Cryovoltammetrically probing functional group reductive cleavage: Alkyl-sulfur versus aryl-sulfur bond cleavage in an alkyl naphthyl thioether under single electron-transfer is temperature switchable

Article abstract of DOI:10.1039/b606638k

A series of single electron-transfer (SET) reactions on a naphthyl thioether have shown that the reductive cleavage mechanism changes at low temperatures and this selectivity is proved using an electrochemical analysis that mimics the SET reaction conditi

Full text of DOI:10.1039/b606638k

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Cryovoltammetrically probing functional group reductive cleavage:
alkyl–sulfur versus aryl–sulfur bond cleavage in an alkyl naphthyl
thioether under single electron-transfer is temperature switchable{
Christopher A. Paddon,a Farrah L. Bhatti,b Timothy J. Donohoe*b and Richard G. Compton*a
Received (in Cambridge, UK) 10th May 2006, Accepted 29th June 2006
First published as an Advance Article on the web 10th July 2006
DOI: 10.1039/b606638k
mechanism of reactivity at 278 uC.5–10 At this temperature, a
A series of single electron-transfer (SET) reactions on a
significant improvement in the resolution of voltammetric waves
and peaks is observed, vide infra. In general, there is much
literature concerning the organo-electrochemistry of sulfur com-
pounds at 20 uC and a number of reviews provide excellent
overviews of the field.11 However, few reports on low temperature
electrochemistry of such compounds exist to date.
naphthyl thioether have shown that the reductive cleavage
mechanism changes at low temperatures and this selectivity is
proved using an electrochemical analysis that mimics the SET
reaction conditions.
The reductive cleavage of functional groups (FGs) using single
electron-transfer (SET) reactions is widely employed in synthetic
organic chemistry. Typical reaction conditions involve the use of
an electron-transfer reagent (e.g. naphthalene or 4,49-di-tert-
butylbiphenyl (DBB)) and lithium metal, often resulting in
synthetically useful anionic intermediates that can be utilized for
the construction of complex organic molecules.1–4 As part of a
synthetic study, we report reactions involving the naphthyl
thioether: 2-[(3-{[trans-4-(methoxymethoxy)cyclohexyl]oxy}pro-
pyl)thio]naphthalene, I, at 20 uC, 0 uC and 278 uC in
tetrahydrofuran (THF) that show a change in the cleavage
mechanism based solely upon temperature control of the SET
reaction. At 20 uC or 0 uC, alkyl–sulfur bond fission was favoured
whilst at 278 uC, aryl–sulfur bond cleavage was the major
pathway (Scheme 1).
As part of a synthetic study, the thioether I was treated with
lithium and DBB at different temperatures; the result was surpris-
ing, and showed a clear switch in behaviour based upon tempera-
ture. The results of the SET reactions are summarized in Table 1.
The mechanism of reductive cleavage was proved by a detailed
electrochemical analysis using platinum electrodes in THF and
controlled-potential bulk-electrolyses at 20 uC and 278 uC. A
preliminary electrochemical analysis of I was carried out at 20 uC
using a platinum microelectrode to record the voltammetric
(steady-state) response as shown in Fig. 1 (a). A reduction wave,
poorly resolved from the solvent decomposition, was observed and
an estimate of the half-wave potential, E1/2, is given in Table 2
which summarizes all following electrochemical data obtained at
With a desire to understand the exact mechanism of reductive
cleavage following electron-transfer (ET) we used electrochemistry,
specifically cyclic voltammetry (CV), in a method designed to
mimic the conditions of the SET reaction at 20 uC and 278 uC.
Following the pioneering work by Van Duyne and Murray et al.
which has shown that electrochemistry may be conducted at low
temperatures, we have recently extended the use of cryoelectro-
chemical methodologies to a range of functionally activated
organo-sulfur compounds with a view to investigating their
Table 1 Percentage yield(s) of product(s) following SET reduction of
I at various temperatures
Temperature/uC
I/%
II/%
III/%
20
0
278
23
0
0
0
5
45
32
54
7
Scheme 1
aPhysical and Theoretical Chemistry Laboratory, Oxford University,
South Parks Road, Oxford, UK OX1 3QZ.
E-mail: Richard.compton@chem.ox.ac.uk; Fax: 44 1865-275-470
bResearch Chemistry Laboratory, Oxford University, Mansfield Road,
Oxford, UK OX1 3TA
{ Electronic supplementary information (ESI) available: Experimental
details and characterisation data for compounds IV and V. See DOI:
10.1039/b606638k
Fig. 1 Voltammetric response of I (3 mM) as a function of temperature:
(a) 20 uC; (b) 0 uC; (c) 220 uC; (d) 250 uC; and (e) 278 uC. Inset:
Magnification of steady-state response of I at 278 uC in the voltammetric
region of interest. Electrode radius: 5.4 mm; scan rate: 10 mV s21; 0.1 M
TBAP in THF.
