Amphiphilic fullerene-cholesterol derivatives: Synthesis and preparation of Langmuir and Langmuir-Blodgett films

Article abstract of DOI:10.1002/1522-2675(20010516)84:5<1119::AID-HLCA1119>3.0.CO;2-3

Amphiphilic fullerene bis-adducts 11 and 14 containing two and four cholesterol moieties, respectively, were prepared starting from the corresponding bis-malonate derivatives. In a systematic study, their spreading behavior at the air-water interface was compared to that of bis-adduct 6 with no polar head-group. Compared to 6, for which some three-dimensional aggregation occurs, the polar head-group in 11 and 14 is responsible for an attractive interaction with the aqueous subphase, forcing the molecules towards the water surface into a two-dimensional arrangement. Even if homogeneous Langmuir films were obtained with both 11 and 14, only the films of 14 show a reversible compression/expansion behavior. This suggests that, by increasing the number of cholesterol subunits, the encapsulation of the C-sphere in its addend is more efficient, thus preventing fullerene-fullerene interactions and aggregation phenomena. The Langmuir films of 11 and 14 were also efficiently transferred onto hydrophilic quartz slides, yielding Langmuir-Blodgett films.

Full text of DOI:10.1002/1522-2675(20010516)84:5<1119::AID-HLCA1119>3.0.CO;2-3

Helvetica Chimica Acta ± Vol. 84 (2001)
1119
Amphiphilic Fullerene-Cholesterol Derivatives: Synthesis and
Preparation of Langmuir and Langmuir-Blodgett Films
by Delphine Felder, Maria del Pilar CarreoÂn1), Jean-Louis Gallani, Daniel Guillon*,
and Jean-François Nierengarten*
Â
Â
Groupe des Materiaux Organiques, Institut de Physique et Chimie des Materiaux de Strasbourg,
Â
Universite Louis Pasteur et CNRS, 23 rue du Loess, F-67037 Strasbourg Cedex
and Thierry Chuard and Robert Deschenaux*
Â
Ã
Ã
Institut de Chimie, Universite de Neuchatel Av. de Bellevaux 51, Case postale 2, CH-2007 Neuchatel
Amphiphilic fullerene bis-adducts 11 and 14 containing two and four cholesterol moieties, respectively,
were prepared starting from the corresponding bis-malonate derivatives. In a systematic study, their spreading
behavior at the air-water interface was compared to that of bis-adduct 6 with no polar head-group. Compared to
6, for which some three-dimensional aggregation occurs, the polar head-group in 11 and 14 is responsible for an
attractive interaction with the aqueous subphase, forcing the molecules towards the water surface into a two-
dimensional arrangement. Even if homogeneous Langmuir films were obtained with both 11 and 14, only the
films of 14 show a reversible compression/expansion behavior. This suggests that, by increasing the number of
cholesterol subunits, the encapsulation of the C-sphere in its addend is more efficient, thus preventing fullerene-
fullerene interactions and aggregation phenomena. The Langmuir films of 11 and 14 were also efficiently
transferred onto hydrophilic quartz slides, yielding Langmuir-Blodgett films.
1. Introduction. ± Growing attention is currently devoted to fullerene derivatives for
applications in supramolecular chemistry and materials science [1]. In this respect, the
incorporation of such compounds into thin ordered films appears as an important issue
[2][3]. One of the most widely pursued approach towards structurally ordered
fullerene assemblies has been the preparation of Langmuir films at the air-water
interface and their transfer onto solid substrates [2]. However, monolayers of fullerene
derivatives are difficult to prepare due to strong fullerene-fullerene interactions and
three-dimensional aggregation [2]. Indeed, fullerene derivatives with good spreading
characteristics and reversible compression/decompression behavior are quite rare
[4][5]. In collaborative work by Diederich, Stoddart, Echegoyen, and Leblanc,
fullerene derivatives bearing dendritic branches with peripheral acylated glucose units
have been investigated [4]. These derivatives are able to form stable ordered
monolayers at the air-water interface and show reversible behavior in successive
compression/decompression cycles. The dendritic portion is effective in preventing the
irreversible aggregation usually observed for amphiphilic fullerene derivatives. We
have recently shown that good spreading characteristics and a reversible compression/
expansion behavior can also be obtained with amphiphilic cyclic fullerene bis-adducts.
In this case, the encapsulation of the C-sphere in a cyclic addend surrounded by long
alkyl chains also prevents efficiently the aggregation of the fullerene moieties [5]. As
1
)
Permanent address: Instituto de Ciencias Nucleares, UNAM, Circuito exterior, C.U., A. Postal 70-543,
Â
Â
Mexico, D.F., Mexico.

