One-pot synthesis of indolino[2′,3′:1,2][60]fullerenes from fullerene epoxide: Lewis aeid-assisted nueleophilie addition followed by intramolecular cyclization

Article abstract of DOI:10.1246/cl.2008.1018

An efficient one-pot method for the synthesis of indolino-[2′, 3′:1,2][60]fullerene derivatives was developed, in which the formation and cyclization of a β-amino alcohol intermediate by the nueleophilie reaction of fullerene epoxide with aromatic amines was promoted in the presence of aprotic heterogeneous catalysts. Copyright

Full text of DOI:10.1246/cl.2008.1018

1018
Chemistry Letters Vol.37, No.10 (2008)
One-pot Synthesis of Indolino[20,30:1,2][60]fullerenes from Fullerene Epoxide:
Lewis Acid-assisted Nucleophilic Addition Followed by Intramolecular Cyclization
Youhei Numata,1 Jun-ichi Kawashima,2 Takumi Hara,2 and Yusuke Tajimaꢀ1;2
1Nano-Integration Materials Research Unit, RIKEN, 2-1 Hirosawa, Wako 351-0198
2Graduate School of Science and Engineering, Saitama University,
255 Shimo-Ohkubo, Sakura-ku, Saitama 338-8570
(Received June 23, 2008; CL-080634; E-mail: tajima@riken.jp)
An efficient one-pot method for the synthesis of indolino-
C60-fused indolines from C60O and various amine compounds.
The reaction mechanism is also discussed in reference to charac-
terization.
[20,30:1,2][60]fullerene derivatives was developed, in which
the formation and cyclization of a ꢀ-amino alcohol intermediate
by the nucleophilic reaction of fullerene epoxide with aromatic
amines was promoted in the presence of aprotic heterogeneous
catalysts.
Our studies were initiated by heating a suspension of
fullerene oxide, C60O (100 mg) and 4-dodecylaniline (355 mg)
in chlorobenzene at 100 ꢁC in the presence of Montmorillonite
K10 (2.0 g). On processing, the reaction mixture afforded a
product in 56.7% yield, which was characterized as 50-dodecyl-
indolino[20,30:1,2]-1,2-dihydro[60]fullerene (3a) (75 mg).
The product was characterized on the basis of spectroscopic
data. The 1H NMR spectrum of 3a shows three peaks corre-
sponding to aromatic protons, while the 13C NMR spectrum
shows thirty-six peaks corresponding to the sp2 carbons of the
fullerene cage and indoline moiety and two peaks corresponding
to the two quaternary carbons of the fullerene cage. The atmo-
spheric pressure photochemical ionization (APPI) mass spec-
trum of 3a shows a molecular ion peak at m=z 979, which corre-
sponds to C60O (MW 736) and 4-dodecylaniline (MW 261)–
H2O (MW 18). These results indicate that 3a has an indoline
moiety fused with the 6–6 bond of the C60 cage, and the fullerene
cage of 3a has quasi-Cs symmetry.
In order to elucidate the reaction mechanism, the progress of
the reaction was followed by high-pressure liquid chromatogra-
phy coupled with mass spectrometry. In this investigation, it was
confirmed that the indolino[60]fullerene was formed as a result
of two continuous steps. The first step was the formation of
the intermediate, 1-anilino-2-hydroxy-1,2-dihydro[60]fullerenes
(2) by the nucleophilic addition of anilines to 1 in the presence of
a Lewis acid compound. The second step was the formation of an
indoline moiety from 2. We could directly observe the conver-
sion from 2 to 3 (Figure S5, see Supporting Information).8 This
reaction is thought to be the Lewis acid-assisted intramolecular
cyclization of 2 with the elimination of the –OH moiety. The
molecular structure of 2a was also characterized by the spectro-
scopic analyses. The 1H NMR spectrum of 2a shows peaks
Fullerenes exhibit anomalous physicochemical properties
by characteristics such as high electron affinity, widely expanded
ꢁ-conjugation, rigid spherical skeleton, and steric limitations.
