR compensation).
0.5
0.4
b
 app
 app
a
0.5
0.3
0.2
0.1
E (V)
-2.4
-2.2
-2
-1.8
0
-1.6
0.4
0.3
0.2
E (V)
-2.5
0.1
-2.3
-2.1
-1.9
0
-1.7
Figure: Variation of app with E for (a) 1 (0.85 mM) at scan rate v = 7.2, 10, 20, 30, 40, 60 and
80 V/s; (b) 2 (0.69 mM) at scan rate v = 7.2, 10, 20, 30, 40, 60 and 80 V/s.
For p-methyl phenyl thiocyanate (1) the maximum is observed at
ca. -2.14 V for 1 corresponding to an average  value of 0.31.
For p-methoxy phenyl thiocyanate (2) the maximum is observed
at ca. -2.08 V for 1 corresponding to an average  value of 0.33.
*A. Homam, E. M. Hamed and Ian Still J. Am. Chem. Soc. 2003 in press.
Example 2: Electrochemical reduction of peroxides*
O
O
O
O
O
+ e
tBu
+ O
tBu
CN
CN
O
O
O
tBu
CN
*Antonello, S.; Maran, F. J. Am. Chem. Soc. 1999, 121, 9668.
Example 3: Electrochemical reduction of sulfonium salts*
S
CH3
S
+ e
CH3
CH2
CH2
S
CH3 +
CH2
* Andrieux, C. P.; Robert, M.; Saeva, F. D.; Savéant, J-M. J. Am. Chem. Soc. 1994, 116,
7864.
Electrochemical reduction of
a sulfonium cation (see
previous Scheme) showing
the transition from the
concerted to the stepwise
mechanism as driving force
increases upon raising the
scan ate. The apparent
transfer coefficient, a, is
derived from the peak width
according
to
reported
equation (page 8).
Does the Concerted ET Mechanism Mean that the Intermediate
“Does Not Exist”?
The occurrence of a concerted mechanism may result from transition state
energy advantage over the stepwise mechanism or from the fact that the
intermediate “does not exist”, i.e. its lifetime is shorter that one vibration.
Even if examples exist of the latter alternative, there is no reason to view it
as an absolute requirement for the mechanism to be concerted. What is true
is that it is a sufficient condition for the concerted mechanism to occur.
However it is not a necessary condition. In the examples discussed
previously, the intermediate “exists”. It transpires along the reaction
pathway at high driving forces. Nevertheless, a concerted mechanism is
followed at low driving forces because it is then energetically more
advantageous. Such competition between stepwise and concerted
mechanisms is usually not easy to characterize. This is why the previous
examples have a general bearing in the theory of chemical reactivity.
Thermodynamics
The variation of  with the potential as obtained by convolution
analysis can be used to estimate the value of the standard reduction
potential.

00.10.20.30.40.50.60.7-2.5-2.3-2.1-1.9-1.7-1.5
E0
RX / R .  X 
E
Consequently the bond dissociation energy of the cleaved bond can be
estimated (BDE).
X
Ex. Electrochemical reduction of 1,3-dihaloadamantanes
X
Y
DC-X
(eV)
I
I
Br
Cl
Y
Br
F
H
Br
Cl
F
H
2.07 2.18 2.20 2.29 2.32 2.70 2.82 2.91 2.94
Global Mechanisms
How Molecular Structure Controls the Global Mechanism?
An excellent example resides in the electrochemical reduction of
benzyl thiocyanates, where electron-donating substituents induce an
-cleavage as a result of an ET while electron-withdrawing
substituents induce a -cleavage.

CH2
Current (A)
X

S
CN
1: X = H
2: X = NO2
-4.E-05
-3.E-05
-2.E-05
-1.E-05
2.E-06
E (V)
0.5
-0.5
-1.5
-2.5
-3.5
Current (A)
-2.E-05
0.E+00
1.E-05
E (V vs SCE)
1.3
0.8
0.3
-0.2
-0.7
-1.2
2.E-05
-1.7
Figures : Cyclic Voltammetry in CH3CN/TBAF (0.1M) at a glassy carbon electrode, v = 0.2
V/s, temperature = 20 oC of (a): 1: 2.35 mM (____), 4: 1.3 mM (_ _ _) and (b): 2: 2 mM (____),
5: 1.5 mM (_ _ _).
