Synthesis of dicarboxylic acid derivatives of [60]fullerene using Diels- Alder reaction with bis(methylene)butanedioates

Article abstract of DOI:10.1016/S0040-4039(00)00122-2

3-Sulfolene-3,4-dicarboxylates effective for generation of bis(methylene)butanedioates were applied to [4+2] cycloaddition reaction of C₆₀ to give fullerocyclohexenedicarboxylates, among which a t-butyl ester was hydrolyzed to a dicarboxylic acid derivative, useful for further conversion into its anhydride and half-esters. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00122-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2153–2156
Synthesis of dicarboxylic acid derivatives of [60]fullerene using
Diels–Alder reaction with bis(methylene)butanedioates
a,∗
b,∗
Hiroshi Ishida, Hirotaka Asaji, Toshiki Hida, Kenji Itoh and Masatomi Ohno
a
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Chikusa,
Nagoya 464-8603, Japan
b
Department of Materials Science and Engineering, Toyota Technological Institute, 2-12-1, Hisakata, Tempaku,
Nagoya 468-8511, Japan
Received 10 November 1999; accepted 14 January 2000
Abstract
3-Sulfolene-3,4-dicarboxylates effective for generation of bis(methylene)butanedioates were applied to [4+2]
cycloaddition reaction of C60 to give fullerocyclohexenedicarboxylates, among which a t-butyl ester was hydro-
lyzed to a dicarboxylic acid derivative, useful for further conversion into its anhydride and half-esters. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: [60]fullerene; 3-sulfolene; Diels–Alder reaction; dicarboxylic acid; anhydride.
Surface modification of fullerenes is an attractive approach in materials science and pharmaceutical
1
2
applications, and a wide variety of functionalized derivatives have been prepared especially using C .
60
The cycloaddition reaction is now recognized as the most promising protocol for such functionalization,
because the number of addends is controlled with relative ease, and the addition site is limited to the
6
,6 junction. Based on these merits, we have continuously reported [4+2] and [ 3+2] cycloadditions to
3
the double bond of C , and our recent effort revealed that a prototypical tetrahydrothiophene-fused
C60 could be obtained with a thiocarbonyl ylide. The C60 derivative having two functional groups is
believed to be advantageous for effective use, for example, for cyclization, polymerization, and the
evolution of characteristic supramolecular systems. In this sense, functionalization with two carboxyl
6
0
4
5
6
7
8
groups is representative. We envisaged that synthesis of a dicarboxylic acid derivative of C60 such as 6
can be achieved by exploiting the above thiocarbonyl ylide; a feasible four-step route includes: (1) 1,3-
dipolar cycloaddition reaction of the ylide with acetylenedicarboxylates; (2) oxidation of the cycloadduct
to 3-sulfolenes, (3) Diels–Alder reaction of the 3-sulfolene-3,4-dicarboxylates with C ; and finally, (4)
60
acid-catalyzed hydrolysis of the esters. Reported here are fruitful results we have achieved along this line
and the further conversion into an anhydride and half-esters.
