New crown annelated tetrathiafulvalenes: Synthesis, electrochemistry, self-assembly of thiol derivatives, and metal cation recognition

Article abstract of DOI:10.1021/jo000936q

The synthesis of new S₂O₄-crown annelated tetrathiafulvalene (TTF) derivatives substituted with one terminal thiol group is described. Self-assembled monolayers (SAMs) of these compounds have been assembled on gold and platinum surfaces, the latter substrate giving improved quality films. SAMs of TTF derivative 16b are the most stable of those we have studied. Electrochemical data for SAMs of 5a, 5b, 8, 16a, and 16b in acetonitrile reveal two reversible one-electron waves, typical of the TTF system; the current increased linearly with scan rate, indicating a surface wave response. SAMs of 8, 16a, and 16b exhibited an electrochemical response in aqueous electrolytes, which was observed between 50 and 100 cycles. Moreover, if the potential scanned was limited to the first TTF oxidation, the cyclic voltammetry response was observed for at least 1000 cycles. Metal complexation by the crown ionophore of the SAMs in acetonitrile has been monitored by a positive shift in the first oxidation potential of the TTF unit (maximum ΔE₁(1/2) = 80 mV for Ag⁺). We also report the X-ray crystal structure of TTF - crown derivative 21 bearing two hydroxymethyl substituents, synthesized during the course of this work. The structure is characterized by infinite chains of molecules linked by strong intrachain hydrogen bonds between the terminal hydroxy groups.

Full text of DOI:10.1021/jo000936q

J . Org. Chem. 2000, 65, 8269-8276
8269
New Cr ow n An n ela ted Tetr a th ia fu lva len es: Syn th esis,
Electr och em istr y, Self-Assem bly of Th iol Der iva tives, a n d Meta l
Ca tion Recogn ition
Adrian J . Moore,† Leonid M. Goldenberg,†,‡ Martin R. Bryce,*,† Michael C. Petty,‡
J anet Moloney,† J udith A. K. Howard,† Malcolm J . J oyce,§ and Simon N. Port§
Department of Chemistry, School of Engineering, and Centre for Molecular Electronics, University of
Durham, South Road, Durham DH1 3LE, United Kingdom, and British Nuclear Fuels Research and
Technology, Springfields, Preston, Lancashire PR4 0XJ , United Kingdom
M.R.Bryce@durham.ac.uk
Received J une 20, 2000
The synthesis of new S2O4-crown annelated tetrathiafulvalene (TTF) derivatives substituted with
one terminal thiol group is described. Self-assembled monolayers (SAMs) of these compounds have
been assembled on gold and platinum surfaces, the latter substrate giving improved quality films.
SAMs of TTF derivative 16b are the most stable of those we have studied. Electrochemical data
for SAMs of 5a , 5b, 8, 16a , and 16b in acetonitrile reveal two reversible one-electron waves, typical
of the TTF system; the current increased linearly with scan rate, indicating a surface wave response.
SAMs of 8, 16a , and 16b exhibited an electrochemical response in aqueous electrolytes, which was
observed between 50 and 100 cycles. Moreover, if the potential scanned was limited to the first
TTF oxidation, the cyclic voltammetry response was observed for at least 1000 cycles. Metal
complexation by the crown ionophore of the SAMs in acetonitrile has been monitored by a positive
shift in the first oxidation potential of the TTF unit (maximum ∆E1 ) 80 mV for Ag+). We also
1/2
report the X-ray crystal structure of TTF-crown derivative 21 bearing two hydroxymethyl
substituents, synthesized during the course of this work. The structure is characterized by infinite
chains of molecules linked by strong intrachain hydrogen bonds between the terminal hydroxy
groups.
In tr od u ction
sensors in organic media.4 The presence of a bound metal
cation imposes an inductive effect on the polarizable TTF
system, resulting in a positive shift of the first oxidation
potential as indicated by cyclic voltammetry (CV) experi-
ments; the second oxidation potential is usually un-
changed or shifts (also positively) only very slightly.
Recent data imply that complete expulsion of the metal
does not occur until the dication stage.4e Near planarity
of the TTF system is a prerequisite for reversible redox
behavior.4a,d,e Yip and Ward first reported that redox-
active SAMs of TTF derivative 1 could be obtained on
gold electrodes.5 Subsequently, new TTF SAMs with
increased stability have been described.6 We now report
the synthesis, electrochemistry, SAM formation, and
metal cation recognition in a series of functionalized
TTF-S2O4 crowns. Following our initial communication,7
Echegoyen et al. described a different series of TTF-
Self-assembled monolayers (SAMs) of organic com-
pounds provide chemically tailored substrate surfaces
which have technological applications as sensors, devices,
and switches.1 There is current interest in the study of
molecular recognition processes within SAM nanostruc-
tures.2 Examples have been reported recently in which
specific interactions of a guest analyte with a host SAM
are transduced to a signaling unit which responds by
undergoing a change in its electronic state, which is
measured by spectroscopic, structural, or electrochemical
techniques.3
It is well documented that crown annelated tetrathia-
fulvalene (TTF) derivatives function as metal cation
* To whom correspondence should be addressed: Department of
Chemistry, University of Durham, South Road, Durham DH1 3LE,
U.K. Phone: +44 (0) 191 3743118. Fax: +44 (0)191 3844737.
† Department of Chemistry and Centre for Molecular Electronics,
University of Durham.
(3) Review: Finklea, H.O. In Electroanalytical Chemistry; Bard, A.
J ., Rubenstein, I., Eds.; Marcel Dekker: New York, 1996; Vol. 19, p
109.
‡ School of Engineering and Centre for Molecular Electronics,
University of Durham.
(4) (a) Hansen, T. K.; J ørgensen, T.; Stein, P. C.; Becher, J . J . Org.
Chem. 1992, 57, 6403. (b) Gasiorowski, R.; J ørgensen, T.; Møller, J .;
Hansen, T. K.; Pietraszkiewicz, M.; Becher, J . Adv. Mater. 1992, 4,
568. (c) Dieing, R.; Morisson, V.; Moore, A. J .; Goldenberg, L. M.; Bryce,
M. R.; Raoul, J .-M.; Petty, M. C.; Gar´ın, J .; Saviro´n, M.; Lednev, I. K.;
Hester, R. E.; Moore, J . N. J . Chem. Soc., Perkin Trans. 2 1996, 1587.
(d) LeDerf, F.; Mazari, M.; Mercier, N.; Levillain, E.; Richomme, P.;
Becher, J .; Gar´ın, J .; Orduna, J .; Gorgues, A.; Salle´, M. Chem.
Commun. 1999, 1417. (e) LeDerf, F.; Mazari, M.; Mercier, N.; Levillain,
E.; Richomme, P.; Becher, J .; Ga´rin, J .; Orduna, J .; Gorgues, A.; Salle´,
M. Inorg. Chem. 1999, 38, 6096. (f) Liu, S.-G.; Echegoyen, L. Eur. J .
Org. Chem. 2000, 1157.
§ British Nuclear Fuels Research and Technology.
(1) (a) Ulman, A. An Introduction to Ultrathin Organic Films;
Academic Press: London, 1991. (b) Kumar, A.; Abbott, N. L.; Kim, E.;
Biebuyck, H. A.; Whitesides, G. M. Acc. Chem. Res. 1995, 28, 219. (c)
Velzen, E. U. T.; Engbersen, J . F. J .; Lange, P. J .; Mahy, J . W. C.;
Reinhoudt, D. N. J . Am. Chem. Soc. 1995, 117, 6853. (d) Ulman, A.
Chem. Rev. 1996, 96, 1533.
(2) (a) Review: Goldenberg, L. M.; Bryce, M. R.; Petty, M. C. J .
Mater. Chem. 1999, 9, 1957. (b) Beulen, M. W. J .; Bu¨gler, J .; de J ong,
M. R.; Lammerink, B.; Huskens, J .; Scho¨nherr, H.; Vancso, G. J .;
Boukamp, B. A.; Wieder, H.; Offenha¨user, A.; Knoll, W.; van Veggel,
F. C. J . M.; Reinhoudt, D. N. Chem. Eur. J . 2000, 6, 1176. (c)
Bandyopadhyay, K.; Shu, L.; Liu, H.; Echegoyen, L. Langmuir 2000,
16, 2706.