To improve the availability of fullerenes for various applica-
tions, many effective methods for fullerene functionalization
for preparing the intended fullerene derivatives have been re-
ported.1 The endowment of characteristics such as excellent sol-
ubility and controlled redox potentials enhances the commercial
value of fullerenes. Such functionalization is worthy of consid-
eration in advanced research toward industrial materials. The
simplification of the synthesis procedures for fullerene deriva-
tives is also required for reducing the manufacturing cost. In par-
ticular, the high regioselectivity of reaction sites onto fullerene
cages by the addition of functional groups is extremely impor-
tant. We recently observed the substitution of fullerene epoxides
C60On from the viewpoint of regioselective functionalization.
We reported that regioselective pure mono- or di-functionalized
fullerenes could be transformed efficiently from the correspond-
ing fullerene epoxides.2 These results demonstrate that even
poly-functionalized fullerene derivatives can be manufactured
on a large scale.
A number of indoline compounds have been known to
exhibit useful pharmaceutical,3 and photovoltaic properties.4
As a general rule, such organic functional compounds are
required to be durable and stable. For instance, the indoline dyes
in dye-sensitized organic solar cells (OSCs) require increased
weathering durability. Indolino[60]fullerene derivatives in
which a fullerene moiety is attached to an indoline ring are very
stable. However, the direct formation of C60-fused indoline com-
pounds has been scarcely explored, and numerous cycloaddition
reactions using amino compounds are utilized in the functional-
ization of fullerenes, including the Prato reaction.5 Previously,
we reported the reaction of carbonyl compounds with C60O (1)
to give C60-fused 1,3-dioxolane compounds in the presence of
a Lewis acid catalyst. Therefore, in accordance with our previ-
ous results,2 we hypothesized that the reaction of C60O with
aniline would give anilinohydroxyl- and/or dianilino fullerene
derivatives. However, the reaction between C60O and 4-dodecyl-
aniline with Montmorillonite K10 as a Lewis acid catalyst
in chlorobenzene unexpectedly gave a C60-fused indoline
compound. In this paper, we report the one-pot synthesis of
R
R
O
R
NHR'
HO
NR'
H
N
R'
∆
– Cat.
Cat.
O
Lewis acid
R
1
R
2
R'
N
Cat.
H
H
O
NR'
– H2
O
∆
– Cat.
2
Lewis acid
3
Scheme 1. Proposed reaction mechanism for the formation of
indolino[60]fullerene derivatives from C60O.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.10 (2008)
1019
Table 1. Examination results of catalytic activities of selected
compounds for the formation of 3a
Table 2. Isolated yields of indolino[60]fullerenes
Aromatic amine
Product
R
R0 Yield/%a
Catalyst
Time
Yield of 3a/%a
4-Dodecylaniline
4-n-Butylaniline
p-Toluidine
4-Fluoroaniline
Aniline
N-Methyl-p-toluidine
3a
3b
3c
3d
3e
3f
C12H25
C4H9
Me
F
H
Me
H
H
H
H
H
Me
77.7
Montmorillonite K10
Sepiolite
BiCl3
6 h
6 h
56.7
63.8
64.1
84.0
75.7
78.9
29.3
2 h
over 5 days
over 5 days
50.3
0 (C60 was given)
trace (C60 was given)
p-TsOH
Amberlyst 15
aIsolated yields, estimated from HPLC areas.
aIsolated yields, estimated from HPLC areas.
corresponding to phenyl, amino, hydroxy, and alkyl protons,8
while the APPI mass spectrum shows a molecular ion peak at
m=z 998, which corresponds to the sum of the molecular weights
of C60O (MW 736) and 4-dodecylaniline (MW 262). On the
basis of these data, we proposed a possible reaction mechanism
(Scheme 1). To the best of our knowledge, the one-pot synthesis
of indoline derivatives from ordinal epoxides and aromatic
amines has not yet been reported. To assist effective intramolec-
ular cyclization (1) hydroxy and aniline groups can be fixed
in the neighborhood and (2) fullerenes cannot be subjected
to backside attack and bond rotation on the basis of their cage
structures.
Table 3. First reduction potentials of indolino[60]fullerenes
Er1ed/V vs. Fc/Fcþ
Fullerenes
C60
1
ꢂ1:089
ꢂ1:052
ꢂ1:143
ꢂ1:135
ꢂ1:138
ꢂ1:127
ꢂ1:141
ꢂ1:145
3a
3b
3c
3d
3e
3f
We examined the catalytic activity of several Lewis and
Brønsted acids in this reaction under similar conditions.8 The re-
sults are summarized in Table 1. The reactions with Sepiolite
and BiCl3 rapidly gave 3a and in good yields. The reactions with
Amberlyst 15 and p-toluenesulfonic acid (p-TsOH), which are
Brønsted acids, gave pristine C60 with a trace amount of 3a.