3402 | Chem. Commun., 2006, 3402–3404
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Table 2 Summary of electrochemical data for the reduction of I at
20 uC
EIp,c1
/
EV
/
EIV
/
p,c2
p,a
Compound E1/2/Va
22.93
n
D/10210 m2 s21 mAa,b mAa,b
mAa,b
I
1
21.2c
23.19 22.35d 20.48d
a
2
b
Potentials measured versus Fc/Fc+PF6
denote peak, cathodic, and anodic, respectively. Obtained from ln
.
Subscripts p, c, and a
c
D vs. T21 plot. Peak potentials (Ep) measured at 250 mV s21
.
d
20 uC. Fig. 1 shows two important features of electrochemistry in
THF: (i) voltammetry at 20 uC is affected by the electroactivity of
the solvent window which ‘overlaps’ with the electrochemical
process of interest, and (ii) voltammetry at lower temperatures
leads to a significant improvement in the resolution of voltam-
metric waves and thus subsequent accuracy and interpretation of
the electrochemical data. Highlighting this latter point is the
voltammetric response shown in Fig. 1 (e), where a well-defined
current plateau is seen for the first reduction wave. In addition, a
second reduction wave is also observed. Therefore, analyses were
possible at 20 uC; however, better resolved data could be obtained
at 278 uC.
Fig. 2 Cyclic voltammograms obtained at a 1 mm platinum disc
electrode for I (3 mM) at a scan rate of 250 mV s21. Scans 1–4. Start
scan: 21.5 V, first reverse: 23.8 V, and second reverse: 0.5 V versus
Fc/Fc+PF62. Electrode diameter: 1 mm; 0.1 M TBAP in THF at 20 uC.
‘fingerprints’ of the species formed following reduction of I, a salt,
tetra-n-butylammonium 2-thionaphtholate (nBu4N+ NaphS2),
IV, and 2,29-dinaphthyl disulfide, V, were prepared and their
structures are shown in Fig. 3. For the sake of brevity, experi-
mental details and characterization data can be found in the ESI.
Next, we performed an exhaustive electrolysis of I at constant
potential to verify the SET result. Following the passage of the
required number of Coulombs assuming a one electron reduction,
the crude products were analysed using 1H NMR in CDCl3. It was
shown by integral analysis of 1H NMR peaks, that III (Scheme 1)
was present in a ratio of 2.3 : 1 relative to the starting material. A
full electrochemical conversion was not achieved, however
(ca. 56%), and this was most likely due to the close proximity of
the solvent window which led to inherent difficulties in defining a
potential at which to perform the exhaustive electrolysis without
electrolyzing the solvent.
Next, microdisc chronoamperometric experiments were run at
278 uC; the procedure used is described fully in the electronic
supplementary information (ESI) and the data are summarized in
Table 3.
A diffusion coefficient, D, and the number of electron(s), n, for
the reduction of I were determined. Using the first reduction-wave,
steady-state data obtained at 220 uC and 250 uC, Fig. 1(c) and (d)
respectively, n and D values were obtained and a plot of ln
D versus T21 allowed extrapolation to obtain a D value for I at
20 uC.3
CV of I was recorded at 20 uC using a platinum macroelectrode
(Fig. 2), where a single, electrochemically irreversible reduction
peak was observed. Anodic scanning of the potential window
following reduction showed the appearance of an electrochemi-
cally irreversible oxidation peak and, with subsequent cycling of
the potential, an additional reduction peak was observed. In a
previous study of 1- and 2-naphthyl methyl sulfides at a glassy
carbon electrode in acetonitrile a similar response was observed;
however, adsorption of the electroactive species appeared to limit
the voltammetryand no reports of follow-up reduction peaks were
described.12 Based upon electrochemical studies of various phenyl
sulfides in aprotic media, it can be reasonably assumed that the
reduction of I leads to the formation of a naphthyl thiolate which
is readily oxidised upon reverse scanning of the potential.13,14
Upon oxidation this then dimerises via a second-order chemical
process to form the dimer, 2,29-dinaphthyl disulfide, V, which
would then undergo reduction at less negative potentials than
the parent, I. In order to characterize these electrochemical
As a function of decreasing temperature, the effect on the
voltammetry of I was investigated and is shown in Fig. 4. In
particular we wanted to observe any changes in the ET
characteristics that might accompany the decrease in temperature
that could explain the change in reductive cleavage mechanism.