(5) Yip, C.-M.; Ward, M. D. Langmuir 1994, 10, 549.
(6) Fujihara, H.; Nakai, H.; Yoshihara, M.; Maeshima, T. Chem.
Commun. 1999, 737.
10.1021/jo000936q CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/02/2000

8270 J . Org. Chem., Vol. 65, No. 24, 2000
Moore et al.
(obtained by reduction of 2, as described previously)4c was
converted into thiol analogue 8, using Volante’s modifica-
tion9 of the Mitsunobu reaction.10 Treatment of compound
6 with the diisopropylazodicarboxylate (DIAD)/triphen-
ylphosphine complex in tetrahydrofuran and subsequent
in situ displacement of the resulting leaving group with
thioacetic acid cleanly afforded compound 7. The thiol 8
was then obtained by reduction of 7 using lithium
aluminum hydride in diethyl ether (70% overall yield for
the two steps). During the course of this work, analogous
methodology was utilized for the preparation of bis-
(sulfanylmethyl)TTF derivatives.11 The instability of
TTF-CH2X systems (X ) anionic leaving group, e.g., Br,
tosyl)12 precluded their use as intermediates in the
synthesis of 8 from 6.
Sch em e 1a
We have also synthesized compounds 16a and 16b
which possess two alkylsulfanyl chains appended to the
TTF-crown, one of which is terminally substituted with
a thiol group for self-assembly (Scheme 2). We considered
that the steric bulk of the additional alkylsulfanyl chain
should facilitate a more ordered monolayer packing
within a SAM. Deprotection of the thiolate group in
compounds 9a 13 and 9b with cesium hydroxide followed
by in situ trapping with 6-bromohexan-1-ol afforded
compounds 10a and 10b (90 and 82% yields, respec-
tively). Reaction with tert-butyldiphenylsilyl chloride in
the presence of imidazole in N,N-dimethylformamide
afforded compounds 11a and 11b (96 and 89% yields,
respectively). (This protection reaction was necessary as
alcohol functionality is generally incompatible with the
trialkyl phosphite-mediated cross-coupling reaction,14
although there are exceptions.15) Reaction of compounds
11a and 11b with compound 124a in the presence of
triethyl phosphite afforded TTF derivatives 13a and 13b
(35 and 31% yields, respectively, after chromatographic
separation from symmetrically coupled products). Depro-
tection of 13a and 13b with tetrabutylammonium fluo-
ride gave alcohols 14a and 14b (95 and 76% yields,
respectively). The two-step Mitsunobu protocol, as de-
scribed for 5 and 8, afforded compounds 16a and 16b as
air-stable orange oils (63 and 65% yields, respectively,
for the two-step reaction).
In light of the improved electrochemical response of
SAMs of 16 compared to 5 and 8 (see below), we sought
to attach two thiol-terminated chains to the TTF-crown
framework, following the methodology for the monothiols
above. The hydrolysis of diester 174c occurred readily
under basic conditions (aqueous 1 M sodium hydroxide
in refluxing dioxane) to afford diacid 18 (88% yield) which
was insoluble in many organic solvents. Esterification of
18 with 2-bromohexanol in the presence of DCC and
DMAP in refluxing dichloromethane using ultrasound
afforded cleanly diester 19 (75% yield). However, all
attempts to convert 19 into 20 under the conditions used
for the preparation of 5 were unsuccessful (mass spec-
a
Reagents and Conditions: (i) 1 M NaOH (aq), dioxane, reflux;
then 1 M HCl (aq) (ref 4c); (ii) Br(CH2)nOH (n ) 12 or 6), DCC,
DMAP, CH2Cl2, 20 °C; (iii) thiourea, EtOH, reflux; then 1 M KOH
(aq); (iv) DIBAL-H, CH2Cl2, -80 °C; then HCl-MeOH (ref 4c); (v)
DIAD, Ph3P, THF, 20 °C; then compound 6, THF, 20 °C; then
MeC(O)SH, 20 °C; (vi) LiAlH4, Et2O, 20 °C; then aqueous hydroly-
sis.
crown SAMs and their alkali metal cation binding
properties.8
Resu lts a n d Discu ssion
Syn t h esis. The synthetic strategy described by Yip
and Ward for the preparation of 15 was adapted for
compounds 5a and 5b as shown in Scheme 1. The key
starting reagent is compound 2,4c which was converted
into the carboxylic acid derivative 3 (75% yield) as
reported previously.4c Treatment of 3 with either 12-
bromo-1-dodecanol or 6-bromo-1-hexanol in the presence
of dicyclohexylcarbodiimide and N,N-(dimethylamino)-
pyridine afforded bromoester derivatives 4a and 4b (75
and 85% yields, respectively). Subsequent conversion of
the terminal bromide into a thiol group was achieved by
treatment with thiourea followed by basic hydrolysis of
the intermediate isothiouronium salt to afford the target
derivatives 5a and 5b (42 and 33% yields, respectively).
In both cases, this last step gave a complex reaction
mixture containing unidentified byproducts; conse-
quently, the purified yields for compounds 5a and 5b
were significantly reduced as a result of repeated chro-
matography. The overall yields compare favorably with
those reported by Yip and Ward for 1.5
We considered the possibility that the ester linkage
was contributing to the electrochemical inactivity of
SAMs of compounds 5 in aqueous media (see below).
Therefore, analogues without this linkage were synthe-
sized as follows. The TTF-crown methanol derivative 6
(9) Volante, R. P. Tetrahedron Lett. 1981, 22, 3119.
(10) Mitsunobu, O. Synthesis 1981, 1.
(11) Hudhomme, P.; Blanchard, P.; Salle´, M.; Le Moustarder, S.;
Riou, A.; J ubault, M.; Gorgues, A.; Duguay, G. Angew. Chem., Int. Ed.
Engl. 1997, 36, 878.
(12) Hudhomme, P.; Liu, S. G.; Kreher, D.; Cariou, M.; Gorgues, A.
Tetrahedron Lett. 1999, 40, 2927.
(13) Becher, J .; Lau, J .; Leriche, P.; Mørk, P.; Svenstrup, N. J . Chem.
Soc., Chem. Commun. 1994, 2715.
(14) Marshallsay, G. J .; Bryce, M. R.; Cooke, G.; J ørgensen, T.;
Becher, J .; Reynolds, C. D.; Wood, S. Tetrahedron 1993, 49, 6849.
(15) Ozturk, T.; Rice, C. R.; Wallis, J . D. J . Mater. Chem. 1995, 5,
1553.
(7) (a) Moore, A. J .; Goldenberg, L. M.; Bryce, M. R.; Petty, M. C.;
Monkman, A. P.; Marenco, C.; Yarwood, J .; J oyce, M. J .; Port, S. N.
Adv. Mater. 1998, 10, 395. (b) Moore, A. J .; Goldenberg, L. M.; Bryce,
M. R.; Petty, M. C.; Monkman, A. P.; Marenco, C.; Yarwood, J .; J oyce,
M. J .; Port, S. N. International Patent Application No. PCT/GB98/
01632.
(8) (a) Liu, H.; Liu, S.; Echegoyen, L. Chem. Commun. 1999, 1493.
(b) Liu, S. G.; Liu, H. Y.; Bandyopadhyay, K.; Gao, Z. Q.; Echegoyen,
L. J . Org. Chem. 2000, 65, 3292.

New Crown Annelated Tetrathiafulvalenes
J . Org. Chem., Vol. 65, No. 24, 2000 8271
Sch em e 2a
a
Reagents and Conditions: (i) CsOH‚H2O, MeOH, 20 °C; then Br(CH2)6OH, 20 °C; (ii) t-BuPh2SiCl, imidazole, DMF, 20 °C; (iii) 12,
P(OEt)3, 130 °C; (iv) TBAF, THF, 20 °C; (v) DIAD, Ph3P, THF, 20 °C; then MeC(O)SH, 20 °C; (vii) LiAlH4, Et2O, 20 °C; then aqueous
hydrolysis.
Sch em e 3a
a
Reagents and Conditions: (i) 1 M NaOH (aq), dioxane, reflux;
then 1 M HCl (aq); (ii) Br(CH2)6OH, DCC, DMAP, CH2Cl2, reflux;
(iii) NaBH4, ZnCl2, THF, reflux; then aqueous hydrolysis; (iv)
DIAD, Ph3P, THF, 20 °C; then 21; then MeC(O)SH, 20 °C.
