Aryl-substituted dithiafulvenes: Synthesis, electronic properties, and redox reactivity

Article abstract of DOI:10.1016/j.tetlet.2014.09.110

A series of aryl-substituted dithiafulvenes (DTFs) has been synthesized and characterized by single crystal X-ray diffraction analysis, UV-Vis absorption spectroscopy, and cyclic voltammetry. The studies indicate that the aryl-substituents not only affect

Full text of DOI:10.1016/j.tetlet.2014.09.110

Tetrahedron Letters 55 (2014) 6362–6366
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Aryl-substituted dithiafulvenes: synthesis, electronic properties, and
redox reactivity
⇑
Kathleen Woolridge, Luana C. Goncalves, Stephen Bouzan, Guang Chen, Yuming Zhao
Department of Chemistry, Memorial University, St. John’s, NL A1B 3X7, Canada
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of aryl-substituted dithiafulvenes (DTFs) has been synthesized and characterized by single crys-
tal X-ray diffraction analysis, UV–Vis absorption spectroscopy, and cyclic voltammetry. The studies indi-
cate that the aryl-substituents not only affect the structures and electronic properties of the DTF
derivatives, but also impose significant impact on their stability and reactivity when oxidized into radical
cations.
Received 3 September 2014
Revised 22 September 2014
Accepted 24 September 2014
Available online 2 October 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Dithiafulvene
Oxidative coupling
Substituent effect
Redox activity
Recently, a significant advancement has been made in the
research of tetrathiafulvalene vinylogues (TTFVs),1 a class of
appealing p-extended analogues of tetrathiafulvalene (TTF). In par-
to regenerate the desired neutral TTFV product (step V). In most of
the cases, the structures of aryl-TTFVs assume a non-planar
pseudo-cisoid conformation as a result of balanced steric interac-
ticular, the versatile redox activity and conformational switching
properties of TTFVs have provided access to a number of novel
functional molecular devices and materials, ranging from chemo-
sensors,2 redox-responsive ligands and receptors,3 supramolecular
hosts for fullerenes4 and carbon nanotubes,5 molecular rotors,6
macrocycles,7 and so on. The growing application of TTFVs has thus
driven much of our attention to their synthetic methodologies,
with the most commonly used one being oxidative dimerization
of the corresponding dithiafulvene (DTF) precursors.8 Aryl-substi-
tuted DTFs have been known to readily undergo such a reaction
proceeding via the mechanism8a,b illustrated in Scheme 1.
tions and p
-conjugation effects.1f,5,7,9
Upon examining this mechanism, one can reasonably identify
that steps II and III are key to the formation of TTFV, wherein the
Reactions of this type are generally deemed as straightforward
and reliable, as long as other functional groups present in the DTF
precursors bear sufficient tolerance to the oxidative conditions. As
shown in Scheme 1, the reaction begins with DTF precursor being
oxidized into a radical cation by an oxidant (step I). As the concen-
tration of the DTF radical cation builds up, a bimolecular reaction
follows (step II), in which two molecules of DTF radical are com-
bined via a new CAC bond formation process. The resulting dica-
tion intermediate then undergoes a double deprotonation (step
III) to yield the TTFV product, which would then be quickly oxi-
dized into TTFV dication under oxidative reaction conditions. Once
the dimerization is accomplished, a reductive workup is performed
⇑
Corresponding author. Tel.: +1 709 864 8747; fax: +1 709 864 3702.
E-mail address: yuming@mun.ca (Y. Zhao).
Scheme 1. General mechanism for oxidative dimerization of an aryl-substituted
DTF.
http://dx.doi.org/10.1016/j.tetlet.2014.09.110
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

K. Woolridge et al. / Tetrahedron Letters 55 (2014) 6362–6366
6363
aryl group should play an important role. For instance, in our
recent study on the oxidative dimerization of a series of bromophe-
nyl-DTFs,10 ortho-bromo substitution was found to hinder the
deprotonation step (step III) to such a significant extent that the
reaction actually deviates from the typical mechanism, resulting
in the formation of an unexpected bis-spiro product (vide infra).
Clearly, the substituent effect of aryl-DTFs on molecular properties
and reactivity is a topic that warrants further investigation, but it
has not yet been sufficiently addressed in the present literature.
