chapter 4: electron transfer initiated reactions · chapter 4: electron transfer initiated...
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ORGANIC REACTIVITY - CHEM*4720 - COURSE NOTES W2012
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CHAPTER 4: ELECTRON TRANSFER INITIATED REACTIONS
1- Grimshaw, J. Electrochemical reactions and mechanisms in organic chemistry.
Elsevier, New York, 2000.
2- Nelsen S. F. Electron Transfer in Organic Chemistry. In Electron Transfer Chemistry.
Balzani, V. (Ed.) Vol. 1, 2001.
3- Schäfer, H. J. Organic Electrochemistry. In Encylopedia of Electrochemistry. Vol 8.
Wiley-VCH, Weinheim, 2004.
4- Torii, S. Electroorganic Reduction Synthesis. Wiley-VCH, Weinheim, 2006.
5- Savéant, J.-M. Elements of Molecular and Biomolecular Electrochemistry. An
Electrochemical Approach to Electron Transfer Chemistry. Wiley & Sons, Inc., Hoboken,
New Jersey, 2006.
6- Evans, D. H.; O’Connell, K. M. Conformation Changes and Isomerizations Associated
with Electrode Reactions. In Electroanalytical Chemistry, Bard, A. J., Ed., Marcel
Dekker: New York, 1985, Vol. 14, pp.113-207.
7- Eberson, L. Electron Transfer in Organic Chemistry. In Advances in Physical Organic
Chemistry; Gold V. and Bethell D. Eds.; Academic press, London, 1982. vol. 18, pp. 78-
185.
8- Houmam A. Electron Transfer Initiated Reactions: Bond Formation and Bond
Dissociation, Chem. Rev. 2008, 128, pp. 2180-2237.
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Electron transfer reactions are among the most elementary of all chemical reactions and
play a fundamental role in many areas including organic synthesis, biological processes,
novel energy sources, energy storage devices, amperometric sensors, etc. A field that
has attracted considerable attention is that involving electron transfer to organic and
bioorganic molecules.
Electron transfer reactions can be initiated using electrochemistry (an electrode),
photochemistry, or an electron donor (reducing) or acceptor (oxidizing) compound.
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 carbon-carbon bond:
2 CH3COO CH3CH3 + 2CO2-2e-
Pt
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. This is the reason why dynamics and
mechanisms of ET initiated reactions are well understood compared to “traditional”
organic synthetic reactions.
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I. ET INITIATED REACTIONS
A wide variety of chemical transformations that are initiated by a single initial electron
transfer are described in the literature and can be encountered under both oxidative and
reductive conditions
ET initiated 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).
Cl
Br
O
Cl
H
O
+ 2e-, Et4NBr
DMF 96%
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.
NH2
CO2H
NH2
Me
NO2
R
R = Me, + 6e-
(Pb), H2SO4
R = CO2H, + 6e-
(Pb), HCl
92% 100%
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ET induced substitution
ET generated anionic intermediates can react with “electrophiles” to yield substitution products. Example: 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)
S S S
O
2 e-, DMF
Ac2O 90%
b)
Br
CCl3
O
H BrO
Cl Cl
O
Cl
Cl
2 e-, LiClO4
DMF+
- Br 40%
c) Remember SRN1 reactions?
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 gem-
dihalogenocyclopropanes.
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Ex. 1: Electrosynthesis of 1,1-dichlorotrimethylcyclopropane from tetrachloromethane.
MeMe
Me
Cl Cl
Me
H
Me
MeCCl2 Cl CCl2+2 e-, -2Cl
CH3Cl-ClCCl4 82%
Ex. 2: Electrosynthesis of gem-difluorocyclopropane derivatives from
dibromodifluoromethane.
+2e-, -2Br
CH2Cl2CF2Br2 CF2
Me
Ph
F F
Ph
Me57%
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
Cl
+2e-, Et4NBF4
DMF100%
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.
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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 N-substituted acetamide, often in good yields
(introduction of an amino-substituent.
