Crown ether vinylogous tetrathiafulvalene receptors: Complexation interference on the molecular movements triggered by electron transfer

Article abstract of DOI:10.1021/jo0701841

(Chemical Equation Presented) The synthesis of a series of crown ether substituted vinylogous tetrathiafulvalenes (TTFVs) has been carried out through oxidative coupling of bisdithiafulvenes. These new receptors have been fully characterized using electrochemical, spectroelectrochemical, and molecular modeling experiments. These studies show that, upon oxidation, either a clip movement (TTFVs 3a,b) or a stretch movement (TTFV 3c) occurs, depending on the length of the crown ether chains. Preliminary electrochemical studies, undertaken on TTFV 3c in dichloromethane, show a little shift of the first standard oxidation potential toward more positive values upon addition of the Pb²⁺ ion, but a considerable variation of the electron-transfer kinetics. This result introduces an interesting concept for the preparation of sensors not based on thermodynamic variations but on kinetic modifications of the electron transfer.

Full text of DOI:10.1021/jo0701841

Crown Ether Vinylogous Tetrathiafulvalene Receptors:
Complexation Interference on the Molecular Movements Triggered
by Electron Transfer
Julien Massue, Nathalie Bellec, Michel Guerro, Jean-Franc¸ois Bergamini,
Philippe Hapiot,* and Dominique Lorcy*
Sciences Chimiques de Rennes, UMR 6226 CNRS-UniVersite´ de Rennes 1, Campus de Beaulieu, Baˆt 10A,
35042 Rennes cedex, France
dominique.lorcy@uniV-rennes1.fr
ReceiVed January 30, 2007
The synthesis of a series of crown ether substituted vinylogous tetrathiafulvalenes (TTFVs) has been
carried out through oxidative coupling of bisdithiafulvenes. These new receptors have been fully
characterized using electrochemical, spectroelectrochemical, and molecular modeling experiments. These
studies show that, upon oxidation, either a clip movement (TTFVs 3a,b) or a stretch movement (TTFV
3c) occurs, depending on the length of the crown ether chains. Preliminary electrochemical studies,
undertaken on TTFV 3c in dichloromethane, show a little shift of the first standard oxidation potential
toward more positive values upon addition of the Pb2+ ion, but a considerable variation of the electron-
transfer kinetics. This result introduces an interesting concept for the preparation of sensors not based on
thermodynamic variations but on kinetic modifications of the electron transfer.
Introduction
information and an easily controllable mobile unit for encoding
the information. An interesting electrochemically driven motion
has already been observed in the redox-active vinyloguous
tetrathiafulvalene (TTFV) framework. Indeed, all the neutral
TTFVs substituted (R) on the central conjugation exhibit
nonplanar structures, due to steric hindrance,3 while for the
oxidized species, the TTFV cores become planar with the R
substituents located in planes perpendicular to that formed by
The concept of induced molecular movement has been
proposed as a convenient tool for transforming chemical
information to electrical information.1-2 The design of molecular
systems capable of realizing this transformation would involve
a transducer such as a redox-active species for transferring the
* To whom correspondence should be addressed. Fax: (+33)-2-23-23-
67-38.
(1) (a) Balzani, V.; Venturi, M.; Credi, A. Molecular DeVices and
Machines: A Journey into the Nanoworld; Wiley-VCH: Weinheim,
Germany, 2003. (b) Willner, I.; Basnar, B.; Willner, B. AdV. Funct. Mater.
2007, 17, 702.
(2) For some examples of molecular motions triggered by electron
transfers see: (a) Acc. Chem. Res. 2001, 34, 410-522 (“Molecular
Machines” special issue). (b) Carella, A.; Coudret, C.; Guirado, G.; Rapenne,
G.; Vives, G.; Launay, J.-P. Dalton Trans. 2007, 177. (c) Nygaard, S.;
Laursen, B. W.; Flood, A. H.; Hansen, C. N.; Jeppesen, J. O.; Stoddart, J.
F. Chem. Commun. 2006, 144. (d) Christensen, C. A.; Batsanov, A. S.;
Bryce, M. R. J. Am. Chem. Soc. 2006, 128, 10484.
(3) (a) Hopf, H.; Kreutzer, M.; Jones, P. G. Angew. Chem., Int. Ed. Engl.
1991, 30, 1127. (b) Lorcy, D.; Carlier, R.; Robert, A.; Tallec, A.; Le,
Maguere`s, P.; Ouahab, L. J. Org. Chem. 1995, 60, 2443. (c) Ohta, A.;
Yamashita, Y. J. Chem. Soc., Chem. Commun. 1995, 1761. (d) Moore, A.
J.; Bryce, M. R.; Skabara, P. J.; Batsanov, A. S.; Goldenberg, L. M.;
Howard, J.A. K. J. Chem. Soc., Perkin Trans. 1 1997, 3443. (e) Yamashita,
Y.; Tomura, M.; Braduz Zaman, M.; Imaeda, K. J. Chem. Soc., Chem.
Commun. 1998, 1657. (f) Jia, C.; Liu, S-X.; Neels, A.; Stoeckli,-Evans, H.
Decurtins, S. Synthesis 2005, 2157. (g) Guerro, M.; Lorcy, D. Tetrahedron
Lett. 2005, 46, 5499.
10.1021/jo0701841 CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/24/2007
J. Org. Chem. 2007, 72, 4655-4662
4655

Massue et al.