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Helvetica Chimica Acta ± Vol. 84 (2001)
part of this research, we now show that substitution of the amphiphilic cyclic fullerene
bis-adduct substructure with cholesterol groups is also a convenient way to prepare
suitable derivatives for efficient incorporation into Langmuir films.
2. Results and Discussion. ± 2.1. Synthesis. We planned to attach the cholesterol
moieties to the [5,6]fullerene-C60-Ih (C60) core by taking advantage of the versatile
regioselective reaction developed in the group of Diederich [6], which led to
macrocyclic bis-adducts of C60 by a macrocyclization reaction at the fullerene sphere
with bis-malonate derivatives in a double Bingel cyclopropanation [7]. Therefore, we
prepared the bis-malonate 4 substituted with two cholesterol residues starting from
cholesterol (ˆ(3b)-cholest-5-en-3-ol) (Scheme 1). Compound 1 was prepared in two
steps from cholesterol as previously described [8]. In this synthetic process, the ether
derivative 1 is obtained with the natural (3S)-configuration [8]. All efforts to efficiently
prepare acid 3 towards formation of the desired bis-malonate 4 were disappointing. The
preparation of 3 was initially attempted by heating alcohol 1 with 2,2-dimethyl-1,3-
dioxane-4,6-dione (ˆ Meldrumꢀs acid) [9]. Decomposition was observed under these
conditions, and compound 3 was thus obtained in low yield. N,N'-Dicyclohexylcarbo-
diimide(DCC)-mediated esterification of 1 with tert-butyl malonate followed by
selective hydrolysis of the tert-butyl ester moiety of the resulting 2 under acidic
conditions gave 3 in poor yield. Indeed, deprotection of 2 under various conditions led
to decomposition, and no further efforts were made to prepare 4 by this route. In
Scheme 1
a)
3O
O
OH
O
O
O
O
1
2
c)
b)
HO
O
O
OH
O
OH
O
O
O
O
O
5
O
O
3
d)
O
O
O
O
O
O
O
O
O
O
4
a) t-BuO2CCH2CO2H, DCC, DMAP, BtOH, CH2Cl2, 08 to r.t. (65%). b) CF3CO2H, CH2Cl2, r.t. (non-
reproducible yields). c) Meldrumꢀs acid, 1208 (10 ± 35%). d) DCC, DMAP, BtOH, CH2Cl2 (93%).

Helvetica Chimica Acta ± Vol. 84 (2001)
1121
contrast, the reaction of 1 with diacid 5 [10] in CH2Cl2 under esterification conditions
(DCC, N,N-dimethylpyridin-4-amine (DMAP), and 1-hydroxy-1H-benzotriazole
(BtOH)) gave the desired bis-malonate 4 in 74% yield.
Treatment of C60 with 4, I2, and diazabicyclo[5.4.0]undec-7-ene (DBU) in toluene
at room temperature afforded the desired cyclization product 6 in 28% yield
(Scheme 2). It is well-established that the 1,3-phenylenebis(methylene)-tethered bis-
malonates produce regioselectively the cis-2 addition pattern at C60 [6][10][11]. All the
spectroscopic data obtained for compound 6 are in agreement with such a cis-2 addition
pattern. In particular, the UV/VIS spectra of the bis-cyclopropanated fullerene
derivative 6 shows all the characteristic features of a cis-2 bis-adduct [10].
Scheme 2
a)
4
O
O
O
O
O
O
O
O
O
O
6
a) C60, I2, DBU, toluene, r.t. (28%).
The preparation of the corresponding fullerene derivative bearing a triethylene
glycol-type polar head group was achieved by a similar route (Schemes 3 and 4).
Treatment of triethylene glycol monomethyl ether with p-toluene sulfonyl chloride
(TsCl) and pyridine, followed by reaction of the resulting tosylate with dimethyl 5-
hydroxyisophthalate in the presence of K2CO3 in DMF at 708 afforded 7 in 88% yield
Scheme 3
OH
O
OH
O
O
O
O
O
O
O
MeO
OMe
HO
OH
HO
O
a) b)
c)
d)
O
O
O
O
O
O
O
O
O
O
O
9
7
8
O
O
O
a) TsCl, pyridine, CH2Cl2, 08 (69%). b) Dimethyl 5-hydroxyisophthalate, K2CO3, DMF, 808 (88%). c) LiAlH4,
THF, 08 to r.t. (88%). d) Meldrumꢀs acid, 1108 (98%).

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Helvetica Chimica Acta ± Vol. 84 (2001)
Scheme 4
O
O
O
O
a)
b)
9
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
10
11
O
O
O
O
O
O
O
a) 1, DCC, DMAP, BtOH, CH2Cl2 (73%). b) C60, I2, DBU, toluene, r.t. (50%).
(Scheme 3). Lithium aluminum hydride (LiAlH4) reduction then gave diol 8.
Subsequent treatment with Meldrumꢀs acid afforded diacid 9 in 98% yield.
Reaction of alcohol 1 with diacid 9 in CH2Cl2 under esterification conditions (DCC,
DMAP, and BtOH) gave bis-malonate 10 in 73% yield (Scheme 4). Subsequent
reaction with C60, I2, and DBU in toluene at room temperature afforded the cis-2 bis-
adduct 11 in 50% yield.
The synthesis of the fullerene derivative bearing four cholesterol subunits is shown
in Schemes 5 and 6. Treatment of 1 with TsCl and pyridine, followed by reaction of the
resulting tosylate with KBr in refluxing acetone and subsequent treatment of the
resulting bromide with 5-(hydroxymethyl)benzene-1,3-diol in the presence of K2CO3 in
DMF at 708 afforded 12 (Scheme 5). Reaction of alcohol 12 with diacid 9 in CH2Cl2
under esterification conditions (DCC, DMAP, and BtOH) gave bis-malonate 13 in
85% yield. Reaction of 13 with C60, I2, and DBU in toluene at room temperature
afforded the cis-2 bis-adduct 14 in 44% yield (Scheme 6).
Whereas liquid-crystalline properties were observed for some of the cholesterol
precursors (see the Table in the Exper. Part), no mesomorphic behavior was detected
for the three cholesterol-fullerene derivatives 6, 11, and 14. Actually, they are
amorphous glassy compounds at room temperature. Decomposition was observed at
ca. 1508 for compound 6. In contrast, differential scanning calorimetry (DSC) analysis
of 11 and 14 revealed glass transitions at 678 and 358, respectively. In both cases, an
isotropic liquid was obtained after the glass transition.
2.2. Langmuir Films at the Air-Water Interface. In spite of the lack of a polar head
group, compound 6 is apparently able to form Langmuir films at the air-water interface:
well-defined isotherms with a rather high collapse pressure (40 mN/m) were recorded

