A straightforward access to mono- and bis(pyrrolo)tetrathiafulvalenes

Article abstract of DOI:10.1055/s-2006-942520

An alternative efficient synthetic procedure to mono-and bis(pyrrolo)tetrathiafulvalenes is proposed starting from 4,4-diethoxybut-2- ynal. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942520

SHORT PAPER
2815
A Straightforward Access to Mono- and Bis(pyrrolo)tetrathiafulvalenes
A
S
traight
e
forwardAc
a
c
esstoMo
n
no- andBis(p
-
yrrolo)t
Y
e
trathiafulvalenesves Balandier, Ahmed Belyasmine, Marc Sallé*
Laboratoire de Chimie et Ingénierie Moléculaire des Matériaux d’Angers (CIMMA), Groupe Synthèse Organique et Matériaux
Fonctionnels (SOMaF), UMR CNRS 6200, Université d’Angers, 2 Bd Lavoisier, 49045 Angers, France
Fax +33(2)41735405; E-mail: marc.salle@univ-angers.fr
Received 20 April 2006; revised 19 May 2006
trans isomerization encountered with disubstituted deriv-
atives of the parent TTF. This characteristic puts com-
pound 1a, as well as the mono(pyrrolo) analogue 1b,
among the most popular TTF derivatives studied in the
last few years, in particular for supramolecular assemblies
such as bistable rotaxanes,2c,5 redox-responsive
ligands,2c,6 or as p-extended donors.7
Abstract: An alternative efficient synthetic procedure to mono-
and bis(pyrrolo)tetrathiafulvalenes is proposed starting from 4,4-di-
ethoxybut-2-ynal.
Key words: acetals, ring closure, pyrroles, tetrathiafulvalene, 4,4-
diethoxybut-2-ynal
The synthetic route developed by the Danish group to
reach pyrrolo derivatives 1a and 1b is shown in
Scheme 1.2c,4 The key [c]-fused 1,3-dithiolepyrrole inter-
mediate 7 was obtained in six steps from dimethylacety-
lenedicarboxylate and ethylenetrithiocarbonate, in an
overall yield of 30% in about one week.
Tetrathiafulvalene (TTF) derivatives have been exten-
sively used as key precursors for molecular materials pre-
senting a rich variety of solid state physical properties.1
Recently, TTF has appeared as a powerful building block
in various molecular or supramolecular architectures, in
particular by taking advantage of its remarkable electronic
properties (TTF derivatives are easily and reversibly oxi-
dized in two successive one-electron steps).1,2 In this con-
text, much has been done in order to introduce diverse
functionalities onto the periphery of the TTF skeleton.3
An important step in the design of such TTF derivatives,
was achieved by Becher and co-workers, who
described2c,4 an access to bis(pyrrolo)tetrathiafulvalene
1a. This electroactive derivative exhibits similar electron-
ic properties to TTF, but the corresponding N,N¢-disubsti-
tuted analogues avoid the well-known problems of cis–
We present here an alternative and straightforward syn-
thetic strategy to reach the key intermediate 7 (Scheme 2).
As for the above-mentioned approach, the first step in our
strategy involves a cycloaddition between ethylenetrithio-
carbonate and an electrophilic alkyne. In our case, the lat-
ter corresponds to the commercially available 4,4-
diethoxybut-2-ynal (2).8,9 Our motivation in using this
alkyne was based on the idea that the aldehyde oxidation
level could be kept throughout the synthetic route, thus
avoiding an oxidation step subsequent to the ring closure.
NaBH4, LiBr
THF, MeOH
–10 °C, 2 h
CO2Me
CO2Me
HOH2C
HOH2C
BrH2C
BrH2C
MeO2C
MeO2C
PBr3
THF, r.t., 16 h
S
S
S
S
S
S
S
S
toluene, reflux, 8 h
68%
S
S
S
S
85%
91%
NaHNTs (2equiv)
DMF, 80 °C, 2 h
61%
Hg(OAc)2
CHCl3–AcOH, r.t., 4 h
P(OEt)3
120 °C, 5 h
DDQ
PhCl, reflux, 2 h
S
S
S
S
S
S
S
S
TsN
S
TsN
NTs
TsN
O
O
NTs
99%
84%
95%
S
S
7
NaOMe
THF–MeOH, reflux, 30 min
99%
1) 4,5-dimethylsulfanyl-1,3-dithiole-2-thione, P(OMe)3
2) NaOMe
THF–MeOH, reflux, 30 min
SCH3
S
S
S
S
S
S
HN
NH
HN
S
S
SCH3
1a
1b
Scheme 1 Access to mono- and bis(pyrrolo)tetrathiafulvalene derivatives according to references 2c and 4.