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00122-2
tetl 16401

2
154
3
b
C has a low LUMO level and prefers to cycloadd with electron-rich 1,3-dienes. Yet, it was indicated
6
0
to have adequate reactivity even with electron-deficient dienes, and this feature was utilized for facile
3
b
introduction of a mono-functionality to C
and further extension to synthesis of a free monocarboxylic
6
0
3
c
acid derivative. This strategy can be applied to synthesis of the related dicarboxylic acid derivative
with bis(methylene)butanedioates 3. Previously, we demonstrated that the thermal decomposition of 3-
sulfolenes to 1,3-dienes gave Diels–Alder cycloadducts of C satisfactorily, and hence, it is reasonable
to use this type of reagent as a reaction partner also in the present case. The required 3-sulfolene-
9
3
b
60
10
1
1
3
,4-dicarboxylates 2 could be obtained by 1,3-dipolar cycloaddition of the thiocarbonyl ylide with
1
2
acetylenedicarboxylates followed by OXONE oxidation of the cycloadduct 1 (Scheme 1). Since
the model [4+2] cycloaddition reaction of 2a with typical dienophiles showed that the yields were
comparable to or even better than those reported,11 the aimed cycloaddition reaction with C60 was
conducted in the same manner. Thus, C60 was allowed to react with 2a (5 equiv.) in o-dichlorobenzene
at 180°C for 30 min under an argon atmosphere. The reaction occurred smoothly (the color of solution
immediately changed from violet to brown), and the product was separated by silica gel chromatography
(
elution with hexane/toluene 1/1) to give the desired cycloadduct 4a in 44% yield. The structure was
+
unambiguously elucidated by spectral data; FAB-MS peaks were observed at m/z 890 (M ) and 720
−
base), and IR absorption indicated the presence of an ester moiety and a C core at 1721 and 527 cm ,
60
1
(
1
respectively. C2v symmetry was confirmed by H NMR signals (500 MHz, CHCl /CS 5/3) at δ 3.95 (s,
6
1
3
2
1
3
H) and 4.33 (s, 4 H) and C NMR signals (125 MHz, CDCl /CS 5/3) at δ 65.12 for fused carbons,
3
2
1
3
2
35.87–155.28 (17 lines ) for sp carbons, and 166.22 for ester carbonyl groups. These facts evidence
the usual addition at the 6,6 junction and the rapid flipping of a cyclohexene ring occurring at room
1
4
temperature. Analogous products 4b–d were obtained with other 3-sulfolenes 2b–d (Scheme 1).
Scheme 1.
Among the cycloadducts obtained here, the t-butyl ester is a good candidate for conversion into a
free dicarboxylic acid derivative, because its hydrolysis, which occurs quite readily under mild acidic
conditions, is desirable particularly in C60 chemistry.3 In fact, treatment of the ester 4d (30 mg) with
excess trifluoroacetic acid (2 ml) in toluene (20 ml) at room temperature for 3 h afforded half-hydrolyzed
product 5 (27 mg) in 96% yield. The expected dicarboxylic acid 6 was successfully obtained in 75%
c
yield by further hydrolysis for another 5 h and purification with chromatography [silica gel, elution with
+
CHCl /EtOH (5/1)]. The structure was supported by FAB-MS which had the expected M peak at m/z
3
−1
8
62 together with IR absorptions at 3387, 1701 (COOH) and 527 (C ) cm . Although the dicarboxylic
60

2
155
acid 6 is slightly soluble in aq. K CO as documented in the case of methanofullerenedicarboxylic acid by
2
3
8
Hirsch, its extremely low solubility in organic solvents did not allow NMR measurement. Nevertheless,
this drawback could be cleared by further transformation of 6 to a soluble anhydride 7 by dehydration
with acetic anhydride using a large amount of the reagent (20 equiv.) in dry toluene at 80°C for 2 h
(
quantitative yield). Again, the structure was shown to have C2v symmetry by NMR patterns similar to
1
13
those of 4 [ H NMR (500 MHz, CDCl /CS 4/1) δ 4.55 (s, 4 H); C NMR (125 MHz, CDCl /CS 4/1)
δ 65.45 (fused carbons), 135.85–155.44 (17 lines, sp carbons), and 163.02 (C_O)]. Until now, this
functionality has not been utilized for surface modification of C . Thus, the reaction of 7 with alcohol
3
2
3
2
15
2
60
can lead to a functionalized fullerenecarboxylic acid. The anhydride 7 was treated with several alcohols
10 equiv.) in dry toluene at 60°C for 3–8 h and chromatographic separation [silica gel, elution with
(
CHCl /EtOH (5/1)] gave half-esters 8a–c in good yields. Particularly, a protected amino acid derivative
3
of C60 such as 8b was obtainable in this way (Scheme 2).
Scheme 2.