Helvetica Chimica Acta ± Vol. 84 (2001)
1123
Scheme 5
O
O
O
O
O
O
O
O
O
a) b) c)
d)
1
O
O
O
O
O
O
O
O
O
O
O
12
13
O
O
OH
O
O
a) TsCl, pyridine, 08 (85%). b) KBr, acetone, DMF, D (90%). c) 5-(Hydroxymethyl)benzene-1,3-diol, K2CO3,
DMF, 808 (75%). d) 9, DCC, DMAP, BtOH, 08 to r.t. (85%).
(Fig. 1). However, these isotherms are not reversible. Furthermore, the molecular area,
2
extrapolated to zero surface pressure, is 73 Æ 3 Š for compound 6, which is obviously
too small for such a molecule. One must then conclude that some three-dimensional
aggregation occurs, and the film is at least partly multilayered.
Brewster angle microscopy (BAM) observations gave clear evidence for imperfect
films in the case of 6 (Fig. 2). The pictures taken at different values of the molecular
areas reveal that the molecules form aggregates. It should be noted that some large
domains appeared birefringent, implying the presence of some degree of molecular
alignment. However, since the formation of such domains could not be controlled, no
further studies on this particular behavior were attempted.
Comparison of the pressure-area isotherm for compound 11 (Fig. 3) with that of 6
reveals that, apparently, the presence of the polar head group in 11 does not change the
general shape of the isotherm. However, the molecular area, extrapolated to zero
surface pressure, for compound 11 is 170 Æ 5 Š2, and is in good agreement with the
value estimated by molecular modeling. This observation suggests that a monomo-
lecular film was obtained. The polar head group in 11 is responsible for a strong
attractive interaction with the aqueous subphase, forcing the molecules towards a two-
dimensional arrangement on the water surface. Unfortunately, the isotherm still shows
poor reversibility, even when the highest pressure is kept below the collapse value
(Fig. 4).

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Scheme 6
O
O
O
O
O
O
O
O
a)
13
O
O
O
O
O
O
O
O
O
14
O
O
O
a) C60, I2, DBU, toluene, r.t. (44%).
Fig. 1. Pressure-area isotherm for 6
BAM Images show that the Langmuir film obtained with compound 11 is
homogeneous at the end of the compression (Fig. 5). In addition to the observation of
the expected molecular area for 11, the high-quality film observed by BAM clearly

Helvetica Chimica Acta ± Vol. 84 (2001)
1125
2
Fig. 2. Brewster angle microscopy images for 6 at a) A ˆ 95 Š2, b) A ˆ 94 Š2, c) A ˆ 74 Š2, and d) A ˆ 67 Š
Fig. 3. Pressure-area isotherms for 11 and 14

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Fig. 4. Hysteresis curves showing the reversibility of the isotherm a) of 11 and b) of 14
indicates the formation of a homogeneous monomolecular layer. As shown in Fig. 5,
during decompression, the film broke, hence the lack of reversibility of the iso-
therms.
The pressure-area isotherm for compound 14 is depicted in Fig. 3. Films of good
quality were obtained, and the BAM picture of the film at the end of the compression
looks like the picture shown in Fig. 5,c for 11 (not shown here). When compared to 11,