SYNTHESIS 2006, No. 17, pp 2815–2817
x
x.
x
x
.
2
0
0
6
Advanced online publication: 25.07.2006
DOI: 10.1055/s-2006-942520; Art ID: Z07706SS
© Georg Thieme Verlag Stuttgart · New York

2816
J.-Y. Balandier et al.
SHORT PAPER
O
O
NHTs
S
CH(OEt)2
TsNH2, MS
PhMe, reflux, 4 h
S
S
NaBH4
EtOH, THF, 15 min
S
S
H
O
PhMe, reflux, 12 h
N
S
S
S
S
S
S
H
(EtO)2HC
S
CHO
(EtO)2HC
S
5 (75% from 3)
3 (70%)
4
(EtO)2HC
2
Amberlyst A15, 5 min
NHTs
Hg(OAc)2
CH2Cl2–AcOH,
r.t., 15 min
H
TsN
HO
S
S
S
S
S
S
S
TsN
O
TsN
S
S
1a,b
H
S
S
C
O
7 (98%)
H+
6 (99%)
Scheme 2 New route to mono- and bis(pyrrolo)tetrathiafulvalene derivatives
The resulting 1,3-dithiol-2-thione derivative 310 was re-
acted with tosylamine in refluxing toluene in the presence
of molecular sieves. Filtration and evaporation afforded
the N-tosyl imine 4 which was directly engaged in the sub-
sequent reduction step.11 Treatment of 4 with sodium
borohydride afforded the corresponding N-tosyl amino
derivative 5 in a global yield of 75% for the two steps
(from 3), after purification of compound 5 by silica gel
chromatography.12 The key step in our strategy was per-
formed by treating compound 5 with Amberlyst® 15 in
dichloromethane at room temperature, which allowed the
direct and quantitative conversion to the N-tosyl protected
pyrrole 6. Three successive elementary reactions are in-
N-{[5-(Diethoxymethyl)-2-thioxo-1,3-dithiol-4-yl]}methyl-4-
methylbenzenesulfonamide (5)
Thione 3 (4.2 g, 15.9 mmol) and p-toluenesulfonamide (13.7 g, 5
equiv) were dissolved in anhyd toluene (450 mL) in the presence of
molecular sieves (4 Å). The reaction mixture was refluxed under ni-
trogen for 4 h, [3 was completely consumed, monitored by TLC,
CH2Cl2–cyclohexane (6:4), 1% Et3N]. The molecular sieves were
discarded after filtration and the toluene was evaporated in vacuo to
afford thione 4, which was used directly in the following step. The
corresponding brown oil was dissolved in anhyd MeOH (300 mL)
under nitrogen and reacted with NaBH4 (643 mg, 17 mmol) at r.t.
for 15 min. The solvent was removed in vacuo, the resulting mate-
rial was dissolved in CH2Cl2 (300 mL), and washed with H2O (3 ×
400 mL). The organic phase was dried over MgSO4 and evaporated
to dryness. The resulting oil was then chromatographed (CH2Cl2,
volved in this step: acetal deprotection, ring closure, and 1% Et3N) to afford the target amine 5 as a dark yellow oil; yield:
4.99 g (11.9 mmol; 75% from 3); Rf 0.32 (CH2Cl2, 4% Et3N).
dehydration. The intermediates could be detected by TLC,
but were not isolated considering the very short reaction
time (compound 6 was formed within ten minutes at room
temperature in dichloromethane). Key compound 6 was
then converted into the keto analogue 7 through transchal-
cogenation [Hg(OAc)2, CH2Cl2–AcOH)] in quantitative
yield. Conversion to bis(pyrrolo[3,4-d])tetrathiafulvalene
1H NMR (acetone-d6): d = 7.74 (d, J = 7.9 Hz, 2 H, Ar), 7.41 (d,
J = 7.9 Hz, 2 H, Ar), 7.21 (m, 1 H, NH), 5.64 [s, 1 H, CH(OEt)2],
4.26 (m, 2 H, CH2N), 3.63 (m, 4 H, OCH2), 2.41 (s, 3 H, ArCH3),
1.17 (t, J = 7.1 Hz, 6 H, CH3).
