Pyrrolo annelated tetrathiafulvalenes: The parent systems

Article abstract of DOI:10.1021/ol9902428

The synthesis of the parent bis(pyrrolo[3,4-d])tetrathiafulvalene via a nonclassical and simple pyrrole synthesis is reported, together with a detailed study of the fundamental redox behavior of some of this class of heterocycles.

Full text of DOI:10.1021/ol9902428

ORGANIC
LETTERS
1999
Vol. 1, No. 8
1291-1294
Pyrrolo Annelated Tetrathiafulvalenes:
The Parent Systems
Jan Oskar Jeppesen, Kazuo Takimiya,† Frank Jensen, and Jan Becher*
Department of Chemistry, Odense UniVersity (UniVersity of Southern Denmark),
CampusVej 55, DK-5230, Odense M, Denmark
jbe@chem.sdu.dk
Received August 23, 1999
ABSTRACT
The synthesis of the parent bis(pyrrolo[3,4-d])tetrathiafulvalene via a nonclassical and simple pyrrole synthesis is reported, together with a
detailed study of the fundamental redox behavior of some of this class of heterocycles.
The chemistry of tetrathiafulvalene (TTF, 1) and its deriva-
tives has been intensively studied since the discovery of the
first metallic charge-transfer TTF complex.1 The TTF
skeleton has been extensively modified over the past two
decades to favor enhanced dimensionality in the related
charge-transfer salts.2 Among those modifications, the het-
erocyclic-fused TTF donor, bis(ethylenedithio)tetrathiaful-
valene (BEDT-TTF, 2) has given rise to more supercon-
ducting salts than any other TTF derivative, with κ-(BEDT-
TTF)2-Cu[N(CN)2]Br as the current record holder.3
Many other donor molecules have been synthesized in
which the TTF core is annelated to benzenoid (3),4 furan,5
thiophene,6 or selenophene7 units (4) (Figure 1); all of these
† Current address: Department of Applied Chemistry, Faculty of
Engineering, Hiroshima University, Kagamiyama 1-4-1, Higashi-Hiroshima
739-8527, Japan.
Figure 1.
(1) Ferraris, J. P.; Cowan, D. O.; Walatka, V.; Perlstein, J. H. J. Am.
Chem. Soc. 1973, 95, 948-949.
(2) (a) Otsubo, T.; Aso, Y.; Takimiya, K. AdV. Mater. 1996, 8, 203-
211. (b) Bryce, M. R. J. Mater. Chem. 1995, 5, 1481-1496. (c) Garin, J.
AdV. Heterocycl. Chem. 1995, 62, 249-304. (d) Adam, M.; Mu¨llen, K.
AdV. Mater. 1994, 6, 439-459. (e) Schukat, G.; Fangha¨nel, E. Sulfur Rep.
1996, 18, 1-294.
(3) Kini, A. M.; Geiser, U.; Wang, H. H.; Carlson, K. D.; Williams, J.
M.; Kwok, W. K.; Vandervoort, K. G.; Thompson, J. E.; Stupka, D. L.;
Jung, D.; Whangbo, M.-H. Inorg. Chem. 1990, 29, 2555-2557.
(4) Lerstrup, K.; Talham, D.; Bloch, A.; Cowan, D. J. Chem. Soc., Chem.
Commun. 1982, 336-337.
(5) Siquot, Y.; Fre`re, P.; Nozdryn, T.; Cousseau, J.; Salle´, M.; Jubault,
M.; Orduna, J.; Gar´ın, J.; Gorgues, A. Tetrahedron Lett. 1997, 38, 1919-
1922.
compounds have oxidation potentials appreciably higher than
that of TTF itself. Cava and co-workers have recently
presented a detailed study of bis(2,5-dimethylpyrrolo[3,4-
d])tetrathiafulvalene (5) and its N-alkylated derivatives.8 The
synthesis of 5 involves classical pyrrole chemistry, building
up the 1,3-dithiole-2-thione moiety from a 2,5-dimethylpyr-
role core.9 Annelation of TTF to two electron rich 2,5-
dimethylpyrrole rings produces a donor system with a lower
(8) (a) Zong, K.; Chen, W.; Cava, M. P.; Rogers, R. D. J. Org. Chem.
