Open-cage fullerene derivatives having 11-, 12-, and 13-membered-ring orifices: Chemical transformations of the organic addends on the rim of the orifice

Article abstract of DOI:10.1021/jo070796l

(Chemical Equation Presented) A novel open-cage [60]fullerene derivative, having two sulfur atoms on the rim of its 13-membered-ring orifice, has been isolated and characterized. Extensive studies on the N-MEM group reactivity of this as well as other previously reported open-cage [60]fullerene derivatives led to several new open-cage [60]-fullerene adducts.

Full text of DOI:10.1021/jo070796l

Open-Cage Fullerene Derivatives Having 11-, 12-, and
3-Membered-Ring Orifices: Chemical Transformations of the
Organic Addends on the Rim of the Orifice
1
Manolis M. Roubelakis, Georgios C. Vougioukalakis, and Michael Orfanopoulos*
Department of Chemistry, UniVersity of Crete, Iraklion, Voutes 71003, Crete, Greece
orfanop@chemistry.uoc.gr
ReceiVed April 16, 2007
A novel open-cage [60]fullerene derivative, having two sulfur atoms on the rim of its 13-membered-ring
orifice, has been isolated and characterized. Extensive studies on the N-MEM group reactivity of this as
well as other previously reported open-cage [60]fullerene derivatives led to several new open-cage [60]-
fullerene adducts.
Introduction
fullerenes. This innovative premise led several research groups
to the development of a number of techniques for transforming
the fullerenes’ σ-framework, resulting open-cage derivatives.8
According to this technique, a series of organic reactions creates
an effective aperture on the surface of the fullerenes, allowing
Endohedral fullerenes are currently being prepared by utilizing
the evaporation of graphite-metal composites, high-temperature
and high-pressure conditions, ion implantation, or high-energy
-12
1-4
plasma insertion into pure fullerenes.
The disadvantages of
+
one small atom, molecule, or ion, such as He, H2, or Li , to
the above-mentioned methods are the low yields of the so
formed endohedral complexes, as well as the difficult and
tedious separation processes from the empty fullerene mol-
(8) Schick, G.; Jarrosson, T.; Rubin, Y. Angew. Chem., Int. Ed. 1999,
38, 2360-2363.
5
ecules.
(
9) (a) Murata, Y.; Murata, M.; Komatsu, K. Chem.sEur. J. 2003, 9,
6
The proposal of the “molecular surgery approach”, soon after
the isolation of the first open-cage fullerene derivative, came
up as an alternative route to the production of endohedral
1
600-1609. (b) Murata, Y.; Murata, M.; Komatsu, K. J. Am. Chem. Soc.
7
2003, 125, 7152-7153. (c) Carravetta, M.; Murata, Y.; Murata, M.;
Heinmaa, I.; Stern, R.; Tontcheva, A.; Samoson, A.; Rubin, Y.; Komatsu,
K.; Levitt, M. H. J. Am. Chem. Soc. 2004, 126, 4092-4093. (d) Stanisky,
C. M.; Cross, R. J.; Saunders, M.; Murata, M.; Murata, Y.; Komatsu, K. J.
Am. Chem. Soc. 2005, 127, 299-302. (e) Komatsu, K.; Murata, M.; Murata,
Y. Science 2005, 307, 238-240. (f) Vougioukalakis, G. C.; Prassides, K.;
Orfanopoulos, M. Org. Lett. 2004, 6, 1245-1247.
(
1) Shinohara, H. Rep. Prog. Phys. 2000, 63, 843-892.
(2) Nagase, S.; Kobayashi, K.; Akasaka, T. Bull. Chem. Soc. Jpn. 1996,
6
9, 2131-2142.
3) (a) Mauser, H.; Van Eikema Hommes, N. J. R.; Clark, T.; Hirsch,
A.; Pietzak, B.; Weidinger, A.; Dunsch, L. Angew. Chem., Int. Ed. Engl.
997, 36, 2835-2838. (b) Pietzak, B.; Waiblinger, M.; Murphy, T. A.;
Weidinger, A.; H o¨ hne, M.; Dietel, E.; Hirsch, A. Chem. Phys. Lett. 1997,
79, 259-263.
4) Stevenson, S.; Rice, G.; Glass, T.; Harich, K.; Cromer, F.; Jordan,
(
(10) (a) Inoue, H.; Yamaguchi, H.; Iwamatsu, S.-i.; Uozaki, T.; Suzuki,
T.; Akasaka, T.; Nagase, S.; Murata, S. Tetrahedron Lett. 2001, 42, 895-
897. (b) Murata, Y.; Komatsu, K. Chem. Lett. 2001, 30, 896-897. (c)
Murata, Y.; Murata, M.; Komatsu, K. J. Org. Chem. 2001, 66, 8187-8191.
(11) (a) Iwamatsu, S.-i.; Ono, F.; Murata, S. Chem. Commun. 2003,
1268-1269. (b) Iwamatsu, S.-i.; Ono, F.; Murata, S. Chem. Lett. 2003, 32,
614-615. (c) Iwamatsu, S.-i.; Kuwayama, T.; Kobayashi, K.; Nagase, S.;
Murata, S. Synthesis 2004, 2962-2964. (d) Vougioukalakis, G. C.; Prassides,
K.; Campanera, J. M.; Heggie, M. I.; Orfanopoulos, M. J. Org. Chem. 2004,
69, 4524-4526. (e) Chen, Z.-X.; Wang, G.-W. J. Org. Chem. 2005, 70,
2380-2383.
1
2
(
M. R.; Craft, J.; Hadju, E.; Bible, R.; Olmstead, M. M.; Maitra, K.; Fisher,
A. J.; Balch, A. L.; Dorn, H. C. Nature 1999, 401, 55-57.
(
(
5) Rubin, Y. Top. Curr. Chem. 1999, 199, 67-91 and references therein.
6) (a) Rubin, Y. Chem.sEur. J. 1997, 3, 1009-1016. (b) Rubin, Y.;
Jarrosson, T.; Wang, G.-W.; Bartberger, M. D.; Houk, K. N.; Schick, G.;
Saunders, M.; Cross, R. J. Angew. Chem., Int. Ed. 2001, 40, 1543-1546.