R-X + e-
R + X
(1)
R
R
(2)
R-R + X
(3)
+ e-
R + R-X
CH2SS CH2
O2N
CH2 CH2
NO2
For both compounds, the driving force is in favor of a b-cleavage
(mainly due to big difference in the standard oxidation potentials of
the 2 leaving groups (NC- and NCS-), whereas the intrinsic barrier is
in favor of an a-cleavage, due to a weaker a-bond for both compounds.
Example 1: SRN1 reaction
-Consist
of reducing a convenient substrate in the presence of
nucleophile.
-The SRN1 reaction is catalytic in electrons.
Ar-X + e-
Ar-X
Ar-X
Ar + X
Ar + Nu
ArNu + Ar-X
k
ArNu
ArNu + Ar-X
Arylazo Sulfides in SRN1 Aromatic Nucleophilic Substitutions
(electrosynthesis of functionalized aromatic compounds)
- The electrochemical reduction of aryl azosulfides yields the
corresponding sulfides and decompositions products.
- The mechanism of the global reaction is an SRN1 mechanism.
NC
H

NC
NN S

NC
S

Figure: Cyclic voltammogram of paracyano phenyl azo phenylsulfide (c=1mM) in ACN +
0.1M NBu4ClO4 on a glassy carbon electrode
Electrochemistry of Arylazo Sulfides in the Presence of Cyanide
NC
CN

Figure: Cyclic voltammogram of paracyano phenyl azo phenylsulfide (c=1mM) in ACN +
0.1M NBu4ClO4 on a glassy carbon electrode (a) [CN-] = 0 mM, …; (b) [CN-] = 10 mM, - - -;
(c) [CN-] = 320 mM, ____.
NC
N N S
+ e-.
NC
N N S
. + N2 + - S
NC
+ CN
-.
NC
CN
-.
NC
S
+A
+A
.
A- + NC
.
A-
CN
NC
S
.
+ A-
k= 1,5 1011 M-1s-1 in CAN and 2,4 1011 M-1s-1 in DMSO
Important kinetic and stereochemical aspects
- Solvent effect (Noyes theory of cage effect reactions).
- Higher yields of trapped radicals for trans compounds.
a
b
Figures: Trapping by CN- of 4-cyanophenyl radicals produced by reduction of
1a (a) in CH3CN and (b) in DMSO: (A) fraction trapped by; (B) fraction
trapped by the solvent or reduced; (C) sum of A and B.
Generality of the reaction:
R
N N S R'
Nu-
R
Nu + N2 + RS-
R = CN, NO2, F, Cl, CH3, CH3O, CF3.
R’ = tBu, C6H5
E and Z isomers
Good substitution products yields
Various nucleophiles can be used including: cyanide, thiolates,
phosphides, aryloxides and carbanions.
Example 2: Autocatalytic reductive processes
A: Electrochemical reduction of aryl thiocyanates
SCN
X = H; p-CH3; p-CH3O; p-F; p-Cl; p-NO2; m-CF3;
o-NO2; 2,4-diNO2; 3,5-diNO2; p-NO2-o-Cl.
X
ArS - + CN -
ArSCN + 2e
ArS - + ArSCN
k
(1) E1
ArSSAr + CN - (2)
ArSSAr + 2e
2 ArS -
ArSCN + 2e
ArS - + CN -
(3) E2>E1
Figure: Cyclic Voltammetry in CH3CN/TBAF (0.1M) at a glassy carbon
electrode, v = 0.2 V/s, temperature = 20 oC of (a) p-CH3PhSCN (1) 3.26 mM
and (b) p-CH3OPhSCN (2) 3.45 mM at v = 2 V/s.
Figure: successive CVs of p-CH3PhSCN
(3.26 mM), (——) 1st scan and (——) 2nd
scan. In CH3CN/TBAF (0.1M) at a
glassy carbon electrode; v = 0.2 V/s.
While the first scan shows a CV
similar to the one described earlier,
the second scan shows a much
broader reduction peak at a less
negative potential and with no trace
crossing. The CV of this second scan
corresponds to the reduction of 4,4’dimethylphenyl
disulfide
(3)
produced as a result of a nucleophilic
substitution of 1 by the aryl
thiocyanate (see previous Scheme).