F igu r e 1. Crystal structure of 21 (H atoms are omitted for
clarity), showing the disorder and hydrogen bonds (dashed
lines).
1
trometric and H NMR evidence). Reduction of 17 using
sodium borohydride/zinc chloride16 in refluxing tetrahy-
drofuran gave 21 as a highly crystalline solid (55% yield).
(In accord with the literature precedent,16 attempted
reductions of 17 with lithium aluminum hydride and
diisobutyl aluminum hydride yielded complex reaction
mixtures.) Compound 21 was converted into 22, but all
attempts to prepare dithiol derivative 23 (by analogy with
the conversion of 7 into 8) were unsuccessful; 22 was
recovered unchanged.
dered between two orientations (in a 3:1 ratio), partici-
pating in different hydrogen bonds. The macrocycle
adopts a crown conformation, favorable for metal coor-
dination.18 All four oxygen atoms and S(6) lie within
(0.25 Å from their mean plane (inclined by 43° to the
TTF plane), with lone electron pairs pointing into the
transannular cavity; S(5) lies 1.2 Å away from this plane.
The molecules are linked by hydrogen bonds into an
infinite double ribbon, parallel to the x axis of the crystal.
The ribbons pack in a herringbone motif, so that the TTF
planes in adjacent ribbons form a dihedral angle of 86°.
F ilm Assem bly. Monolayers of compounds 5a , 5b, 8,
16a , and 16b were assembled from saturated acetonitrile
or acetonitrile-benzene solutions onto silver, gold, or
platinum surfaces (see Experimental Section for details).
Initial proof of SAM formation was provided by FTIR and
surface plasmon resonance data. We have previously
reported7 FTIR data for SAMs of 5a , and these data will
not be repeated here. A monolayer of compound 5a self-
X-r a y Cr ysta l Str u ctu r e of 21. In view of the current
interest in crystal structures of TTF crowns4d,e and in
hydrogen-bonded networks in TTF derivatives,17 we
studied the crystal structure of 21 (Figure 1) which
combines both these structural features. The TTF moiety
is nearly planar, folding by 7° along the S(2)‚‚‚S(3) vector.
One of the hydroxymethyl groups is rotationally disor-
(16) Blanchard, P.; Duguay, G.; Cousseau, J .; Salle´, M.; J ubault,
M.; Gorgues, A.; Boubekeur, K.; Batail, P. Synth. Met. 1993, 56, 2113.
(17) (a) Bryce, M. R. J . Mater. Chem. 1995, 5, 1481. (b) Moore, A.
J .; Bryce, M. R.; Batsanov, A. S.; Heaton, J . N.; Lehmann, C. W.;
Howard, J . A. K.; Robertson, N.; Underhill, A. E.; Perepichka, I. F. J .
Mater. Chem. 1998, 8, 1541. (c) Heuze´, K.; Fourmigue´, M.; Batail, P.
J . Mater. Chem. 1999, 9, 2372. (d) Li, H.; Zhang, D.; Zhang, B.; Yao,
Y.; Xu, W.; Zhu, D.; Wang, Z. J . Mater. Chem. 2000, 10, 2063.
(18) Izatt, R. M.; Pawlak, K.; Bradshaw, J . S.; Bruening, R. L. Chem.
Rev. 1995, 95, 2529.

8272 J . Org. Chem., Vol. 65, No. 24, 2000
Moore et al.
Ta ble 1. Red ox P oten tia ls in Va r iou s Med ia (As
In d ica ted ) for 5a , 5b, 8, 16a , a n d 16b in Solu tion a n d a s
Self-Assem bled F ilm s on P la tin u m
1/2
1/2
ox
E1
compound (V)a
E2
electroactive coverage
∆E1 (mV)
(V)a (10-10 molecules cm-2
solutiond (MeCN)
)
+ Ag+ c
b
TTF
5a
5b
8
16a
16b
0.34 0.78
0.48 0.76
0.52 0.76
0.42 0.63
0.44 0.63
0.45 0.63
80
65
65
90
85
SAMd (MeCN)
3.5-5.0
3.0-4.0
3.5-10.0
3.0-4.0
4.5
5a
5b
8
16a
16b
0.52 0.76
0.50 0.76
0.38 0.65
0.41 0.62
0.42 0.62
75
80
65
70
70
F igu r e 2. CV data for self-assembled monolayers of compound
5a on a Pt 1.6 mm diameter electrode vs Ag/AgCl reference,
0.2 M LiClO4/acetonitrile, at scan rates of 100 (lowest current),
200, 500, and 1000 mV s-1 (highest current).
SAMe (0.5 M HClO4)
5a
5b
8
16a
16b
0.35 0.65
0.40 0.62
0.40 0.63
3.0-5.0
3.0
4.0
a
Corrected to Fc/Fc+ as 0.35 V vs Ag/AgCl in acetonitrile and
measured directly against Ag/AgCl in aqueous solution. b Obtained
by graphical integration of the first oxidation peak during the first
scan, as described by Yip and Ward (ref 5); an electroactive
coverage of 5 × 10-10 molecule cm-2 represents a monolayer
coverage, as calculated from Langmuir-Blodgett film studies of
compound 5a . c Ag+ added as AgBF4 to a concentration of 0.02 M.
d
Errors are estimated at (5 mV. 0.2 M Bu4NBF4 as supporting
electrolyte. e Adsorbed onto platinum disk electrode (1.6 mm
diameter, commercial BAS).
adsorbed on a Ag surface showed a shift in the surface
plasmon resonance (SPR) minimum compared to a clean
Ag surface indicating film formation. Fitting of the SPR
curve gave a calculated monolayer thickness of ca. 2.2
nm. From space-filling models for compound 5a , the
molecular length (if the alkyl chain is normal to the
substrate) is ca. 3.4 nm. This would indicate that the
molecules in the SAM are tilted at ca. 40° to the substrate
normal, in agreement with analysis of the FTIR data.7
A similar tilt angle was calculated for a SAM of 16b on
silver from SPR data.
Electr och em istr y. We have studied the solution
electrochemistry of compounds 5a , 5b, 8, 16a , and 16b
in solution and as SAMs, both in the absence and in the
presence of metal cations, by cyclic voltammetry (CV).
All these compounds showed a CV response typical of the
TTF system in acetonitrile solution and as SAMs in
acetonitrile (i.e., two reversible one-electron redox couples)
at potentials consistent with their substitution patterns
(Table 1). Predictably, the electron-withdrawing ester
substituent of 5a and 5b raises the oxidation potentials19
relative to TTF and 8; the additional alkylsulfanyl chains
in 16a and 16b also slightly raise the oxidation potential
(as observed for bis(ethylenedithio)tetrathiafulvalene-
TTF in comparison with TTF).20 The electrochemical
response of the SAMs of all these compounds was stable
if the potential was limited to the first TTF oxidation;
however, as noted by Yip and Ward for SAMs of 1,5 the
CV response gradually decreased when the potential was
F igu r e 3. CV data for self-assembled monolayers of compound
16b (same conditions as Figure 2).
scanned beyond the first oxidation. Compound 16b was
notably more stable in this respect than 5a , 5b, 8, or 16a ,
presumably as a result of the beneficial effect of the
space-filling hexylsulfanyl chain. Adsorption onto plati-
num gave a slightly more reproducible electrochemical
response (less variation in electroactive coverage between
several different samples) than adsorption onto gold. The
quality of the films obtained was unchanged by admix-
ture of the TTF derivative with hexadecylthiol (2:1 or 1:1
molar ratio). For SAMs of 5a , 5b, 8, 16a , and 16b, the
peak current was observed to be proportional to the scan
rate, indicating a “surface wave” response, and the peak
potentials and peak-to-peak separations were indepen-
dent of the scan rate at least up to 1 V s-1, indicating
that kinetic effects at the surface-confined redox centers
were insignificant on the voltammetric time scale. These
data for 5a and 16b are shown in Figures 2 and 3,
respectively. It is notable that the peak shapes were
significantly cleaner for 16b than for the other com-
pounds. The electroactive coverage for compound 8 was
more varied than those for compounds 5a , 5b, and 16a ,
ranging from submonolayer to multilayers, and the
coverage for 16b was by far the most reproducible (Table
1), which is consistent with the improved stability of
SAMs of 16b noted above. The response for 16b was
unchanged after storage of the films in air for several
days. Preliminary X-ray photoelectron spectroscopy (XPS)
(19) (a) Green, D. C. J . Org. Chem. 1979, 44, 1476. (b) Batsanov, A.