FIGURE 1. Schematic representation of the stretch movement observed with TTFVs upon oxidation.
chemistry.7-8 To test our hypothesis, we investigated the
synthesis of a series of crown ether vinylogous TTFs where a
poly(oxyethyl) ligand of variable length is linked via the two
phenyl groups to the central conjugation of these cyclic
vinylogous TTFs 3. First, electrochemical and spectroelectro-
FIGURE 2. Schematic representation of the clip movement observed
with some cyclic TTFVs upon oxidation.
the TTFV core (Figure 1).4 These large and fast reversible
structural changes associated with the electron transfer at easily
attainable oxidation potentials can be compared to stretch
movement.5
chemical investigations were performed to analyze the influence
of the crown ether ligand length on the nature of the molecular
movements induced by electron transfer. Molecular geometry
optimizations were realized to rationalize the observed experi-
ments. Preliminary experiments on the ligating ability of these
crown ether vinylogous TTFs 3 are also reported. Even if the
ligating part of the molecule is far from the redox-active center,
complexation alters the structural changes and therefore the
redox properties.
According to the molecular structure of the TTFVs, a second
type of movement can be triggered by electron transfer. Indeed,
the presence of a short bisthioalkyl link between the two dithiole
rings such as in cyclic TTFVs prevents any stretch motion, and
upon oxidation, the two dithiolium rings become closer and a
clip movement occurs (Figure 2).6 It is worth noting that with
a longer bisthioalkyl link (e.g., (CH2)12), the motion is similar
to that observed in the noncyclic derivative.
Interestingly, the presence of the bisthioalkyl link modifies
marginally the donor ability of these molecules compared to
the noncyclic one but has an influence on the oxidation
processes. For instance, when R ) p-MeOC6H4, two close,
reversible, monoelectronic transfers occur for 1 and 2c (A )
(CH2)12) while for 2a,b (A ) (CH2)3, (CH2)4) a bielectronic
transfer leads directly to the dication species.6 The different
exchange processes are tightly bound to the different types of
molecular movement, so if an external element impedes or
delays the stretch motion, the information should be translated
by the electrochemical process. In this connection, the introduc-
tion of a crown ether moiety attached to each mobile part of
the redox-active framework instead of the bisthioalkyl link
should not modify the redox answer of the molecule, provided
no cation is present. Indeed, crown ethers are well-known as
efficient ligands toward various cations depending on the size
of the cavity and therefore as the basis for host-guest
Results and Discussion
The main approach to the synthesis of substituted vinylogous
TTFs consists first of the preparation of the 1,4-dithiafulvene
derivative and then the formation of the vinylogous TTF core
by oxidative coupling of two dithiafulvenyl moieties.9-10 The
(7) (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017. (b) Gokel, G.
W.; Leevy, W. M.; Weber, M. E. Chem. ReV. 2004, 104, 2723.
(8) Cram, D. J.; Cram, J. M. In Container molecules and their guests;
Stoddart, J. F., Ed.; RSC, University of Birmingham: Birmingham, U.K.,
1994.
(9) (a) Kirmse, W.; Horner, L. Liebigs Ann. Chem. 1958, 614, 4. (b)
Mayer, K.; Kro¨ber, H. J. Prakt. Chem. 1974, 316, 907. (c) Cava, M. P.;
Lakshmikantham, M. V. J. Heterocycl. Chem. 1980, 17, S39. (d) Scho¨berl,
U.; Salbeck, J.; Daub, J. AdV. Mater. 1992, 4, 41. (e) Benahmed-Gasmi,
A.; Fre`re, P.; Roncali, J.; Elandaloussi, E.; Orduna, J.; Garin, J.; Jubault,
M.; Gorgues, A. Tetrahedron Lett. 1995, 36, 2983. (f) Bellec, N.; Lorcy,
D.; Robert, A.; Carlier, R.; Tallec, A. J. Electroanal. Chem. 1999, 462,
137.
(10) (a) Fourmigue´, M.; Johannsen, I.; Boubekeur, K.; Nelson C.; Batail,
P. J. Am. Chem. Soc. 1993, 115, 3752. (b) Fre`re, P.; Benahmed-Gasmi, A.
S.; Roncali, J.; Jubault, M.; Gorgues, A. J. Chim. Phys. Phys.-Chim. Biol.
1995, 92, 863. (c) Gonzalez, S.; Martin, N.; Sanchez, L.; Segura, J. L.;
Seoane, C.; Fonseca, I.; Cano, F. H.; Sedo, J.; Vidal-Gancedo, J.; Rovira,
C. J. Org. Chem. 1999, 64, 3498. (d) Roncali, J. J. Mater. Chem. 1997, 7,
2307. (e) Lorcy, D.; Guerin, D.; Boubekeur, K.; Carlier, R.; Hascoat, P.;
Tallec, A.; Robert, A. J. Chem. Soc., Perkin Trans. 1 2000, 2719. (f)
Hascoat, P.; Lorcy, D.; Robert, A.; Carlier, R.; Tallec, A.; Boubekeur, K.;
Batail, P. J. Org. Chem. 1997, 62, 6086.
(4) (a) Lorcy, D.; Le Maguere`s, P.; Rimbaud, C.; Ouahab, L.; Delhaes,
P.; Carlier, R.; Tallec, A.; Robert, A. Synth. Met. 1997, 86, 1831. (b)
Rimbaud, C.; Le Maguere`s, P.; Ouahab, L.; Lorcy, D.; Robert, A. Acta
Crystallogr. 1998, C54, 679. (c) Yamashita, Y.; Tomura, M.; Tanaka, S.
Imaeda, K. Synth. Met. 1999, 102, 1730. (d) Yamashita, Y.; Tomura, M.;
Imaeda, K. Tetrahedron Lett. 2001, 42, 4191. (e) Yamashita, Y.; Tomura,
M. J. Solid State Chem. 2002, 168, 427.
(5) Bellec, N.; Boubekeur, K.; Carlier, R.; Hapiot, P.; Lorcy, D.; Tallec,
A. J. Phys. Chem. A 2000, 104, 9750.
(6) Guerro, M.; Carlier, R. Boubekeur, K.; Lorcy, D.; Hapiot, P. J. Am.
