Regioselective synthesis and complexation behavior of novel [60]fullerene bisadducts containing dibenzo-18-crown-6 moiety

Article abstract of DOI:10.1016/S0040-4039(00)00134-9

The reaction of [60]fullerene with bis-o-quinodimethane precursor 3 containing a dibenzo-18-crown-6 moiety provided preferentially trans-4 bisadduct 5a along with a small amount of cis-2 bisadduct 5b. These bisadducts showed different ionophoric propertie

Full text of DOI:10.1016/S0040-4039(00)00134-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2193–2197
Regioselective synthesis and complexation behavior of novel
[60]fullerene bisadducts containing dibenzo-18-crown-6 moiety
Yosuke Nakamura,a Aya Asami,a Seiichi Inokuma,a Toshio Ogawa,a Munehiro Kikuyama b and
Jun Nishimura a,∗
aDepartment of Chemistry, Gunma University, Tenjin-cho, Kiryu, Gunma 376-8515, Japan
bBiological Laboratory, The University of the Air, Wakaba, Mihama-ku, Chiba 261-8586, Japan
Received 22 December 1999; revised 11 January 2000; accepted 14 January 2000
Abstract
The reaction of [60]fullerene with bis-o-quinodimethane precursor 3 containing a dibenzo-18-crown-6 moiety
provided preferentially trans-4 bisadduct 5a along with a small amount of cis-2 bisadduct 5b. These bisadducts
showed different ionophoric properties from each other; 5a exhibited a high complexing ability toward K+ ion,
while 5b hardly showed complexation with any alkali metal ions. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: fullerenes; Diels–Alder reaction; regioselective synthesis; crown ethers; complexation.
Although multiple addition toward [60]fullerene becomes of increasing interest from the view-
points of electronic,1 electrochemical,2 photophysical,3 and chiroptical properties,4 it usually affords
regioisomeric mixtures. Even in the bisaddition reactions occurring exclusively at [6,6]-junctions, eight
regioisomers are theoretically possible. Several research groups regioselectively prepared a variety of
bisfunctionalized [60]fullerene derivatives by the tether-directed remote functionalization.5 We have
succeeded in the regioselective synthesis of [60]fullerene-o-quinodimethane bisadducts modified within
one hemisphere of [60]fullerene by connecting the two precursors with an oligomethylene linkage; 1a
(n=2) and 1b (n=3) provide the cis-2 and cis-3 isomers, while 1c (n=5) exclusively the e-isomer.6 This
regioselectivity is apparently derived from the constrained distance between the two reactive species,
governed by the oligomethylene linkage. For the improvement of regioselectivity, we have designed the
reaction of dibenzo-18-crown-6 derivative 3. The macrocyclic moiety in 3, which can serve as double
bridging linkages connecting two o-quinodimethane precursors, should control the relative arrangement
as well as the distance between the reactive species, probably leading to the preferential addition at
two sites located almost in parallel. Furthermore, the resulting bisadducts seem to display ionophoric
properties different from dibenzo-18-crown-6 itself. Here we report the regioselectivity produced by 3
and the intriguing complexation behavior of the resulting bisadducts. The comparison with the reaction of
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00134-9
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2 possessing a single oxyethylene linkage is also discussed. These investigations are expected to provide
a guide for preparing specific bisadducts.
We have first examined the reaction using 2, which can be regarded as a reference compound of both
1c and 3. The preparation of 2 is depicted in Scheme 1. Equimolar amounts of [60]fullerene and 2 were
refluxed in toluene in the presence of KI (10 equiv.) and 18-crown-6 (40 equiv.) for 24 h under high-
dilution conditions (1–4×10−4 M). After insoluble oligomeric materials were removed, the reaction
mixture was purified by column chromatography (silica gel) and GPC, to give mainly two bisadduct
regioisomers 4a and 4b in 26 and 10% yields, respectively (Scheme 2). The 1H NMR spectral patterns of
4a and 4b were different from each other; the former shows four aromatic and two methoxy proton peaks,
while the latter only two aromatic and one methoxy proton peak,7 indicating that 4a has C1 symmetry
and 4b C2 or Cs. These symmetries were also confirmed by the 13C NMR spectra. It is most reasonable
to assign 4a as e-isomer, because the other regioisomers should usually adopt higher symmetry.8 In 4b,
one of the aromatic proton peaks was resonated at much lower field (δ 7.60) than any protons in 4a (δ
6.85–7.25). Since this behavior is characteristic of cis-2 isomers due to steric compression as reported
previously,6 4b is reasonably assigned as the cis-2 isomer. These assignments are also supported by their
UV–vis spectra, which are similar to those of the bisadducts obtained from precursors 1, since the UV–vis
spectra of bisadducts are known to depend mainly on addition patterns.3,6 The formation of cis-2 isomer,
which was not obtained from 1c, is ascribed to the increase in flexibility in bridging linkage of 2 due to
the C–O ether bond. The presence of a single oxygen atom in 2 remarkably altered the regioselectivity.