S.; Bryce, M. R.; Heaton, J . N.; Moore, A. J .; Skabara, P. J .; Howard,
J . A. K.; Ort´ı, E.; Viruela, P. M.; Viruela, R. J . Mater. Chem. 1995, 5,
1689.
(20) Lichtenberger, D. L.; J ohnston, R. L.; Hinkelman, K.; Suzuki,
T.; Wudl, F. J . Am. Chem. Soc. 1990, 112, 3302.

New Crown Annelated Tetrathiafulvalenes
J . Org. Chem., Vol. 65, No. 24, 2000 8273
data suggested submonolayer coverage on gold with
compounds 5a and 5b, whereas almost complete coverage
was achieved with 16b.21 Multilayer formation has been
observed previously for a ferrocene derivative substituted
with an alkylthiol chain;22 the extensive variation with
8 is consistent with decreased order within the film
structure because of the very short thiol chain, and hence
the coverage for this compound is critically dependent
on the pretreatment (and hence the roughness) of the
electrode surface. The parent system TTF-CH2-SH23
showed similarly variable behavior. This is consistent
with the report of Fujihara et al. that monolayers of the
tetrathiol TTF[S(CH2)3SH]4 are more stable than those
of the monothiol TTFS(CH2)3SH.6
F igu r e 4. The shift in the potentials of E1ox and E2ox for SAMs
of 16b on a Pt 1.6 mm diameter electrode, 0.2 M LiClO4/
acetonitrile, scan rate 200 mV s-1, with added AgBF4.
The SAMs of 5a and 5b were not electroactive in
aqueous electrolytes (cf. compounds 1, which have a
similar ester linkage and also exhibited no CV response
in water).5 However, SAMs of 8, 16a , and 16b exhibited
an electrochemical response in aqueous electrolytes
which was observed between 50 and 100 cycles. More-
over, if the potential scanned was limited to the first TTF
oxidation, the CV response was observed for at least 1000
The binding constants for the formation of 1:1 com-
plexes 5a ‚Ag+ and 16b‚Ag+ in acetonitrile solution were
calculated from UV-vis and CV data, using procedures
described previously for TTF crowns,4c to be log Kobs
)
2.3-2.4 and 2.5-2.6, respectively. This is a suitable value
for an ionophore to be applicable in practical sensor
applications, as a binding constant that is too high results
in irreversible binding.18
ox
cycles. It should be noted that the peak separation (E1
- E1red) in aqueous electrolyte was always larger (>80
mV) than that in acetonitrile, possibly because of a
change in solvation after the redox reaction and/or a
phase change in the SAM as suggested for other sys-
tems.24
Con clu sion s
Synthetic routes have been developed for S2O4-crown
annelated TTFs bearing one terminal thiol group, and
electrochemically active SAMs have been assembled. The
stability and electrochemical behavior of the SAMs is
enhanced by the presence of an additional space-filling
alkyl chain (compounds 16a and 16b). Although multiple
anchor points are certainly beneficial for the electro-
chemical stability of some SAMs,8,25 it seems they are not
necessarily a prerequisite for TTF derivatives which have
a high propensity to form ordered stacks. SAMs of 5a ,
5b, 8, 16a , and 16b are voltammetric sensors for metal
cations, and binding to the ionophore site can be moni-
tored by a positive shift in the first oxidation potential
Ca tion Recogn ition . Electrochemical recognition for
compounds 5a , 5b, 8, 16a , and 16b has been studied in
solution and as SAMs in the presence of different metal
cations. There was a small but highly reproducible
positive response in the value of E11/2 to Li+ and K+ (10-
20 mV in solution), a significant response to Na+ and
Ba2+ (45-55 mV in solution), and a greater response to
Ag+ (65-90 mV in solution), whereas E21/2 was essentially
unaffected. Collectively, these data are consistent with
previous observations of other S2O4-crown compounds.4a,c
For SAMs of 5a , 5b, 8, 16a , and 16b, the CV response
to metal cations in acetonitrile was similar to the solution
result, with the largest response for Ag+ (Table 1). It is
notable that the response seems to be independent of the
length of the thiol chain. Figure 4 shows the shift in both
of the TTF unit (maximum ∆E1 ) 80 mV for Ag+).
1/2
These results and those of Echegoyen et al.8 demonstrate
that TTF is a suitable transducer unit for thin layer
molecular devices for sensing applications.
ox
ox
E1 and E2 for SAMs of 16b in acetonitrile with added
AgClO4. For this compound (but not for 5a , 5b, 8, or 16a ),
a small shift in E2 was also observed at higher [Ag+].
ox
Exp er im en ta l Section
This could be a consequence of surface aggregation or
cooperativity effects between adjacent crowns in the more
densely packed SAMs of this compound, as suggested by
Liu and Echegoyen for SAMs of a TTF-S2O5-crown which
showed a shift in both E1 and E2 in the presence of
NaPF6.8 No voltammetric response to metal cations was
observed for the SAMs of 8, 16a , and 16b in aqueous
media.
Gen er a l Meth od s. Column chromatography was per-
formed on Merck silica gel (70-230 mesh). All reagents were
of commercial quality and were used as supplied unless
otherwise stated; solvents were dried when necessary using
standard procedures and were distilled for chromatographic
use. The gold and platinum substrates for electrochemistry
(disk electrodes, 1.6 mm diameter) were purchased from
Bioanalytical System Inc. (BAS). Pretreatment of the metal
surface for electrochemical experiments involved polishing
with alumina (sequentially decreasing particle size, 1.00-0.05
mm) and washing sequentially with water, dilute sulfuric acid
(2 min), distilled water, and distilled methanol before drying
in a stream of nitrogen. Monolayers were assembled from
saturated acetonitrile or acetonitrile/benzene solutions onto
gold or platinum electrodes or freshly evaporated metal on a
silicon wafer substrate. The electrode or wafer substrate was
removed from the solution containing the TTF derivative after
24 h (Ag and Au) or 72 h (Pt) and then washed with
dichloromethane and dried in a stream of nitrogen. Cyclic
ox
ox
(21) XPS data were obtained on films assembled on gold grown on
a mica substrate as described by Nie et al.: Nie, H. Y.; Mizutani, W.;
Tukumoto, H. Surf. Sci. Lett. 1994, 311, L649. Peaks from the gold
surface were clearly visible in the XPS spectra of films of 5a and 5b,
whereas their intensity was considerably reduced for films of 16b.
(22) Creager, S. F.; Rowe, G. K. J . Electroanal. Chem. 1993, 347,
327.
(23) Moore, A. J .; Goldenberg, L. M.; Petty, M. C.; Bryce, M. R.
Unpublished results. TTF-CH2-SH was obtained from TTF-CH2-
OH (Gar´ın, J .; Orduna, J .; Uriel, J .; Moore, A. J .; Bryce, M. R.;
Wegener, S.; Yufit, D. S.; Howard, J . A. K. Synthesis 1994, 489.) by
analogy with the preparation of 8 from 6 and was isolated as a yellow
solid. δH (CDCl3): 6.31 (2 H, s), 6.17 (1 H, s), 3.48 (2 H, d, J ) 7.9),
1.89 (1 H, t, J ) 7.9).
(25) Beulen, M. W. J .; Kastenberg, M. I.; van Veggel, F. C. J . M.;
Reinhoudt, D. N. Langmuir 1998, 14, 7463.
(24) Reference 3, p 242.

8274 J . Org. Chem., Vol. 65, No. 24, 2000
Moore et al.
voltammetry was performed using an EG&G PARC model 273
potentiostat using iR compensation with an Advanced Bryans
XY recorder. Pt mesh served as the counter electrode, and a
saturated calomel electrode (in aqueous solution) or Ag/Ag+
(in acetonitrile solution) served as the reference electrode. A
ferrocene/ferrocenium couple was used as the internal refer-
ence to test that the reference electrode did not change
potential with added metal salts. Experiments were performed
using either 0.2 mol L-1 Bu4NPF6 (Fluka, electrochemical
grade) in acetonitrile (Aldrich, HPLC grade) or 0.2 mol L-1
HClO4 (Aldrich, ACS reagent) in ultrapure water. For solution
studies, platinum disk electrodes (BAS, 1.6 mm diameter) were
employed as the working electrodes; for studies on the self-
assembled films, the electrodes with assembled layers de-
scribed above were used directly. Metal salts were added to
acetonitrile solutions as LiPF6, NaPF6, KPF6 (Fluka), Ba-
(ClO4)2, NaClO4, or AgBF4 (Aldrich) and to aqueous solutions
as perchlorate salts (Fluka, microselect). In the following
discussion, values of J are given in Hz.