Chem. Soc. 2003, 125, 3159.
4656 J. Org. Chem., Vol. 72, No. 13, 2007

Crown Ether Vinylogous TetrathiafulValene Receptors
TABLE 1. Redox Potentials of Bisdithiafulvenes 8a-c and TTFV
3a-ca
SCHEME 1
E
pa (V),
E1, E2 (V),
E (V),
CH2Cl2
CH2Cl2
CH3CN
8a
8b
8c
0.46
0.47
0.49
3a
3b
3c
0.33
0.31
0.19, 0.34
0.28
0.30
0.25
a E in volts vs SCE, n-Bu4NPF6, Pt, 0.1 M, scanning rate 0.1 V/s.
SCHEME 2
a reversible oxidation system at a less positive potential than
the starting dithiafulvenes. The electrochemical behavior is quite
similar for both the monodithiafulvenes 6 and 7 and the
bisdithiafulvenes 8a-c. It can be noticed that the Epa values of
bisdithiafulvenes 8a-c are not influenced by the chain length
and are close to that observed for the dithiafulvene 7 (Epa
)
0.46 V vs SCE), while for 6 (Epa ) 0.65 V vs SCE) the Epa
value is positively shifted due to the presence of the electron-
withdrawing effect of the substituent C6H5CO2. These electro-
chemical investigations carried out on the bisdithiafulvenes
8a-c show that upon oxidation two dithiafulvene cores couple
into a redox-active vinylogous TTF. However, since elec-
trodeposition occurs at the electrode, forming an insoluble film,14
we could not perform electrochemical synthesis of the vinylo-
gous TTF, as realized previously for other TTFV derivatives.
To avoid the electrodeposition, we favor the chemical
coupling instead of the electrochemical one for the preparation
of the vinylogous TTFs 3a-c (Scheme 3). The bisdithiafulvenes
8a-c were oxidized in the presence of iodine, and the solution
was then treated with a large excess of Na2S2O4.3g,15 The
vinylogous TTFs 3a-c resulting from the intramolecular
coupling are isolated as viscous oils. The redox behavior of
these derivatives has been analyzed by cyclic voltammetry in
acetonitrile and dichloromethane, and their redox potentials are
collected in Table 1.
In acetonitrile, it can be noticed that they all present only
one reversible bielectronic oxidation wave and that the size of
the poly(oxyethyl) chain does not influence significantly the
electron-donating properties of the TTFVs 3a-c. Interestingly,
in dichloromethane the redox behavior depends on the size of
the poly(oxyethyl) chain. For the shorter chains, such as those
in 3a and 3b, one reversible oxidation wave was observed, while
for 3c two close reversible monoelectronic processes were
observed.
This behavior can be compared to what was observed on
cyclic vinylogous TTFs 2, where the two dithiole rings are
linked through the outer sulfur atoms with an alkyl chain of
various lengths (A ) (CH2)3, (CH2)4, (CH2)12). All these
derivatives exhibited only one reversible bielectronic oxidation
wave in acetonitrile, while in dichloromethane the signature of
the electroactive species was dependent on the size of the alkyl
chain. For the shorter bridging chains (A ) (CH2)3 or (CH2)4)
only one reversible wave was observed; thus, in this case the
neutral TTFVs 2a,b are directly oxidized to their dicationic form.
Contrariwise, when the bisthioalkyl chain was longer (A )
(CH2)12), the redox behavior of 2c was found to be similar to
that of the noncyclic vinylogous TTF 1, which is two close
monoelectronic waves.3b The poly(oxyethyl) chain in 3 and the
SCHEME 3
bisdithiafulvenyl derivatives were synthesized according to the
chemical pathway described in Scheme 1. Our key material is
the dithiafulvene 7 substituted with a p-phenol group which is
smoothly prepared, starting from p-hydroxybenzaldehyde. First,
we protected the phenol group with a benzoate moiety to prepare
the aldehyde 4,11 and the reaction of 4 with the 4,5-dimethyl-
1,3-dithiolylphosphonate anion 5, generated from the 4,5-
dimethyl-1,3-dithiolylphosphonate in the presence of BuLi,
afforded dithiafulvene 6 in 65% yield. Treatment of 6 with
cesium carbonate in refluxing dimethoxyethane (DME)12 in-
duces the deprotection of the phenol group and the formation
of dithiafulvene 7 in excellent yield (90%).
Bis(p-toluenesulfonates) of polyethylene glycol with a chain
of various lengths, tri-, tetra-, and pentaethylene glycol, were
used in the following step. The dithiafulvenylphenol 7 was first
treated with sodium hydride in dry THF, and 1/2 equiv of the
polyethylene glycol bis(p-toluenesulfonates) was added in dilute
conditions (Scheme 2). The corresponding bisdithiafulvenes
8a-c were isolated in good yields after column chromatography.
All the dithiafulvenes 8a-c have been analyzed by cyclic
voltammetry in dichloromethane, and their oxidation potentials
are listed in Table 1. These derivatives exhibit on the first anodic
scan an irreversible oxidation wave, and upon successive scans
a reversible system appears at a lower potential than the first
oxidation peak. This is classical behavior for dithiafulvenes as,
upon oxidation, the radical cation which forms dimerizes to a
protonated species, leading, after deprotonation, to the vinylo-
gous TTF.13 The vinylogous TTFs formed in the medium exhibit
(11) (a) Staedler, P. A. HelV. Chim. Acta. 1978, 61, 1675-1680. (b)
Greene, T. W.; Wuts, P. G. W. ProtectiVe groups in organic synthesis, 3rd
ed.; Wiley: New York, 1999; see also references cited therein.