Once the disulfide is formed, it is
immediately reduced since it is easier
to reduce than the corresponding aryl
thiocyanate and will thus induce the
autocatalytic process.
Figure: Cyclic voltammetry, in
CH3CN/TBAF (0.1M) at glassy carbon
electrode, temperature = 20 oC, of (—
—) 1 (2.55 mM) and (——) 1 (2.55
mM) + 4% of 3, at (a) 0.2 V/s, (b) 2.4
V/s and (c) 10 V/s.
Adding catalytic amounts of
disulfide allows consumption of 1 at the reduction peak of 3 through the
catalytic process and only one peak is seen located at the reduction potential of
3. When the scan rate is increased the catalytic process is diminished and two
peaks appear (Figure b). At higher scan rates, the catalysis is totally eliminated
and one can identify the peaks corresponding respectively to 4 and 1 (Figure c).
Interesting features: Variation of the peak shape and position with the scan rate
Figure: Cyclic voltammetry of 1: (a1) 0.85 mM, 0.2 V/s; (a2) 0.85 mM, 2.4 V/s;
(a3) 0.85 mM, 7.2 V/s; (b1) 5 mM, 0.2 V/s; (b2) 5 mM, 2.4 V/s; (b3) 5 mM, 60 V/s.
In CH3CN/TBAF (0.1M) at a glassy carbon electrode. Temperature = 20 oC.
At low concentration (0.85 mM), the crossing seen at 0.2 V/s (Figure 4a 1), is
readily eliminated by increasing the scan rate to 2.4 V/s (Figure 4a 2) and at 7.2
V/s (Figure 4a3).
At higher concentration (5 mM) a higher scan rate is needed to eliminate the
crossing and to allow consumption of all the thiocyanate directly at the
electrode. At 2.4 V/s (Figure 4b2) trace crossing is still observed and the
autocatalytic process is thus efficient.
Moreover, one can clearly see the positive shift of the reduction potential of 1
as C0 increases confirming again the existence of an autocatalytic mechanism.
The difference in the reduction potential of 1 between 0.5 V/s and 80 V/s is
about 700 mV which is too large to be due only to the type of ET mechanism.
For a well behaving system reduced following a concerted mechanism with a
value of 0.3, the difference would be of the order of 300 mV. This is also a
consequence of the autocatalytic process.
-2
a
b
-2.1
Ep (V/Fc)
-2.8
-2.5
-2.9
log (v)
log (v)
-3.2
-1.5
-0.5
0.5
1.5
Ep (V/Fc)
-2.4
2.5
-3.3
-1.5
-0.5
0.5
1.5
2.5
Figure: Variation of the reduction peak potential with the log of the scan rate
(log (v)) for (a) 1,  (3.45 mM),  (0.69 mM); (b) 2,  (5 mM),  (1.25 mM).
An important feature is that the variation of the reduction peak
potential with the log of the scan rate does not have the same slope
over the entire studied scan rate range and three major regions can be
discerned in all cases. For the high concentrations one can distinguish
the following: (i) at low scan rates, the variation of the peak potential
is linear with a relatively low slope (120 and 122 mV per unit log (v)
for 1 and 2 respectively). Within this range the crossing exists and the
autocatalytic process is very efficient and the reduction peak is
consequently pushed towards more positive potentials. The
intermediate region shows a much larger slope since it corresponds to
the competition between autocatalysis and diffusion (520 and 565 mV
per unit log (v) for 1 and 2 respectively): diffusion being favored as v
increases. The peak potential shifts dramatically to more negative
values and the higher the value of v, the less efficient the autocatalytic
process. At higher scan rates (third region), where the crossing is no
longer observed, the slope is much smaller (84 and 86 mV) and the
autocatalysis is totally eliminated. At lower concentrations, similar
behavior is seen, but competition between the autocatalytic process
and direct electrochemical consumption (intermediate region) of the
aryl thiocyanate at the electrode takes place at lower scan rates. An
important factor is the total independence of peak potential of
concentration at these high scan rates, for both compounds 1 and 2,
indicating clearly that the autocatalytic process is not involved
anymore.