(M+, 25), 470 (55). HRMS: found, 714.1323; calcd, 714.1329.
NMR (CDCl3): δH 7.34 (1 H, s), 4.20 (2 H, t, J ) 6.7), 3.74 (4
H, t, J ) 6.0), 3.68-3.66 (12 H, m), 3.04 (2 H, t, J ) 6.0), 3.03
(2 H, t, J ) 6.0), 2.68 (2 H, t, J ) 7.0), 1.67 (4 H, m), 1.28 (16
H, m).
13 ′-(6-S u lfa n y l-1-h e x y lo x y c a r b o n y l)-5,8,11,14-t e t -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (5b). By analogy with the preparation
of 5a , compound 4b (186 mg, 0.27 mmol) and thiourea (65 mg,
0.85 mmol) in dry ethanol (50 mL) and 1 M potassium
hydroxide (40 mL) after workup and chromatography of the
residue (silica) eluting with dichloromethane/ethyl acetate (1:1
v/v) afforded compound 5b as an orange oil (40 mg, 23%) (three
columns were necessary in order to obtain a pure sample of
the product). Found: C, 43.5; H, 5.2; S, 35.9%. C23H34O6S7
requires: C, 43.8; H, 5.4; S, 35.6%. m/z (EI) (%): 630 (M+, 25),
470 (10). HRMS: found, 630.0393; calcd, 630.0389. NMR
(CDCl3): δH 7.34 (1 H, s), 4.20 (2 H, t, J ) 6.5), 3.72 (4 H, t, J
) 6.2), 3.67-3.65 (12 H, m), 3.03 (2 H, t, J ) 6.2), 3.02 (2 H,
t, J ) 6.2), 2.68 (2 H, t, J ) 7.2), 1.69 (4 H, m), 1.42 (4 H, m).
13′-Meth oxysu lfa n ylm eth yl-5,8,11,14-tetr a oxa ,12,2′,5,5′,2,-
17-h exa th ia -1(3,4)-bicyclop en t-3-en -1-ylid en a )cycloh ep -
ta d eca n e (7). A mixture of diisopropyl azodicarboxylate (0.16
mL, 0.8 mmol) and triphenylphosphine (210 mg, 0.8 mmol)
was stirred in dry tetrahydrofuran (30 mL) under argon at 0
°C for 1 h. A solution of compound 64c (200 mg, 0.4 mmol) in
dry tetrahydrofuran (10 mL) was slowly added, and the
mixture was stirred for 1 h at 20 °C. Thioacetic acid (0.06 mL,
0.8 mmol) was added, and the reaction was stirred for a further
12 h. After evaporation of the solvent, the residue was
chromatographed (silica), eluting initially with dichloromethane
to remove the fast-running impurities. Subsequent elution
with ethyl acetate afforded compound 7 as an orange wax (160
mg, 72%). Found: C, 40.7; H, 4.5%. C19H25O5S7 requires: C,
40.9; H, 4.5%. m/z (DCI) (%): 576 (M+ + NH4+, 20), 558 (M+,
15), 286 (70), 267 (45), 103 (75). NMR (CDCl3): δH 6.21 (1 H,
s), 3.86 (2 H, s), 3.73 (4 H, t, J ) 6.2), 3.68-3.66 (12 H, m),
3.02 (4 H, t, J ) 6.2), 2.38 (3 H, s).
13′-(12-Br om o-1-d od e cyloxyca r b on yl)-5,8,11,14-t e t -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (4a ). To a suspension of compound 34c
(336 mg, 0.65 mmol) in dry dichloromethane (30 mL) was
added dicyclohexylcarbodiimide (215 mg, 1.0 mmol), and the
mixture was stirred at 0 °C under argon for 10 min. 12-Bromo-
1-dodecanol (217 mg, 0.81 mmol) and 4-(dimethylamino)-
pyridine (25 mg, 0.19 mmol) were then added, and the mixture
was stirred at 20 °C for 48 h. The mixture was filtered, and
the filtrate was evaporated. Chromatography of the residue
(silica) eluting with dichloromethane/ethyl acetate (1:1 v/v)
afforded the product initially as an orange oil. Compound 4a
was obtained as a yellow solid from a methanol solution stored
at -5 °C overnight (371 mg, 74%); mp 49 °C (from diethyl
ether/ethanol). Found: C, 45.8; H, 6.1; S, 25.0%. C29H45BrO6S6
requires: C, 45.7; H, 5.9; S, 25.2%. m/z (EI) (%): 762, 760 (M+,
100 and 75), 683 (30), 514 (30), 446 (25), 383 (30). NMR
(CDCl3): δH 7.34 (1 H, s), 4.20 (2 H, t, J ) 6.5), 3.73 (4 H, t, J
) 6.1), 3.67-3.65 (12 H, m), 3.40 (2 H, t, J ) 6.8), 3.04 (2 H,
t, J ) 6.1), 3.02 (2 H, t, J ) 6.1), 1.86 (2 H, p, J ) 6.1), 1.65 (2
H, p, J ) 6.1), 1.27 (16 H, m).
13′-S u lfa n y lm e t h y l-5,8,11,14-t e t r a o x a ,12,2′,5,5′,2,17-
h exa t h ia -1(3,4)-b icyclop en t -3-en -1-ylid en a )cycloh ep t a -
d eca n e (8). To a solution of compound 7 (120 mg, 0.21 mmol)
in dry diethyl ether (25 mL) at 20 °C under argon was added
lithium aluminum hydride (25 mg, 0.63 mmol), and the
reaction was stirred for 4 h. After the reaction was quenched
(ethyl acetate, 5 mL), water (100 mL) was added and the
mixture was extracted with dichloromethane. The combined
organic extracts were washed with water and dried (MgSO4),
and the solvent was evaporated. Chromatography of the
residue (silica) eluting with ethyl acetate afforded compound
8 as a yellow solid (92 mg, 83%); mp 85 °C. Found: C, 39.9;
H, 4.8%. C17H24O4S7 requires: C, 39.5; H, 4.7%. m/z (DCI)
(%): 534 (M+ + NH4+, 25), 516 (M+, 10), 502 (25), 485 (20),
131 (70). HRMS: found, 515.9719; calcd, 515.9715. NMR
(CDCl3): δH 6.18 (1 H, s), 3.74 (4 H, t, J ) 6.3), 3.68-3.66 (12
H, m), 3.49 (2 H, d, J ) 7.9), 3.02 (4 H, t, J ) 6.3), 1.89 (1 H,
t, J ) 7.9).
4-Met h ylt h io-5-(6-h yd r oxyh exylt h io)-1,3-d it h iole-2-
th ion e (10a ). To a suspension of compound 914 (3.0 g, 0.011
mol) in dry methanol (50 mL) under argon at 20 °C was added
a solution of cesium hydroxide monohydrate (1.90 g, 0.011 mol)
in dry methanol (10 mL), and the mixture was stirred for 2 h.
6-Bromohexanol (2.22 mL, 0.0165 mol) was added, and the
reaction was stirred overnight. After evaporation of the solvent
and removal of excess 6-bromohexanol by distillation using a
Kugelro¨hr apparatus (160 °C, 1 mmHg), the residue was
chromatographed (silica), eluting with dichloromethane to
afford compound 10a as an orange oil (3.12 g, 88%). Found:
C, 38.5; H, 5.3%. C10H16OS5 requires: C, 38.4; H, 5.2%. m/z
(DCI): 313 (MH+). HRMS: found, 311.9807; calcd, 311.9802.
NMR (CDCl3): δH 3.65 (2 H, t, J ) 6.0), 2.87 (2 H, t, J ) 7.0),
2.50 (3 H, s), 1.66 (2 H, m), 1.58 (2 H, m), 1.42 (4 H, m), 1.26
(1 H, s).