(12) (a) Iwamatsu, S.-i.; Uozaki, T.; Kobayashi, K.; Re, S.; Nagase, S.;
Murata, S. J. Am. Chem. Soc. 2004, 126, 2668-2669. (b) Iwamatsu, S.-i.;
Murata, S. Tetrahedron Lett. 2004, 45, 6391-6394.
(
7) Hummelen, J. C.; Prato, M.; Wudl, F. J. Am. Chem. Soc. 1995, 117,
7
003-7004.
10.1021/jo070796l CCC: $37.00 © 2007 American Chemical Society
6
526
J. Org. Chem. 2007, 72, 6526-6533
Published on Web 07/27/2007

1
1-, 12-, and 13-Membered-Ring Orifice Fullerenes
FIGURE 3. Doubly sulfur-inserted products 5 and 6.
Herein, we report for the first time the isolation and
characterization of the novel open-cage fullerene derivative 5,
shown in Figure 3, bearing two sulfur atoms on the rim of its
orifice. Several transformations of the N-MEM protective group
from adducts 1, 4, and 5 are also reported.
FIGURE 1. Open-cage fullerene structures reported earlier.
Results and Discussion
Synthesis, Isolation, Characterization, and Chemical Trans-
formations of 5: Thermal treatment of 1 at 180 °C together
with S8 in 1,2-dichlorobenzene (ODCB) as the solvent for 40
min, in the presence of tetrakis(dimethylamino)ethylene (TDAE),
afforded 4 and 5 in yields of 72 and 11%, respectively (based
on the amount of the isolated adducts). Compound 4 has been
previously reported and fully characterized in a preliminary
FIGURE 2. Open-cage fullerene derivatives bearing a sulfur heteroa-
tom along the rim of their orifice.
9
f
communication. The molecular ion peak of 5 was observed at
m/z 920 in its MALDI-TOF mass spectrum. On the basis of
NMR and MALDI-TOF mass data, we suggest that two sulfur
atoms have been incorporated into the fullerene skeleton of 5
as shown in Figure 3: one sulfur atom is inserted into the central
C-C single bond of each butadiene unit of the starting material
pass through the hole and to be placed inside the cavity of these
hollow structures. Restoration of the disrupted cage gives back
the pristine fullerene with the desired species encapsulated.
Thus, open-cage fullerene derivatives have attracted much
attention as key intermediates to endohedral complexes. Fur-
thermore, due to the fact that they can trap and release a
1
molecule reversibly,13 these compounds could be used for
1. The H NMR spectrum of adduct 5 is almost identical to
that of the precursor 1, apart from a slight upfield shift of the
molecular storage.
two double peaks that correspond to the protons adjacent to
The first open-cage fullerene derivative (N-MEM-ketolactam
13
7
the carbon next to the nitrogen. The ketone C NMR absorption
1
, Figure 1) was reported in 1995 by Wudl and co-workers.
is shifted from δ 198.5 ppm in the starting material 1 to δ 183.8
However, even small atoms, such as He, could not pass through
13
5
ppm in the adduct 5, while the lactam C chemical shift change
this small-sized orifice, at the temperature of 200 °C. The first
is insignificant (the lactam carbon resonances are at 163.6 and
successful attempt in introducing an atom or molecule inside
1
63.1 ppm in 1 and 5, respectively). The lactam carbonyl
the fullerene cavity by the “molecular surgery approach” was
-
1
reported in 2001 by Rubin and co-workers.6b Open-cage
absorption in the IR spectrum of 5 is shifted to 1680 cm ,
from 1693 cm in the starting material 1, while the ketone
-
1
bislactam derivative 2 (Figure 1), with an elliptic 14-membered-
ring orifice, was prepared, and both a He atom and a H2
molecule were inserted in the cage with yields of 1.5 and 5%,
respectively.
carbonyl is practically unaffected since it moves from 1727 to
-
1
1
724 cm . The UV-vis spectrum of the new adduct in
chloroform is similar to the starting material N-MEM-ketolac-
tam, showing absorption maxima at 251 and 320 nm, whereas
the corresponding absorptions of 1 are at 260 and 328 nm,
respectively.
Later on, Komatsu and co-workers synthesized open-cage
fullerene derivative 3 (Figure 2) bearing a 13-membered-ring
9
a
orifice. The circular-like shape of the aperture in 3 allowed,
Treatment of adduct 5 with 1000 equiv of trifluoroacetic acid
(vide infra) in chlorobenzene at 100 °C for 40 min afforded
adduct 6 (Figure 3), without organic addends on the rim of the
orifice, in 78% isolated yield. The solubility of this fully
deprotected compound is extremely low even in ODCB. The
molecular ion peak of 6 was clearly observed at m/z 831 in its
for the first time, 100% encapsulation of molecular hydrogen
at an applied H2 pressure of 800 atm at 200 °C.9b Furthermore,
it was shown that, upon laser irradiation, generation of H2@C60
is possible in the gas phase by self-restoration of H2@3. More
recently, they achieved the complete closure of the orifice of
H2@3 by means of conventional chemistry, accomplishing the
1
MALDI-TOF mass spectrum. The H NMR spectrum of adduct
first preparation of the endohedral complex H2@C60 from empty
C60 by organic synthesis.9e That work demonstrates that the
6 (ODCB-d4) showed only a D2O exchangeable singlet at δ
9
.48 ppm.
molecular surgery approach might be an efficient methodology
for the preparation of other kinds of endohedral fullerenes.
Recently, we demonstrated the versatility of Komatsu’s
We next tried to improve the yield for 5 by increasing the
sulfur as well as the TDAE equivalents used in the previous
reaction. As shown in Table 1, the 4 to 5 ratio, determined by
HPLC analysis, remained unaffected even in the presence of
9
a
method in enlarging the aperture of an open-cage fullerene,
by inserting a sulfur atom along its rim. Thereby, N-MEM-
1
00 equiv of elemental sulfur at a reaction time of 2 h. We also
9
f
ketolactam 1 was converted into compound 4 (Figure 2).
used adduct 4 as starting material in the place of N-MEM-
ketolactam 1. Again, the change in the yield of 5 was
insignificant. These results indicate that the ratio of derivatives
4/5 is independent of the concentration of both sulfur and TDAE.