R
NHCOCH 3
R NHCOCH 3
1) Pt anode,
CH3CN, LiClO4
2) H2O
R
Et
iPr
tBu
CO2CH3
%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 non-bonding 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.
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Ex1:
CH2IPt anode
CH3CN, LiClO4
CH3
NHCOCH 3
Ex2:
CH2I
I
Pt anode
CH3CN, LiClO4
Pt anode
CH3CN, LiClO4
CH2NHCOCH 3
NHCOCH 3
+
10%
90%
Oxidative dimerization of alkenes.
DDD
DD
D
D
D
Nu
Nu
or (A,-e-)
A
A
- 2H
+ 2Nu
- e-
D = EDG (OR, Ph, NHCOR, OSiMe3, ...)
Oxidative cycloaddition of alkenes.
Olefins also undergo cycloaddition reactions through a similar mechanism involving the
formation of a new chemical bond in a step subsequent to the ET oxidation.
DD
A
ADD
DD
+ e-- e-
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An interesting example: Reaction of Levoglucosenone in the presence of
electrogenerated superoxide anion
In ET initiated reactions it is possible to control the stereoselectivity by changing (i) the
concentration of the reagents, (ii) the current density (or potential), (iii) the added
reagents, or (iv) the reactions conditions.
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II. INITIATION MODES AND EXPERIMENTAL METHODOLOGIES
A very important aspect of ET reactions is that they can be initiated by a variety of
procedures. These include thermal (homogeneous and heterogeneous),
photochemical and through use of solvated electrons as in pulse radioysis. This has
stimulated the development of a wide range of techniques and analytical methodologies
for the study of ET reactions with a view to gaining insights into various aspects of their
dynamics and mechanisms. All these techniques have an obvious common factor: the
addition or removal of an electron to or from a reactant. But the fact that their similarity
may end here means that sometimes these techniques provide different information
regarding such ET transfer-initiated reactions. They differ in terms of the analysis
time windows thus making them useful for different systems and capable of studying
different types of intermediates. The other issue concerns the fact that the initiation step
itself, as well as subsequent steps may differ from one initiation technique to another
despite the fact that in all cases an electron is added or removed. As a result the
chemistry following the initial ET step may differ totally from one initiation mode
to another. So while thermal homogenous initiation is a reaction usually leading to
the transfer of a single electron, electrochemical initiation is a heterogeneous
process very often involving the transfer of multiple electrons. Photoinduced
electron transfer involves reactants in the excited state and therefore differs from
both the homogeneous thermal as well as the electrochemical heterogeneous cases.
Pulse radiolysis is different again in the sense that it generates solvated electrons
and strong oxidizing and reducing agents, and the ET initiation is usually subject to a
large standard free energy. An aspect where these initiation modes do not present the
same value is ET-initiated organic synthesis. It is nevertheless possible, when all these
factors are taken into consideration, to acquire complementary information regarding the
nature of the ET process and its kinetics with respect to the chemical step that follows
through use of different initiation modes.
We will only briefly describe cyclic voltammetry because of its crucial importance in
gaining dynamic and mechanistic information.
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Cyclic Voltammetry: A very important tool for studying electron transfer initiated
reactions. It provides information regarding the kinetics, the thermodynamics and the
mechanisms of the investigated reactions.
Important characteristics:
- Peak Potential
- Number of electrons exchanged per molecule (n)
- Transfer coefficient
Potential (mV)
Time(s)E1
E2
Reversible System
-E
i
B + CA + e- A.-
D
Ek1 k2
k3+e-
k4
workstation
RECE WE
Irreversible System
-E
i
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Let’s look at the following example involving the electrochemical reduction of arylazo
sulfides
- The electrochemical reduction of aryl azosulfides yields the corresponding sulfides
and decompositions products.
- The mechanism of the global reaction is an SRN1 mechanism.