1996, 61, 8117-8124. (b) Chen, W.; Cava, M. P.; Takassi, M. A.; Metzger,
R. M. J. Am. Chem. Soc. 1988, 110, 7903-7904.
(9) The two methyl groups are mandatory in this synthesis because the
first step is an electrophile thiocyanation at the â-positions and they serve
to block the more reactive R-positions.
(6) Shu, P.; Chiang, L.; Emge, T.; Holt, D.; Kistenmacher, T.; Lee, M.;
Stokes, J.; Poehler, T.; Bloch, A.; Cowan, D. J. Chem. Soc., Chem. Commun.
1981, 920-921.
(7) Ketcham, R.; Ho¨rnfeldt, A.-B.; Gronowitch, S. J. Org. Chem. 1984,
49, 1117-1119.
10.1021/ol9902428 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/28/1999

oxidation potential than that of the parent TTF (1), and we
have found 5 to be a useful building block in supramolecular
chemistry, devoid of cis/trans isomerism as in the simple
TTFs.10 However, the four methyl groups in 5, acting as
protecting groups during synthesis, block the R-positions in
the pyrrole units and exclude the possibility for further
C-functionalization in addition to N-alkylations. Furthermore,
steric hindrance can be expected from the methyl groups,
when 5 is incorporated in macrocyclic systems.
nitrogen during the harsh triethyl phosphite coupling reaction.
Finally, the tosyl groups can be removed almost quantita-
tively under mild conditions from the aromatic pyrrole ring.
The π-donor ability of the new systems was investigated
by cyclic voltammetry as well as preliminary formation of
a tetracyanoquinodimethane (TCNQ) complex.
The starting material in our synthesis is diol 11,14 which
was dibrominated with phosphorus tribromide (PBr3) to give
dibromide 12 (Scheme 2).15,16
In this context bis(pyrrolo[3,4-d])tetrathiafulvalene (6)
appeared interesting and we present here a straightforward
access to 6 and the related monopyrrolo annelated TTF 19,
through a nonclassical pyrrole synthesis.11
Scheme 2. Synthesis of (1,3)-Dithiolo[4,5-c]pyrrole-
2-chalcogenones
The construction of R,R′-unsubstituted N-tosyl-2,5-dihy-
dropyrrole annelated heterocycles 8 from tosylamide/sodium
tosylamide (Scheme 1) and unsaturated 1,2-bishalomethyl
Scheme 1 Nonclassical and Novel Pyrrole Synthesis
Cyclization was performed by treatment of 12 with sodium
tosylamide, affording the dihydropyrrolo compound 13a in
61% yield. Transchalcogenation of thione 13a with mercuric
acetate gave ketone 13b in 99% yield.17 Dehydrogenation
of 13a,b with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ) afforded the N-tosylated (1,3)-dithiolo[4,5-c]pyrrole-
2-chalcogenones 14a,b in 75% and 95% yields, respectively.
Detosylation of 14a was carried out by treatment of 14a with
sodium methoxide, affording the pyrrole 15 in 84% yield.18
Self-coupling of the ketone 14b to the TTF 16 using
triethyl phosphite proceeded in 84% yield (Scheme 3).
precursors 7 has been sporadically described in the litera-
ture.12 However, to the best of our knowledge subsequent
oxidations to the corresponding N-tosylpyrroles 9 and
complete detosylation to give R,R′-unsubstituted pyrroles 10
have apparently not been reported.13
In our approach the pyrrole ring is constructed in two steps
from a 1,3-dithiole-2-thione core bearing two vicinal bro-
momethyl groups, where the first step is a ring closure
reaction with sodium tosylamide followed by oxidation of
the annelated dihydropyrrole ring to give the N-tosyl-
protected pyrrole. The tosyl group plays a triple role. First,
it activates the nitrogen in the ring closure reaction. Second,
it works as an excellent protecting group for the pyrrole
Scheme 3. Synthesis of Bis(pyrrolo[3,4-d])tetrathiafulvalenes
(10) (a) Simonsen, K. B.; Zong, K.; Rogers, R. D.; Cava, M. P.; Becher,
J. J. Org. Chem. 1997, 62, 679-686. (b) Lau, J.; Nielsen, M. B.; Thorup,
N.; Cava, M. P.; Becher, J. Eur. J. Org. Chem. In press.