In this Letter, we report the synthesis and characterization of a
selection of aryl-substituted DTFs, aiming at further understanding
how the nature of the aryl groups affects the structure and
electronic and electrochemical properties of DTFs.
Figure 1. ORETP plots of compounds (A) 3b, (B) 3d, and (C) 3g at 50% ellipsoid
probability.
As shown in Scheme 2, a series of phenyl-substituted DTFs 3a–f
was synthesized via a phosphite-promoted olefination reaction9a,11
between thione 1 with various benzaldehydes. In the same way, an
anthryl-substituted DTF 3g was prepared by coupling thione 1 with
anthracene-9-carbaldehyde. Compounds 3a, 3b, and 3g were
obtained as stable yellow colored solids with very good yields
(80–91%). Crude products of m-tolyl-DTF 3c and o-tolyl-DTF 3d
appeared to be relatively unstable when subjected to silica column
separation. As a result, their yields after chromatographic purifica-
tion became moderate to low. Compounds 3e is a purple needle-like
crystalline solid with reasonable stability. However, the presence of
the NO2 group induced significant side reactions, such as reduction
of NO2 by P(OMe)3,16 competing with the olefination reaction. This
problem could be somehow mitigated by using lowered reaction
temperature and shortened reaction time; nevertheless, the yield
of 3e was still kind of low (23%) even under optimized conditions.
Compound 3f was synthesized by reacting thione 1 with excess
terephthalaldehyde (ca. 4 equiv) in refluxing P(OMe)3. Such
conditions allowed mono-olefinated product 3f to be formed in a
reasonable yield of 51%. In addition to the phenyl and anthryl-
substituted DTFs, a triptycenyl-substituted DTF 3h was targeted in
our synthesis. The phosphite-promoted olefination failed to pro-
duce 3h due the significant steric crowdedness of triptycene. To
solve the problem, a more reactive Wittig–Horner olefination strat-
egy was resorted to, in which triptycene-9-carbaldehyde 5 was
reacted with the phosphonate ylide generated from 4 at low tem-
perature. This olefination method successfully led to compound
3h in a satisfactory yield of 46%.
The molecular structures of aryl-DTFs 3a–g were convincingly
elucidated by NMR, IR, and MS analyses (see Supplementary mate-
rial for details). Moreover, single-crystals of compounds 3b, 3d,
and 3g were successfully obtained by slow solvent evaporation
methods at 4 °C, and their solid-state structures were determined
by single-crystal X-ray diffraction analysis (Fig. 1). In the structure
of 3b, the DTF unit slightly deviates from the p-tolyl plane by 17.5°,
where in o-tolyl-DTF 3d the twist angle is considerably increased
to 44.6° as a result of the steric effect arising from ortho-methyl.
For compound 3g, the twist angle between DTF and anthracene
units becomes even much greater (71.0°), and the nearly perpen-
dicular orientation minimizes the disfavored allylic interactions
between DTF and hydrogens at the 1 and 8 positions of anthracene.
The electronic absorption properties of the aryl-DTFs 3a–h were
characterized by UV–Vis analysis and detailed absorption spectra
are given in Figure 2. For phenyl and tolyl-substituted DTFs 3a–
d, their spectra exhibit similar maximum absorption peaks at ca.
340 nm. For compounds 3e and 3f, the absorption peaks are sub-
stantially redshifted to 448 and 413 nm, respectively, as a result
of the strong electron-withdrawing effect exerted by the formyl
and nitro groups at the para position of the phenyl ring. In the
Figure 2. Normalized UV–Vis absorption spectra of compounds 3a–h measured in
Scheme 2. Synthesis of aryl-substituted DTFs 3a–h.
CH2Cl2 (ca. 10À4–10À5 M) at room temperature.