(
13) (a) Iwamatsu, S.-i.; Murata, S. Synlett 2005, 2117-2129 and
references therein. (b) Chuang, S.-C.; Murata, Y.; Murata, M.; Mori, S.;
Maeda, S.; Tanabe, F.; Komatsu, K. Chem. Commun. 2007, 1278-1280.
J. Org. Chem, Vol. 72, No. 17, 2007 6527

Roubelakis et al.
TABLE 1. Reaction of Open-Cage Compounds 1 and 4 with
Elemental Sulfur
starting
material
sulfur
equiv
TDAE
equiv
reaction
time (min)
ratio 4/5
1
1
1
1
1
4
2
4
8
50
100
4
2
4
8
4
4
4
40
120
120
60
120
40
6.5/1a
b
∼6.5/1
b
∼6.5/1
b
∼6.5/1
b
∼6.5/1
b
∼6.5/1
a
Based on the amount of the isolated product. b Based on peak area %
of HPLC observed at the end of the reaction.
FIGURE 4. The structures of thioaza[60]fullerene dimer 12, carboca-
tion 13, and fully deprotected derivative 14.
SCHEME 1. Mechanism for the Formation of the (C59N)
Dimer 11 from N-MEM-ketolactam 1 Proposed by Wudl
and Co-workers
2
FIGURE 5. Open-cage fullerene derivatives with a 19-membered ring
orifice.
co-workers.12b They succeeded in the preparation of a new open-
cage fullerene derivative 15a (Figure 5), with a 19-membered
ring orifice, by sequential cage scission reactions of N-MEM-
ketolactam 1 with o-phenylenediamine, and next, they managed
a gradual deprotection of the MEM protecting group by
treatment with trifluoroacetic acid in toluene at ambient tem-
perature. These mild conditions for the removal of the MEM
group afforded derivatives 15b and 15c (Figure 5).
Thus, following Iwamatsu’s experimental procedure, open-
cage fullerene derivative 4 was treated with a large excess of
trifluoroacetic acid (600 equiv) in both toluene and chloroben-
zene solutions at ambient temperature. According to TLC and
HPLC analysis, 4 remained intact even after 3 days of stirring
in each solvent. Thereupon, we increased the reaction temper-
ature to 60 °C. After 1 day of stirring, for the reaction in toluene,
a new spot appeared on TLC with an Rf value larger than that
of S-ketolactam 4. Both reactions were left at 60 °C for 2 more
days.
In order to confirm the necessity for the TDAE presence in
the formation of the open-cage fullerene derivatives 4 and 5,
we tried to perform the reaction without adding any TDAE.
After 4 h of heating N-MEM-ketolactam with 4 equiv of sulfur
in ODCB at 180 °C, no products were detected. However, when
TDAE was added, formation of adducts 4 and 5 was observed
immediately.
Chemical Transformations of the Organic Addends of
Derivatives 1 and 4. A Comparative Study: In an earlier work,
Wudl and co-workers have shown that, upon refluxing keto-
lactam 1 with p-toluenesulfonic acid monohydrate in ODCB
for 10 min, azafullerene dimer (C59N)2 is formed (11, Scheme
14
1
). That mechanism includes the initial formation of carboca-
tion 7 which, subsequently, rearranges to the four-membered
,3-oxazetidinium ring compound 8, which in turn loses
HPLC analysis for the reaction in toluene showed two new
peaks with retention times longer than that for 4. Some starting
material was still present in the solution. The integration of the
three peaks, as determined by HPLC analysis, was 43% for the
N-MEM-S-ketolactam 4, 30% for the first adduct, and 27% for
the second adduct. After column chromatographic purification,
we isolated and characterized the two products. The first one,
with retention time close to that of S-ketolactam 4, was identified
1
formaldehyde and carbon monoxide to yield the azafulleronium
ion 9. Intermediate 9 can be reduced to the azafullerenyl radical
1
0, which dimerizes to yield the azafullerene dimer 11.
In our efforts to synthesize the respective thioaza[60]fullerene
dimer 12 from the S-ketolactam derivative 4, through the
corresponding carbocation 13 (Figure 4), we utilized the above-
1
9f
mentioned method for compound 4.9f However, instead of the
by H NMR spectroscopy to be the already known adduct 14.
1
2b
According to the related work of Iwamatsu,
we initially
thioaza[60]fullerene 12, we isolated adduct 14 (Figure 4) after
the removal of the MEM protective group from the fullerene
core. We anticipated that milder deprotection conditions could
possibly lead to the formation of the thioazafullerene dimer 12.
Such mild conditions were recently reported by Iwamatsu and
thought that the second adduct would have been the open-cage
1
derivative 16 (Figure 6). Nevertheless, on the basis of H NMR,
1
3
1
1
13
C NMR, HMQC, H- H COSY, and C DEPT experiments
as well as MS (MALDI), FT-IR, and UV-vis spectroscopy,
we concluded that this new derivative is a mixture of the two
isomers 17a and 17b (66/34 ratio based on H NMR), shown
1
(14) Hummelen, J. C.; Knight, B.; Pavlovich, J.; Gonz a´ lez, R.; Wudl,
F. Science 1995, 269, 1554-1556.
in Figure 6. We propose that these new adducts are produced
6528 J. Org. Chem., Vol. 72, No. 17, 2007

1
1-, 12-, and 13-Membered-Ring Orifice Fullerenes
FIGURE 6. Molecular structures of 16, 17a, and 17b.
FIGURE 7. Molecular structures of isomers 18a and 18b.
SCHEME 2. Reaction of the N-MEM-ketolactam Derivative
of C60 1 with Anisole
by the electrophilic aromatic substitution reaction between
toluene and the intermediate carbocation 13 at para and ortho
positions, respectively (traces of the meta isomer were observed
1
by H NMR).
The reaction in chlorobenzene, after 3 days of heating at
60 °C, led to the formation of only one new derivative
(determined by HPLC analysis), with exactly the same retention
time as that for 14, along with traces of starting material. Indeed,
1
this was identified by H NMR spectroscopy to be product 14.