(12) Zaugg, H. E. J. Org. Chem. 1976, 41, 3419.
(13) Hapiot, P.; Lorcy, D.; Tallec, A.; Carlier, R.; Robert, A. J. Phys.
Chem. 1996, 100, 14823.
(14) Massue, J.; Ghilane, J.; Bellec, N.; Lorcy, D.; Hapiot, P. Electro-
chem. Commun. 2007, 9, 677.
(15) (a) Mu¨ller, H.; Salhi, F.; Divisia-Blohorn, B. Tetrahedron Lett. 1997,
38, 3215. (b) Lorcy, D.; Rault-Berthelot, J.; Poriel, C. Electrochem.
Commun. 2000, 2/6, 382.
J. Org. Chem, Vol. 72, No. 13, 2007 4657

Massue et al.
TABLE 2. λmax (nm) Associated with the Different Species
functional theory) gives good agreement between the X-ray data
and calculated conformations for cyclic and noncyclic TTFVs.
Therefore, calculations could provide useful information on the
molecular geometries of 3a-c since we did not obtain crystals
of these derivatives. As can be seen in Figure 4, the chain link
does not considerably affect the geometry of the molecules at
the neutral state. However, when the TTFVs 3a-c are viewed
along the central C-C axis (Figure 4, bottom), the molecular
geometry seems slightly more constrained with the shortest link,
TTFV 3a. The acute dihedral angle based on this central C-C
bond for the two dithiole rings in 3a, 3b, and 3c increases with
the length of the crown ether chain and amounts to 61.0°, 66.7°,
and 68.1°, respectively. The comparison of these angle values
to that observed in the neutral structure of 1, which amounts to
74(1)°, evidences the strain release from 3a to 3b, while the
further addition of one oxyethyl spacer in 3c moderately
influences the value of this angle.
As far as the dicationic forms are concerned, two isomers
were obtained depending on the length of the poly(oxyethyl)
chain. For 3a2+ and 3b2+ the calculations evidence the Z isomer
on the central CdC double bond with the two dithiolium rings
on the same side resulting from a clip movement, whereas for
3c2+, the E isomer is obtained with the two dithiolium rings on
each side of the central double bond resulting from a stretch
movement. The evolution of the acute dihedral angles based
Produced upon Oxidation
radical
TTFV
neutral
cation
dication
1
3b
3c
335
344
340
597, 700
585
380
450
585, 704
p-MeO substituents in 1 and 2 induce close electronic effects
on the aromatic ring, and therefore, the different redox behavior
observed here is unambiguously attributable to steric hindrance
induced by the size of the poly(oxyethyl) links and can be
correlated to molecular movements of opposite nature associated
with the electron transfer. Indeed, for the cyclic vinylogous TTFs
2 with short bisthioalkyl links, a fast molecular clip was
activated upon electron transfer, while for the longest chain or
the noncyclic vinylogous TTF 1, a stretch movement was
induced upon oxidation.6 Therefore, the redox behavior of the
cyclic TTFVs 3a-c appears to be similarly dependent on the
size of the bridging poly(oxyethyl) chain. If this link is long
enough (3c), it will allow a stretch movement upon electron
transfer, while if it is shorter, a clip movement occurs (3a,b).
To confirm the influence of the poly(oxyethyl) chain on the
molecular movements, we performed spectroelectrochemical
experiments on 3b and 3c, where the species produced during
exhaustive oxidation are followed by spectral changes and
compared with noncyclic TTFV 1. The absorption values of
the neutral, radical cation, and dication species are summarized
in Table 2. All the neutral species exhibit similar UV-vis
spectra with a λmax ≈ 340 nm, indicating that, with or without
the bridging chain, the vinylogous TTF skeletons present the
same conformations with no significant influence of the bridge.
Actually, the X-ray molecular structure of 1 was previously
reported showing nonplanar geometry; thus, a similar spatial
arrangement of the electroactive core in 3 can be envisaged.3b
Analyses of the UV-vis spectra upon oxidation show two
different cases (Figure 3). On one hand, with the longest
bridging chain such as with 3c the formation of the radical cation
(large peak around 585 nm and absorbance in the 704 nm range)
was initially visible before the formation of the dication (only
one peak around 450 nm). On the other hand, for 3b the dication
on this central CdC bond for the two dithiole rings in 3a2+
and 3b2+ amounts to 46.9° and 51.1°, respectively, evidencing
a decrease of the value of this angle in the dicationic species
compared to those observed in the neutral species. In 3c, the
poly(oxyethyl) chain is long enough to allow an opening out
of the molecule evidenced by the fact that 3c2+ exhibits an acute
dihedral angle of 154.8° (Figure 5C). Moreover, compared to
the 180° expected for a planar geometry of the TTFV core and
is produced directly with a broad absorption band at λmax
≈
380 nm, evidencing a completely different dicationic backbone
for the vinylogous TTF core. The spectroelectrochemical
experiments confirm that the nature of the molecular movement,
and therefore the redox behavior, is influenced by the size of
the bridge and that only the poly(oxyethyl) chain in 3c is long
enough to enable a stretch movement as observed in the
nonrestrained molecule 1 or 2c (A ) (CH2)12).