6364
K. Woolridge et al. / Tetrahedron Letters 55 (2014) 6362–6366
electron-withdrawing 4-formyl group in 3f does not reduce the
reactivity of the DTF radical as much as the nitro group. The cyclic
voltammogram of 9-anthryl-DTF 3g shows a prominent anodic
peak at +0.88 V, along with a weak shoulder anodic peak at
+0.99 V. The first oxidation peak is assigned to the oxidation of
the DTF unit, while the second one is paired with a cathodic peak
+0.91 V in the reverse scan. The origin of this redox wave pair is
likely due to the electron transfers at the anthracene unit.12 There
are no cathodic peak(s) to indicate the occurrence of DTF oxidative
dimerization. Rather, the CV data of 3g suggest its radical cation
tends to form some non-electroactive species and the process is
electrochemically irreversible. The voltammogram of 9-triptyce-
nyl-DTF 3h shows
a quasi-reversible redox wave pair (at
Epa = +1.00 V and Epc = +0.86 V), which is due to the single-electron
redox process taking place at the DTF unit. The bulky 9-triptycyl
group renders the radical cation of 3h highly unreactive toward
chemical reactions, allowing the unprecedented observation of
the quasi-reversible redox couple of DTF in the CV scans. Besides
the DTF redox couple, a second anodic peak is seen at +1.33 V in
the voltammogram of 3h, and its origin is ascribed to the oxidation
of the triptycenyl group.13
Figure 3. Cyclic voltammograms of aryl-DTFs 3a–b and 3d–h measured in CH2Cl2
at room temperature. Electrolyte: Bu4NBF4 (0.1 M); working electrode: glassy
carbon; counter electrode: Pt wire; reference electrode: Ag/AgCl (aq 3 M NaCl); scan
rate: 100 mV/s.
Overall, the CV characterizations reveal very different redox
reactivities of aryl-DTFs, which are strongly dependent on the
nature of the aryl group. A general trend can be summarized as
follows. (i) For phenyl, p-tolyl, and p-benzaldehyde substituted
DTFs (3a, 3b, and 3f), oxidative dimerization can readily happen
upon electrochemical oxidation. (ii) The radical cation of triptyce-
nyl-DTF 3h is so well stabilized by the crowded surrounding that
it cannot undergo any further chemical reaction once formed. (iii)
For p-nitrophenyl and anthryl-substituted DTFs 3e and 3g, the
radical cations seem to follow some chemical processes other
than the typical oxidative dimerization as outlined in Scheme 1.
Strong resonance effect can reasonably explain their unusual
behavior. Particularly in the case of 3g, two canonical forms can
be drawn for its radical cation as shown in Figure 4. The reso-
nance structure in which the radical is located at the 10-position
of anthracene is actually the more significant contributor accord-
ing to Clar’s rule,14 since it manifests two aromatic sextets. Den-
sity functional theory (DFT) calculations15 also concur well with
the classical model, showing the high spin density region being
concentrated at the 10-position rather than the vinylidene car-
bon. Such a delocalized feature disfavors the general DTF dimer-
ization reactivity and hence accounts for the irreversible redox
patterns in the cyclic voltammogram of 3g.
spectrum of anthryl-substituted DTF 3g, a low-energy absorption
shoulder is observed at 415 nm, while a series of bands appear in
the range of 330–390 nm characteristic of the vibronic progression
of anthracene. The spectrum of triptycenyl-DTF 3h shows an
absorption shoulder at 327 nm along with two bands at 296 and
281 nm. The fact that these bands are significantly blueshifted rel-
ative to the other aryl-DTFs can be accounted for by the lack of
direct p-conjugation between the DTF and triptycene units in 3h.
The electrochemical properties of aryl-DTFs 3a–h were investi-
gated by cyclic voltammetry (CV). Figure 3 lists the cyclic voltam-
mograms of all the compounds except 3c due to its poor stability
under the CV experimental conditions. Phenyl and p-tolyl substi-
tuted DTFs 3a and 3b show very similar CV profiles, in which an
anodic peak appears at ca. +1.0 to +1.1 V due to the oxidation of
DTF into a radical cation by single electron transfer.7–9 After oxida-
tion, the DTF radical can undergo a dimerization reaction on the
electrode surface, yielding TTFV dication following the mechanism
described in Scheme 1. As a result, in the reverse scan a cathodic
peak emerges in the range of +0.30–+0.35 V, which can be assigned
to the two-electron reduction of the TTFV dication.1,7–9 Surpris-
ingly, the cyclic voltammogram of o-tolyl substituted DTF 3d
exhibits very different electrochemical behavior than 3a and 3b.