Heating a mixture of N-MEM-S-ketolactam 4 with 600 equiv
of trifluoroacetic acid in chlorobenzene at 100 °C for 2 h and
4
5 min afforded the fully deprotected N-MEM-S-ketolactam,
which was purified and isolated in 90% yield. This procedure
proved to be a more efficient way of producing adduct 14 than
9f
the one previously reported, due to its higher yield (90 versus
8%).
We must also note that, when N-MEM-S-ketolactam 4 was
5
heated in toluene at 60 °C without any trifluoroacetic acid, it
remained intact even after 4 days. In order to investigate the
influence of pKa on the removal of the MEM protective group,
we replaced trifluoroacetic acid with acetic acid, a weaker acid.
After heating the reaction for 18 h at 100 °C, the N-MEM-S-
ketolactam moiety was intact in both toluene and chlorobenzene
solutions, revealing that the use of strong acids, such as
trifluoroacetic and p-toluenesulfonic, is crucial for the removal
of the MEM protective group in these derivatives. Finally, we
also carried out the deprotection of 4 by using milder conditions
9f
than those reported in our earlier work. Namely, 4 was treated
with p-toluenesulfonic acid in ODCB, at 60 °C, instead of
1
50 °C. We anticipated that under these conditions removal of
the MEM protective group may lead to the originally desired
thioazafullerene dimer 12. Unfortunately, we observed that
derivative 14 was again the only product of the reaction.
We then also reduced the equivalents of the trifluoroacetic
acid used to 50, 100, and 300 equiv in solutions of S-ketolactam
Similar reactions in PhCl and toluene were performed
utilizing N-MEM-ketolactam 1 as starting material. After 3 days
of heating at 60 °C in the presence of 600 equiv of trifluoroacetic
acid, HPLC analysis on both reactions showed a single peak
corresponding to the starting material. To make the conditions
harsher, the reaction in toluene was placed in an oil bath at
100 °C and left overnight. HPLC analysis showed the appear-
ance of a new peak. This new adduct was isolated as a mixture
of the two isomers 18a and 18b (Figure 7), derived from the
aromatic substitution of toluene by the electrophilic carbocation
7 on para and ortho positions, respectively (18a/18b ≈ 3/2;
again, traces of the meta isomer were present in the mixture).
When the reaction temperature was set at 150 °C and the
equivalents of the trifluoroacetic acid were raised to 1000,
complete consumption of 1 was observed within 5 h and adducts
18a and 18b were formed in 65% yield.
4
in toluene. The reaction mixtures were heated at 60 °C for 3
days; however, none of them gave any of the expected products
14 or 17) and only starting material 4 was present in the
(
solutions. Therefore, at least 600 equiv of trifluoroacetic acid
is necessary for the reaction to occur.
Our next step was to improve the yield of the new adduct 17
and reduce the reaction time. Accordingly, derivative 4 along
with 600 equiv of trifluoroacetic acid were heated in toluene at
1
00 °C. The reaction was monitored by HPLC, and after 19 h,
starting material had almost fully disappeared giving products
4 and 17 in a 2/3 ratio. In an effort to minimize the reaction
1
time, we placed S-ketolactam 4 together with 1000 equiv of
trifluoroacetic acid in toluene into a Schlenk tube. The reaction
temperature was set at 150 °C. S-Ketolactam was completely
consumed in 1 h and 40 min, affording again products 14 and
Next, we investigated whether electrophilic aromatic substitu-
tion reaction of N-methyl carbonium ions 7 and 13 can take
place with the activated aromatic ring of anisole. Therefore,
similar deprotection reactions were carried out in anisole as a
solvent for 1 and 4. Compound 4, upon heating at 150 °C for
1
7 in a 2/3 ratio.
J. Org. Chem, Vol. 72, No. 17, 2007 6529

Roubelakis et al.
1
FIGURE 8. Expanded 5.5-8.0 ppm region of the H NMR (500 MHz, CDCl
3
) spectrum for 19a, 19b mixture (o, aromatic protons of the ortho
isomer; p, aromatic protons of the para isomer; *, methylene protons of the ortho isomer; #, methylene protons of the para isomer).
1
h and 40 min in the presence of 1000 equiv of trifluoroacetic
acid, was smoothly converted into the expected derivatives 19a
and 19b (Figure 8) in quantitative yield. In this case, the meta
isomer was not formed at all. The 5.5-8.0 ppm region of the
1
H NMR spectrum for the mixture of the isomers 19a and 19b
is displayed in Figure 8 (for the whole spectrum, refer to
Supporting Information). Two AB systems reveal the presence
of two methylene carbons, whereas the aromatic region of the
spectrum reveals the existence of both the ortho and the para
isomers. The ratio of the two isomers was 1/1.
On the other hand, N-MEM-ketolactam 1 after 11 h of heating
afforded the respective adducts 20a and 20b (1/1 ratio) in 48%
isolated yield, along with the closed shell adduct 21 in 20%
yield (Scheme 2). The latter reaction pathway has already been
reported by Hirsch, under slight different reaction conditions
FIGURE 9. Molecular structures of the open-cage fullerene derivatives
2, 23, and 24.
2
electrophilic attack of C59N+ on the aromatic ring in the first
step, followed by hydrogen abstraction in a rate-determining
second step.
N-MEM-ketolactam 1 has been already known to afford the
N-chloromethyl ketolactam 22 (Figure 9) by treatment with
1
4
excess TiCl4 in ODCB at room temperature. When adduct 4
was treated with 5 equiv of TiCl4 in ODCB at room temperature,
N-chloromethyl S-ketolactam 23 was formed (Figure 9) after 2
h in 66% yield (Figure 9). This new compound was fully
(
i.e., reaction of 1 with anisole in a refluxing 5:3 ODCB/anisol
15
mixture in the presence of 50 equiv of p-toluenesulfonic acid).
This compound is the para-substitution product of anisole from
+
the azafulleronium ion C59N (9, Scheme 1) and is also
1
13
1
1
characterized by H NMR, C NMR, H- H COSY, HMQC,
accessible through thermal treatment of the azafullerene dimer
1
3
1
5
and C DEPT experiments as well as MS (MALDI), UV-vis,
and FT-IR spectroscopy. By increasing the TiCl4 equivalents
and the reaction time, apart from the major product 23, which
was obtained in 40% yield, formation of the fully deprotected
derivative 14 was also observed in 28% yield.