(11) For a comprehensive review on pyrrole synthesis, see: Bird, C. W.
ComprehensiVe Heterocyclic Chemistry II, Vol. 2; Katritzky, A. R., Rees,
C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; pp 1-257.
(12) (a) Scheffer, J. R.; Ihmels, H. Liebigs Ann./Recl. 1997, 1925-1929.
(b) Kim, W.-J.; Kim, B.-J.; Lee, T.-S.; Nam, K.-S.; Kim, K.-J. Heterocycles
1995, 41, 1389-1397. (c) Jendralla, H.; Fisher, G. Heterocycles 1995, 41,
1291-1298. (d) Bottino, F.; Grazia, M. D.; Finocchiaro, P.; Fronczek, F.
R.; Mamo, A.; Pappalardo, S. J. Org. Chem. 1988, 53, 3521-3529. (e)
Stapler, J. T.; Bornstein, J. J. Heterocycl. Chem. 1973, 10, 983-988.
(13) The dehydrogenation of N-alkyl/arylsulfonyl-2,5-dihydropyrroles
with different oxidation agents has been described, see: (a) Suzuki, T.;
Ohyabu, H.; Takayama, H. Heterocycles 1997, 46, 199-202. (b) Xu, Z.;
Lu, X. Tetrahedron Lett. 1997, 38, 3461-3464. (c) Ando, K.; Kankake,
M.; Suzuki, T.; Takayama, H. Tetrahedron 1995, 51, 129-138. (d) Suzuki,
T.; Takayama, H. J. Chem. Soc., Chem. Commun. 1995, 807-808. (e) Ando,
K.; Kankake, M.; Suzuki, T.; Takayama, H. J. Chem. Soc., Chem. Commun.
1992, 1100-1102.
Removal of the tosyl protecting groups of 16 was carried
out by treatment of 16 with sodium methoxide to give the
1292
Org. Lett., Vol. 1, No. 8, 1999

novel bis(pyrrolo)-TTF 6 in quantitative yield. Finally 6 was
dialkylated to give the N,N′-dialkyl derivatives 17a,b in 82-
83% yields (Scheme 3).
1
2
Table 1. Oxidation Potentials E1/2 and E1/2 of New TTF
Derivatives 6, 16, 17a,b, 18, 19, and 20a,b Determined by
Cyclic Voltammetrya,b
The asymmetrical monopyrrolo-TTF 19 (Scheme 4) was
obtained in optimum yield by cross-coupling of 14b with
4,5-bis(methylthio)-1,3-dithiole-2-thione in neat triethyl
phophite followed by detosylation of 18 using sodium
methoxide. Likewise, alkylation of 19 proceeded smoothly
to give the N-alkylated derivatives 20a,b. Single crystals of
20b were obtained by recrystallization from dichloromethane-
hexane, and its structure was confirmed by X-ray crystal-
lography.19
1
2
compound
E1/2 [V]
E1/2 [V]
∆Ep [V]
Eox1(DFT) [eV]
TTF (1)
5
6
16c
17a
17b
18
0.34
0.33
0.38
0.55
0.36
0.36
0.59
0.44
0.42
0.42
0.42
0.73
0.74
0.72
0.96
0.70
0.70
0.86
0.75
0.74
0.73
0.76
0.39
0.41
0.34
0.41
0.34
0.34
0.27
0.31
0.32
0.31
0.34
4.65
4.45
4.56
4.91
4.49
4.82
4.65
4.61
19
20a
20b
21
Scheme 4. Synthesis of Monopyrrolo[3,4-d]tetrathiafulvalenes
4.59
a Conditions: Ag/AgCl electrode, Pt electrode, 20 °C, Bu4NPF6 (0.1 M
in CH3CN), scan rate 0.1 Vs-1, [compound] 10-3 M. Eox1(DFT) is the
calculated first oxidation potentials using the B3LYP/6-31G(d) method and
the PCM solvent model. b The oxidation potentials for parent TTF, bis(2,5-
dimethylpyrrolo-[3,4-d])tetrathiafulvalene (5),8 and 4,6-dimethyl-2-{4,5-
bis(methylthio)-1,3-dithiole-2-yliden}-(1,3)-dithiolo[4,5-c]pyrrole (21) (i.e.,
R,R′-dimethyl-substituted analogue of 19)22 were for comparison measured
under identical conditions. c [16] , 10-3 M, due to the low solubility in
CH3CN.