By contrast with the noncyclic analogue 1, the signature of
the dicationic species is observed at different wavelengths (450
nm for 3c and 585 nm for 1). As already mentioned above, the
dicationic species of TTFV 12+ has been characterized by X-ray
diffraction analysis and the vinylogous TTF skeleton was proved
to be planar. Therefore, the hypsochromic shift of λmax observed
for the absorption band of the dicationic species 3c2+ might
indicate a slightly distorted dicationic conformation.
observed in 12+ 4b the slightly folded structure obtained for 3c2+
,
is in agreement with the hypsochromic shift of λmax noticed
during the spectroelectrochemical experiments above.
All these experiments, electrochemical and spectroelectro-
chemical, and calculations support the fact that the presence of
at least a hexakis(oxyethyl) chain connecting the two aromatic
rings on the para position of the TTFV is necessary to allow a
stretch movement upon oxidation in the case of 3.
Poly(oxyethyl) chains are well-known for complexing a large
variety of cations depending on the sizes of the cation and the
poly(oxyethyl) chain.16 Several redox-active moieties such as
ferrocene17 or tetrathiafulvalene18 have been functionalized with
To get additional information on the neutral and the dicationic
states of the TTFVs 3a-c, we used molecular modeling
calculations to determine their geometries. As previously
reported for cyclic and noncyclic TTFVs, when the X-ray
structure is obtained, molecular modeling based on DFT (density
(16) Boulas, P. L.; Gomes-Kaifer, M.; Echegoyen, L. Angew. Chem.,
Int. Ed. 1998, 37, 216.
(17) (a) Beer, P. D.; Gale, P. A.; Zheng, Cheng G. Coord. Chem. ReV.
1999, 185-186, 3. (b) Miyaji, H.; Collinson, R. S.; Prokes, I. Chem.
Commun. 2003, 1, 64. (c) Oton, F. O.; Tarraga, A.; Velasco, D. M.; Molina,
P. Dalton Trans. 2005, 7, 1159.
4658 J. Org. Chem., Vol. 72, No. 13, 2007

Crown Ether Vinylogous TetrathiafulValene Receptors
FIGURE 3. UV-vis spectroelectrochemistry of 3b (5 × 10-4 M) (top) and 3c (5 × 10-4 M) (bottom) in CH2Cl2 (0.2 M Bu4NPF6). Oxidation on
a platinum grid (N ) neutral, RC ) radical cation, DC ) dication).
either crown ether or acyclic receptors to make receptors capable
of electrochemically monitoring the complexation of the cations.
In the case of TTF-derived receptors, the recognition, monitored
by cyclic voltammetry, usually results in a positive shift of the
first redox potential due to the binding of the positively charged
ion in close vicinity of the TTF core. However, as soon as the
ether ligand is not directly linked to the donor core, via for
instance a phenyl ring, only a very weak positive shift (∆E <
10 mV) of the first oxidation process associated with the
complexation can be detected by cyclic voltammetry, due to a
lack of communication between the receptor and the electro-
active unit.19 Basically, a similar situation can be envisioned
with TTFV 3, where the poly(oxyethyl) chain could also behave
as a ligand toward guest cations, but the fact that the binding
site is located far away from the redox-active core should render
the electrostatic repulsion usually observed in simple TTF
receptors negligible.
as Li+, Na+, K+, Cd2+, Pb2+, and Ba2+. If the studies are
performed in acetonitrile, no significant modification of the
voltammograms of 3a-c is observed, regardless of the tested
cations. Similarly, using a dichloromethane solution of 3a,b,
no modifications of the cyclic voltammograms are observed.
Actually, only the cyclic voltammograms of the TTFV 3c exhibit
some modifications in the presence of Pb2+ (Figure 6A). As
shown above, in the absence of cation, TTFV 3c exhibits the
classical two-reversible-wave behavior. After progressive aliquot
addition of Pb2+, the first oxidation wave becomes broader and
the anodic peak potential Epa is shifted to more positive values
whereas the corresponding cathodic peak potential Epc is
negatively shifted. In fact, the modification mainly affects the
peak to peak separation (∆Ep ) Epa - Epc) which passes from
65 to 185 mV between curves a and d and not the midpoint
value that is characteristic of the redox potential of the couple
(E° ) (Epa + Epc)/2), which changes by around 10 mV. It is
noticeable that these modifications are observed for a low ratio
of Pb2+ to 3c. When the Pb2+ ratio is higher than 0.2 equiv, the
complex formed in situ becomes insoluble in dichloromethane
and a precipitate in the medium is observed. This suggests that
one Pb2+ is presumably ligated to more than one redox-active
TTFV, inducing the precipitation of the aggregate.19 This
unexpected feature unfortunately impedes the in-depth inves-
tigations of the process through either electrochemical or
Complexation studies have been performed on TTFVs 3a-c
using cyclic voltammetry by adding aliquots of test guest cations
solubilized in CH3CN. Several cations have been tested such
(18) (a) Le Derf, F.; Mazari, M.; Mercier, N.; Levillain, E.; Trippe´, G.;
Riou, A.; Richomme, P.; Becher, J.; Garin, J.; Orduna, J.; Gallego-Planas,
N.; Gorgues, A.; Salle, M. Chem.sEur. J. 2001, 7, 447. (b) Lyskawa, J.;
Le Derf, F.; Levillain, E.; Mazari, M.; Salle, M.; Dubois, L.; Viel, P.;
Bureau, C.; Palacin, S. J. Am. Chem. Soc. 2004, 126, 12194. (c) Lyskawa,
J.; LeDerf, F.; Levillain, E.; Mazari, M.; Salle, M. Eur. J. Org. Chem 2006,
10, 2322. (d) Delogu, G.; Fabbri, D.; Dettori, M. A.; Salle, M.; LeDerf, F.;
Blesa, M. J.; Allain, M. J. Org. Chem. 2006, 71, 9096.