0.15
a
0.2
0.15
0.1
Ep-Ep/2 (V)
0.2
0.25
Ep-Ep/2 (V)
0.25
b
0.1
0.05
0.05
log (v)
log (v)
0
-1.5
-0.5
0.5
1.5
2.5
0
-1.5
-0.5
0.5
1.5
2.5
Figure: Variation of the reduction peak width with the scan rate v of (a) 1,  (3.45 mM), 
(0.69 mM); (b) 2,  (5 mM),  (1.25 mM).
At high concentrations, the autocatalytic process is very efficient and
the peak is very sharp (peak width around 50 mV for both for 1 and 2)
at low scan rates. At higher scan rates, corresponding to more
competition between diffusion and autocatalysis, the peak width
increases dramatically (to higher values than 150 mV for both 1 and
2), before settling on some more or less stable values (around 150
mV) at much higher scan rates where the autocatalysis is eliminated.
At lower concentrations, similar phenomenon are seen, with the
difference that the competition (increase of the peak width) takes
place at lower scan rates. It is important to notice here again that at
high scan rates, the peak width is independent of concentration,
proving again that these values correspond to the intrinsic
characteristics of the direct electrochemical reduction of 1 and 2 and
not to secondary chemical reactions, i.e. the autocatalysis process.
Organic Electrosynthesis
Agrochemicals
(fluorinated compounds)
Pharmaceuticals
(Chiral products)
Fine chemicals
(free base of cysteine)
Organic electrosynthesis
Complex natural products
(b-hydroxyalkonates)
Precursors
intermediates
Ex.: chiral drugs, market: $ 50 billion USD, annual growth > 25%
Example: Reaction of Levoglucosenone in the presence of
electrogenerated superoxide anion
Possibility to control the stereoselectivity by changing current density
or potential.
Example: Electrosynthesis of sulfonium and bisulfonium salts*
- Radical source (polymer initiators, surfaces modifications,…).
- Good starting materials for synthesis (C-glycosides).
- Understanding electron transfer to organic molecules and factors
controlling it.
- The electrosynthesis consists of oxidizing thianthrene in the
presence of a convenient “nucleophile” (alkene, alkyne, ketone).
S
S
O
S
+
S
Cyclic voltammogram in CH3CN + 0.1 NBu4ClO4, on a glassy carbon
electrode, at v = 0.1 V/s of (a) thianthrene (c = 2 mM) and (b) thianthrene
(2mM) + acetophenone (c = 320 mM)
Upon Adding the ketone, the CV of thianthrene becomes irreversible
and the oxidation peak increases (corresponds to 2e-/molecule).
* A. Houmam; D. Shukla; D. D. M. Wayner. J. Org. Chem. 1999, 64, 3342
Electrolysis of thianthrene in the presence of ketones
R
O
O
ClO4
S
S
+
S
- 2e-
+H
CH3CN, NaClO4
S
R = H,
95%
R = CH3, 97%
.
S
The chemical method:
CH3CN
+ e-
NaClO4
S
O
- Making a solution of the
radical cation by adding a
strong acid to thianthrene
(explosive).
- The reaction is possible only
in
carbon
tetrachloride
(toxicity).
- The yield <50%.
- Longer time.
- Difficulties to isolate the
compound.
- Mechanism cannot be solved.
S+
S
O
.
HO
HO
S
S
-e-
S
S
,ClO4
O
S
+ H
S
Electrosynthesis of bis-sulfonium salts
S
S
2
S
- 2e-
+
CH3CN, NaClO4
S
,2ClO4
95-100%
.
S+
S
CH3CN
NaClO4
S
+ eS
.
Th+
.
S
S
S
S
,2ClO4
S
.
Th+
- In the presence of an
alkyne, The CV of
thianthrene
becomes
irreversible but does not
increase to two electrons
per molecule.
- Excellent yields are
obtained.
S
X-ray crystal structure
of
the
electrosynthesized cyclohexyl
bis-thianthrenium salt.
Inability to synthesize
and isolate this bissulfonium salt lead
chemists to believe it
was very unstable.
Electrochemistry
allowed
quantitative
synthesis of such salt.
