Synthesis of BEDT-TTF derivatives with carboxylic ester and amide functionalities

Article abstract of DOI:10.1016/j.tetlet.2004.04.176

Synthetic routes to BEDT-TTF derivatives bearing side chain carboxylic ester and amide groups are reported. Methyl ET-ethanoate was prepared in five steps from vinylacetic acid; amide groups were installed early in the synthesis by mixed anhydride methods before the final coupling reaction.

Full text of DOI:10.1016/j.tetlet.2004.04.176

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5103–5107
Synthesis of BEDT-TTF derivatives with
carboxylic ester and amide functionalities
R. James Brown,a,b Gemma Camarasa,a Jon-Paul Griffiths,a
Peter Dayb and John D. Wallisa,*
aSchool of Science, The Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK
bThe Royal Institution of Great Britain, 21 Albemarle Street, London W1S 4BS, UK
Received 20 February 2004; revised 22 April 2004; accepted 29 April 2004
Abstract—Synthetic routes to BEDT-TTF derivatives bearing side chain carboxylic ester and amide groups are reported. Methyl
ET-ethanoate was prepared in five steps from vinylacetic acid; amide groups were installed early in the synthesis by mixed anhydride
methods before the final coupling reaction.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
conductors.5 Despite the interest in using ET for these
studies, there has been a gradually increasing amount of
work on the preparation and study of substituted ETs.
The synthesis and radical cation salts of the chiral tet-
ramethyl derivative were reported 15 years ago,6 and
results from the tetraethyl derivative (TEET) have been
published recently.7 Indeed, the charge transfer com-
pound (TEET)Ni(dmit)2 is being evaluated as a molec-
ular ruler for nanotechnology. Ozturk has prepared
unsaturated phenyl8 and tetraphenyl9 derivatives of ET,
2 and 3, and poly-chloro and -fluoro analogues of ET
The organosulfur donor BEDT-TTF 1, also known as
ET, has played an important role in the development of
electroactive organic materials.1 It forms a very wide
range of radical cation salts with conducting, semi-
conducting and superconducting properties.2;3 ET has
been co-crystallised and electrocrystallised with C60,4
and it has been used to prepare radical cation salts with
magnetic anions to produce a paramagnetic super-
conductor and ferrimagnetic and paramagnetic semi-
Keywords: Organosulfur donors; Hydrogen bonding; BEDT-TTF; Amides.
* Corresponding author. Tel.: +44-0115-848-3149; fax: +44-0115-848-6636; e-mail: john.wallis@ntu.ac.uk
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.176

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R. J. Brown et al. / Tetrahedron Letters 45 (2004) 5103–5107
have been prepared by Fourmigue as isomeric mix-
tures.10 We have prepared hydroxymethyl and hy-
droxyethyl derivatives 411 and 6,12 the corresponding
amino compounds 513 and 713 and other polyhydroxy
functionalised systems.14 The increasing interest in
bifunctional materials,15 has led us to incorporate metal
binding groups,12 for example, 8 and 9 and chiral moi-
eties16 on to the ET framework. To widen the scope for
attachment of such groups to the ET system we now
report results on the preparation of ETs functionalised
with carboxylic ester and amide functionalities. Fur-
thermore, amide groups will introduce hydrogen bond-
ing into the system, of particular interest for ordering
the anions in their radical cation salts.
from homo-coupled products. Thus, racemic donor 18 is
a readily accessible molecule for the organic materials
community. Conditions for hydrolysing the ester to the
acid 19 without decomposing the molecule were not easy
to establish. This was achieved finally with potassium
hydrogen carbonate in a THF/methanol/water mixture
to give a fine powder after drying in 75% yield. The
enantiopure version of the donor 18 has also been pre-
pared; the key step is reaction of the dithiolate 14 with
the cyclic sulfate ester 20 and will be reported with the
synthesis of other chiral ET derivatives.16
The related donor, which carries two vicinal, trans ori-
ented, –CH2CO2Me side-chains has also been prepared.
In this case the corresponding thione 22 was prepared by
the hetero Diels–Alder reaction of the trithione 21 with
dimethyl E-hex-3-endioate in 55% yield (Scheme 2).