Helvetica Chimica Acta ± Vol. 84 (2001)
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Fig. 5. Brewster angle microscopy images for 11 at a) A ˆ 300 Š2, b) A ˆ 200 Š2, c) A ˆ 162 Š2, and d) during
the decompression
one immediately sees (Fig. 3) that the additional two cholesterol moieties increase the
molecular area, which becomes 270 Æ 10 Š2. It can also be noticed that the shape of the
isotherm is different; the surface pressure starts to increase slowly at a molecular area
of 400 Š2, before rising in a steeper way at ca. 250 Š2. This liquid-expanded phase
between 400 and 250 Š2, not observed with compound 11, is indicative for long-range
intermolecular interactions in the Langmuir film. Extra evidence of better film
cohesion is confirmed by the hysteresis curve, which shows a better reversibility of the
isotherm (Fig. 4). By increasing the number of cholesterol subunits, the encapsulation
of the C-sphere in its addend is more effective, thus limiting fullerene-fullerene
interactions and aggregation phenomena.
2.3. Langmuir-Blodgett Films. It was possible to transfer the Langmuir films of 11
onto hydrophilic quartz slides. The transfer ratio was 1 Æ 0.1, and Y-type multilayers
were assembled. The deposition occurred regularly, as shown by the plot of the
absorbance at 260 nm obtained from the UV/VIS spectra of the LB films as a function
of the number of layers (Fig. 6). A straight line was obtained, indicating efficient
stacking of the layers.
The Langmuir films of 14 were also efficiently transferred onto hydrophilic quartz
slides with a transfer ratio of 1 Æ 0.1, and Y-type LB films were obtained. As for the LB
films prepared with 11, absorbance measurements indicate that the film obtained from
14 grows regularly.

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Fig. 6. Plot of the absorbance at 260 nm against the layer number for Langmuir-Blodgett films of 11
3. Conclusions. ± The amphiphilic fullerene bis-adducts 11 and 14, containing two
and four cholesterol residues, respectively, were prepared. Their spreading behavior
was compared to that of bis-adduct 6 with no polar head-group. For 6, some three-
dimensional aggregation occurred, whereas, in the case of 11 and 14, the polar head-
group was responsible for an attractive interaction with the aqueous subphase, forcing
the molecules towards the water surface into a two-dimensional arrangement.
Homogeneous Langmuir films were obtained for both 11 and 14, but only the films
obtained with 14 showed a reversible compression/expansion behavior. This suggests
that, by increasing the number of cholesterol subunits, the encapsulation of the C-
sphere in its addend is more efficient, thus limiting fullerene-fullerene interactions and
aggregation phenomena. We also showed that the Langmuir films of 11 and 14 can be
efficiently transfered onto solid substrates. Therefore, 11 and 14 appear to be
interesting compounds for future applications in materials science. Having already
shown that the functionalization of the fullerene sphere with cholesterol subunits is an
efficient way to produce C60 derivatives with liquid-crystalline properties [12], we have
now established that related derivatives can be efficiently incorporated into thin
ordered films.
Experimental Part
General. Reagents and solvents were purchased as reagent grade and used without further purification.
Compounds 1 [8] and 5 [10], triethylene glycol monomethyl ether tosylate [13] and (3b)-cholest-5-en-3-yl 6-
bromohexyl ether [8] were prepared according to the literature. All reactions were performed in standard
glassware under Ar. Evaporation and concentration were done at water-aspirator pressure and drying in vacuo
2
at 10 Torr. Column chromatography (CC): silica gel 60 (230 ± 400 mesh, 0.040 ± 0.063 mm) from E. Merck.
TLC: glass sheets coated with silica gel 60 F254 from E. Merck; visualization by UV light. UV/VIS Spectra (lmax
in nm (e)): Hitachi-U-3000 spectrophotometer. IR Spectra (cm 1): ATI-Mattson-Genesis instrument, series
FTIR. NMR Spectra: Bruker AC-200 (200 MHz) or Bruker AM-400 (400 MHz); solvent peaks as reference; d in