Simulation of the CV of thianthrene at different concentration of the nucleophile
allows determination of the rate constant of the reaction of thianthrene radical
cation with the “nucleophile”
Alkene or ketone
k (M-1s-1) 10-2
10
OEt
1.6
1.2
Ph
OMe
50
Me
Ph
Ph
5
Ph
90
Ph
2.7
4
4
0.1
O
Ph
Me
0.9
O
p-MePh
Me
Generality of the process: Electrosynthesis of sulfonium and
ammonium
Possibility to control the reaction product by monitoring the reaction
potential and the concentration of the “nucleophile”.
Electrochemical Oxidation and Reduction of Organic Compounds
Oxidation of alkanes
Alkanes are functionalized by anodic oxidation in acetonitrile,
methanol, acetic acid and more acidic solvents such as trifluoroacetic
acid and fluorosulphuric acid. Reaction requires very positive
electrode potentials and platinum has generally been used as anode in
laboratory scale experiments.
The first stage of these reactions involves the removal of an electron
from either a carbon-hydrogen or a carbon-carbon -bond, with
simultaneous bond cleavage to yield the most stable carbon radical
and carbonium anion. These are dissociative processes where the
radical cation cannot be detected as an intermediate.
In acetonitrile, carbon ions combine with the solvent to form a
nitrilium ion. The latter reacts with added water to form the Nsubstituted acetamide, often in good yields (introduction of an aminosubstituent.
R
1) Pt anode,
CH3CN, LiClO4
2) H2O
R
Et
iPr
tBu
CO2CH3
NHCOCH3
R
NHCOCH3
%yield
0
9
62
64
%yield
77
75
7
0
In acetic acid and trifluoroacetic acid, the carbonium ion is quenched
by reaction with the carboxylate anion. Electrochemical oxidation in
these solvents is a route for the introduction of a hydroxyl substituent.
Electrochemical oxidation of haloalkanes
Oxidation of alkyl bromides and iodides leads to loss of a nonbonding electron from the halogen substituent, followed by cleavage
of the carbon-halogen bond to form a carbonium ion and a halogen
atom. The products isolated are formed by further reactions of the
carbonium ion while two halogen atoms combine to form the halogen
molecule. In acetonitrile, the carbonium ion reacts with a solvent
molecule to form a nitrollium ion. The latter is quenched with water to
give the N-alkylacetamide.
Ex1:
CH2I
CH3
Pt anode
CH3CN, LiClO4
NHCOCH3
Ex2:
CH2NHCOCH3
10%
CH2I
Pt anode
CH3CN, LiClO4
+
NHCOCH3
90%
Pt anode
CH3CN, LiClO4
I
Electrochemical oxidation of alkenes
Alkenes are electrochemically oxidized in nucleophilic solvents such
as alcohols, acetic acid or acetonitrile using an undivided cell and the
products isolated result from quenching of intermediate carbonium
ions by nucleophiles. The radical cation reacts with the nucleophile to
form a radical intermediate, which is then oxidized to the carbonium
ion, usually at a potential less positive potential.
Ex. 1: Electrochemical oxidation of cyclohexene.
OMe
+ MeOH
- e-
- e-
-H
+ MeOH
OMe
- e-
CH(OMe)2
CHOMe
+ MeOH
Ex. 2: The oxidation potential for the alkene bond is closed to that for
a carboxylate ion. In the styrene derivative below, the alkene moiety is
preferentially oxidized and intramolecular capture of a carbocation
leads to a lactone product.
Ph
PhCH CHCH2CH2CO2
Pt anode
MeOH, NaOMe
OMe
O
O
H
Ex. 3: Electrochemical oxidation of alkyl substituted butadienes in the
presence of dimethylurea as a 1,3-dibentate nucleophile, leads to the
formation of a five membered ring heterocycle.
O
Me
+ MeNHCONHMe
C anode
CH3CN, NaClO4
N
N
Me
Electrochemical oxidation of alcohols and esters
The direct oxidation of alcohols, 1,3- or higher 1,n-diols is carried out
in absence of solvents or in acetonitrile and presence of perchlorates
or tetrafluoroborates as supporting electrolytes.
Depending on the structures of the alcohols and on the electrolytic
systems the electrooxidation of alcohols may lead to the formation of
aldehydes, acetals, acids and esters.
Ex. 1: Anodic oxidation of 2-butin-1,4-diol to acetylene dicarboxylic
acid.