Two anodic peaks are clearly seen at +0.75 V and +0.97 V, which
can be attributed to the oxidation processes at the DTF unit. Spe-
cific assignments for the two anodic peaks cannot be made at this
moment and still await further study. However, a tentatively ratio-
nalization is proposed that 3d may adopt two possible conforma-
tions in solution, where the o-methyl assumes either a cis or
trans-like orientation with respect to the DTF group. In the reverse
scan of 3d, a major cathodic peak emerges at +0.08 V, with a very
weak cathodic peak still discernible at ca. +0.37 V. The CV patterns
indicate that compound 3d does not dimerize to form TTFV prod-
uct at a significant degree during the CV scans.
Of great interest to us is the observation that the electrochem-
ical properties of o-tolyl-DTF 3d appear to be very different from
those of its isomer, p-tolyl-DTF 3b. Previously, we have disclosed
a unique ortho-bromo substitution effect on the redox reactivity
of aryl-DTF in examining a series of bromophenyl-substituted
DTFs.10 As shown in Scheme 3, o-bromophenyl-DTF 3i when sub-
jected to chemical oxidation using iodine as oxidant formed a
bis-spiro product 6 in 50% isolated yield, while the typical TTFV
product was only found in a trace amount. It is believed that the
For p-nitrophenyl substituted DTF 3e, an anodic peak is
observed at +0.95 V, while two cathodic peaks are noticeable at
+0.59 V and +0.34 V but with very weak current intensity. The
results indicate that compound 3e does not undergo efficient
dimerization upon electrochemical oxidation. The lack of reactivity
toward dimerization can be ascribed to the 4-nitro group that sta-
bilizes the DTF radical through a large resonance effect. Compound
3f gives an anodic peak at +0.82 V and a cathodic peak at +0.55 V in
its cyclic voltammogram, which is clear indicative of electrochem-
ically induced dimerization. Obviously, the relatively weak
Figure 4. Resonance structures of the radical cation of anthryl-DTF 3g and its spin
density map calculated at the
xB97XD/6-311+G(d,p) level of theory (blue color
denotes high spin density region).

K. Woolridge et al. / Tetrahedron Letters 55 (2014) 6362–6366
6365
MeS
SMe
MeS
MeS
SMe
SMe
except steric hindrance. So, examination of the oxidative reactivity
of 3i should tell whether the reaction pathways are subject to the
influence of ortho steric effect. In our experiments, oxidative
dimerization of 3d in the presence of iodine was performed
(Scheme 3). The reaction yielded a mixture of products that could
not be separated by silica chromatography due to their nearly
identical Rf values. 1H NMR analysis (Fig. 5) shows that the mixture
contains two compounds. The major component is identified as
bis-spiro compound 8 mainly based on the presence of tetrahydro-
thiophene protons at 4.61 ppm (labeled as Ha in Fig. 5A). The minor
component shows NMR patterns in agreement with TTFV 7, which
is the typical oxidative dimerization product. MS analysis also
offers support for the two structures. Comparison of the integra-
tion values for the SMe and o-tolyl methyl protons reveals that
compounds 7 and 8 are formed at a molar ratio of 1.0:3.4 (see
Fig. 5B). The results indicate that ortho steric effect can signifi-
cantly slow down the deprotonation step in the DTF oxidative
dimerization reaction, and this fact must be taken into serious con-
sideration in planning the synthesis of TTFV derivatives using
ortho-substituted phenyl-DTFs as precursors.