Such reactions of trithione 21 were reported by Neilands
et al.21 and we have applied it to the synthesis of a
number of such thiones.12;13;16 The thione was converted
to the oxo compound 23, which was coupled with the
unsubstituted thione 17 to give the disubstituted donor
24 in a yield of 29%. In contrast, reaction of the
disubstituted cyclic sulfate ester 25 with the dithiolate 14
gave only a trace of thione. Only two small substituents
on the cyclic sulfate ester are consistent with satisfactory
yields of the corresponding thiones,11 for example, the
bis(methoxymethyl)-substituted thione 27 was prepared
in only ca. 5% yield from cyclic sulfate ester 26.
ETs are usually prepared by coupling reactions of thi-
ones or oxo compounds 10 or 11. However, direct
attachment of a carboxylic ester or nitrile to these sys-
tems led to the attempted coupling reactions mediated
by triethyl phosphite failing, for example, for the thiones
1217 and 13.18 The ring carbon atom is activated to
nucleophilic attack by the electron withdrawing prop-
erties of the carbonyl and this can lead to Arbuzov
reactions with triethyl phosphite yielding tetra(ethyl-
thio)TTF. So the syntheses of materials with a methyl-
ene group between the ET and carboxyl function were
targeted.
To prepare amide derivatised ETs it was found best to
install the amide group early in the synthesis, since direct
reaction of donor 18 with amines to give amides was
unsuccessful, and the initial attempts to use acid 19 were
not promising, partly due its low solubility in common
organic solvents. Thus, cycloaddition of vinylacetic acid
and trithione 21 in refluxing toluene, followed by
removal of polymeric material by chromatography and
distillation of residual vinylacetic acid afforded carboxy-
lic acid 28 as a brown solid in 56% yield. The alternative
approach to 28 by reaction of 3,4-dibromobutanoic acid
and the dithiolate 14 proved unsuccessful. Amides were
prepared using mixed anhydride chemistry (Scheme 3).
Thus carboxylic acid 28 was converted to mixed anhy-
dride 29 by treatment with ethyl chloroformate and
triethylamine in THF under nitrogen at 0 °C. In situ
treatment with an amine followed by stirring overnight
Dithiolate 14, prepared by deprotection of its dibenzoyl
derivative with sodium methoxide, was reacted with
methyl 3,4-dibromopropionate, obtained from vinyl-
acetic acid in two steps,19 to give a precipitate of the
thione 15 in 72% yield. Conversion to the oxo com-
pound 16 using the standard procedure with mercuric
acetate and coupling with the unsubstituted thione 17 in
triethyl phosphite afforded the novel donor 1820 in a
35% yield from thione 15 (Scheme 1). The reactions were
clean and efficient, and chromatography was only
required at the final step to separate the desired donor
Scheme 1.

R. J. Brown et al. / Tetrahedron Letters 45 (2004) 5103–5107
5105
Scheme 2.
Scheme 3.
at room temperature and chromatography yielded the
amides as yellow solids. Thus, using ammonia, ethyl-
amine, aniline, 4-aminophenol, 2-amino- and 4-amino-
pyridine, or 3-amino-1,2,4-triazole gave the amide
functionalised thiones 30–36 in 23–64% yields. Further-
more, reaction with phenyl hydrazine gave the hydrazide
37. The hydroxyl group of thione 33 was then protected
as an acetate to give thione 38, prior to conversion to an
ET derivative.
their oxo compounds (20–24%) suggest that preparation
by coupling of the substituted thione may be preferable.
Thiones 35, 36 and 37 failed in the coupling reactions
with 41, possibly due to triethyl phosphite breaking the
bond to the nitrogen of the amide group, generating
amide anions, which could attack the dithiin ring.
We prepared thione 48 with an amide group attached to
the ring skeleton by cycloaddition of trithione 21 and
acrylamide in 43% yield and converted this material to
the oxo compound 49. However, attempted reaction of
48 or 49 with the unsubstituted oxo compound 41 or
thione 17, respectively, in triethyl phosphite gave no ET-
carboxamide.