Ar-X + e-
Ar-X
Ar + Nu
ArNu + Ar-X
Ar-X
Ar + X
ArNu
ArNu + Ar-X
k
The following Figure shows the Cyclic voltammogram of paracyano phenyl azo phenylsulfide
(c=1mM) in ACN + 0.1M NBu4ClO4 on a glassy carbon electrode.
N N SNC
NC H
NC S
The mechanism of the reaction can be written as per the following scheme.
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Adding increasing amounts of cyanide during the electrochemical investigation of the
arylazo compound induces important changes to cyclic voltammogram. The first
reduction peak decreases while a new reduction peak appears. This new peak is due to
the reduction of the newly formed terephtalonitrile (NCC6H4CN).
NC CN
Cyclic voltammogram of
paracyano phenyl azo
phenylsulfide (c=1mM)
in CH3CN + 0.1M
NBu4ClO4 on a glassy
carbon electrode
(a) [CN-] = 0 mM, …
(b) [CN-] = 10 mM, - - -
(c) [CN-] = 320 mM, ____
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The global mechanism is:
The kinetics of the reaction of the cyanide nucleophile were thus calculated in two
solvents (CH3CN and DMSO) and shown a slight dependence of the solvent’s viscosity.
k= 1,5 1011 M-1s-1 in CAN and 2,4 1011 M-1s-1 in DMSO
- Understanding ET reactions (outer sphere ET vs dissociative ET)
- Structure dependence:
- Representative examples
NNC N S
NNC N S
NC SN2+ +-
SNCNC
+ e-
A
+ CN
NC SNCCN
+ A
+
-
CN
+ A
+ AA
.
-.
-.-.
-.
-.
-.
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III. ET reactions (outer sphere ET vs dissociative ET)
Unravelling the nature of the fundamental steps involved in the electron transfer and the
subsequent reactions has always been an essential step towards reaching a molecular
understanding of ET processes. In these multiple step reactions important questions
arise not only concerning their mechanisms and the factors controlling them but also the
associated energies and kinetics and any similarity to certain non-electron transfer
processes. Extensive studies have already shed considerable new light on many of
these important questions.
Outer sphere electron transfer:
Certain organic chemical compounds can accept or loose an electron without
undergoing considerable structural changes (bond cleavage or formation). These
electron transfer reactions are usually associated with only some reorganization and are
called “outer sphere” ET reactions.
For example, the electron transfer to nitrobenzene leads to the corresponding radical
anion. Nitrobenzene is able to host the incoming electron without undergoing any bond
dissociation.
NO2NO2+ e-
The nitrobenzene shows a totally reversible cyclic voltammogram indicating the stability
of both the neutral and the reduced forms.
Chemistry consuming the resulting radical anion can still be initiated by adding
various reagents.
Example: Oxidative formation of C-S bond in the synthesis of thianthrenium salts.
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Ar
O
OH
Ar
Th+
OH
Ar
Th+
+
O
Ar
Th+
R4
R2
R3
R1
R4
R2
R3
R1
Th+
R3
R1
Th
R2
R4
Th+ +Th
-H+
Th
S
S
-e-
For many other organic chemical compounds the addition (or removal) of an electron will
induce more important structural changes (usually a bond dissociation). Alkyl halides for
example undergo the dissociation of the C-halogen chemical bond.
Br + e- + Br
In cyclic voltammetry these compounds show an irreversible cyclic voltammogram. The
example below is that of Bromoadamantane in acdtonitrile on a glassy carbon electrode.
Ep = -2.30V
n = 2e- /molecule
= 0.3
Important: An irreversible
cyclic voltammogram does not
mean the non-existence of an
intermediate radical anion. The
intermediate may exist but
could have a lifetime that is too
short to allow its detection by
cyclic voltammetry.
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ET reactions not involving an ET intermediate (a radical anion, radical cation, or radical
depending on the starting material) follow a: dissociative electron transfer
mechanism. In this case the ET and bond cleavage are simultaneous.