13 ′-(6-B r o m o -1-h e x y lo x y c a r b o n y l)-5,8,11,14-t e t -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (4b). By analogy with the preparation
of 4a , compound 3 (500 mg, 0.97 mmol) in dry dichloromethane
(75 mL), dicyclohexylcarbodiimide (320 mg, 1.6 mmol), 6-bromo-
1-hexanol (0.16 mL, 1.25 mmol), and 4-(dimethylamino)-
pyridine (25 mg, 0.19 mmol) were reacted to give a product
mixture which was filtered, the filtrate was evaporated, and
the excess 6-bromo-hexanol was removed by distillation using
a Kugelro¨hr apparatus (125 °C at 1 mmHg). Chromatography
of the residue (silica) eluting with dichloromethane/ethyl
acetate (4:1 v/v) afforded compound 4b as an orange oil (530
mg, 81%). Found: C, 41.0; H, 5.1; S, 28.1%. C23H33BrO6S6
requires: C, 40.8; H, 4.9; S, 28.4%. m/z (EI) (%): 678, 676 (M+,
60 and 35), 599 (40), 446 (20). NMR (CDCl3): δH 7.34 (1 H, s),
4.12 (2 H, t, J ) 6.5), 3.71 (4 H, t, J ) 6.1), 3.65-3.63 (12 H,
m), 3.40 (2 H, t, J ) 6.6), 3.02 (2 H, t, J ) 6.1), 3.01 (2 H, t, J
) 6.1), 1.86, (2 H, p, J ) 6.4), 1.70 (2 H, p, J ) 6.5), 1.44 (4 H,
m).
13′-(12-Su lfa n yl-1-d od ecyloxyca r b on yl)-5,8,11,14-t et -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (5a ). A mixture of compound 4a (284
mg, 0.37 mmol) and thiourea (84 mg, 1.12 mmol) in dry ethanol
(80 mL) was stirred at reflux under argon for 24 h. After the
solution was cooled , the solvent was removed, 1 M potassium
hydroxide (40 mL) was added to the residue, and the resultant
mixture was stirred at reflux for 18 h. After the mixture was
cooled, it was extracted with diethyl ether (4 × 50 mL), the
combined extracts were dried (MgSO4), and the solvent was
evaporated. Chromatography of the residue (silica) eluting
with dichloromethane/ethyl acetate (2:1 v/v) afforded com-
pound 5a as an orange oil (112 mg, 42%) (four columns were
necessary in order to obtain a pure sample of the product).
Found: C, 49.0; H, 6.6; S, 31.2%. C29H46O6S7 requires: C, 48.7;
H, 6.5; S, 31.4%. m/z (DCI) (%): 732 (M+ + NH4+, 45), 714
4-H e xylt h io-5-(6-h yd r oxyh e xylt h io)-1,3-d it h iole -2-
th ion e (10b). By analogy with the preparation of 10a ,
compound 914 (5.0 g, 0.015 mmol) in dry methanol (75 mL),

New Crown Annelated Tetrathiafulvalenes
J . Org. Chem., Vol. 65, No. 24, 2000 8275
cesium hydroxide monohydrate (2.50 g, 0.015 mol) in dry
methanol (10 mL), and 6-bromohexanol (2.22 mL, 0.0165
mmol) after chromatography (silica) eluting with dichlo-
romethane afforded compound 10b as an orange oil (4.67 g,
82%). Found: C, 47.3; H, 7.0%. C15H26OS5 requires: C, 47.1;
H, 6.9%. m/z (DCI): 383 (MH+). HRMS: found, 382.0577;
calcd, 382.0582. NMR (CDCl3): δH 3.62 (2 H, t, J ) 6.0), 2.86
(4 H, t, J ) 7.2), 1.67 (4 H, m), 1.57 (2 H, m), 1.42 (6 H, m),
1.31 (4 H, m), 0.88 (3 H, t, J ) 6.9).
4-Meth ylth io-5-(6-d ip h en yl-t-bu tylsilyloxyh exylth io)-
1,3-d ith iole-2-th ion e (11a ). To a solution of compound 10a
(2.60 g, 8.33 mmol) in dry dimethylformamide (50 mL) under
argon at 20 °C was added imidazole (6.0 g, 88 mmol) and tert-
butyldiphenylsilyl chloride (2.29 g, 8.33 mmol), and the
mixture was stirred for 12 h. The solvent was evaporated in
vacuo. The residue was dissolved in dichloromethane, washed
with water, and dried (MgSO4), and the solvent was evapo-
rated. Chromatography of the residue (silica) eluting with
dichloromethane afforded compound 11a as an orange oil (4.45
g, 97%). Found: C, 57.0; H, 6.0%. C26H34OS5Si requires: C,
56.7; H, 6.2%. m/z (DCI) (%): 551 (MH+, 100), 473 (80), 367
(70), 196 (80). NMR (CDCl3): δH 7.68-7.64 (4 H, m), 7.42-
7.38 (6 H, m), 3.65 (2 H, t, J ) 7.1), 2.83 (2 H, t, J ) 7.1), 2.47
(3 H, s), 1.68 (2 H, m), 1.56 (2 H, m), 1.36 (4 H, m), 1.05 (9 H,
s).
argon at 20 °C was added tetrabutylammonium fluoride (1 M
in tetrahydrofuran, 2 mL, excess), and the mixture was stirred
for 12 h. After evaporation of the solvent, the residue was
chromatographed (silica), eluting with ethyl acetate to afford
compound 14a as an orange oil (200 mg, 91%). Found: C, 42.6;
H, 5.7%. C23H36O5S8 requires: C, 42.6; H, 5.7%. m/z (DCI)
(%): 668 (M+ + NH4+, 85), 649 (MH+, 80), 367 (60), 279 (100),
168 (95). NMR (CDCl3): δH 3.74 (4 H, t, J ) 6.3), 3.68-3.66
(12 H, m), 3.64 (2 H, t, J ) 6.2), 3.03 (4 H, t, J ) 6.2), 2.82 (2
H, t, J ) 7.1), 2.43 (3 H, s), (1.66-1.25 8 H, m), OH not
observed.
13′-(6-H yd r oxy-1-h exylt h io)-4′-h exylt h io-5,8,11,14-t et -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (14b). By analogy with the prepara-
tion of 14a , 13b (1.40 g, 1.46 mmol), tetrahydrofuran (50 mL),
and tetrabutylammonium fluoride (1 M in tetrahydrofuran, 2
mL, excess) gave a product which was chromatographed
(silica), eluting with dichloromethane/ethyl acetate (5:1 v/v)
to afford compound 14b as an orange oil (800 mg, 76%).
Found: C, 46.6; H, 6.6%. C28H46O5S8 requires: C, 46.8; H,
6.5%. m/z (DCI) (%): 736 (M+ + NH4+, 15), 719 (MH+, 25),
473 (100). NMR (CDCl3): δH 3.74 (4 H, t, J ) 6.3), 3.68-3.63
(12 H, m), 3.60 (2 H, t, J ) 6.6), 3.00 (4 H, t, J ) 6.2), 2.78 (4
H, t, J ) 7.2), 1.65-1.51 (6 H, m), 1.36-1.21 (10 H, m), 0.85
(3 H, t, J ) 6.5), OH not observed.
4-H exylt h io-5-(6-d ip h en yl-t-b u t ylsilyloxyh exylt h io)-
1,3-d ith iole-2-th ion e (11b). This compound was prepared
analogously to 11a from 10b (4.00 g, 10.5 mmol), dimethyl-
formamide (50 mL), imidazole (5.0 g, 73.5 mmol), and tert-
butyldiphenylsilyl chloride (2.73 mL, 10.5 mmol). Chromatog-
raphy of the residue (silica) eluting with hexane/dichloro-
methane (1:1 v/v) afforded compound 11b as an orange oil (5.78
g, 89%). Found: C, 59.7; H, 6.9%. C31H44OS5Si requires: C,
60.0; H, 7.1%. m/z (DCI): 621 (MH+, 100%). NMR (CDCl3):
δH 7.68-7.64 (4 H, m), 7.43-7.37 (6 H, m), 3.65 (2 H, t, J )
6.3), 2.87 (2 H, t, J ) 7.2), 2.84 (2 H, t, J ) 7.2), 1.65 (4 H, m),
1.59 (2 H, m), 1.37 (6 H, m), 1.30 (4 H, m), 1.07 (9 H, s), 0.89
(3 H, t, J ) 6.9).