The thiones were converted into their corresponding
donors, usually pink or orange solids, by one of two
methods. Three thiones 30, 32 and 38 were coupled
directly with the unsubstituted oxo compound 41 to give
donors 44,22 4523 and 46 in 34–50% yield. A further two
thiones, 31 and 34, were converted to their oxo com-
pounds 39 and 40, which were then coupled with the
unsubstituted thione 17 to give donors 4224 and 43.25 The
lower overall yields for conversion of thione to donor via

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R. J. Brown et al. / Tetrahedron Letters 45 (2004) 5103–5107
11. Saygili, N.; Brown, R. J.; Day, P.; Hoelzl, R.; Kathir-
gamanathan, P.; Mageean, E. R.; Ozturk, T.; Pilkington,
M.; Qayyum, M. M. B.; Turner, S. S.; Vorwerg, L.; Wallis,
J. D. Tetrahedron 2001, 57, 5015–5026.
12. Griffiths, J.-P.; Brown, R. J.; Vital, B.; Day, P.; Matthews,
C. J.; Wallis, J. D. Tetrahedron Lett. 2003, 44, 3127–
3131.
13. Griffiths, J.-P.; Arola, A. A.; Appleby, G.; Wallis, J. D.
Tetrahedron Lett. 2004, 45, 2813–2816.
14. Ozturk, T.; Saygili, N.; Ozkara, S.; Pilkington, M.; Rice,
C. R.; Tranter, D. A.; Turksoy, F.; Wallis, J. D. J. Chem.
Soc., Perkin Trans. 1 2001, 407–414.
15. (a) Zhang, B.; Tanaka, H.; Fujiwara, H.; Kobayashi, H.;
Fujiwara, E.; Kobayashi, A. J. Am. Chem. Soc. 2002, 124,
9982–9983; (b) Tanaka, H.; Kobayashi, H.; Kobayashi, A.
J. Am. Chem. Soc. 2002, 124, 10002–10003; (c) Coronado,
E.; Galan-Mascaros, J. R.; Gomez-Garcia, C. J.; Laukhin,
V. Nature 2000, 408, 447–449; (d) Ouahab, L. Coord.
Chem. Rev. 1998, 178, 1501–1531; (e) Segura, J. L.;
Martin, N. Angew. Chem., Int. Ed. 2001, 40, 1372–
1409.
16. Griffiths, J.-P.; Brown, R. J.; Wallis, J. D., unpublished
results.
17. Ozturk, T.; Povey, D. C.; Wallis, J. D. Tetrahedron 1994,
50, 11205–11212.
Thus a range of amide substituted organosulfur donors,
with a variety of hydrogen bonding possibilities, is now
available for conversion to radical cation salts. The 4-
acetyloxyphenylamide 46 was hydrolysed to give the
donor 47, which has both a N–H and an O–H donor.
Donor 43 is of interest since it has the potential for
binding a metal cation at the pyridyl side chain. The
cyclic voltammetries26 of the novel ET derivatives
showed two reversible oxidation peaks: 42–45 at very
similar potentials to ET (0.48 and 0.89 V), and 18 (0.50
and 0.91 V) and 24 (0.52and 0.94 V) at slightly higher
values. Preliminary electrocrystallisation experiments
have produced several microcrystalline salts.
Acknowledgements
We thank the EPSRC and Nottingham Trent University
for studentships (R.J.B. and J.P.G.) and the EPSRC
Mass Spectrometry Service for measurements. We thank
the Chemistry Department, University of Warwick for
help with several spectroscopic measurements.
18. Yang, X.; Rauchfuss, T. B.; Wilson, S. J. Chem. Soc.,
Chem. Commun. 1990, 34–36.
19. Kasina, S.; Fritzberg, A. R.; Johnson, D. L.; Eshima, D.
J. Med. Chem. 1986, 29, 1933–1940.
20. Compound 18: Mp 149–150 °C; 1H NMR (270 MHz,
CDCl3) d: 4.03 (1H, m, 5-H), 3.73 (3H, s, OCH3), 3.33
(1H, dd, J ¼ 13:2, 3.1 Hz, 6-Ha), 3.29 (4H, s, 50, 60-H2),
3.14 (1H, dd, J ¼ 13:2, 5.6 Hz, 6-Hb), 2.84 (2H, d,
J ¼ 6:9 Hz, CH2CO); 13C NMR (67.8 MHz, CDCl3) d:
170.8 (C@O), 113.8, 113.5, 112.7, 112.0, 111.4 (sp2-C),
52.1 (OCH3), 39.4 (CH2CO), 38.6 (5-C) 34.7 (6-C), 30.2
(50-, 60-C); mmax /cmÀ1 (KBr) 2947, 1730, 1432, 1303, 1253,
1202, 1014, 772. Found C, 34.3; H, 2.6%, C13H12O2S8
requires C, 34.2; H, 2.7%.