Helvetica Chimica Acta ± Vol. 84 (2001)
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ppm; J in Hz. Elemental analysis were performed by the analytical service at the Institut Charles Sadron,
Strasbourg, France.
Phase Behavior. Liquid-crystalline properties were observed for compound 10 and 12. They were deduced
from the observation of the compounds by polarized optical microscopy and confirmed by X-ray analysis.
Details on the equipment used for X-ray investigations were recently reported [14]. The phase transition and the
melting points were determined by DSC analyses Perkin-Elmer DSC-7 apparatus, scan rate 108 min 1). Results:
Table.
Table. Phase Behavior of Compounds 10 and 12. Chol. ˆ cholesteric; SmA ˆ smectic A; SmC* ˆ chiral smectic
C; I ˆ isotrope. In the case of a smectic type arrangement, the layer thickness obtained from the X-ray patterns
is indicated in parenthesis
Transitions
10
12
Glass 208 SmA (60 Š at 258) 698 Chol 778 I
SmC* (51 Š at 258) 1048 I
Langmuir and Langmuir-Blodgett Films. Spreading solns. were prepared by dissolving the compounds in
CHCl3 (analysis grade, from Carlo Erba) at 1.0 ± 3.0 mg/ml concentrations. For a typical experiment, the fresh
soln. (50 ml) was spread on the water surface with a microsyringe, and the film was then left 15 ± 20 min to
equilibrate before the compression started. Data were collected with a KSV-LB5000 system (KSV Instruments,
Helsinki, Finland) in a symmetrical compression Teflon trough equipped with hydrophilic barriers in a dust-free
environment. The whole setup was in a Plexiglas enclosure resting on a vibration-free table, and the trough
temp. was controlled to Æ0.18. All isotherms were taken at 208. Ultra pure water (1 ˆ 18.2 MW´ cm) obtained
from a Milli-RO3-Plus system combined with a Milli-Q185-Ultra-Purification system from Millipore was used
for the subphase. Surface pressure was measured with the Wilhelmy plate method. The monolayers were
compressed with speeds ranging from 2.5 to 10 Š2/(molecule ´ min), with almost no incidence of the barrier
velocity on the observed behavior. Brewster-angle microscopy (BAM) was performed with a BAM 2 plus setup
from Nanofilm Technologies GmbH. Illumination came from an Ar laser, images were recorded on a CCD
camera; field: 620 mm width  500 mm height. Langmuir-Blodgett (LB) films were obtained by transfer onto
quartz slides. Dipping parameters were not very stringent, and usually a dipping speed Vdip ꢀ 2 mm/min was
used. Transfers were performed at a surface pressure of 25 mN/m and 40 mN/m for 11 and 14, resp. In both
cases, the transfer ratios were 1 Æ 0.1, and Y-type multilayer films were obtained.
Propanedioic Acid 1,3-Phenylenebis(methylene) Bis{6-[(3b)-cholest-5-en-3-yloxy]hexyl} Ester (4). DCC
(1.06 g, 5.13 mmol) was added to a stirred soln. of DMAP (0.10 g, 0.82 mmol), HOBt (cat. amount),
propanedioic acid 1,3-phenylenebis(methylene) (5; 0.64 g, 2.05 mmol), and 6-[(3b)-cholest-5-en-3-yloxy]hex-
anol (1; 2.50 g, 5.13 mmol) in CH2Cl2 (100 ml) at 08. After 1 h, the mixture was allowed to slowly warm to r.t.
(within 1 h), then stirred for 15 h, filtered, and evaporated. CC (SiO2, 2% MeOH/CH2Cl2) yielded 4 (2.40 g,
1
93%). Colorless solid. M.p. 788: IR (CH2Cl2): 1747 (CˆO). H-NMR (CDCl3, 200 MHz): 0.70 (s, 6 H); 0.70 ±
2.42 (m, 96 H); 3.14 (m, 2 H); 3.42 (t, J ˆ 6, 4 H); 3.45 (s, 4 H); 4.15 (t, J ˆ 6, 4 H); 5.20 (s, 4 H); 5.36 (m, 2 H);
7.48 (m, 4 H). 13C-NMR (CDCl3, 50 MHz): 11.85; 18.72; 19.36; 21.05; 22.55; 22.81; 23.82; 24.27; 25.64; 25.84;
27.98; 28.23; 28.39; 28.45; 30.05; 31.87; 31.93; 35.77; 36.18; 36.88; 37.27; 39.18; 39.50; 39.77; 41.51; 41.89; 42.30;
50.19; 56.15; 56.76; 65.63; 65.78; 67.83; 78.96; 121.42; 127.96; 128.20; 128.89; 135.75; 141.05; 166.34; 166.39. Anal.
calc. for C80H126O10 ´ 1/2 H2O (1265.87): C 76.45, H 10.18; found: C 76.21, H 10.11.
4'',15''-Dioxo-3',3''-(methanoxymethano[1,3]benzenomethanoxymethano)-3',3''-dicyclopropa[1,9 :3,15][5,6]-
fullerene-C60-Ih-3',3''-dicarboxylic Acid Bis{6-[(3b)-cholest-5-en-3-yloxy]hexyl} Ester (6). DBU (0.41 ml,
2.77 mmol) was added at r.t. to a stirred solution of C60 (400 mg, 0.55 mmol), I2 (352 mg, 1.38 mmol), and 4
(727 mg, 0.58 mmol) in toluene (800 ml). The soln. was stirred for 6 h. The crude material was filtered through a
short plug of SiO2, eluting first with toluene (to remove unreacted C60) and then with CH2Cl2. CC (SiO2,
CH2Cl2) yielded 6 (304 mg, 28%). Dark orange glassy product. IR (CH2Cl2): 1748 (CˆO). 1H-NMR (CDCl3,
200 MHz): 0.70 (s, 6 H); 0.90 ± 2.42 (m, 96 H); 3.14 (m, 2 H); 3.45 (t, J ˆ 6, 4 H); 4.35 (t, J ˆ 6, 4 H); 5.15 (d, J ˆ
12, 2 H); 5.34 (m, 2 H); 5.90 (d, J ˆ 12, 2 H); 7.20 ± 7.52 (m, 4 H). 13C-NMR (CDCl3, 50 MHz): 11.85; 18.71;
19.39; 21.05; 22.55; 22.82; 23.82; 24.29; 25.74; 25.79; 28.00; 28.23; 28.43; 28.48; 30.11; 31.87; 31.96; 35.77; 36.17;
36.88; 37.27; 39.20; 39.49; 39.78; 42.30; 49.35; 50.17; 56.14; 56.76; 67.03; 67.17; 67.39; 67.83; 70.71; 78.97; 121.49;
123.63; 126.60; 128.67; 134.80; 135.88; 136.27; 136.62; 137.64; 139.97; 141.03; 141.31; 142.36; 143.06; 143.29;
143.61; 143.80; 143.99; 144.21; 144.28; 144.40; 144.63; 145.08; 145.23; 145.40; 145.68; 145.78; 146.10; 146.16;