1
solution H NMR studies.20
In other words, the effect of the addition is consistent with a
(19) Beer, P. D.; Danks, J. F.; Hesek, D. Polyhedron 1995, 14, 1327.
decrease of the electron-transfer rate constant ks, which varies
J. Org. Chem, Vol. 72, No. 13, 2007 4659

Massue et al.
FIGURE 4. Optimized geometries calculated at the B3LYP/6-31G* level of the neutral cyclic TTFV derivatives 3a (A), 3b (B), and 3c (C).
FIGURE 5. Optimized geometries calculated at the B3LYP/6-31G* level of the dicationic cyclic TTFV derivatives 3a2+ (A), 3b2+ (B), and 3c2+ (C).
by at least 1.5 orders of magnitude and has very little effect on
the thermodynamics (variation of E°). It is also noticeable that
the second wave remains almost unmodified, which indicates
that a possible passivation of the electrode surface is likely not
responsible for the kinetics decrease. Also directed to this end,
the peak to peak separation of the first transfer increases with
4660 J. Org. Chem., Vol. 72, No. 13, 2007

Crown Ether Vinylogous TetrathiafulValene Receptors
framework of the Marcus-Hush model,22,23 the reorganization
free energy of the electron transfer λelec is composed of a solvent
reorganization term, λ0,elec, and an intramolecular reorganization
term, λi,elec, λelec) λ0,elec + λi,elec. The electrochemical standard
rate constant ks, which characterizes the electron-transfer
kinetics, is then derived from the reorganization terms:
F(λ0,elec + λi,elec
4RT
)
ks ) Zel exp -
[
]
with Zel ) (RT/2πM)1/2 (M ) molar mass) and λ0,elec ) 3/a (a
) radius of the equivalent sphere, Å). λ0,elec characterizes the
solvent reorganization and should not be considerably modified
by the complexation. On the contrary, we can postulate that
when the lead cation is complexed by the crown ether ring in
the neutral TTFV 3c, this complexation brings some more
rigidity to the molecule that will mainly affect the molecular
movement and thus λi,elec. The origin of the effects is thus
different from that of the “classical cases reported in the
litterature”. Here the complexation is not visible because of some
electrostatic interactions between the TTFV and the cation which
affect the stability of the reduced and oxidized species and thus
the apparent E°, but we can propose that complexation induces
an increase of the rigidity and thus a higher activation energy
of the concerted electron transfer with the conformational
changes. Considering the estimation of the ks variation, the
change of the activation energy, due to the higher rigidity of
the molecular framework, can be estimated to be on the order
of 0.3 eV.
Conclusion
FIGURE 6. Voltammograms of TTFV 3c (1.4 × 10-3 M) in CH2Cl2
with 0.1 M n-Bu4NPF6 (A) at a 0.5 V/s scan rate in the presence of
increasing amounts of Pb2+(Pb(ClO4)2) [(a) without Pb(ClO4)2, (b) 0.05
equiv of Pb(ClO4)2, (c) 0.1 equiv of Pb(ClO4)2, (d) 0.15 equiv of Pb-
(ClO4)2] and (B) with 0.15 equiv of Pb(ClO4)2 at different scan rates.
A series of vinylogous TTFs bearing a crown ether binding
site of variable length have been synthesized. Both spectro-
electrochemistry and molecular modeling based on DFT support
the fact that a crown ether chain comprised of six oxygens is
necessary to obtain a stretch movement of the TTFV core upon
oxidation. Complexation studies have been undertaken on these
derivatives, and preliminary results suggest that the recognition
process involves both selectivity and sensitivity. Indeed, the
TTFV bearing the longest crown ether chain (composed of six
oxygens) is the only one in the series synthesized to provide an
optimal coordination environment for Pb2+ cations. Besides, the
low concentrations of Pb2+ involved in the complexation process
suggest a high sensitivity of these receptors for cations, which
might be due to the rigidification of the crown ether ring after
complexation. This rigidification appears as a decrease of the
apparent electron-transfer kinetics and has little effect on the
thermodynamics as the crown ether is far from the redox center.
Unfortunately, the lack of solubility of the metallic salts in
dichloromethane limits deeper investigations, as the complex
formed in situ precipitates out in the medium after addition of
0.2 equiv of Pb2+. Current investigations are in progress to
synthesize new crown ether based receptors which would exhibit
the scan rate from 0.2 to 2 V/s in the presence of 0.15 equiv of
Pb(ClO4)2 (Figure 6B). This behavior is clearly different from
those previously reported when complexation occurs. Generally,
the addition of a cation in a solution containing the electroactive
molecules bearing a crown ether moiety results in a modification
of the apparent oxidation potential, i.e., of the electron-transfer
thermodynamics due to the existence of fast equilibrium. To
explain our observations, we should recall some previous results
concerning the factors controlling the activation energy of the
electron transfer. For similarly hindered TTFVs, we found that
the molecular movement is concerted with the electron transfer,
which implies that the “extra” reorganization energy due to the
conformational changes is part of the total activation energy of
the electron transfer, and we have shown that most of the
molecular movement occurs during the first electron transfer.5
Experimentally, for 3c the presence of the molecular modifica-
tion is visible from the lower rate constant measured for the
first electron transfer than the value for the second one; ks )
0.035 cm‚s-1 and ks ) 0.12 cm‚s-1, respectively, for the first
and the second electron-transfer processes.21 Indeed, in the
(21) (a) Assuming the Buttler-Volmer law, a transfer coefficient of R
) 0.5, and a value for the diffusion coefficient D ) 10-5 cm‚s-1. (b)
Save´ant, J.-M. Elements of molecular and biomolecular electrochemistry:
an electrochemical approach to electron transfer chemistry; Wiley-
Interscience: Hoboken, NJ, 2006.