Concerted vs stepwise ET mechanism
The mechanism of the initial ET step is very important. Consider the electron transfer
reaction below leading to the dissociation of the R-X chemical bond. This process is a
very common process to most organic compounds with a good leaving group such as
alkyl and aryl halides. The outcome of the generated radical greatly depend on whether
a radical anion is formed as an intermediate (outer sphere ET) or not (dissociative ET).
The radical can undergo a multitude of potential reactions as shown below.
RX + e- R + X
RX
?
R R-RRH
RNu
Nu(SRN1)
SH
e-
R
.-
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IV. Hush Marcus Theory vs the Dissociative ET Theory (Savéant’s Theory)
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, ‡
0G , which involves only the solvent ( 0 ) and
the inner ( i ) reorganization energies for a stepwise mechanism (eq 2). ‡G (the
activation free energy), 0G (the reaction free energy) and ‡
s,0G and ‡
c,0G (i.e. the
activation energy at zero driving force) represent the intrinsic barriers for a stepwise and
a concerted ET respectively.
2
‡0
‡0
‡
41
G
GGG
o
(1)
4G and
4 G 0‡
c0,0‡
s0,XRi BDE
(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) 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.
R-X + e
R-X
R + X
?
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How does the driving force affect the ET mechanism?
0
/ .RXRXE
0
/ . XRRXE
Potential Energy
Reaction Coordinate
RX + e-
RX + e-
Stepwise
Concerted
RX.-
R X+. -
-E
-E
Passage from a stepwise to a concerted mechanism upon decreasing the driving
force. Potential energy profiles. E: electrode potential.
How do know, in practice, whether one or the other mechanism is followed?
1- Experimental detection of the electron transfer intermediate (radical or radical ion):
a) 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.
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Example (increasing the scan rate in CV): reduction of 3,5-dinitrophenylthiocyanide
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).
b) Homogeneous catalysis allows the extension of the lifetime range up to the ns.
Homogeneous catalysis: consists of using a redox catalyst (P/Q) as an intermediate to
transfer electrons between the electrode and the substrate.
Homogeneous redox catalysis; (a) general process at electrode; (b) reaction sequence for a homogeneous dissociative electron transfer reduction.
SCN
O2N
O2N
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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:
‡0
0
0
‡
41
2
1
G G
GG (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.
at 25o C
at 25o C
pE is the peak potential and 2/pE 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.
11
)log(6.29
)log(2
v
Ep
v
Ep
F
RT
pppp EEEEF
RT
2/2/
15.47
85.1
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Photochemical initiation.
Photochemical irradiation is another efficient way to initiate ET reactions. Many
processes in nature are based on photoinduced ET. The most widely known one is of
course photosynthesis.
Under photochemical irradiation the ET can occur through a variety of mechanisms
(shown below): from irradiation of the donor (i) or of the acceptor (ii). A charge transfer
complex may also be formed: either before irradiation between ground state reactants,
or after irradiation between excited and ground state structures (iv). It is also possible to
generate solvated electrons, through irradiation of a sensitizer that is trapped by an
acceptor. Electron photo-ejection has been reported for anions such as phenolates and
thiolates as well as for neutral structures such as 4,4’-dimethoxystilbene. This latter
process is similar to pulse radiolysis.
Of the different techniques that have been developed to study photo-induced electron
transfer reactions the most widely used one is laser flash photolysis.
D
RX
D
D* + RX D + R + X
D*h
RX*h
D + RX*
D + RX (D,RX) h
RX + e-
D + e-h
(i)
(ii)
(iii)
(iv)
D + R + X
D + R + X
D + R + X
Different mechanisms for the photochemical initiation of a dissociative electron transfer.
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SUBSTITUENT' EFFETC ON ET INITIATED REACTIONS
a) Substituents' effect on the redox properties
b) Substituents's effect on the initial ET mechanism
c) Substituents effect on the kinetics
b) Substituents' effect on the product distribution
Products of the electrochemical reduction of substituted benzyl thiocyanates.