1
1 with anisole in the presence of p-TsOH and air. Most
probably, due to steric hindrance factors, only the para isomer
is observed in this case. A mechanistic study on the reactivity
of azafulleronium ion 9 was published earlier by our research
1
6
group. On the basis of kinetic isotope effect (KIE) measure-
ments, we proposed that the arenium cation is formed by
Finally, we attempted to trap carbocation 13 with hydro-
quinone, in accordance to the similarly reported reactivity for
17
N-MEM-ketolactam 1. However, when N-MEM-S-ketolactam
was refluxed in an ODCB solution of excess p-toluenesulfonic
acid monohydrate and hydroquinone under argon, the resulting
(
15) Nuber, B.; Hirsch, A. Chem. Commun. 1998, 405-406.
4
(16) Vougioukalakis, G. C.; Chronakis, N.; Orfanopoulos, M. Org. Lett.
2
003, 5, 4603-4606.
6530 J. Org. Chem., Vol. 72, No. 17, 2007

1
1-, 12-, and 13-Membered-Ring Orifice Fullerenes
atmosphere. Following the heating of the reaction mixture at 180 °C,
tetrakis(dimethylamino)ethylene (30.5 µL, 0.12 mmol) was added.
The reaction was stirred at 180 °C for 40 min, and the resulting
solution was concentrated under reduced pressure to about 10 mL.
The mixture was added to pentanes (100 mL) with vigorous stirring
to give brown precipitates. The precipitates were dissolved in ODCB
(6 mL), subjected to flash column chromatography (silica gel, 3%
EtOAc in toluene), and the two isolated products (4 and 5) were
washed three times with HPLC grade acetonitrile (centrifugation
at 1500 c/min) to afford 50.0 mg (71%) of 4 (brown in solution)
and 8.1 mg (11%) of 5 (orange in solution) as brown solids. Data
FIGURE 10. Structures of the deprotected N-MEM-ketolactam (25)
and the 1,3-oxazetidinium intermediate 26.
-1
for 5: IR (KBr, cm ) ν 1724, 1680, 1563, 1525, 1452, 1427, 1399,
reaction mixture was rather complicated and only traces of the
desired hydroquinone ether 24 (Figure 9) were detected. The
fully deprotected derivative 14 was only isolated from this
mixture in 50% yield.
N-MEM-ketolactam 1 was unable, under any of the herein
reported conditions, to afford the fully deprotected derivative
1
7
359, 1261, 1220, 1214, 1201, 1080, 1056, 1010, 841, 814, 794,
48, 610, 594, 560, 534, 477; UV-vis (CHCl , nm) λmax 251, 320;
) δ 6.68
3
+
1
MS (MALDI) m/z 920 (M ); H NMR (500 MHz, CDCl
3
(
d, J ) 10.5 Hz, 1H), 5.95 (d, J ) 10.5 Hz, 1H), 4.07 (m, 2H),
13
3.70 (m, 2H), 3.42 (s, 3H); C NMR (125 MHz, CDCl ) δ 183.84,
163.13, 152.24, 152.11, 149.85, 149.72, 149.50, 149.44, 149.33,
3
25 (Figure 10). On the other hand, N-MEM-S-ketolactam 4 was
149.30, 148.98, 148.79, 148.48, 148.38, 148.19, 147.97, 147.47,
146.52, 145.76, 145.10, 144.79, 144.12, 143.78, 143.02, 141.46,
readily converted into 14 in most of the cases. According to
Wudl and co-workers,14 N-methyl carbonium ion 7 most
141.18, 141.06, 140.77, 140.21, 140.15, 139.67, 139.12, 139.10,
1
1
1
38.94, 138.71, 138.66, 138.60, 138.28, 138.07, 136.31, 136.15,
35.54, 133.46, 132.17, 132.02, 131.95, 131.84, 128.07, 126.90,
26.85, 122.72, 80.27, 72.14, 70.57, 59.56.
probably forms the 1,3-oxazetidinium intermediate 8, which
leads to the azafullerene iminium cation 9 (Scheme 1) because
the cyclopentanone carbonyl group and the N-methyl carbonium
ion are parallel and buttressed against each other by the cage
network. Our experiments suggest that the insertion of a sulfur
atom in the rim of the orifice of 1 has disturbed this proper
orientation for the two moieties, and thus, carbonium ion 13
does not form a corresponding 1,3-oxazetidinium intermediate
Synthesis of the Open-Cage Fullerene Derivative 6. A Schlenk
tube was charged with 10.0 mg (0.01 mmol) of 5, 0.9 mL of CF -
3
COOH (∼1000 equiv), and 10 mL of chlorobenzene. Reaction
progress was monitored by HPLC. The reaction mixture was stirred
at 100 °C for 40 min. The solution was then concentrated to ∼2
mL and purified by flash column chromatography (silica gel, eluted
with gradient ranging from toluene to 4% ethyl acetate in toluene).
The isolated product was washed three times with HPLC grade
acetonitrile (centrifugation at 1500 c/min) to yield 7.0 mg (78%)
26 (Figure 10) toward the formation of the thioaza[60]fullerene
dimer. In this case, the route to the fully deprotected adduct 14
is preferable.
-
1
of 6 as a brown solid: IR (KBr, cm ) ν 1726, 1682, 1581, 1565,
1
5
3
425, 1339, 1263, 1234, 1147, 1103, 1042, 924, 818, 801, 610,
59, 536; UV-vis (CHCl /ODCB: 60/1, nm) λmax 263, 270, 277,
18; MS (MALDI) m/z 831 (M ); H NMR (500 MHz, ODCB-d
Conclusions
3
+
1
4
)
Open-cage [60]fullerene derivative 5, bearing two sulfur
atoms on the rim of its 13-membered-ring orifice, has been
isolated and characterized for the first time. Moreover, the
chemical behavior of N-MEM-ketolactam 1, as well as that of
N-MEM-sulfur-ketolactams 4 and 5, was extensively studied.