(20) At this lead concentration, a voltammogram with two distinct waves
similar to the first voltammogram obtained without lead but with this time
a lower current is observed. As the complex formed between TTFV 3c and
Pb2+ precipitates in the medium, the only electroactive species in solution
is some uncomplexed TTFV 3c.
(22) (a) Marcus, R. A. J. Chem. Phys. 1956, 24, 966. (b) Marcus, R. A.
J. Chem. Phys. 1956, 24, 979. (c) Hush, N. S. J. Chem. Phys. 1958, 28,
962. (d) Hush, N. S. Trans. Faraday Soc. 1961, 57, 557. (e) Marcus, R. A.
J. Chem. Phys. 1965, 43, 679.
(23) Kojima, H.; Bard, A. J. J. Am. Chem. Soc. 1975, 97, 6317.
J. Org. Chem, Vol. 72, No. 13, 2007 4661

Massue et al.
Data for compound 8b: yield 74%; Rf ) 0.38; 1H NMR (CDCl3,
300 MHz) δ 1.94 (s, 6H, CH3), 1.95 (s, 6H, CH3), 3.72 (m, 8H, CH2),
3.85 (m, 4H, CH2), 4.13 (m, 4H, CH2), 6.38 (s, 2H, CH), 6.91 (d,
4H, CH Ar) 7.18 (d, 4H, CH Ar); 13C NMR (CDCl3, 75 MHz) δ
13.3, 14.1, 67.9, 70.2, 71.1, 71.2, 121.0, 121.1, 111.8, 115.1, 128.1,
130.7, 131.5, 156.8; HRMS (m/z) calcd for C32H38O5S4 [M + Na]+
653.1500, found 653.1492. Anal. Calcd for C32H38O5S4‚0.75CH2-
Cl2: C, 56.64; H, 5.69. Found: C, 56.70; H, 5.77.
Data for compound 8c: yield 77%; Rf ) 0.30; 1H NMR (CDCl3,
300 MHz) δ 1.93 (s, 6H, CH3), 1.94 (s, 6H, CH3), 3.70 (m, 12H,
CH2), 3.84 (m, 4H, CH2), 4.12 (m, 4H, CH2), 6.36 (s, 2H, CH),
6.89 (d, 4H, CH Ar), 7.16 (d, 4H, CH Ar); 13C NMR (CDCl3, 75
MHz) δ 11.9, 12.6, 66.4, 68.7, 69.6, 69.7, 110.3, 113.6, 119.6,
119.7, 126.7, 129.2, 130.1, 155.3; HRMS (m/z) calcd for C34H42O6S4
[M + H] 675.1943, found [M + H]•+ 675.1934. Anal. Calcd for
C34H42O6S4‚0.33CH2Cl2: C, 58.84; H, 5.81. Found: C, 58.56; H,
5.68.
General Procedure for the Synthesis of Cyclic Vinylogous
TTFs 3a-c. To a solution of the bisdithiafulvene 8 (1 mmol, 586
mg for 8a, 630 mg for 8b, and 674 mg for 8c) in 40 mL of
dichloromethane under an inert atmosphere was added I2 (750 mg,
3 mmol), and the medium was heated to reflux for 8 h. To the
solution was added a large excess of Na2S2O4 (2 g) to reduce the
dicationic TTFV formed in the medium. The reaction mixture was
refluxed overnight and allowed to reach room temperature. After
filtration of the suspension, the filtrate was washed with water (2
× 50 mL) and dried over MgSO4, and the solvent was removed
under vacuum. The TTFVs 3a-c were purified by column
chromatography on silica gel using ethyl acetate as the eluent and
obtained as waxy compounds.
Data for compound 3a: yield 54%; 1H NMR (CDCl3, 300 MHz)
δ 1.94 (s, 12H, CH3), 3.60 (s, 4H, CH2), 3.75-3.79 (m, 4H, CH2),
4.11-4.19 (m, 4H, CH2), 6.71 (d, 4H, CH Ar), 7.14 (d, 4H, CH
Ar); 13C NMR (CDCl3, 75 MHz) δ 12.9, 13.7, 67.3, 69.8, 70.8,
112.1, 114.5, 115.9, 121.2, 122.0, 127.7, 130.4, 157.3; HRMS (m/
z) calcd for C30H32O4S4 584.1184, found 584.1163.
a better solubility in dichloromethane, especially when a cation
is inserted inside the complexing cavity, and would allow the
in-depth investigation of the process.
Experimental Section
Dithiafulvene 6. To a solution of dithiole phosphonate 5 (1 g,
3.73 mmol) in 80 mL of freshly distilled anhydrous THF was added
dropwise n-BuLi (2.57 mL, 4.1 mmol, of a 1.6 M solution in
hexane) at -78 °C under an inert atmosphere. After the resulting
solution was stirred for 20 min at -78 °C, a solution of
4-formylphenyl benzoate (4; 928 mg, 4.1 mmol) in 5 mL of THF
was added. The reaction mixture was then allowed to reach room
temperature and stirred for an additional 12 h. The solvent was
then removed under vacuo, and 60 mL of CH2Cl2 was added to
the residue. The organic phase was washed with water and dried
over MgSO4, and the solvent was evaporated. After chromatography
on silica gel using dichloromethane/n-pentane (1:1) as eluent, the
dithiafulvene 6 was obtained as a yellow powder (824 mg, 65%):
mp 164 °C; 1H NMR (CDCl3, 300 MHz) δ 2.01 (s, 6H, CH3), 6.48
(s, 1H, CH), 7.21-7.26 (m, 4H, CHAr), 7.51-7.68 (m, 3H, CHAr),
8.23-8.27 (m, 2H, CH Ar); 13C NMR (CDCl3, 75 MHz) δ11.8,
12.6 109.5, 119.9, 120.0, 120.6, 126.3, 127.4, 128.5, 129.1, 132.5,
133.4, 133.9, 146.9, 164.1 IR (KBr; ν, cm-1) 1732 (CdO); HRMS
(EI, m/z) calcd for C19H16O2S2 340.0591, found 340.0581. Anal.