Scheme 1.
Scheme 2.

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Precursor 3 was prepared from commercially available dibenzo-18-crown-6 in a manner similar to that
in 2. The reaction of 3 with [60]fullerene was carried out under conditions similar to those in 2, except
for heating for 60 h (Scheme 3). Purification of the reaction mixture by GPC gave mainly two bisadducts
5a (major) and 5b (minor) (total 64% yield), which were successfully separated by preparative TLC. The
1H and 13C NMR spectra of both 5a and 5b apparently indicated C2 or Cs symmetry.9 In 5b, downfield-
shifted aromatic protons were again observed (δ 7.58), leading to the assignment as cis-2. The addition
sites of 5a could not be clarified by the NMR spectra alone. The UV–vis spectrum of 5a, however,
exhibits two broad maxima at 643 and 708 nm, which are characteristic of the trans-4 bisadduct as
reported in the literature.10 This addition pattern is compatible with the symmetry observed in the NMR
spectra. The UV–vis spectrum of 5b, similar to that of the cis-2 bisadduct from precursors 1a or 1b,
supports the cis-2 bisaddition. The preferential formation of trans-4 bisadduct 5a from 3, in remarkable
contrast with the formation of e-bisadduct from 1c or 2, seems quite reasonable, since the dibenzo-18-
crown-6 moiety of 3 is expected to force the two o-quinodimethane precursors to be almost parallel,
making favorable for trans-4 rather than e-bisaddition. Thus, the double bridging linkages proved to be
effective for the regulation of relative arrangement of the two reactive species.
Scheme 3.
The complexation of 5a and 5b with alkali metal ions was investigated by electrospray ionization MS
(ESI-MS). The mixed solution containing equimolar amounts of 5a (or 5b) and MClO4 (M+=Li+, Na+,
K+, Rb+, and Cs+) in methanol:chloroform (1:1) was subjected to ESI-MS. Each solution of 5a afforded
the peak due to the [5a+M]+ ion, implying the complexation with the alkali metal ions in a ratio of 1:1.
On the other hand, 5b hardly showed the peaks of [5b+M]+ with any alkali metal ions. In the competition
experiments using 5a and all the alkali metal ions listed above, the peak of [5a+K]+ was observed with the
highest intensity. The difference in complexing ability between 5a and 5b can be readily explained by the
difference in the shape of dibenzo-18-crown-6 moiety. According to the molecular dynamics calculations,
the dibenzo-18-crown-6 moiety in 5b suffers from considerable deformation, which is apparently caused
by the reduced distance and relative arrangement between the two addition sites that are not situated in
parallel.
The selectivity of 5a toward K+ over Na+ ion was further investigated with an ion-selective electrode.11
The selectivity coefficients (KNa,Kpot) for the electrode consisting of 5a and dibenzo-18-crown-6 as a
pot
reference were determined by the separate solution method.12 Surprisingly, the KNa,K value (=42) for
5a was much higher than that (=13) of dibenzo-18-crown-6 electrode, indicating high selectivity toward
K+.
In summary, in contrast with 1c or 2 having a single bridging linkage, the reaction of [60]fullerene with
3 containing a dibenzo-18-crown-6 moiety that can be regarded as double bridging linkages connecting
two o-quinodimethane precursors provided preferentially trans-4 bisadduct 5a, which exhibits intriguing
complexation behavior. This method using double bridging linkages enables the control of relative

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arrangement as well as distance between the reactive species and appears to be versatile for the re-
gioselective synthesis of specific bisadducts. The reactions of o-quinodimethane precursors incorporated
into other macrocyclic systems are now under investigation.