13′-(6-Meth oxysu lfa n yl-1-h exylth io)-4′-m eth ylth io-5,8,-
11,14-tetr a oxa ,12,2′,5,5′,2,17-h exa th ia -1(3,4)-bicyclop en t-3-
en -1-ylid en a )cycloh ep ta d eca n e (15a ). A mixture of diiso-
propyl azodicarboxylate (0.09 mL, 0.46 mmol) and triphenyl-
phosphine (120 mg, 0.46 mmol) was stirred in dry tetrahy-
drofuran (50 mL) under argon at 0 °C for 1 h. A solution of
compound 14a (150 mg, 0.23 mmol) in dry tetrahydrofuran
(10 mL) was slowly added, and the mixture was stirred for 1
h at 20 °C. Thioacetic acid (0.035 mL, 0.46 mmol) was added,
and the reaction was stirred for a further 12 h. After evapora-
tion of the solvent, the residue was chromatographed (silica),
eluting initially with dichloromethane and subsequently with
dichloromethane/ethyl acetate (1:1 v/v) to afford compound 15a
as an orange oil (117 mg, 71%). Found: C, 42.5; H, 5.2%.
13′-(6-Dip h en yl-t-b u t ylsilyloxy-1-h exylt h io)-4′-m et h yl-
t h io-5,8,11,14-t et r a oxa ,12,2′,5,5′,2,17-h exa t h ia -1(3,4)-b icy-
clop en t-3-en -1-ylid en a )cycloh ep ta d eca n e (13a ). A mix-
ture of compound 11a (1.0 g, 1.82 mmol) and compound 124a
(0.75 g, 1.87 mmol) in triethyl phosphite (20 mL) was stirred
at 130 °C for 5 h. After the mixture was cooled, the solvent
was evaporated under reduced pressure and the residue was
chromatographed (silica) eluting with dichloromethane/ethyl
acetate (1:1 v/v) to afford in order of elution (i) the self-coupled
product from 11a (250 mg, 25%), (ii) compound 13a as an
orange oil (325 mg, 20%), and (iii) the self-coupled product from
C
25H38O5S9 requires: C, 42.5; H, 5.4%. m/z (DCI) (%): 724 (M+
+ NH4+, 30), 705 (MH+, 15), 383 (35), 228 (60), 168 (100). NMR
(CDCl3): δH 3.71 (4 H, t, J ) 6.3), 3.66-3.63 (12 H, m), 3.01
(4 H, t, J ) 6.1), 2.84 (2 H, t, J ) 6.9), 2.81 (2 H, t, J ) 6.9),
2.40 (3 H, s), 2.30 (3 H, s), 1.61-1.53 (4 H, m), 1.40-1.33 (4
H, m).
13′-(6-Meth oxysu lfa n yl-1-h exylth io)-4′-h exylth io-5,8,11,-
14-tetr a oxa ,12,2′,5,5′,2,17-h exa th ia -1(3,4)-bicyclop en t-3-en -
1-ylid en a )cycloh ep ta d eca n e (15b). By analogy with the
preparation of 15b, diisopropyl azodicarboxylate (0.13 mL, 0.62
mmol), triphenylphosphine (165 mg, 0.62 mmol), tetrahydro-
furan (50 mL), compound 14b (220 mg, 0.31 mmol) in dry
tetrahydrofuran (10 mL), and thioacetic acid (0.045 mL, 0.62
mmol) gave a product which was chromatographed (silica),
eluting initially with dichloromethane and subsequently with
dichloromethane/ethyl acetate (3:1 v/v) to afford compound 15b
12 (240 mg, 35%). 13a Found: C, 53.0; H, 6.0%. C39H54O5S8Si
+
requires: C, 52.8; H, 6.1%. m/z (DCI) (%): 904 (M+ + NH4
,
75), 887 (MH+, 25), 295 (100). NMR (CDCl3): δH 7.67-7.64 (4
H, m), 7.42-7.36 (6 H, m), 3.72 (4 H, t, J ) 6.1), 3.68-3.66
(12 H, m), 3.61 (2 H, t, J ) 6.3), 3.04 (2 H, t, J ) 6.1), 3.02 (2
H, t, J ) 6.1), 2.83 (2 H, t, J ) 6.4), 2.47 (3 H, s), 1.61-1.53 (4
H, m), 1.35-1.31 (4 H, m), 1.04 (9 H, s).
1
as an orange oil (218 mg, 92%) (ca. 90% pure by H NMR and
used directly in the next step). m/z (DCI) (%): 794 (M+ + NH4
,
+
13′-(6-Diph en yl-t-bu tylsilyloxy-1-h exylth io)-4′-h exylth io-
5,8,11,14-tetr a oxa ,12,2′,5,5′,2,17-h exa th ia -1(3,4)-bicyclop en t-
3-en -1-ylid en a )cycloh ep ta d eca n e (13b). By analogy with
the preparation of 13a , 11b (1.12 g, 1.82 mmol) and compound
124a (0.75 g, 1.87 mmol) in triethyl phosphite (20 mL) gave a
residue which was chromatographed (silica), eluting with
dichloromethane/ethyl acetate (3:1 v/v) to afford 13b as an
orange oil (535 mg, 31%) after separation from self-coupled
products. Found: C, 55.3; H, 6.9%. C44H64O5S8Si requires: C,
55.2; H, 6.7%. m/z (DCI) (%): 956 (MH+, 35), 295 (100). NMR
(CDCl3): δH 7.67-7.64 (4 H, m), 7.41-7.37 (6 H, m), 3.72 (4
H, t, J ) 6.1), 3.68-3.65 (12 H, m), 3.61 (2 H, t, J ) 6.3), 3.04
(2 H, t, J ) 6.1), 3.02 (2 H, t, J ) 6.1), 2.87 (2 H, t, J ) 7.2),
2.84 (2 H, t, J ) 7.2), 1.65 (4 H, m), 1.59 (2 H, m), 1.37 (6 H,
m), 1.29 (4 H, m), 1.03 (9 H, s), 0.87 (3 H, t, J ) 6.9).
30), 777 (MH+, 20), 531 (80), 383 (70), 222 (100). HRMS: found,
776.0982; calcd for C30H48O5S9, 776.0978. NMR (CDCl3): δH
3.71 (4 H, t, J ) 6.2), 3.66-3.64 (12 H, m), 3.00 (4 H, t, J )
6.3), 2.83 (2 H, t, J ) 6.9), 2.81 (2 H, t, J ) 6.9), 2.79 (2 H, t,
J ) 6.9), 2.29 (3 H, s), 1.63-1.54 (6 H, m), 1.38-1.27 (10 H,
m), 0.88 (3 H, t, J ) 6.6).
13′-(6-Su lfa n yl-1-h exylth io)-4′-m eth ylth io-5,8,11,14-tet-
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (16a ). To a solution of compound 15a
(100 mg, 0.14 mmol) in dry diethyl ether (25 mL) at 20 °C
under argon was added lithium aluminum hydride (10 mg,
0.26 mmol), and the reaction was stirred for 4 h. After the
reaction was quenched (ethyl acetate, 1 mL), water (30 mL)
was added and the mixture was extracted with dichlo-
romethane. The combined organic extracts were washed with
water and dried (MgSO4), and the solvent was evaporated.
Chromatography of the residue (silica) eluting with ethyl
acetate afforded compound 16a as yellow oil (80 mg, 88%).
13′-(6-Hyd r oxy-1-h exylth io)-4′-m eth ylth io-5,8,11,14-tet-
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (14a ). To a solution of compound 13a
(300 mg, 0.34 mmol) in dry tetrahydrofuran (25 mL) under

8276 J . Org. Chem., Vol. 65, No. 24, 2000
Moore et al.