Calcd for C19H16O2S2: C, 67.03; H, 4.74; S, 18.84. Found: C,
67.11; H, 4.74; S, 18.08.
Dithiafulvene 7. Cs2CO3 (1.24 g, 3,82 mmol) was added to a
stirred solution of dithiafulvene 6 (1 g, 2.94 mmol) in 40 mL of
dimethoxyethane. The reaction mixture was refluxed for 24 h, and
the solvent was removed under vacuum. The residue was dissolved
in 60 mL of CH2Cl2, washed with water (3 × 50 mL), and dried
over MgSO4. After removal of the solvents, column chromatography
of the crude product on silica gel with dichloromethane/n-pentane
(1:1) as the eluent afforded 7 as a beige powder (694 mg, 90%):
mp 139 °C; 1H NMR (CDCl3, 200 MHz) δ 1.98 (s, 6H, CH3), 5.24
(s, 1H, OH), 6.40 (s, 1H, CH) 6.86 (d, 2H, CHAr) 7.18 (d, 2H, CH
Ar); 13C NMR (CDCl3, 50 MHz) δ 14.08, 13.4, 111.8, 115.8, 128.4,
121.1, 130.0, 130.7, 131.6, 153.4; HRMS (EI, m/z) calcd for C12H12-
OS2 236.0329, found 236.0321. Anal. Calcd for C12H12OS2: C,
61.02; H, 5.08; S, 27.12. Found: C, 60.93; H, 5.17; S, 26.78.
General Procedure for the Synthesis of Bisdithiafulvenes 8a-
c. NaH (186 mg, 4.66 mmol) was added to a solution of
dithiafulvene 7 (1 g, 4.23 mmol) in 40 mL of distilled THF. The
reaction mixture was refluxed for 1 h, and the appropriate tosylate
was then added (1.9 mmol, 870 mg for 8a, 955 mg for 8b, and
1.04 g for 8c) in 5 mL of THF. The solution was refluxed for an
additional 24 h. After removal of the solvent, 60 mL of dichlo-
romethane was added. The organic phase was washed with water
(3 × 50 mL) and dried over MgSO4. After column chromatography
on silica gel using dichloromethane/n-pentane (1:1) as the eluent,
the bisdithiafulvenes were obtained as a viscous oil.
Data for compound 3b: yield 48%; 1H NMR (CDCl3, 300 MHz)
δ 1.86 (s, 12H, CH3) 3.25-3.42 (m, 4H, CH2) 3.65-4.05 (m, 8H,
CH2) 4.20-4.22 (m, 4H, CH2) 6.82 (d, 4H, CH Ar) 7.32 (d, 4H,
CH Ar); 13C NMR (CDCl3, 75 MHz) δ 12.3, 13.1, 66.8, 67.7, 68.7,
69.6, 113.5, 114.5, 119.5, 126.9, 128.8, 130.5, 132.8, 155.8; HRMS
(ESI, m/z) calcd for C32H36O5S4 628.1446, found 628.1487, and
calcd for C32H36O5NaS4 651.1343, found 651.1345.
Data for compound 3c: yield 52%; 1H NMR (CDCl3, 300 MHz)
δ 1.97 (s, 12H, CH3), 3.41 (s, 4H, CH2), 3.48 (m, 4H, CH2), 3.61
(m, 4H, CH2), 3.78 (m, 4H, CH2), 4.18 (m, 4H, CH2), 6.85 (d, 4H,
CH Ar), 7.40 (d, 4H, CH Ar); 13C NMR (CDCl3, 75 MHz) δ 13.3,
13.8, 67.8, 69.9, 70.4, 70.5, 70.8, 115.1, 120.9, 122.3, 123.2, 127.9,
131.0, 134.2, 156.9; HRMS (ESI, m/z) calcd for C34H40O6S4
672.1707, found 672.1717.
Data for compound 8a: yield 69%; Rf ) 0.42; 1H NMR (CDCl3,
300 MHz) δ 1.84 (s, 12H, CH3), 3.65 (s, 4H, CH2), 3.74-3.77 (m,
4H, CH2), 4.00-4.03(m, 4H, CH2), 6.26 (s, 2H, CH), 6.79 (d, 4H,
CH Ar), 7.07 (d, 4H, CH Ar); 13C NMR (CDCl3, 75 MHz) δ 11.9,
12.6, 66.4, 68.8, 69.8, 110.5, 113.6, 119.5, 119.7, 126.7, 129.6,
130.1, 155.3; HRMS (ESI, m/z) calcd for C30H34O4S4 [M + H]
Supporting Information Available: 1H and 13C NMR spectra
of 3a-c and 8a-c, HRMS spectrum of 3b, drawings of the
optimized geometries at the B3LYP/6-31G* level, values of the
energies in hartrees, and the Cartesian coordinates for the neutrals
and dications of the investigated TTFVs 3a-c. This material is
available free of charge via the Internet at http://pubs.acs.org.
587.1418, found [M
+
H]•+ 587.1387. Anal. Calcd for
C30H34O4S4: C, 61.40; H, 5.84. Found: C, 61.33; H, 6.08.
JO0701841
4662 J. Org. Chem., Vol. 72, No. 13, 2007