21 (20 mV) due to the electron-donating effect of the
1
R-methyl groups. The first half-wave oxidation potential E1/2
of 6 is higher (40 mV) than that of TTF (1), indicating that
annelation of two pyrrolo units to the TTF framework results
in a decrease of the electron-donating ability. Both for the
bis(pyrrolo)-TTF series and the monopyrrolo-TTF series the
N-tosylated pyrrolo-TTFs (i.e., 16 and 18) showed the highest
1
oxidation potentials (both E1/2 and E1/22), whereas the
N-alkylated pyrrolo-TTFs (i.e., 17a,b and 20a,b) showed the
lowest oxidation potentials (both E1/21 and E1/22), due to the
inductive effect exhibited from the tosyl groups and alkyl
groups, respectively. As shown in Table 1, the calculated
Solution oxidation potentials obtained from cyclic volta-
mmograms (CVs) of pyrrolo-TTF π donors (D) and DFT
calculated first oxidation potentials are summarized in Table
1.20,21
Eox1(DFT) reproduces the major trends in the experimental
1
first oxidation potentials E1/2
.
The CVs of all compounds showed two pairs of reversible
redox waves, indicating good stability of the corresponding
radical cation (D•+) and dication (D2+). Compound 6 showed
An interesting feature of the monopyrrolo-TTFs is found
in their 13C chemical shifs, which are summarized in Table
1
1
2 together with the H chemical shifts.
a higher first half-wave oxidation potential E1/2 (50 mV)
As expected, the tosyl group has a strong influence on
the chemical shift of the pyrrole protons. The most remark-
able fact, however, is that the tosyl group is able to shift
most of the 13C resonances in 18. Especially for the fulvene
CadC, which is located six bonds away from the tosyl group,
a significant change in the chemical shift is observed,
indicating a pronounced extension of the π-surface in
monopyrrolo-TTFs.
than its R,R′,R′′,R′′′-tetramethylated analogue 5. This effect
was also observed for 19 and its R,R′-bismethylated analogue
(14) Jeppesen, J. O.; Takimiya, K.; Thorup, N.; Becher, J. Synthesis 1999,
5, 803-810.
(15) Recently an experimental procedure using CBr4/PPh3 has been
reported by Mu¨llen and co-workers, see: Skabara, P. J.; Mu¨llen, K.; Bryce,
M. R.; Howard, J. A. K.; Batsanov, A. S. J. Mater. Chem. 1998, 8, 1719-
1724.
(16) The use of PBr3 has been reported in a communication from Gorgues
and co-workers, see: Durand, C.; Hudhomme, P.; Duguay, G.; Jubault,
M.; Gorgues, A. Chem. Commun. 1998, 361-362.
(17) Self-coupling of 13b using triethyl phosphite afforded bis(2,5-
dihydro-N-tosylpyrrolo[3,4-d])tetrathiafulvalene in 35% yield. All attempts
to remove the tosyl groups failed due to the chemical stability of the
sulfamide bond.
(18) Care must be taken during workup, especially with regard to
temperature; otherwise ring opening occurs in the 1,3-dithiole ring and a
mixture of 15 and 3,4-bis(methylthio)pyrrole is isolated.