Whereas thermal treatment of sulfur ketolactams 4 and 5, under
harsh acidic conditions, led to complete removal of the N-MEM
group, this has been proved impossible for ketolactam 1. It may
very well be the case that for the latter the restoration of the
13
δ 9.48; a C NMR spectrum of good quality was not acquired due
to low solubility.
Synthesis of the Open-Cage Fullerene Derivatives 17a and
17b. A Schlenk tube was charged with 15.0 mg (0.02 mmol) of
S-ketolactam 4, 1.3 mL of CF
3
COOH (∼1000 equiv), and 15 mL
of toluene. The reaction mixture was stirred at 150 °C. Reaction
progress was monitored by HPLC. After 1 h and 40 min,
S-ketolactam was completely consumed, affording the two isomers
17a and 17b (giving a single peak in the HPLC analysis) along
with derivative 14. The solution was then concentrated under
reduced pressure to ∼2 mL and purified by flash column chroma-
tography (silica gel, eluted with gradient ranging from toluene to
[60]fullerene cage to the azafullerene iminium cation 9 is more
favorable than the full removal of the N-MEM group, due to
the feasible formation of the 1,3-oxazetidinium intermediate 8.
It has been also observed that, under milder conditions, 1 and
3% ethyl acetate in toluene). The 17a, 17b fraction was collected
first and the 14 fraction second. Separation of the two isomers 17a
and 17b was impossible. This solution was stripped of solvent, and
the resulting material was washed three times with HPLC grade
4
1
ketolactams afforded open-cage [60]fullerene adducts 17, 18,
9, and 20. The formation of these novel open-cage adducts
was attributed to an electrophilic aromatic substitution reaction.
Treatment of the open-cage [60]fullerene derivative 4 with TiCl4
in ODCB yielded the corresponding N-chloromethyl sulfur
ketolactam 23 in a similar way to N-chloromethyl ketolactam
acetonitrile (centrifugation at 1500 c/min) to yield a 7.0 mg (46%)
mixture of 17a and 17b: IR (KBr, cm-1) ν 1736, 1691, 1491, 1454,
1401, 1305, 1262, 1199, 1169, 1145, 1095, 1027, 801, 742, 705,
3
659, 639, 625, 617, 598, 576, 555, 544, 532, 521; UV-vis (CHCl ,
+
1
nm) λmax 261, 323; MS (MALDI) m/z 903 (M ). 17a: H NMR
500 MHz, CDCl /CS
.7 Hz, 2H), 6.83 (d, J ) 15.2 Hz, 1H), 5.65 (d, J ) 15.2 Hz, 1H),
2
2.
(
7
2
3
2
) δ 7.46 (d, J ) 7.7 Hz, 2H), 7.16 (d, J )
Experimental Section
1
3 2
.34 (s, 3H). 17b: H NMR (500 MHz, CDCl /CS ) δ 7.44 (d,
Synthesis of the Open-Cage Fullerene Derivative 5. Sixty-
eight milligrams (0.08 mmol) of ketolactam 1 was dissolved in
degassed HPLC grade ODCB (40 mL) together with 32.0 mg of
overlapped with the doublet of 17a, 1H), 7.21 (m, 2H), 7.16
(overlapped with the doublet of 17a, 1H), 6.79 (d, J ) 15.9 Hz,
13
1H), 5.87 (d, J ) 15.9 Hz, 1H), 2.60 (s, 3H); C NMR (125 MHz,
S
8
(0.12 mmol) in a 100 mL round-bottomed flask under an argon
CDCl
1
1
3
/CS
48.64, 147.75, 147.72, 147.58, 147.42, 147.34, 147.07, 147.01,
46.98, 146.95, 146.87, 146.80, 146.50, 146.38, 146.01, 145.97,
2
) δ 189.44, 162.40, 149.72, 149.69, 149.27, 149.06,
(17) Keshavarz-K. M.; Gonz a´ lez, R.; Hicks, R. G.; Srdanov, G.; Sdarnov,
V. I.; Collins, T. G.; Hummelen, J. C.; Bellavia-Lund, C.; Pavlovich, J.;
Wudl, F.; Holczer, K. Nature 1996, 383, 147-150.
145.96, 145.93, 145.80, 145.65, 145.59, 145.48, 145.42, 145.39,
145.35, 145.17, 145.13, 145.07, 145.05, 143.56, 143.54, 143.10,
J. Org. Chem, Vol. 72, No. 17, 2007 6531

Roubelakis et al.
1
1
1
1
1
1
1
1
1
43.03, 142.98, 142.94, 142.58, 142.56, 142.29, 142.14, 141.82,
41.75, 141.67, 140.98, 140.79, 140.58, 140.55, 140.31, 140.28,
40.25, 140.10, 139.97, 139.66, 139.25, 138.32, 138.28, 138.16,
38.14, 137.92, 137.87, 137.83, 136.73, 136.70, 136.29, 136.13,
35.97, 135.76, 135.01, 134.95, 134.74, 134.00, 133.93, 131.95,
31.83, 131.27, 131.26, 130.02, 129.78, 129.48, 129.38, 129.19,
29.14, 129.03, 128.69, 128.58, 128.47, 126.81, 126.04, 125.96,
146.32, 145.96, 145.89, 145.80, 145.77, 145.71, 145.61, 145.52,
145.42, 145.40, 145.37, 145.29, 145.15, 145.11, 145.06, 144.99,
143.53, 143.47, 143.03, 142.99, 142.96, 142.92, 142.64, 142.56,
142.52, 142.27, 142.23, 141.95, 141.74, 141.60, 140.92, 140.90,
140.53, 140.48, 140.32, 140.27, 140.22, 140.20, 140.09, 140.08,
139.65, 139.54, 139.20, 139.16, 138.29, 138.26, 138.16, 137.91,
137.88, 137.84, 137.81, 137.65, 137.05, 136.73, 136.65, 136.12,
135.91, 135.89, 134.99, 134.94, 134.92, 133.98, 133.57, 132.24,
132.12, 131.78, 130.49, 130.07, 129.86, 129.08, 129.04, 128.63,
128.60, 126.04, 125.90, 125.20, 121.12, 114.63, 114.26, 110.79,
25.84, 125.77, 56.36 (CH
2
2
carbon of 17a), 53.25 (CH carbon of
7b), 21.69 (CH carbon of 17a), 20.39 (CH
3
3
carbon of 17b).