Found: C, 41.7; H, 5.4; S, 43.6%. C23H36O4S9 requires: C, 41.5;
H, 5.5; S, 43.4%. m/z (DCI) (%): 682 (M+ + NH4+, 35), 665
(MH+, 10), 372 (90), 317 (70), 279 (100). HRMS: found,
664.0099; calcd, 664.0093. NMR (CDCl3): δH 3.73 (4 H, t, J )
6.2), 3.68-3.66 (12 H, m), 3.03 (4 H, t, J ) 6.2), 2.81 (2 H, t,
J ) 7.5), 2.68 (2 H, t, J ) 7.2), 2.42 (3 H, s), 1.72-1.60 (4 H,
m), 1.50-1.39 (4 H, m), SH not observed.
sodium borohydride (65 mg, 1.7 mmol) and zinc chloride (232
mg, 1.7 mmol), and the mixture was refluxed for 4 h. After
the mixture was cooled, the reaction was quenched (ethyl
acetate, 5 mL), water was added (100 mL), and the mixture
was extracted with dichloromethane. The combined organic
extracts were washed with water and dried (MgSO4), and the
solvent was evaporated. Chromatography of the residue (silica)
eluting with acetone afforded compound 21 as an orange solid
(115 mg, 50%); mp 148-149 °C (from acetone). Found: C, 40.7;
H, 4.9%. C18H26O6S6 requires: C, 40.7; H, 4.9%. m/z (EI): 530
(M+, 80%). NMR (CDCl3): δH 4.41 (4 H, d, J ) 5.7), 3.73 (4 H,
t, J ) 6.2), 3.68-3.66 (12 H, m), 3.02 (4 H, t, J ) 6.2), 2.48 (2
H, t, J ) 5.7).
13′-(6-Su lfa n yl-1-h exylt h io)-4′-h exylt h io-5,8,11,14-t et -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (16b). By analogy with the prepara-
tion of 16a , compound 15b (200 mg, 0.14 mmol, ca. 90% pure
from previous reaction), diethyl ether (25 mL), and lithium
aluminum hydride (10 mg, 0.26 mmol) gave a product that
when chromatographed (silica) eluting with dichloromethane/
ethyl acetate (6:1 v/v) afforded compound 16b as an orange
oil (134 mg, 71%). Found: C, 46.0; H, 6.2%. C28H46O4S9
13 ′, 4 ′-B i s (M e t h o x y s u lfa n y lm e t h y l)-5,8,11,14-t e t -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (22). A mixture of diisopropyl azodi-
carboxylate (0.15 mL, 0.75 mmol) and triphenylphosphine (200
mg, 0.75 mmol) was stirred in dry tetrahydrofuran (50 mL)
under argon at 0 °C for 1 h. A solution of compound 21 (100
mg, 0.19 mmol) in dry tetrahydrofuran (10 mL) was slowly
added, and the mixture was stirred for 1 h at 20 °C. Thioacetic
acid (0.06 mL, 0.8 mmol) was added, and the reaction was
stirred for a further 12 h. After evaporation of the solvent,
the residue was chromatographed (silica), eluting initially with
dichloromethane and subsequently with dichloromethane/ethyl
acetate (1:1 v/v) to afford compound 22 as an orange solid (90
mg, 73%); mp 96-97 °C. Found: C, 41.0; H, 4.6%. C22H30O6S8
requires: C, 40.8; H, 4.7%. m/z (EI): 646 (M+, 100%). NMR
(CDCl3): δH 3.94 (4 H, s), 3.71 (4 H, t, J ) 6.3), 3.67-3.65 (12
H, m), 3.00 (4 H, t, J ) 6.3), 2.37 (6 H, s).
X-r a y Cr ysta llogr a p h y. A single crystal (0.2 × 0.2 × 0.3
mm) of 21 suitable for the X-ray diffraction study was grown
from acetone. The experiment was carried out on a SMART
3-circle diffractometer with a 1K charge-coupled device area
detector, using Mo KR radiation (0.710 73 Å). The structure
was solved by direct methods and refined by full-matrix least
squares against F2 of all data, using SHELX-97 software (G.
M. Sheldrick, Go¨ttingen University, 1997). Crystal data:
requires: C, 45.7; H, 6.3; S, 39.3%. m/z (DCI) (%): 752 (M+
+
NH4+, 45), 735 (MH+, 10), 368 (30), 280 (100). NMR (CDCl3):
δH 3.73 (4 H, t, J ) 6.2), 3.68-3.66 (12 H, m), 3.03 (4 H, t, J
) 6.3), 2.81 (4 H, t, J ) 7.1), 2.67 (2 H, t, J ) 7.1), 1.66-1.60
(6 H, m), 1.43-1.29 (10 H, m), 0.89 (3 H, t, J ) 6.6), SH not
observed.
13′,4′-Bis(car boxy)-5,8,11,14-tetr aoxa,12,2′,5,5′,2,17-h exath ia-
1(3,4)-bicyclop en t-3-en -1-ylid en a )cycloh ep ta d eca n e (18).
A stirred solution of compound 174c (1.0 g, 1.7 mmol) in a
mixture of dioxane (80 mL) and 1 M sodium hydroxide (10 mL)
was refluxed for 24 h. After the mixture was cooled, the solvent
was evaporated and the residue was dissolved in water (125
mL). The aqueous phase was washed with dichloromethane
and acidified with 1 M hydrochloric acid to precipitate the
product as a red solid. The solid was collected by filtration,
washed sequentially with water, ethanol, and diethyl ether,
and air-dried at 60 °C, affording compound 18 as a red solid
of sufficient purity for further reaction (660 mg, 70%). (Because
of insolubility in a wide range of solvents, an analytically pure
sample could not be obtained.) NMR [(CD3)2SO]: δH 4.52 (2
H, br s, OH), 3.62 (4 H, t, J ) 5.8), 3.59-3.51 (12 H, m), 3.02
(4 H, t, J ) 5.8).
13 ′, 4 ′-B i s (2-b r o m o e t h o x y c a r b o n y l)-5,8,11,14-t e t -
r aoxa,12,2′,5,5′,2,17-h exath ia-1(3,4)-bicyclopen t-3-en -1-ylide-
n a )cycloh ep ta d eca n e (19). To a suspension of compound 18
(200 mg, 0.36 mmol) in dry dichloromethane (75 mL) at 20 °C
under argon was added dicyclohexylcarbodiimide (215 mg, 1.0
mmol), and the mixture was stirred with ultrasound for 0.5
h. 2-Bromohexanol (0.5 mL, excess) and 4-(dimethylamino)-
pyridine (25 mg, 0.2 mmol) were added, and the mixture was
refluxed with ultrasound for 24 h. After the mixture was
cooled, the reaction was filtered and the filtrate was evapo-
rated. Chromatography of the residue (silica) eluting with
dichloromethane/ethyl acetate (1:1 v/v) afforded compound 19
C
18H26O6S6, fw 530.75, monoclinic, space group P21/c (No. 14),
a ) 12.517(3) Å, b ) 10.073(3) Å, c ) 20.220(4) Å, â ) 107.14-
(2)°, U ) 2436(1) Å3, Z ) 4, µ ) 0.59 mm-1, 12 075 reflections
(2θ e 51°), 4084 unique, Rint ) 0.059, 280 refined parameters
(H atoms ‘riding’), R ) 0.072 [2695 data with F2 g 2σ(F2)],
wR(F2) ) 0.144, max residual ∆F ) 0.45 e Å-3. Full structural
data (excluding structure factors) have been deposited at the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC-142587.
Ackn owledgm en t. We thank BNFL (British Nuclear
Fuels Research and Technology) and the University of
Durham for funding this work. We thank Dr. J . Cress-
well for SPR data, Dr. C. Pearson for assistance with
SAM formation, Dr. R. Kataky for some of the electro-
chemical data, and Professor J . P. Badyal and E.
Humphries for the XPS data cited in ref 21. J .A.K.H.
thanks the EPSRC for a Senior Research Fellowship.
as a red oil (185 mg, 67%). Found: C, 34.5; H, 3.6%. C22H28
-
Br2O8S6 requires: C, 34.2; H, 3.7%. m/z (EI) (%): 770 (M+,
85), 622 (60). NMR (CDCl3): δH 4.55 (4 H, d, J ) 6.2), 3.73 (4
H, t, J ) 6.2), 3.68-3.66 (12 H, m), 3.56 (4 H, t, J ) 6.2), 3.03
(4 H, t, J ) 6.2).
13′,4′-Bis(h yd r oxym eth yl)-5,8,11,14-tetr a oxa ,12,2′,5,5′,2,17-
h exa t h ia -1(3,4)-b icyclop en t -3-en -1-ylid en a )cycloh ep t a -
d eca n e (21). To a solution of compound 174c (250 mg, 0.43
mmol) in dry tetrahydrofuran (50 mL) under argon was added
J O000936Q