Acknowledgements
This work was financially supported by the Japan Society for the Promotion of Science.
References
1. Lu, Q.; Schuster, D. I.; Wilson, S. R. J. Org. Chem. 1996, 61, 4764.
2. Boudon, C.; Gisselbrecht, J.-P.; Gross, M.; Isaacs, L.; Anderson, H. L.; Faust, R.; Diederich, F. Helv. Chim. Acta 1995, 78,
1334.
3. Nakamura, Y.; Taki, M.; Tobita, S.; Shizuka, H.; Yokoi, H.; Ishiguro, K.; Sawaki, Y.; Nishimura, J. J. Chem. Soc., Perkin
Trans. 2 1999, 127.
4. Taki, M.; Nakamura, Y.; Uehara, H.; Sato, M.; Nishimura, J. Enantiomer 1998, 3, 231; Goto, H.; Harada, N.; Crassous, J.;
Diederich, F. J. Chem. Soc., Perkin Trans. 2 1998, 1719.
5. Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537, and references cited therein.
6. Taki, M.; Sugita, S.; Nakamura, Y.; Kasashima, E.; Yashima, E.; Okamoto, Y.; Nishimura, J. J. Am. Chem. Soc. 1997, 119,
926.
7. Selected spectroscopic data of 4a and 4b are as follows. Compound 4a: 1H NMR (CDCl3, 500 MHz) δ 7.25 (1H, s), 7.04
(1H, s), 7.00 (1H, s), 6.85 (1H, s), 4.67 (1H, m), 4.48 (1H, d, J=12.8 Hz), 4.45 (1H, m), 4.43 (1H, d, J=12.8 Hz), 4.23
(1H, m), 4.21 (1H, d, J=13.4 Hz), 4.12 (1H, d, J=13.7 Hz), 4.07 (1H, m), 3.99 (3H, s), 3.96 (3H, s), 3.90 (1H, d, J=12.8
Hz), 3.88 (1H, m), 3.88 (1H, d, J=13.7 Hz), 3.83 (1H, d, J=12.8 Hz), 3.72 (1H, m), 3.65 (1H, m), 3.55 (1H, m), 3.10 (1H,
d, J=13.4 Hz); 13C NMR (CDCl3, 125 MHz) δ 162.13, 161.07, 155.60, 155.41, 155.27, 155.13, 154.70, 154.40, 150.29,
149.29, 149.14, 148.48, 148.13, 148.03, 147.97, 147.91, 147.53, 147.26, 146.56, 146.47, 146.23, 146.01, 145.94, 145.71,
145.65, 145.45, 145.25, 145.04, 144.94, 144.77, 144.72, 144.65, 144.61, 144.57, 144.52, 144.19, 143.57, 143.50, 143.01,
142.92, 142.58, 142.48, 142.25, 142.20, 142.11, 141.96, 141.58, 141.19, 140.97, 140.07, 140.03, 136.64, 136.47, 136.24,
135.70, 135.49, 133.46, 131.83, 130.86, 128.90, 118.88, 118.61, 113.74, 113.51, 113.29, 113.23, 112.09, 111.84, 70.21,
69.95, 69.51, 69.14, 66.53, 65.73, 64.75, 57.23, 56.95, 45.02, 43.68, 42.87, 42.57; FAB MS m/z 1090 (M+). Compound 4b:
1H NMR (CDCl3, 500 MHz) δ 7.60 (2H, s), 6.97 (2H, s), 4.68 (2H, m), 4.63 (2H, d, J=14.2 Hz), 4.40 (2H, m), 4.24 (2H, m),
4.08 (2H, m), 4.05 (2H, d, J=14.2 Hz), 3.93 (2H, d, J=14.0 Hz), 3.92 (6H, s), 3.90 (2H, d, J=14.0 Hz); 13C NMR (CDCl3, 125
MHz) δ 160.63, 159.08, 150.47, 149.47, 147.48, 147.37, 147.30, 147.15, 147.00, 146.68, 146.20, 145.95, 145.49, 145.21,
145.14, 145.01, 144.77, 144.61, 144.56, 144.29, 144.29, 143.68, 142.65, 141.47, 141.15, 138.70, 133.19, 131.36, 131.15,
129.71, 128.28, 128.12, 117.40, 111.51, 111.16, 71.81, 71.40, 63.03, 62.56, 55.65, 44.84, 42.63; FAB MS m/z 1090 (M+).