OH
HO
-8e-, H2SO4 - H2O
(PbO2)
HOOC
COOH
70-76%
Ex. 2: Anodic oxidation of enolethers and enolacetates.
OR
R = Me, Ac
-2eMeOH
OMe
OMe
OMe
-2eMeOH
COOMe
O
74 - 94 %
Oxidation of organic compounds of sulfur and selenium
The anodic oxidation of thiols and dialkyl or diaryl sulfides makes it
possible to prepare sulfur compounds at different degrees of oxidation
in dependence potential, electrode material (carbon, platinum,
stainless steel) and composition of electrolyte.
(-II)
-4e-
R SH
(II)
R SO2O OSO2 R
R S OR
O
-H ,-e(-I)
-R ,-e-2eR S R
(-II)
(IV)
-4e-
R S S R
R SO2O
O
(0)
-2e-
R S R
(II)
R S R
O
O
Ex. 1: thiophenol oxidation to diphenyl disulfide and to esters of
benzenesulfonic acid.
Ph S OR
O
95 %
AcOH-ROH
AcONa, (Pt)
PhSH MeOH-H2O-KOH Ph S S Ph
KH2PO4, (Pt)
100%
Ex. 2: Oxidation of diphenyl sulfide to diphenyl sulfoxide, diphenyl
sulfone and diphenyl-4-(phenylmercaptophenyl)sulfonium.
O
Ph S Ph
O
AcOH-H2O PhSPh AcOH-H2O (Pt)
Ph S Ph
21,30V, (Pt)
Cl , Br , SO4 , 0.94V
O
96%
MeCN-LiCLO
4
(Pt)
PhS
SPh2,ClO4
71%
Electrochemical oxidation of amines
Simple aliphatic amines have relatively low oxidation potentials. The
course of oxidation depends on the structure of the amine, on the
anode material and on the composition of the electrolyte.
Ex.: amidoalkylation: -methoxyamides and –carbamates generate
iminium ions under the influence of an acid which react then with
sufficiently “nucleophilic” substrates (aromates, alkenes, C-acids etc.)
by an electrophilic substitution.
N
MeOH, Et4NTsO
-2e-
COOMe
N
OMe
H+
- MeOH
COOMe
Si(CH3)3
TiCl4
N
O
N
COOMe
, TsOH
89%
COOMe
N
O
COOMe
OAc
O
N
, TiCl4 (MeCO) CH , HCl
2
2
84%
69%
COOMe
N
Ph2PCl, MeCO2H
89%
P(O)(Ph)2
COOMe
Me3SiCN, SnCl4
90%
COMe
COOMe COMe
N
N
CN
COOMe
Electrochemical oxidation of aromatic systems
Simple aromatic compounds (benzene, naphthalene, toluene, xylene)
have relatively very positive oxidation potentials. A radical cation is
usually formed which, in general, dimerizes or reacts with a
nucleophile to yield a substitution product.
Ex. 1: Electrooxidation of sufficiently “nucleophilic” aromatics.
-eBu4NBF4
CH2Cl2
-e-2 H+
Ex. 2: Electrochemical nitration and cyanation of aromatics.
NO2
-2e-, MeCN
N2O4, Bu4NPF6
91%
CN
-2e-, MeOH
NaCN
74%
Ex. 3: ipso substitution in aromatics.
OMe
NC
O CH2 H
- CH2O
- H+
-2eEt4NCN
MeCN
OMe
OMe
CN
(95%)
OMe
Electrochemical oxidation of carboxylate anions
In the electrochemical oxidation of carboxylate anions two types of
reactive intermediates can be obtained: radicals which dimerize (the so
called Kolbe reaction) and carbocations which can eliminate a proton,
transform to isomeric carbocations and react with nucleophiles (the
so-called Hofer-Moest reaction).
R COO
-e-CO2
R
Rads
-2e-CO2
-e-
-CO2
R COO
-e-CO2
MeCN
R H
alkene
R R
Rads
R
YO -
R NHAc R OY
-H+
alkene
Direct Reductive Reactions
Electrochemical reduction of functional group
Ex. 1: Hydrogenation of multiple C-C bonds can proceed indirectly,
electrocatalytically, or by a direct electron transfer to the multiple
bond. The reaction can proceed with good selectivity.