References and notes
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2. (a) Williams, J. M.; Ferraro, J. R.; Thorn, R. J.; Carlson,
K. D.; Geiser, U.; Wang, H. H.; Kini, A. M.; Whangbo,
M.-H. Organic Superconductors: Synthesis Structure Prop-
erties and Theory; Prentice Hall Englewood Cliffs: New
Jersey, 1992; (b) Ishiguo, T.; Yamaji, K.; Saito, G. Organic
Superconductors; Springer: Berlin, 1998.
3. Kini, A. M.; Geiser, U.; Wang, H. M.; Carlson, K. D.;
Williams, J. M.; Kwok, W. K.; Vandervoort, K. G.;
Thompson, J. E.; Stopka, D. L.; Jung, D.; Whangbo,
M.-H. Inorg. Chem. 1990, 29, 2555–2557.
4. (a) Izuoka, A.; Tachikawa, T.; Sugawara, T.; Suzuki, Y.;
Konno, M.; Saito, Y.; Shinohara, H. J. Chem. Soc., Chem.
Commun. 1992, 1472–1473; (b) Konarev, D. V.; Kovalev-
sky, Yu.; Coppens, P.; Lyubovskaya, R. N. Chem.
Commun. 2000, 2357–2358.
5. (a) Kurmoo, M.; Graham, A. M.; Day, P.; Coles, S.;
Hursthouse, M. J.; Caulfield, J. L.; Singleton, J.; Pratt, F.
L.; Hayes, W.; Ducasse, L.; Guionneau, P. J. Am. Chem.
Soc. 1995, 117, 12209–12217; (b) Turner, S. S.; Michaut,
C.; Durot, S.; Day, P.; Gelbrich, T.; Hursthouse, M. B. J.
Chem. Soc., Dalton Trans. 2000, 905–909; (c) Setifi, F.;
Golhen, S.; Ouahab, L.; Turner, S. S.; Day, P. Cryst. Eng.
Commun. 2002, 4, 1–6.
6. (a) Dunitz, J. D.; Karrer, A.; Wallis, J. D. Helv. Chim.
Acta 1986, 89, 89–90; (b) Karrer, A.; Wallis, J. D.; Dunitz,
J. D.; Hilti, B.; Mayer, C. W.; Burkle, M.; Pfeiffer, J. Helv.
Chim. Acta 1987, 70, 942–953.
7. Kini, A. M.; Parakka, J. P.; Geiser, U.; Wang, H.-H.;
Rivas, F.; DiNino, E.; Thomas, S.; Dudek, J. D.;
Williams, J. M. J. Mater. Chem. 1999, 9, 883–892.
8. Ozturk, T. Tetrahedron Lett. 1996, 2821–2824.
9. Ertas, E.; Ozturk, T. Chem. Commun. 2000, 2039–2040.
10. Dautel, O. J.; Fourmigue, M. J. Chem. Soc., Perkin Trans.
1 2001, 3399–3402.
21. Neilands, O. Y.; Katsens, Y. Y.; Kreitsberga, Y. N. Zh.
Org. Khim. 1989, 25, 658–660.
1
22. Compound 44: Mp 184–185 °C (dec); H NMR (DMSO-
d6) d: 7.49 (1H, br s, NH), 6.84 (1H, br s, NH), 4.14 (1H,
m, 5-H), 3.31 (4H, s, 50-, 60-H2), 3.30 (1H, dd, J ¼ 13:4,
5.7 Hz, 6-Ha), 3.20 (1H, dd, J ¼ 13:4, 3.2Hz, 6- Hb), 2.62
(2H, d, J ¼ 7:2Hz, C H2CO); 13C NMR (67.8 MHz,
DMSO-d6) d: 169.5 (C@O), 112.4, 111.7, 110.4 (sp2-C),
39.3 (CH2CO), 38.9 (5-C), 33.1 (6-C), 28.3 (50-, 60-C); mmax
/
cmÀ1 (KBr) 3379, 3180, 2918, 2855, 1655, 1625, 1407,
1264, 908, 770, 609; HRMS (EI): found: 440.8613
(MþH)þ, C12H11NOS8 þ Hþ requires: 440.8606.