S
S
S
S
S
S
S
(i) I2, CH2Cl2
(ii) Na2S2O3
Br
H
Br
Br
3i
6
50%
MeS
SMe
S
MeS
SMe
MeS
MeS
SMe
SMe
S
S
MeS
SMe
S
S
S
S
S
S
S
S
(i) I2, CH2Cl2
(ii) Na2S2O3
Me
+
Me
H
Me
Me
Me
3d
8
72%
7
21%
O
O
SMe
S
S
S
O
SMe
SMe
MeS
MeS
SMe
SMe
S
MeS
S
S
O
S
S
O
O
MeS
MeS
S
S
S
S
H
S
Ar
- SO3
S
S
Ar
Ar
Ar
S
H
Ar
Ar
H
H
S
SMe
MeS
Scheme 3. Oxidative dimerization of DTFs 3i and 3d, and proposed mechanism for
In summary, we have synthesized and characterized a series of
aryl-substituted DTFs to gain fundamental understanding on the
correlation between the nature of aryl substituent with their struc-
tural, redox, and chemical properties. It should be pointed out that
although oxidative dimerization of aryl-DTFs offers a straightfor-
ward synthetic approach to various TTFV-containing molecular
and macromolecular systems, this reaction is not universally appli-
cable. Substituent effect plays an important role in dictating the
reactivity of aryl-DTFs. In particular, resonance and ortho-substitu-
ent effects can substantially alter the stability and reactivity of DTF
radical cations. Our findings in this study provide useful guidance
to rational design and synthesis of DTF and TTFV-related molecular
materials.
the formation of bis-spiro products.
Acknowledgments
The authors thank NSERC Canada, CFI Canada, and RDC NL for
the financial support. Dr. Hilary A. Jenkins at McMaster University
is acknowledged for assistance in single crystal X-ray structure
analysis.
Supplementary data
Supplementary data (synthetic procedures and spectroscopic
characterizations of compounds 3a–h, as well as crystallographic
data of compounds 3b (CCDC 1020638), 3d (CCDC 1020637), and
3g (CCDC 991661)) associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
09.110.
References and notes
Figure 5. Partial 1H NMR (300 MHz, CD2Cl2) spectra of the mixture products
resulting from the oxidative dimerization of o-tolyl-DTF 3d. Note that the peak at
5.24 ppm is due to residual CH2Cl2 and the HAr signal is an overlap of the aromatic
protons of compounds 7 and 8.
1. (a) Roncali, J. J. Mater. Chem. 1997, 7, 2307–2321; (b) Yamashita, Y.; Tomura,
M.; Zaman, M. B. Chem. Commun. 1998, 1657–1658; (c) Moore, A. J.; Tanner, B.
K.; Whitehead, R.; Clegg, W.; Gerson, F.; Lamprecht, A.; Pfenninger, S. Chem.
Mater. 1996, 8, 1182–1188; (d) Guerro, M.; Lorcy, D. Tetrahedron Lett. 2005, 46,
5499–5502; (e) Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev. 2004, 104,
4891–4945; (f) Zhao, Y.; Chen, G.; Mulla, K.; Mahmud, I.; Liang, S.; Dongare, P.;
Thompson, D. W.; Dawe, L. N.; Bouzan, S. Pure Appl. Chem. 2012, 84, 1005–1025.
2. (a) Mulla, K.; Zhao, Y. Tetrahedron Lett. 2014, 55, 382–386; (b) Lorcy, D.; Guerro,
M.; Bergamini, J.-F.; Hapiot, P. J. Phys. Chem. B 2013, 117, 5188–5194; (c) Mulla,
K.; Dongare, P.; Thompson, D. W.; Zhao, Y. Org. Biomol. Chem. 2012, 10, 2542–
2544.
3. (a) Gontier, E.; Bellec, N.; Brignou, P.; Gohier, A.; Guerro, M.; Roisnel, T.; Lorcy,
D. Org. Lett. 2010, 12, 2386–2389; (b) Guerro, M.; Pham, N. H.; Massue, J.;
Bellec, N.; Lorcy, D. Tetrahedron 2008, 64, 5285–5290; (c) Massue, J.; Bellec, N.;
Guerro, M.; Bergamini, J.-F.; Hapiot, P.; Lorcy, D. J. Org. Chem. 2007, 72, 4655–
4662.
ortho-bromo group considerably slows down the deprotonation
process (step III, Scheme 1) through intramolecular hydrogen
bonding interaction with the vinylidene hydrogens. As such the
intermediate [TTFVÁ2H+] would remain stable until at the workup
stage to react with Na2S2O3 to give bis-spiro product 6.