COOH
COOH
+ 2e-
Ex. 2: Reductive dehalogenation (also very selective).
O
O
Cl + 2e-, Et NBr
4
DMF
Br
Cl
96%
H
Ex. 3: Electrochemical reduction of nitroaromatics. High yields of
amines are obtained in the reduction of nitroaromatics carrying a
group in the para position which prevents a rearrangement.
R
CO2H
Me
R = Me, + 6e(Pb), H2SO4
R = CO2H, + 6e(Pb), HCl
NO2
NH2
92%
NH2
100%
Ex. 4: Reductive transformation of acrylonitrile to allylamine in a cell
with a diaphragma.
CN
(Pb), 30% H3PO4
4 e-
NH2
Electrochemically induced substitution
The electrochemically generated anionic intermediates can react with
“electrophiles” to generate substitution products.
Ex. 1: Electrochemical alkylation and acylation can be achieved when
alkylating or acylating agents (usually: anhydrides, halogenides of
acids, their nitriles and DMF) are present in the reductive process of a
convenient substrate.
a)
O
S S
S
2 e-, DMF
Ac2O
90%
b)
CCl3
+
Br
H
Cl
2 e-, LiClO4
DMF
Cl
O
Br
O
Cl
- Br
Cl
40%
O
c) Remember SRN1 reactions?
Pinacolizations and hydrodimerizations
By electroreduction of aliphatic and aromatic aldehydes and ketones
at cathodes with a different hydrogen over voltage and within a broad
range of potentials, vicinal diols (pinacols) are formed. The new C-C
bond is a result of radicals or of radical ions formed by a “single
electron” reduction of the carbonyl group. The aromatic carbonyl
compounds give higher yields of pinacols than aliphatic ones.
Ex.: synthesis of 1,2-cyclopropanediols.
O
O
OH OH
+ 2 eTHF, (MeCO)2O
The intermolecular electroreductive hydrodimerization of a-bunsaturated compounds (aldehydes, ketones, esters and nitriles) is one
of the most powerful electroorganic synthesis reactions. The best
results were achieved in the case of commercially realized
acrylonitrile dimerization to adiponitrile.
CN
+ eEt4NOTs
1.
CN
2. + e-
H2C CH C N
2 H 2O
2 HO
NC
NC
CN
CN
Initially performed in divided cells, at lead cathodes and in the
presence of tosylate or ethylsulfate as supporting electrolyte.
This has been improved later by using undivided cells. This has been
made possible by applying highly selective cadmium cathodes and an
optimal composition of the electrolyte; the supporting electrolyte
consists is hexamethylene bis(dibutylethylammonium)phosphate
jointly with corrosion inhibitors (NaHPO4, Na2B4O7, Na4-EDTA).
Reductive Eliminations
The cathodic reduction of the geminal polyhalogeno derivatives in he
absence of both electrophiles and protons donors results in the
formation of a carbanion that is stabilized by splitting off a further
halogenide ions which in the presence of a sufficiently “nucleophilic”
alkene adds on to the double bond and forms gemdihalogenocyclopropanes.
Ex. 1: Electrosynthesis of 1,1-dichlorotrimethylcyclopropane from
tetrachloromethane.
CCl4 +2 e-, -2Cl
CH3Cl
CCl2 Cl
-Cl
CCl2
Me
Me
Me
Me
H Me
Me
82%
Cl
Cl
Ex. 2: Electrosynthesis of gem-difluorocyclopropane derivatives from
dibromodifluoromethane.
F
Me
CF2Br2 +2e-, -2Br
CH2Cl2
CF2
Ph
F
Ph
57%
Me
Ex. 3: Electroreduction of vic-dihalogeno derivatives undergo a
stereospecific trans-elimination to yield an alkene. This can be used
for the synthesis of alkenes with strong internal stress, usually isolated
as cycloaddition products of a reaction with dienes.
Br
+2e-, Et4NBF4
DMF
Cl
100%
Reductive Removal of protecting groups
The electrochemical method for the removal of the protecting groups
has a parallel in other cathodic reactions (electrohydrogenolysis and
1,2-elimantion of halogeno-derivatives). An advantage of this method
in comparison with the chemical procedures is its high selectivity and
mild reaction conditions. A high selectivity is achieved by
combination of suitable electrophores-protecting groups, which
sufficiently differ in reduction potentials (∆E1/2 200mV).