13C NMR (acetone-d6): d = 212.3, 143.6, 141.0, 140.7, 137.7, 129.7,
126.9, 96.3, 61.6, 39.8, 20.5, 14.3.
1 was then carried out in two steps, as described,2c,4 by HRMS (EI): m/z calcd for C16H21NO4S4: 419.03535; found:
419.0345.
P(OEt)3-mediated self-coupling to 8, and subsequent re-
moval of the tosyl protecting group with sodium meth-
oxide.
Anal. Calcd for C16H21NO4S4: C, 45.80; N, 3.34; O, 15.25. Found:
C, 45.58; N, 3.26; O, 15.49.
In conclusion, a quick and efficient synthesis of N-tosyl-
(1,3)-dithiolo[4,5-c]pyrrol-2-one (7), the key intermediate
for the synthesis of mono- and bispyrrolo(TTF) deriva-
tives 1a and 1b, is proposed. Compound 7 could be ob-
tained in less than three days, in a global yield of 51%,
starting from commercially available alkyne 2 and ethyl-
enetrithiocarbonate.
5-Tosyl-5H-[1,3]dithiolo[4,5-c]pyrrole-2-thione (6)
Amine 5 (4.99 g, 11.9 mmol) was dissolved in CH2Cl2 (400 mL) un-
der nitrogen and Amberlyst® 15 ion-exchange resin (dry, 15 g) was
added. The mixture was stirred for 5 min (the reaction was moni-
tored by TLC, CH2Cl2), and then the resin was filtered off. The fil-
trate was concentrated in vacuo and chromatographed (CH2Cl2–
cyclohexane, 6:4). Evaporation of the solvent afforded thione 6 as a
deep yellow powder; yield: 3.85 g (11.8 mmol; 99%); Rf 0.49
(CH2Cl2–cyclohexane, 6:4); mp 217–218 °C (Lit.4 215.0–
215.5 °C).
1H NMR (DMSO-d6): d = 7.89 (d, J = 8.35 Hz, 2 H, Ar), 7.64 (s, 2
H, Hpyrrole), 7.48 (d, J = 8.3 Hz, 2 H, Ar), 2.39 (s, 3 H, ArCH3).
13C NMR (DMSO-d6): d = 221.4, 146.9, 134.5, 131.1, 128.3, 127.5,
112.8, 21.6.
1H NMR (500.13 MHz)and 13C NMR (125.75 MHz) spectra were
recorded on a Bruker Avance DRX 500 spectrometer. Chemical
shifts are reported relative to TMS as internal standard. Mass spec-
tra were carried out on a Varian MAT 311 spectrometer (CRMPO,
Rennes). Melting points were determined on a Büchi 510 apparatus.
Amberlyst® 15 ion-exchange resin(dry) was purchased from Acros
Organics. Chromatography was performed on silica gel.
HRMS (EI): m/z calcd for C12H9NO2S4: 326.95162; found:
326.9512.
Synthesis 2006, No. 17, 2815–2817 © Thieme Stuttgart · New York

SHORT PAPER
A Straightforward Access to Mono- and Bis(pyrrolo)tetrathiafulvalenes
2817
5-Tosyl-5H-[1,3]dithiolo[4,5-c]pyrrol-2-one (7)
(4) (a) Jeppesen, J. O.; Takimiya, K.; Jensen, F.; Becher, J. Org.
Lett. 1999, 1, 1291. (b) Jeppesen, J. O.; Takimiya, K.;
Jensen, F.; Brimert, T.; Nielsen, K.; Thorup, N.; Becher, J. J.
Org. Chem. 2000, 65, 5794.