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Helvetica Chimica Acta ± Vol. 84 (2001)
147.34; 147.55; 148.75; 162.85; 162.95 UV/VIS (CH2Cl2): 259 (119210), 320 (sh, 33015), 437 (2885), 469 (2610).
Anal. calc. for C140H122O10 ´ CH2Cl2 (2049.42). C 82.66, H 6.11; found: C 83.20, H 6.04.
5-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}benzene-1,3-dicarboxylic Acid Dimethyl Ester (7). A soln. of
triethylene glycol monomethyl ether tosylate (5.00 g, 16.53 mmol), dimethyl 5-hydroxyisophthalate (2.90 g,
13.78 mmol), and K2CO3 (9.52 g, 68.90 mmol) in DMF (200 ml) was stirred at 808 for 48 h. The mixture was
evaporated and the crude product dissolved in CH2Cl2 (100 ml) and then filtered (Celite). CC (SiO2, Et2O/
acetone 7:3) yielded 7 (4.35 g, 88%). Colorless oil. 1H-NMR (CDCl3, 200 MHz): 3.37 (s, 3 H); 3.53 ± 3.90
(m, 10 H); 3.92 (s, 6 H); 4.16 (t, J ˆ 6, 2 H); 7.75 (d, J ˆ 2, 2 H); 8.26 (t, J ˆ 2, 1 H). 13C-NMR (CDCl3, 50 MHz):
52.11; 58.72; 67.77; 69.24; 70.30; 70.38; 70.62; 71.64; 119.61; 122.77; 131.42; 158.61; 165.73. Anal. calc. for
C17H24O8 (356.36): C 57.29, H 6.78; found: C 56.99, H 6.86.
5-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}benzene-1,3-dimethanol (8). A soln. of 7 (4.00 g, 11.22 mmol) in
dry THF (100 ml) was added dropwise within 1 h to a suspension of LiAlH4 (596 mg, 15.71 mmol) in dry THF
(50 ml) at 08. The resulting mixture was stirred for 7 h at r.t., and a few drops of MeOH were carefully added,
and then 10 ml of MeOH. The resulting mixture was filtered (Celite) and evaporated. CC (SiO2, 10% MeOH/
1
CH2Cl2) yielded 8 (3.0 g, 88%). Colorless oil. H-NMR (CDCl3, 200 MHz): 2.77 (t, J ˆ 5, 2 H); 3.36 (s, 3 H);
3.50 ± 3.90 (m, 10 H); 4.09 (t, J ˆ 6, 2 H); 4.56 (d, J ˆ 5, 4 H); 6.79 (d, J ˆ 2, 2 H); 6.87 (t, J ˆ 2, 1 H). 13C-NMR
(CDCl3, 50 MHz): 58.93; 64.80; 67.38; 69.72; 70.42; 70.57; 70.70; 71.82; 102.07; 117.59; 142.81; 159.06. Anal. calc.
for C15H24O6 (300.35): C 59.98, H 8.05; found: C 59.58, H 8.15.
Propanedioic Acid {5-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}-1,3-phenylene}bis(methylene) Ester (9). A
mixture of Meldrumꢀs acid (2.78 g, 19.31 mmol) and 8 (2.90 g, 9.65 mmol) was heated for 6 h at 1108. After
2
cooling to r.t., drying (10 Torr, 24 h) provided 9 (4.47 g, 98%). Pale yellow oil. IR (CH2Cl2): 1754 (CˆO).
1H-NMR (CDCl3, 200 MHz): 3.36 (s, 3 H); 3.47 (s, 4 H); 3.54 ± 3.86 (m, 10 H); 4.12 (t, J ˆ 6, 2 H); 5.15 (s, 4 H);
6.84 (d, J ˆ 2, 2 H); 6.92 (t, J ˆ 2, 1 H). 13C-NMR (CDCl3, 50 MHz): 40.97; 58.68; 66.57; 67.24; 69.37; 70.08;
70.31; 70.46; 71.57; 113.79; 119.31; 136.97; 158.85; 166.30;169.94. Anal. calc. for C21H28O12 (300.35): C 53.39,
H 5.97; found: C 53.40, H 6.13.
Propanedioic Acid {5-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}-1,3-phenylene}bis(methylene) Bis{6-[(3b)-
cholest-5-en-3-yloxy]hexyl} Ester (10). As described for 4, with DCC (1.09 g, 5.29 mmol), DMAP (103 mg,
0.85 mmol), HOBt (cat. amount), 9 (2.57 g, 5.29 mmol), 1 (1.00 g, 2.11 mmol), and CH2Cl2 (50 ml) (stirring for