23. Compound 45: Mp 196–197 °C; 1H NMR (270 MHz,
DMSO-d6) d: 7.57 (2H, d, J ¼ 8:4 Hz, 2 ꢀ Ar-H), 7.29
(2H, t, J ¼ 8:3 Hz, 2 ꢀ Ar-H), 7.04 (1H, t, J ¼ 8:3 Hz, Ar-
H), 4.23 (1H, m, 5-H), 3.38 (2H, m, 6-H2), 3.32(4H, s, 5 0-,
60-H2), 2.88 (2H, m, 6-CH2CO); 13C NMR (67.8 MHz,
DMSO-d6) d: 167.7 (C@O), 138.8, 128.7, 123.3, 119.1
(6 ꢀ Ar-C), 112.8 (sp2-C), 41.5 (CH2CO), 38.1 (5-C), 34.4
(6-C), 29.5 (50-, 60-C); mmax/cmÀ1 (KBr) 3049, 2966, 2920,
2849, 1654, 1596, 1522, 1497, 1442, 1410, 1311, 1284, 1256,
888; HRMS (EI): found: 516.8930 (MþH)þ,
C18H15NOS8 þ Hþ requires: 516.8919.
24. Compound 42: Mp 170–171 °C; 1H NMR (270 MHz,
CDCl3) d: 5.55 (1H, br s, NH), 4.10 (1H, m, 5-H), 3.37
(1H, dd, J ¼ 13:4, 3.0 Hz, 6-Ha), 3.30 (2H, m, NHCH2),
3.29, (4H, s, 50-, 60-H2), 3.13 (1H, dd, J ¼ 13:4, 5.0 Hz, 6-
Hb), 2.61 (2H, m, CH2CO), 1.13 (3H, t, J ¼ 7:3 Hz, NH-
CH2CH3); 13C NMR (67.8 MHz, CDCl3) d: 168.5 (C@O),
113.9, 111.3 (sp2-C), 41.6 (CH2CO), 38.5 (5-C), 34.8 (6-C),

R. J. Brown et al. / Tetrahedron Letters 45 (2004) 5103–5107
5107
0
34.6 (NH-CH2), 30.2(5 -, 60-C), 14.8 (NHCH2CH3); mmax
/
13C NMR (67.8 MHz, CDCl3) d: 168.2( C@O), 151.3,
147.6, 138.7, 120.2, 114.7 (5 ꢀ Ar-C), 113.9, 113.8, 112.4,
112.1 (sp2-C), 42.2 (CH2CO), 37.9 (5-C), 35.2(6- C),
cmÀ1 (KBr) 3424, 3281, 2972, 2922, 1633, 1560, 1408,
1284, 1253, 1105, 774. Found C, 35.5; H, 3.2; N, 2.9%,
C14H15ONS8 requires C, 35.8; H, 3.2; N, 3.0%.
30.2(5 0-, 60-C);
m
max/cmÀ1 (KBr) 2967, 2920, 2850,
25. Compound 43: Mp 129–131 °C; 1H NMR (270 MHz,
CDCl3) d: 8.87 (1H, br s, NH), 8.27 (1H, dd, J ¼ 5:0,
1.0 Hz, 600-H), 8.19 (1H, dd, J ¼ 8:2, 0.5 Hz, 300-H), 7.72
(1H, dt, J ¼ 8:2, 1.8 Hz, 400-H), 7.07 (1H, ddd, J ¼ 7:3, 5.0,
0.8 Hz, 500-H), 4.20 (1H, m, 5-H), 3.41 (1H, dd, J ¼ 13:4,
2.9 Hz, 6-Ha), 3.29 (4H, s, 50-, 60-H2), 3.21 (1H, dd,
J ¼ 13:4, 2.9 Hz, 6-Hb), 2.92 (2H, d, J ¼ 7:0 Hz, CH2CO);
1684, 1654, 1577, 1434, 1302, 774; HRMS (ES):
found: 518.8949 (MþH)þ, C17H14N2OS8 þ Hþ requires:
518.8950.
26. Data measured in dichloromethane containing 0.1 M
tetrabutylammonium hexafluorophosphate under nitro-
gen, with a scan rate of 100 mV sÀ1, quoted relative to Ag/
AgCl.