Synthesis of the Open-Cage Fullerene Derivatives 18a and
18b. A Schlenk tube was charged with 15.0 mg (0.02 mmol) of
56.15 (CH
2
carbon of 19a), 55.73 (OCH
3
carbon of 19a), 55.66
N-MEM-ketolactam 1, 1.4 mL of CF
3
COOH (∼1000 equiv), and
(OCH carbon of 19b), 52.47 (CH
3
2
carbon of 19b).
15 mL of toluene. The reaction mixture was stirred at 150 °C, and
Synthesis of the Open-Cage Fullerene Derivatives 20a and
the progress of the reaction was monitored by HPLC. N-MEM-
ketolactam was completely consumed in 5 h, affording the two
isomers 18a and 18b (a single peak in the HPLC chromatogram).
The solution was then concentrated under reduced pressure to ∼2
mL and purified by flash column chromatography (silica gel,
toluene). Separation of the two isomers was impossible. 18a and
20b. A Schlenk tube was charged with 10.0 mg (0.01 mmol) of
3
N-MEM-ketolactam 1, 0.9 mL of CF COOH (∼1000 equiv), and
10 mL of anisole. The reaction mixture was stirred at 150 °C, and
the progress of the reaction was monitored by HPLC. N-MEM-
ketolactam was consumed in 11 h, affording the two isomers 20a
and 20b (a single peak in the HPLC chromatogram), along with
the less polar compound 21. The solution was then concentrated
under reduced pressure to ∼2 mL and purified by flash column
chromatography (silica gel, eluted with gradient ranging from
toluene to 3% ethyl acetate in toluene). Compound 21 elutes first
and the 20a, 20b fraction comes second. Characterization of 21
(2.2 mg was isolated, 20% yield) has already been reported (ref
15). The separation of the two isomers was impossible. 20a and
20b solution was stripped of solvent, and the resulting material
was washed three times with HPLC grade acetonitrile (centrifuga-
tion at 1500 c/min) to yield a 5.0 mg (48%) brown solid: IR (KBr,
18b solution was stripped of solvent, and the resulting material
was washed three times with HPLC grade acetonitrile (centrifuga-
tion at 1500 c/min) to yield a 10.0 mg (65%) mixture of 18a and
-
1
1
1
8b: IR (KBr, cm ) ν 1727, 1686, 1561, 1491, 1410, 1386, 1213,
178, 768, 741, 615, 601, 578, 528, 522, 503, 492, 475, 457; UV-
+
vis (CHCl
3
, nm) λmax 259, 319; MS (MALDI) m/z 871 (M ). 18a:
1
H NMR (500 MHz, CDCl
3
) δ 7.47 (d, J ) 8.0 Hz, 2H), 7.20 (d,
J ) 8.0 Hz, 2H), 6.42 (d, J ) 15.0 Hz, 1H), 5.42 (d, J ) 15.0 Hz,
1
1
)
H), 2.36 (s, 3H). 18b: H NMR (500 MHz, CDCl
7.5 Hz, 1H), 7.24 (m, 2H), 7.20 (overlapped with the doublet of
8a, 1H), 6.37 (d, J ) 15.5 Hz, 1H), 5.58 (d, J ) 15.5 Hz, 1H),
.59 (s, 3H); 13C NMR (125 MHz, CDCl
/CS ) δ 197.08, 162.86,
3
) δ 7.53 (d, J
-
1
1
2
1
1
1
1
1
1
1
1
1
1
cm ) ν 1728, 1682, 1609, 1560, 1511, 1493, 1249, 1176, 1119,
1031, 906, 731, 602; UV-vis (CHCl , nm) λmax 259, 327; MS
(MALDI) m/z 887 (M ). 20a: H NMR (500 MHz, CDCl ) δ 7.52
3
2
3
+
1
50.29, 150.26, 149.64, 148.20, 147.79, 147.68, 147.60, 147.17,
46.93, 146.82, 146.75, 146.59, 146.51, 146.46, 146.43, 146.28,
46.25, 146.18, 145.89, 145.81, 145.76, 145.72, 145.70, 145.58,
45.28, 145.25, 144.96, 144.91, 144.66, 144.64, 144.54, 144.52,
44.39, 144.21, 144.08, 143.94, 143.91, 143.86, 143.14, 141.98,
41.62, 141.41, 141.09, 141.02, 140.93, 140.26, 139.90, 139.57,
39.27, 138.50, 138.46, 137.09, 137.05, 136.43, 136.38, 136.11,
35.59, 135.53, 134.63, 134.34, 134.20, 134.14, 133.62, 133.56,
33.53, 132.70, 132.58, 132.50, 131.43, 130.20, 130.17, 129.49,
3
(d, J ) 8.5 Hz, 2H), 6.92 (d, J ) 8.5 Hz, 2H), 6.39 (d, J ) 15.0
1
Hz, 1H), 5.39 (d, J ) 15.0 Hz, 1H), 3.76 (s, 3H). 20b: H NMR
(500 MHz, CDCl ) δ 7.76 (d, J ) 7.5 Hz, 1H), 7.35 (m, 1H), 7.04
3
(m, 1H), 6.89 (d, J ) 8.5 Hz, 1H), 6.16 (d, J ) 14.5 Hz, 1H), 5.61
(d, J ) 14.5 Hz, 1H), 3.82 (s, 3H); 13C NMR (125 MHz, CDCl
)
3
δ 197.69, 197.50, 163.15, 163.06, 160.00, 158.30, 150.27, 150.22,
149.65, 149.61, 148.18, 148.16, 147.78, 147.75, 147.72, 147.64,
147.15, 147.13, 147.06, 146.91, 146.81, 146.75, 146.71, 146.60,
146.55, 146.51, 146.49, 146.46, 146.43, 146.37, 146.29, 146.19,
146.18, 146.11, 145.88, 145.80, 145.74, 145.66, 145.55, 145.44,
145.29, 145.26, 145.23, 145.20, 144.89, 144.85, 144.62, 144.57,
144.53, 144.50, 144.46, 144.38, 144.35, 144.19, 144.13, 144.07,
144.03, 144.00, 143.89, 143.85, 143.81, 143.14, 143.09, 141.91,
141.86, 141.58, 141.52, 141.44, 141.38, 141.12, 140.99, 140.93,
140.91, 140.85, 140.78, 140.21, 140.17, 139.96, 139.93, 139.87,
139.56, 139.54, 139.25, 139.20, 138.45, 138.43, 137.10, 137.04,
136.42, 136.35, 136.31, 136.27, 136.05, 136.03, 135.55, 134.33,
134.26, 134.19, 133.86, 133.81, 133.53, 132.77, 132.57, 132.51,
132.10, 130.63, 130.35, 129.42, 129.10, 128.47, 124.15, 121.24,
29.17, 129.10, 129.03, 128.89, 128.71, 126.94, 125.80, 54.39 (CH
carbon of 18b), 21.75 (CH carbon of
carbon of 18b).