We inferred that the protonation of Brønsted acids to anilines
completely inhibited the nucleophilic addition to fullerene
epoxide.
Reactions of 1 with various aromatic amines in the presence
of Sepiolite were also carried out. Every reaction except for
that with N-methyl-p-toluidine provides the corresponding
indolino[60]fullerene derivatives in good yields (Table 2). For
N-methyl-p-toluidine, the steric hindrance of the methyl group
on the nitrogen atom may inhibit the nucleophilic addition to
the fullerene cage.
In conclusion, we have demonstrated an effective prepara-
tion method for a series of indolino[60]fullerenes by reacting
C60O with aromatic amines in the presence of Lewis acid
compounds. We revealed that this reaction consisted of two steps
via the formation of ꢀ-amino alcohol intermediate 2. Reactions
with various primary aromatic amines also give corresponding
derivatives in good yields, except for 3f, which has a bulky sub-
stituent on the nitrogen atom. The results of electrochemical
measurements reveal that among all the fullerene derivatives,
C60-fused indoline compounds have relatively low reduction
potentials and electrochemical stability.
This work was financially supported by the NEDO
foundation (Grant for Practical Application of University R&D
Results under the Matching Fund Method).
References and Notes
The electrochemical behavior of 3 is similar to those of
typical C60 derivatives. All indolino[60]fullerenes exhibited
well-defined, reversible redox waves in o-dichlorobenzene solu-
tion containing 0.1 M (n-Bu)4NPF6 on multicyclic voltamme-
try.8 The first reduction potentials, E1red, of C60, 1, and the series
of indolino[60]fullerene derivatives were measured by differen-
1
2
3
T. Kitagawa, Y. Murata, K. Komatsu, in Carbon-Rich
Compounds, ed. by M. M. Haley, R. R. Tykwinski, Wiley-
VCH, Weinheim, 2006, Chap. 9, pp. 383–420.
Y. Shigemitsu, M. Kaneko, Y. Tajima, K. Takeuchi,
Chem. Lett. 2004, 33, 1604; Y. Tajima, T. Hara, T. Honma,
S. Matsumoto, K. Takeuchi, Org. Lett. 2006, 8, 3203.
J. G. Varnes, D. A. Wacker, I. C. Jacobson, M. L. Quan,
C. D. Ellis, K. A. Rossi, M. Y. He, J. M. Luettgen, R. M.
Knabb, S. Bai, K. He, P. Y. S. Lam, R. R. Wexler, Bioorg.
Med. Chem. Lett. 2007, 17, 6481.
tial pulse voltammetry, as shown in Table 3. The E1 data of
red
indolino[60]fullerenes ranged from ꢂ1:127 to ꢂ1:145 V (vs.
Fc/Fcþ). These values are lower than those of other fullerene
derivatives. For the 1,2-substituted fullerenes, the electron-do-
nating groups that are attached to the fullerene cage elevate their
LUMO levels.6 Thus, the lowering of the reduction potentials of
indolino[60]fullerenes can be explained in terms of the electron-
donating properties of the nitrogen atom. These electrochemical
properties are attractive for OSCs. It has been proposed that
the theoretical open circuit voltage, which is one of the most
important parameters for developing a high-performance OSC,
is closely related to the difference between the LUMO level
of the accepter material and the HOMO level of the donor
material.7 Thus, the low reduction potentials of indolino[60]-
fullerenes are promising for application as good accepter
materials in OSCs.
4
5
6
7
8
T. P. I. Saragi, T. Spehr, A. Siebert, T. Fuhrmann-Lieker,
J. Salbeck, Chem. Rev. 2007, 107, 1011.
M. Maggini, G. Scorrano, M. Prato, J. Am. Chem. Soc. 1993,
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T. Suzuki, Y. Maruyama, T. Akasaka, W. Ando, K.
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´
B. C. Thompson, J. M. J. Frechet, Angew. Chem., Int. Ed.
2008, 47, 58.
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Published on the web (Advance View) August 30, 2008; doi:10.1246/cl.2008.1018