24 h). CC (SiO2, CH2Cl2/AcOEt 5 :3) yielded 10 (2.20 g, 73%). Colorless compound. See Table. IR (CH2Cl2):
1751 (CˆO). 1H-NMR (CDCl3, 200 MHz): 0.67 (s, 6 H); 0.85 ± 2.36 (m, 96 H); 3.12 (m, 2 H); 3.38 (s, 3 H); 3.43
(t, J ˆ 6, 4 H); 3.44 (s, 4 H); 3.47 ± 3.88 (m, 10 H); 4.14 (m, 6 H); 5.13 (s, 4 H); 5.35 (m, 2 H); 6.88 (d, J ˆ 2, 2 H);
6.91 (t, J ˆ 2, 1 H). 13C-NMR (CDCl3, 50 MHz): 11.76; 18.63; 19.29; 20.97; 22.48; 22.74; 23.74; 24.20; 24.59;
25.35; 25.58; 25.77; 27.91; 28.15; 28.30; 28.38; 29.98; 31.81; 34.82; 35.70; 36.10; 36.78; 37.19; 39.10; 39.42; 39.69;
41.38; 42.21; 50.09; 56.06; 57.67; 58.93; 65.54; 66.58; 67.45; 67.75; 69.53; 70.49; 70.56; 70.74; 71.83; 78.88; 114.12;
119.92; 121.33; 137.03; 140.98; 159.09; 166.24; 166.33. Anal. calc. for C87H140O14 (1410.06): C 74.11, H 10.01;
found: C 74.73, H 10.27.
11''-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}-4'',15''-dioxo-3',3''-(methoxymethano[1,3]benzenomethanoxy-
methano)-3',3''-dicyclopropa[1,9 :3,15][5,6]fullerene-C60-Ih-3',3''-dicarboxylic Acid Bic{6-[(3b)-cholest-5-en-3-
yloxy]hexyl} Ester (11). As described for 6, with DBU C60, I2, 10 (822 mg, 0.58 mmol), and toluene. (SiO2-plug
elution with toluene with CH2Cl2/AcOEt 1:1). CC (SiO2, CH2Cl2/AcOEt 8 :2) yielded 11 (600 mg, 50%). Dark
orange glassy product. UV/VIS (CH2Cl2): 258 (100460), 320 (sh, 27815), 436 (2760), 471 (2345). IR (CH2Cl2):
1747 (CˆO). 1H-NMR (CDCl3, 200 MHz): 0.67 (s, 6 H); 0.80 ± 2.41 (m, 96 H); 3.15 (m, 2 H); 3.40 (s, 6 H); 3.42
(t, J ˆ 6, 4 H); 3.52 ± 3.90 (m, 10 H); 4.19 (t, J ˆ 6, 2 H); 4.35 (t, J ˆ 6, 4 H); 5.14 (d, J ˆ 14, 2 H); 5.35 (m, 2 H);
5.80 (d, J ˆ 14, 2 H); 6.81 (br. s, 2 H); 7.14 (br. s, 1 H). 13C-NMR (CDCl3, 50 MHz): 11.79; 18.65; 19.33; 20.99;
22.51; 22.77; 23.76; 24.23; 25.68; 25.73; 27.94; 28.17; 28.37; 28.41; 29.63; 30.04; 31.81; 35.71; 36.11; 36.81; 37.20;
39.13; 39.43; 39.71; 42.24; 49.26; 50.09; 56.08; 56.69; 58.99; 66.92; 67.11; 67.19; 67.55; 67.76; 69.57; 70.52; 70.61;
70.79; 71.86; 78.89; 112.36; 115.11; 121.43; 134.67; 135.79; 136.14; 137.61; 137.99; 139.95; 140.95; 141.22; 142.27;
143.03; 143.22; 143.54; 143.71; 143.93; 144.12; 144.21; 144.34; 144.53; 145.01; 145.14; 145.33; 145.59; 145.71;
146.03; 146.10; 147.27; 147.46; 148.63; 158.80; 162.76. Anal. calc. for C147H136O14 (2126.69): C 83.02, H 6.45;
found: C 82.54, H 6.45.
3,5-Bis{{6-[(3b)-cholest-5-en-3-yloxy]hexyl}oxy}benzenemethanol (12). A soln. of 5-(hydroxymethyl)ben-
zene-1,3-diol (24 mg, 0.17 mmol), K2CO3 (100 mg, 7.27 mmol), and (3b)-cholest-5-en-3-yl 6-bromohexyl ether
(200 mg, 0.36 mmol) in DMF (20 ml) was stirred at 808 for 24 h. The mixture was then cooled to r.t. and
evaporated. The crude product was dissolved in Et2O/H2O and the org. layer washed with brine, dried (MgSO4),
and evaporated. CC (SiO2, CH2Cl2) yielded 12 (0.140 g, 75%). Colorless compound. See Table. 1H-NMR
(CDCl3, 200 MHz): 0.81 (s, 6 H); 0.92 ± 2.40 (m, 96 H); 3.05 (m, 2 H); 3.40 (t, J ˆ 6, 4 H); 3.83 (t, J ˆ 6, 4 H);