It is evident that the electrochemical reversibility of the first
reduction peak increases with decreasing temperature. Also
observable is the diminished oxidative peak-current height
corresponding to the oxidation of IV. These observations
suggested to us that the formation of a radical anion, I 2, was
?
probably stabilized at lower temperatures on timescales long
enough to accept an additional electron before dissociating.
Fragmentation of a dianion may follow a different route to that
of a radical anion, thus rationalizing the synthetic results. Also
seen at this temperature was an extended cathodic potential
window15,16 relative to Fc/Fc+PF62, within which was observed a
second cathodic peak following the first (Fig. 5). At higher scan
rates a single irreversible oxidation peak was seen, although no
Table 3 Summary of electrochemical data for the reduction of I at
278 uC
Compound
E1/2/Va
nb
D/10210 m2 s21 b
Ic
Id
a
22.97
23.61
1.06 (¡0.03)
1.99 (¡0.05)
1.3 (¡0.01)
—
Potentials measured versus Fc/Fc+PF6
.
Data obtained from
2
b
c
microdisc chronoamperometric experiments. First reduction wave.
Fig. 3 Structures of tetra-n-butylammonium thionaphtholate, IV, and of
2,29-dinaphthyl disulfide, V.
d
Second reduction wave.
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Fig. 4 Cyclic voltammograms (single scans) for I (3 mM) first reduction
peak as a function of temperature: (a) 0 uC; (b) 220 uC; (c) 230 uC; (d)
240 uC; (e) 250 uC; (f) 260 uC; and (g) 270 uC. Start scan: 21.0 V; first
reverse: 23.4 V; and second reverse: 0.5 V. Scan rate: 250 mV s21
;
Scheme 2 Cleavage pathways following reduction of I under single
electron-transfer (SET) conditions at 20 uC and 278 uC.
electrode diameter: 1 mm; 0.1 M TBAP in THF.
electron before dissociating at the alkyl carbon–sulfur bond. The
products following reductive cleavage have been characterised
using known samples of the products. Using a cryoelectrochemical
procedure we observed an improved resolution in the voltammetry
(peaks and waves) that allowed accurate determinations of
electrochemical parameters such as E1/2, Ep, etc. At 278 uC, I is
stabilized at sufficiently longer timescales to accept two electrons in
a stepwise fashion. The dianion then cleaves selectively at the aryl–
sulfur bond forming the alkyl thiol, II. Selective reductive cleavage,
product(s) characterization and determination of the exact mech-
anism following SET reduction of a FG at various temperatures
have been documented, via a cryoelectrochemical analysis.
To conclude, this method of selective C–S bond cleavage,
controllable by the reducing conditions applied, provides the
ability to form either an alkyl thiolate or carbanion from the same
naphthyl protected thiol and may have uses in synthetic organic
chemistry.
additional reduction peaks were noticed even at a scan rate of
1 V s21. On the basis of stability arguments, one would expect a
dialkyl disulfide (formed from the alkyl thiolate, RS2, upon
oxidation and then dimerisation) to be more difficult to reduce
than the corresponding dinaphthyl disulfide due to delocalization
of the charge in the latter molecule and so its reduction might not
observed within the potential window.17
At 278 uC, a preparative electrolysis of I was performed in
order to show that the reductive cleavage of I followed that
observed under synthetic conditions. Holding the potential at
23.77 V vs. Fc/Fc+PF62 and following the passage of the required
number of Coulombs assuming an n 5 2 electron reduction, the
crude product was analysed using 1H NMR in CDCl3. Analysis of
1H NMR integrals showed the presence of II, III and I in a ratio of
1.8 : 0.4 : 1. This result confirmed that the reduction of I under
electrochemical conditions at 278 uC gives the aryl–sulfur bond
cleavage product, II, as observed in the initial SET reduction
reactions. Scheme 2 outlines the possible mechanism of reductive
cleavage of I at both 20 uC and 278 uC.
The authors wish to thank the EPSRC for supporting this work.
Notes and references
Following a series of SET reductions performed on the naphthyl
thioether I, we have used CV to determine the mechanism of
reductive cleavage. At 20 uC, we have found that I accepts a single
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Fig. 5 Cyclic voltammograms of I at 278 uC. Scan rate: 250 mV s21
electrode diameter: 1 mm; 0.1 M TBAP in THF. Scans 1–4. Start scan:
;
21.5 V, first reverse: 24.3 V, and second reverse: 0.5 V versus
Fc/Fc+PF6
2
.
3404 | Chem. Commun., 2006, 3402–3404
This journal is ß The Royal Society of Chemistry 2006