Ex. 1: The difference in the values of reduction potentials of
benzenesulfonyl and formethoxybenzoyl group enables their selective
cleavage and hence also their application in the protection of the
respective amino group, e.g. in the molecule of L-lysine below.
O
COOH
N
H
MeO
N
H
-2.4V
SO2
-2.15V
+ e-, Me4NCl
EtOH
O
COOH
N
H
MeO
NH2
90%
Ex. 2: Synthesis of of 1,2-dibromo-1(3-cyclohexenyl)ethane from 4vinylcyclohexene.
Br
Br
2Br2
Br
Br
Br
Py.HBr3
Br
+ e-, -1.2V(SCE)
DMF
Br
Bu4NBF4
Br
62%
Industrial Applications
Advantages of electrochemical processes:
- Fast and give generally good yields
- Application to compounds thermally unstable
- Simple and low cost (electricity and equipment)
- No (or less) hazardous and toxic reagents
- Large number of known laboratory processes
- Better selectivity
- Mechanistic, kinetic and thermodynamic data
Limitations:
- Industrial cells
- Electrode material, Poisoning:
 Passivation
 Loss of selectivity
- Solvent and supporting electrolyte
Industrial Processes
Product/Precursor
Company
Anode Cathode Yield
Reduction of aromatic C=C bonds
Asahi Chemical
Pt
1,4-cyclohexadiene /
Gulf Res. & Dev.
C
benzene
Mitsubishi Chem.
Pt
Monsanto
S.S
1,4-dihydronaphtalene /
Standard Oil
C
naphtalene
pipyridine / pyridine
Robinson Bros.
Pb
3,5-cyclohexadiene-1,2dicarboxilic acid / ophtalic
BASF
Pb
acid
Dihydro-2methoxynaphtalene /
Hoechst
C
methoxynaphtalene
Reduction of nitro group
p-aminobenzoic acid /
CECRI
Pb
p-nitrobenzoic acid
3-amino-p-cresol /
CECRI
Pb
3nitro-p-cresl
CECRI
Pb
p-aminophenol /
U of Southampton
Pt
p-nitrobenzene
Constructors J. B.
Pt
Miles Laboratories
Pb
o-aminophenol /
CECRI
Pb
o-nitrobenzene
Oxidation of aliphatics and alcohols
BASF
PbO2
Acetylene dicarboxylic acid
General aniline
Pb
Victor Wolf
PbO2
decylaldehyde/ 1-decene
ETHYL
Pb
isobutyric acid
Kryschenko, et al PbO2/Ni
methylethylcetone
ESSO
C
BAYER
Pt/Ti
Propylene oxide
INTERNE
Pt/Ti
KELLOGG
graphite
Hg
C
Hg
Hg
Pb
93
92
96
90
92
Pb
90
Pb
94
Hg/Cu
94
Sn/Cu
75
Cu
75
Hg/Cu
Cu
Cu
C
Zn
70
82
84
85
80
Pb
Cu
Cu
Pb
Cu
Pt
S.S
S.S
S.S
70
75
75
75
50
92
90
99
86
Industrial Cells
In class
Useful Bibliography
1) Marcus, R. A. Theory and Applications of Electron Transfers
at Electrodes and in Solution. In Special Topics in
Electrochemistry; Rock, P. A., Ed.; Elsevier: New York, 1977;
pp 161-179.
2) Savéant, J-M. J. Am. Chem. Soc. 1987, 109, 6788.
3) Savéant, J-M. Dissociative Electron Transfer. In Advances in
Electron Transfer Chemistry; Mariano, P. S., Ed.; JAI Press:
New York, 1994; Vol. 4, p. 53-116.
4) Savéant, J-M.; Electron Transfer, Bond Breaking and Bond
Formation. In Advances in Physical Organic Chemistry;
Tidwell, T. T. Ed.; Academic Press: New York, 2000; Vol. 35,
pp 177-192.
5) Volke, J. and Liska, F; Electrochemistry in Organic Synthesis.
Springer-Verlag; Berlin Heidenberg, 1994.
6) Grimshaw, J.; Electrochemical Reactions and Mechanisms in
Organic Chemistry. Elsevier: New York, 2000.