(19) The X-ray data and molecular structure are included as Supporting
Information.
(20) The first oxidation potentials were calculated from the energy
difference between D and D•+ with the B3LYP/6-31G(d) method and the
PCM solvent model, using PM3-optimized geometries.
(21) Gaussian 98 (Revision A.5). Frisch, M. J.; Trucks, G. W.; Schlegel,
H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.;
Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam,
J. M.; Daniels, A. D.; Nudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.;
Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Comperts, R.; Martin, R. L.; Fox, D. J.; Keith,
T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.;
Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M.
W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian,
Inc., Pittsburgh, PA, 1998.
Org. Lett., Vol. 1, No. 8, 1999
1293

pyrrole rings, similar to that of BEDT-TTF (2) where the
outer sulfur atoms have relatively large HOMO densities with
the same phase as the inner sulfur atoms.24
For the asymmetrical monopyrrolo-TTF 19, approximately
13% of the HOMO density is located on the outer pyrrole
ring, clearly demonstrating an extension of the π-surface in
pyrrolo-TTFs.
Table 2. 1H NMR Chemical Shifts for Pyrrole R-protons and
Selected 13C NMR Chemical Shifts (in ppm) for N-Substituted
Asymmetrical Monopyrrolo-TTF 18, 19, and 20aa
A combination of equimolar amounts of the new donor 6
and TCNQ gave a 1:1 charge transfer complex, and its
conductivity on a single crystal at room temperature was
relatively high, 0.02 S cm-1.
fulvene
fulvene
dithiole
R
CadC
CdCb
dCcCd
pyrrole Cd
HR
In conclusion, we have demonstrated an efficient short
route to the potentially useful symmetric bis(pyrrolo)-TTF
6 and the asymmetric monopyrrolo-TTF 19 and proved that
the new approach for construction of R,R′-unsubstituted
pyrrolo annelated heterocycles is useful for 1,3-dithiole-2-
thione. This route can probably be extended to other fused
pyrroles as well.
Ts
H
Me
112.54
107.27
107.24
117.73
121.95
121.34
126.14
117.16
116.77
112.84
110.88
114.66
7.40
6.81
6.78
a Spectra were recorded in DMSO-d6 (25 °C) at 300 and 75 MHz for
protons and carbons, respectively.
Investigations in the direction of tetrathiafulvalene-
containing polypyrroles and porphyrin25 systems are currently
in progress.
To shed more light on the extension of the π-surface in
pyrrolo-TTFs, the characters of the highest occupied mo-
lecular orbital (HOMO) of 6 and 19 were calculated using
the semiempirical PM3 method.23 Figure 2 shows the electron
Acknowledgment. We thank University of Odense for a
Ph.D. scholarship to J.O.J. and the Danish Research Acad-
emy for a postdoctoral fellowship to K.T.
Supporting Information Available: Compound charac-
terization data; X-ray crystal structure, crystal data, data
collection details and refinement parameters for 20b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL9902428
(22) Lomholt, C.; Nielsen, M. B.; Becher, J. Unpublished results.
(23) (a) Stewart, J. J. P. J. Comput. Chem. 1989, 10, 209-220. (b)
Stewart, J. J. P. J. Comput. Chem. 1989, 221-264.
Figure 2. HOMO orbital of 6: light face numbers ) HOMO
electron density, bold face numbers ) HOMO coefficients.
(24) Mori, T.; Kobayashi, A.; Sasaki, Y.; Saito, G.; Inokuchi, H. Bull.
Chem. Soc. Jpn. 1984, 57, 627-633.
(25) See, for example: Ramondenc, Y.; Schwenninger, R.; Phan, T.;
Gruber, K.; Kratky, C.; Kra¨utler, B. Angew. Chem., Int. Ed. Engl. 1994,
33, 889-891.
distribution of 6, and it is noteworthy that approximately
20% of the HOMO density is located on the outer two
1294
Org. Lett., Vol. 1, No. 8, 1999