2
carbon of 18a), 51.53 (CH
2
3
1
1
8a), 20.38 (CH
3
Synthesis of the Open-Cage Fullerene Derivatives 19a and
9b. A Schlenk tube was charged with 10.0 mg (0.01 mmol) of
S-ketolactam 4, 0.9 mL of CF
3
COOH (∼1000 equiv), and 10 mL
of anisole. The reaction mixture was stirred at 150 °C, and the
progress of the reaction was monitored by HPLC. S-Ketolactam
was completely consumed in 1 h and 50 min, affording the two
isomers 19a and 19b (a single peak in the HPLC chromatogram).
The solution was then concentrated under reduced pressure to ∼2
mL and purified by flash column chromatography (silica gel,
toluene). Separation of the two isomers was impossible. 19a and
114.80, 110.93, 55.78 (OCH
3
3
carbon), 55.69 (OCH carbon), 54.15
(CH carbon of 20a), 50.40 (CH
2
2
carbon of 20b).
1
9b solution was stripped of solvent, and the resulting material
Synthesis of the Open-Cage Fullerene Derivative 23. Ten
milligrams (0.01 mmol) of S-ketolactam 4 dissolved in 10 mL of
ODCB, HPLC grade, was added to a Schlenk tube. A 5-fold excess
was washed three times with HPLC grade acetonitrile (centrifuga-
tion at 1500 c/min) to yield an 11.0 mg (>99%) mixture of 19a
and 19b: IR (KBr, cm ) ν 1735, 1686, 1509, 1491, 1401, 1244,
-
1
of TiCl
temperature. Reaction progress was monitored by HPLC. After 2
h and 50 min, the reaction mixture was washed with concd NaHCO
4
was added, and the resulting solution was stirred at room
1
λ
200, 1170, 1030, 821, 807, 793, 750, 521; UV-vis (CHCl
3
, nm)
max 254, 319; MS (MALDI) m/z 919 (M ). 19a: H NMR (500
) δ 7.51 (d, J ) 8.6 Hz, 2H), 6.88 (d, J ) 8.6 Hz,
H), 6.80 (d, J ) 15.1 Hz, 1H), 5.63 (d, J ) 15.1 Hz, 1H), 3.69 (s,
+
1
3
MHz, CDCl
3
aqueous solution (10 mL), and the organic layer was concentrated
to ∼1 mL under vacuum. This crude product was purified by flash
column chromatography (silica gel, toluene) to yield 6.3 mg (66%)
2
3
)
1
3
1
1
1
1
1
H). 19b: H NMR (500 MHz, CDCl
1.1 Hz, 1H), 7.30 (m, 1H), 7.02 (m, 1H), 6.85 (d, J ) 8.2 Hz,
H), 6.59 (d, J ) 14.9 Hz, 1H), 5.86 (d, J ) 14.9 Hz, 1H), 3.80 (s,
H); 13C NMR (125 MHz, CDCl
) δ 189.78, 189.75, 162.69,
3
) δ 7.81 (dd, J
1
) 7.5 Hz, J
2
-
1
of 23 as a brown solid: IR (KBr, cm ) ν 1737, 1712, 1561, 1492,
1428, 1401, 1355, 1258, 1199, 1142, 822, 814, 751, 728, 692, 625,
3
554, 532, 522; UV-vis (CHCl
3
, nm) λmax 254, 320; MS (MALDI)
+
1
62.61, 159.86, 158.17, 149.69, 149.66, 149.28, 149.23, 149.06,
49.02, 148.63, 148.60, 147.84, 147.75, 147.67, 147.64, 147.63,
47.54, 147.42, 147.36, 147.34, 147.31, 147.07, 147.00, 146.98,
46.97, 146.92, 146.86, 146.77, 146.72, 146.47, 146.43, 146.36,
m/z 847 (M ); H NMR (500 MHz, CDCl ) δ 7.26 (d, J ) 10.7
3
Hz, 1H), 6.32 (d, J ) 10.7 Hz, 1H); 13C NMR (125 MHz, CDCl
3
)
δ 190.44, 162.11, 149.91, 149.32, 149.16, 148.73, 147.99, 147.79,
147.52, 147.35, 147.18, 146.96, 146.89, 146.85, 146.49, 146.44,
6532 J. Org. Chem., Vol. 72, No. 17, 2007

1
1-, 12-, and 13-Membered-Ring Orifice Fullerenes
1
1
1
1
1
6
46.19, 146.12, 146.00, 145.84, 145.53, 145.50, 145.44, 145.41,
45.36, 145.31, 145.14, 145.06, 143.59, 143.40, 143.03, 143.01,
42.63, 142.31, 141.87, 140.94, 140.82, 140.41, 140.33, 140.14,
39.93, 139.37, 139.22, 138.79, 138.40, 137.97, 137.92, 136.64,
35.76, 134.52, 134.32, 133.67, 131.67, 129.14, 128.87, 126.47,
LITOS 2002. We thank Dr T. Drewello for his help in taking
the MS spectra at the University of Warwick.
Supporting Information Available: 1H and 13C NMR, FT-IR,
and UV-vis spectra of all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
2
0.51 (CH carbon).
Acknowledgment. This work was cofunded by the Greek
Ministry of Education and the European Union, through research
and education action programs PYTHAGORAS II and IRAK-
JO070796L
J. Org. Chem, Vol. 72, No. 17, 2007 6533