In summary, the Diels–Alder reaction of C60 with bis(methylene)butanedioate 3 generated by thermal
decomposition of 3-sulfolene-3,4-dicarboxylates 2 afforded functionalized C60 having double ester
groups. Among them, the t-butyl ester 4d was easily hydrolyzed to a dicarboxylic acid derivative of
C , which is useful for a variety of applications. An example is its conversion into an anhydride and
6
0
half-esters, and our further work with the dicarboxylic acid itself is aimed at realizing some sandwich-
type interaction with clays.
Acknowledgements
This work was financially supported by a Grant-in-Aid for Scientific Research on Priority Area (A)
(No.10146101) from the Ministry of Education, Science, Sports, and Culture, Japan.
References
1
2
3
. Hirsch, A. Synthesis 1995, 895.
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Tetrahedron 1996, 52, 4983. (c) Ohno, M.; Shirakawa, Y.; Eguchi, S. Synthesis 1998, 1812. (d) Ohno, M.; Sato, H.; Eguchi,
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2
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4
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7
8
9
. For a geminal case, see: Lamparth, I.; Hirsch, A. J. Chem. Soc., Chem. Commun. 1994, 1727.
. We have previously prepared a bicyclic diester derivative of C60, but the less simple structure and low yield of this compound
prompted us to develop prototypical 4 and 6 (see Ref. 3b).
1
0. Bis(methylene)butanedioates are reported to be produced by the methods of: (a) retro Diels–Alder reaction of
anthracene cycloadduct; (b) pyrolysis of diacetate; (c) ring-opening reaction of cyclobutene; (d) debromination of
bis(bromomethyl)maleate; (e) Horner–Emmons condensation of succinate, and (f), (g) metal-promoted coupling and
insertion reactions. However, most of these methods do not fully meet the purpose of the present reaction with C60: (a)
Tarnchompoo, B.; Thebtaranonth, C.; Thebtaranonth, Y. Tetrahedron Lett. 1987, 28, 6671. (b) Bailey, W. J.; Hudson, R. L.;
Yates, E. T. J. Org. Chem. 1963, 28, 828. (c) Bellus, D.; Weis, C. D. Tetrahedron Lett. 1973, 12, 999. (d) Hamon, D. P. G.;
Spurr, P. R. Synthesis 1981, 873. (e) Davidson, R. M.; Kenyon, G. L. J. Org. Chem. 1977, 42, 1030. (f) Semmelhack, M. F.;
Helquist, P.; Jones, L. D.; Keller, L.; Mendelson, L.; Ryono, L. S.; Smith, J. G.; Stauffer, R. D. J. Am. Chem. Soc. 1981, 103,
6
460. (g) Kiji, J.; Okano, T.; Fujii, E.; Tsuji, J. Synthesis 1997, 869.
1
1. Lee, S. J.; Chien, C. J.; Chou, T. S. Bull. Inst. Chem., Acad. Sin. 1993, 40, 1. Our preparative method for 2 seems to be more
convenient than that reported here (seven-step from 3-alkoxycarbonyl-4-keto-tetrahydrothiophene). By our method, [4+2]
cycloaddition of 2a with maleic anhydride and p-benzoquinone, which have comparable reactivity with C60, was found to
1
0b
10d
give the corresponding cycloadducts in 55% (lit. 23% ) and 73% (lit. 72% ) yields, respectively.
2. Aono, M.; Hyodo, C.; Terao, Y.; Achiwa, K. Tetrahedron Lett. 1986, 27, 4039.
1
1
3. δ 135.87, 138.63, 140.26, 141.72, 142.13, 142.21, 142.67, 143.17, 144.69, 145.06, 145.52, 145.66, 145.80, 146.31, 146.59,
1
47.72, 155.28.
1
1
4. In comparison with bis(methoxycarbonyl)-substituted 4a, restricted flipping was observed in the bis(phenylsulfonyl)-
substituted case (see Ref. 3c).
5. δ 135.85, 141.21, 142.54, 142.77, 142.95, 143.56, 144.02, 145.11, 145.42, 146.41, 146.48, 146.57, 147.19, 147.49, 148.53,
+
−1
1
48.64, 155.44. Also observed are FAB-MS [m/z 844 (M ), 720 (base)] and IR (1848, 1774, and 527cm ).