Helvetica Chimica Acta ± Vol. 84 (2001)
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4.54 (s, 2 H); 5.25 (m, 2 H); 6.28 (t, J ˆ 2, 1 H); 6.41 (d, J ˆ 2, 2 H). 13C-NMR (CDCl3, 50 MHz): 12.12; 18.98;
19.66; 21.33; 22.83; 23.10; 24.09; 24.56; 25.91; 2620; 28.28; 28.51; 28.75; 29.14; 29.46; 30.40; 32.15; 36.06; 36.46;
37.17; 37.55; 39.46; 39.78; 40.04; 42.59; 50.46; 56.43; 57.05; 65.70; 68.17; 79.26; 100.78; 105.31; 121.72; 141.40;
141.90; 160.76.
Propanedioic Acid {5-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}-1,3-phenylene}bis(methylene) Bis{{3,5-
bis{{6-[(3b)-cholest-5-en-3-yloxy]hexyl}oxy}phenyl}methyl} Ester (13). As described for 4, with DCC
(153 mg, 0.74 mmol), DMAP (14 mg, 0.12 mmol), HOBt (cat. amount), 9 (140 mg, 0.29 mmol), 12 (800 mg,
0.742 mmol), and CH2Cl2 (20 ml) (stirring for 24 h). CC (SiO2, CH2Cl2/AcOEt 5 :3) yielded 12 (650 mg, 85%),
which was used in the next step without further purifications. Colorless glassy solid. 1H-NMR (CDCl3,
200 MHz): 0.68 (s, 12 H); 0.85 ± 2.34 (m, 192 H); 3.13 (m, 4 H); 3.43 (s, 3 H); 3.46 (t, J ˆ 6, 8 H); 3.49 (s, 4 H);
3.52 ± 3.88 (m, 10 H); 3.91 (t, J ˆ 6, 8 H); 4.09 (t, J ˆ 6, 2 H); 5.09 (s, 4 H); 5.13 (s, 4 H); 5.34 (m, 4 H); 6.39
(t, J ˆ 2, 2 H); 6.46 (d, J ˆ 2, 4 H); 6.87 (br. s, 2 H); 6.90 (br. s, 1 H).
11''-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}-4'',15''-dioxo-3',3''-(methoxymethano[1,3]benzenomethanoxy-
methano)-3',3''-dicyclopropa[1,9 :3,15][5,6]fullerene-C60-Ih-3',3''-dicarboxylic Acid Bis {{3,5-bis{{6-[(3b)-cho-
lest-5-en-3-yloxy]hexyl}oxy}phenyl}methyl} Ester (14). As described for 6, with DBU (0.16 ml, 1.10 mmol), C60
(158 mg, 0.22 mmol), I2 (140 mg, 0.55 mmol), 13 (600 mg, 0.23 mmol), and toluene (500 ml) (SiO2-plug elution
with toluene CH2Cl2/AcOEt 1:1). CC (SiO2, CH2Cl2/AcOEt 8 :2) yielded 14 (320 mg, 44%). Dark orange
glassy product. IR (CH2Cl2): 1749 (CˆO). 1H-NMR (CDCl3, 200 MHz): 0.67 (s, 12 H); 0.80 ± 2.43 (m, 192 H);
3.14 (m, 4 H); 3.41 (s, 3 H); 3.45 (t, J ˆ 6, 8 H); 3.52 ± 4.15 (m, 10 H); 4.05 (t, J ˆ 6, 8 H); 4.15 (m, 2 H); 5.05
(d, J ˆ 12, 2 H); 5.15 (d, J ˆ 12, 2 H); 5.33 (m, 4 H); 5.45 (d, J ˆ 12, 2 H); 5.75 (d, J ˆ 12, 2 H); 6.33 (br. s, 2 H);
6.48 (br. s, 4 H); 6.80 (br. s, 2 H); 7.05 (br. s, 1 H). 13C-NMR (CDCl3, 50 MHz): 11.79; 18.65; 19.32; 20.98; 22.51;
22.76; 23.76; 24.21; 24.87; 25.56; 25.77; 25.90; 27.59; 27.91; 28.16; 28.40; 28.98; 29.15; 29.63; 30.07; 31.81; 31.85;
33.85; 35.70; 36.11; 36.81; 37.21; 39.12; 39.42; 39.71; 42.23; 48.94; 50.10; 56.08; 56.68; 58.96; 65.28; 66.78; 67.18;
67.50; 67.85; 68.60; 69.56; 70.50; 70.58; 70.77; 71.85; 77.21; 78.88; 101.54; 107.04; 112.41; 121.36; 135.92; 136.02;
136.46; 138.06; 139.97; 140.96; 142.21; 142.65; 142.86; 143.06; 143.48; 143.64; 143.87; 144.06; 144.24; 144.50;
144.88; 145.08; 145.26; 145.48; 145.68; 145.97; 147.22; 147.37; 148.53; 158.76; 160.25; 162.47. UV/VIS (CH2Cl2):
258 (82770), 320 (sh, 22175), 437 (2215), 464 (2020). Anal. calc. for C227H260O20 (3308.35): C 82.41, H 7.92;
found: C 82.64, H 7.98.
This work was supported by the CNRS, the French Ministry of Research, the Swiss National Science
Â
Foundation, the Swiss-French Cooperation Program (CNRS-PICS 742), a doctoral fellowship from the Region
Alsace to D. F., and a post-doctoral fellowship from DGAPA-UNAM and CONACyT to M. del P. C. We further
thank L. Oswald for technical help and Prof. J.-F. Nicoud for his support.
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Received February 5, 2001