The unique reactivity of 3i then led us to conceive that similar
reaction would occur when o-tolyl-DTF 3d was subjected to oxida-
tion. Unlike the case of 3i, however, the methyl group of 3d cannot
impose any significant effects (e.g., induction, hydrogen bonding)
4. Mulla, K.; Shaik, H.; Thompson, D. W.; Zhao, Y. Org. Lett. 2013, 15, 4532–4535.

6366
K. Woolridge et al. / Tetrahedron Letters 55 (2014) 6362–6366
5. (a) Liang, S.; Zhao, Y.; Adronov, A. J. Am. Chem. Soc. 2014, 136, 970–977; (b)
Liang, S.; Chen, G.; Zhao, Y. J. J. Mater. Chem. C 2013, 1, 5477–5490; (c) Liang, S.;
Chen, G.; Peddle, J.; Zhao, Y. Chem. Commun. 2012, 3100–3102.
6. Chen, G.; Zhao, Y. Org. Lett. 2014, 16, 668–671.
7. (a) Chen, G.; Mahmud, I.; Dawe, L. N.; Daniels, L. M.; Zhao, Y. J. Org. Chem. 2011,
76, 2701–2715; (b) Chen, G.; Mahmud, I.; Dawe, L.; Zhao, Y. Org. Lett. 2010, 12,
704–707.
8. (a) Lorcy, D.; Carlier, R.; Robert, A.; Tallec, A.; Le Magueres, P.; Ouahab, L. J. Org.
Chem. 1995, 60, 2443–2447; (b) Hapiot, P.; Lorcy, D.; Tallec, A.; Carlier, R.;
Robert, A. J. Phys. Chem. 1996, 100, 14823–14827; (c) Carlier, R.; Hapiot, P.;
Lorcy, D.; Robert, A.; Tallec, A. Electrochim. Acta 2001, 46, 3269–3277; (d)
Benahmed-Gasmi, A.; Frère, P.; Roncali, J.; Elandaloussi, E.; Orduna, J.; Garín, J.;
Jubault, M.; Gorgues, A. Tetrahedron Lett. 1995, 36, 2983–2985; (e) Naka, K.;
Inagi, S.; Murachi, Y.; Chujo, Y. J. Polym. Sci., Part A: Polym. Chem. 2006, 44,
2027–2033; (f) Inagi, S.; Naka, K.; Chujo, Y. J. Mater. Chem. 2007, 17, 4122–
4135.
Tallec, A. J. Phys. Chem. A 2000, 104, 9750–9759; (c) Lorcy, D.; Le Maguerès, P.;
Rimbaud, C.; Ouahab, L.; Delhaes, P.; Carlier, R.; Tallec, A.; Robert, A. Synth. Met.
1997, 86, 1831–1832; (d) Yamashita, Y.; Tomura, M.; Zaman, M. B.; Imaeda, K.
Chem. Commun. 1998, 1657–1658; (e) Frère, P.; Skabara, P. J. Chem. Soc. Rev.
2005, 34, 69–98.
10. Bouzan, S.; Dawe, L. N.; Zhao, Y. Tetrahedron Lett. 2013, 54, 4666–4669.
11. Christensen, C. A.; Batsanov, A. S.; Bryce, M. R. J. Org. Chem. 2007, 72, 1301–
1308.
12. Majeski, E. J.; Stuart, J. D.; Ohnesorge, W. E. J. Am. Chem. Soc. 1968, 90, 633–636.
13. VanVeller, B.; Schipper, D. J.; Swager, T. M. J. Am. Chem. Soc. 2012, 134, 7282–
7285.
14. (a) Clar, E. Polycyclic Hydrocarbons; Academic Press: London, 1964; (b) Clar, E.
The Aromatic Sextet; Wiley: New York, 1972; (c) Portella, G.; Poater, J.; Solà, M.
J. Phys. Org. Chem. 2005, 18, 785–791.
15. DTF calculations were done using the Gaussian 09 software package.
16. Cadogan, J. I. G.; Mackie, R. K.; Todd, M. J. Chem. Commun. 1996, 491.
9. (a) Bouzan, S.; Chen, G.; Mulla, K.; Dawe, L. N.; Zhao, Y. Org. Biomol. Chem. 2012,
10, 7673–7676; (b) Bellec, N.; Boubekeur, K.; Carlier, R.; Hapiot, P.; Lorcy, D.;