8. The regioisomers such as cis-2, cis-3, and trans-4 can also adopt C1 symmetry under the unsymmetrical bridging mode, but
they were excluded by the UV–vis spectra and molecular dynamics calculations.
9. Selected spectroscopic data of 5a and 5b are as follows. Compound 5a: 1H NMR (CDCl3, 500 MHz) δ 7.01 (2H, s), 6.75
(2H, s), 4.5–4.6 (6H, m), 4.28 (4H, m), 4.15 (2H, m), 3.97 (2H, d, J=12.5 Hz), 3.79 (2H, d, J=13.2 Hz), 3.73 (2H, m), 3.54
(2H, m), 3.18 (4H, m); 13C NMR (CDCl3, 125 MHz) δ 155.57, 155.24, 153.21, 151.06, 149.35, 148.83, 148.57, 146.30,
146.22, 145.98, 145.69, 145.56, 144.85, 144.61, 143.14, 142.87, 142.02, 141.93, 141.64, 141.12, 140.76, 138.86, 136.75,
136.46, 135.38, 131.44, 129.95, 129.23, 122.05, 115.29, 69.10, 68.83, 68.59, 67.40, 66.15, 65.74, 44.35, 43.37; FAB MS
m/z 1132 (M+). Compound 5b: 1H NMR (CDCl3, 500 MHz) δ 7.58 (2H, s), 6.98 (2H, s), 4.70 (4H, m), 4.51 (2H, m), 4.33
(2H, m), 4.31 (2H, d, J=14.4 Hz), 4.1 (2H, m), 4.09 (2H, d, J=14.4 Hz), 3.99 (2H, d, J=13.2 Hz), 3.95 (2H, m), 3.62 (2H,
d, J=13.2 Hz), 3.37 (2H, m), 2.69 (2H, m); 13C NMR (CDCl3, 125 MHz) δ 162.03, 158.20, 151.07, 149.71, 149.37, 149.11,
147.76, 147.25, 147.07, 146.92, 146.71, 146.51, 145.96, 145.95, 145.88, 145.74, 145.31, 145.14, 144.89, 144.62, 144.46,
144.27, 144.24, 143.42, 142.56, 141.86, 141.42, 136.60, 134.51, 133.57, 133.06, 132.93, 129.14, 122.19, 116.45, 71.95,
70.46, 70.45, 68.72, 64.03, 63.65, 43.09, 43.05; FAB MS m/z 1132 (M+).
10. Ishi-i, T.; Nakashima, K.; Shinkai, S.; Ikeda, A. J. Org. Chem. 1999, 64, 984; Ishi-i, T.; Shinkai, S. Tetrahedron 1999, 55,
12515.

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11. Ion sensitive membrane of the poly(vinyl chloride) matrix type was prepared as follows: 5a (0.9 mg), o-nitrophenyl octyl
ether (63 mg), poly(vinyl chloride) (25 mg), and potassium tetrakis(p-chlorophenyl)borate (0.6 mg) were dissolved in THF
(1 mL). The solution was injected to fill the final 4 mm of the tip of a glass pipette (0.74 mm i.d.). A transparent membrane
was obtained by evaporation of the solvent at room temperature. The electrode was conditioned by soaking in 0.3 M KCl
solution during 15 h before use. The reference electrode was an Ag·AgCl electrode with agar bridge containing 50 mM
NaCl. The electrode cell for emf measurement is as follows: Ag·AgCl/4 M KCl/PVC membrane/sample solution/0.05 M
NaCl agar bridge/4 M KCl/AgCl·Ag. Emf was measured at 25±0.5°C with a digital mV meter. The Ki,jpot (i, primary ion; j,
interfering ion) values were calculated from response potential in a 0.1 M cation chloride solution by the separate solution
method.
12. Guilbault, G. G.; Durst, R. A.; Frant, M. S.; Freiser, H.; Hansen, E. H.; Light, T. S.; Pungor, E.; Rechnits, G.; Rice, N. M.;
Rohm, T. J.; Simon, W.; Thomas, J. D. R. Pure Appl. Chem. 1976, 48, 129.