(5) For very recent examples, see for instance: (a) Nygaard, S.;
Laursen, B. W.; Flood, A. H.; Hansen, C. N.; Jeppesen, J. O.;
Stoddart, J. F. Chem. Commun. 2006, 144. (b) Jeppesen, J.
O.; Nygaard, S.; Vignon, S. A.; Stoddart, J. F. Eur. J. Org.
Chem. 2005, 196. (c) Choi, J. W.; Flood, A. H.; Steuerman,
D. W.; Nygaard, S.; Braunschweig, A. B.; Moonen, N. N. P.;
Laursen, B. W.; Luo, Y.; DeIonno, E.; Peters, A. J.;
Jeppesen, J. O.; Xu, K.; Stoddart, J. F.; Heath, J. R. Chem.
Eur. J. 2006, 12, 261.
Thione 6 (1.15 g, 3.52 mmol) was dissolved in a solution of CH2Cl2
(250 mL) and glacial AcOH (20 mL). Hg(OAc)2 (2.24 g, 7.03
mmol) was then introduced in one portion and the reaction mixture
was stirred for 10 min, causing the yellow solution to turn white.13
The mercuric salts were removed by filtration through celite, which
was washed with CH2Cl2 (3 × 50 mL). The filtrate was then treated
with a sat. solution of NaHCO3 (3 × 350 mL), H2O (200 mL), and
finally dried over MgSO4. The solvent was evaporated in vacuo, and
the resulting material was purified through a short column of silica
gel (CH2Cl2–cyclohexane, 6:4) to afford compound 7 as white nee-
dles after evaporation of the solvent; yield: 1.07 g (98%); Rf 0.47;
mp 179–180 °C (Lit.4a 178.5–179 °C).
(6) (a) Trippé, G.; Levillain, E.; Le Derf, F.; Gorgues, A.; Sallé,
M.; Jeppesen, J. O.; Nielsen, K.; Becher, J. Org. Lett. 2002,
4, 2461. (b) Nielsen, K. A.; Cho, W. S.; Jeppesen, J. O.;
Lynch, V. M.; Becher, J.; Sessler, J. L. J. Am. Chem. Soc.
2004, 126, 16296.
(7) (a) Yin, B.; Yang, Y.; Cong, Z.; Imafuku, K. Heterocycles
2004, 63, 1577. (b) Li, H.; Lambert, C. Chem. Eur. J. 2006,
12, 1144.
Acknowledgment
MENRT is gratefully acknowledged for a PhD grant to J.Y.B. We
also wish to thank the Institut Universitaire de France (IUF) for fi-
nancial support to M.S.
(8) Gorgues, A.; Stephan, D.; Belyasmine, A.; Khanous, A.; Le
Coq, A. Tetrahedron 1990, 46, 2817.
(9) Compound 2 is commercially available from Acros
Organics.
References
(1) Molecular Conductors (thematic issue), Chem. Rev; Batail,
P., Ed.; 2004, 104, issue 11.
(2) (a) Segura, J. L.; Martín, N. Angew. Chem. Int. Ed. 2001, 40,
1372. (b) Brøndstedt Nielsen, M.; Lomholt, C.; Becher, J.
Chem. Soc. Rev. 2000, 29, 143. (c) Jeppesen, J. O.; Becher,
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(10) Sallé, M.; Gorgues, A.; Jubault, M.; Boubekeur, K.; Batail,
P. Tetrahedron 1992, 48, 3081.
(11) Attempts to purify imine 4 by silica gel or alumina
chromatography invariably led to a partial reverse reaction
to the starting products.
(12) Alternatively, compound 5 may be directly engaged in the
following step without being chromatographed (no
noticeable loss in the yield of 6). In fact, the purification of
5 by silica gel chromatography is accompanied by formation
of compound 6.
(3) (a) Bendikov, M.; Wudl, F.; Perepichka, D. F. Chem. Rev.
2004, 104, 4891. (b) Yamada, J. I.; Akutsu, H.; Nishikawa,
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Hasegawa, M.; Miyake, Y. Chem. Rev. 2004, 104, 5085.
(d) Jeppesen, J. O.; Brøndsted Nielsen, M.; Becher, J. Chem.
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(13) We observed lower yields with longer times.
Synthesis 2006, No. 17, 2815–2817 © Thieme Stuttgart · New York