1,4-fullerenols C60ArOH: Synthesis and functionalization

Article abstract of DOI:10.1021/ol900110g

A mild and facile process for the preparation of 1,4-fullerenols C ₆₀ArOH was achieved. The key intermediate 1,2-C₆₀Ar (NO₂) was identified to better understand the reaction mechanism. Further functionalizations including

Full text of DOI:10.1021/ol900110g

ORGANIC
LETTERS
2009
Vol. 11, No. 7
1507-1510
1,4-Fullerenols C60ArOH: Synthesis and
Functionalization
Guan-Wu Wang,* Yong-Ming Lu, and Zhong-Xiu Chen
Hefei National Laboratory for Physical Sciences at Microscale and Department of
Chemistry, UniVersity of Science and Technology of China,
Hefei, Anhui 230026, P. R. China
gwang@ustc.edu.cn
Received January 19, 2009
ABSTRACT
A mild and facile process for the preparation of 1,4-fullerenols C60ArOH was achieved. The key intermediate 1,2-C60Ar(NO2) was identified to
better understand the reaction mechanism. Further functionalizations including esterification, etherification, and arylation of the synthesized
1,4-C60ArOH provided efficient access to versatile fullerene derivatives in the presence of p-toluenesulfonic acid.
Fullerenols consisting of 14-20 hydroxy moieties were first
synthesized by Chiang et al. using nitronium chemistry1 or
aqueous acid reaction.2 Other methods for the polyhydroxy-
lation of fullerenes involved the hydrolysis of a fullerene
intermediate formed through aqueous base reaction,3 oleum,4
nitrogen dioxide radicals,5 or hydroboration.6 These synthe-
sized fullerenols were a mixture of fullerene compounds with
different numbers of hydroxy groups and different chemical
structures. In fact, the fullerenols prepared by the aqueous
acid reaction of [60]fullerene (C60) in the presence of sulfuric
acid and potassium nitrate/nitric acid contained hemiketal
moieties.2b In comparison, the fullerenols prepared by the
C60(toluene)/NaOH(aq.)/TBAH method were structurally and
electronically complex C60 radical anions with a molecular
formula of Na+ [C60Ox(OH)y]n- (where n ) 2-3, x ) 7-9,
n
and y ) 12-15).7 The synthesis of more structurally defined
fullerenol with multiple addends was first achieved by Taylor
and co-workers.8 They treated C70Cl10 with benzene/FeCl3
and obtained a minor product of fullerenol C70Ph9OH.
Fullerenols C60Me5OOH, C60Me5O2OH, and C60Me4PhOOH
were synthesized by the reaction of C60 with methyllithium9
or the reaction of C60Cl6 with methyllithium followed by
(1) Chiang, L. Y.; Upasani, R. B.; Swirczewski, J. W. J. Am. Chem.
Soc. 1992, 114, 10154.
(2) (a) Chiang, L. Y.; Swirczewski, J. W.; Hsu, C. S.; Chowdhury, S. K.;
Cameron, S.; Creegan, K. J. Chem. Soc., Chem. Commun. 1992, 1791. (b)
Chiang, L. Y.; Upasani, R. B.; Swirczewski, J. W.; Soled, S. J. Am. Chem.
Soc. 1993, 115, 5453.
(3) Li, J.; Takeuchi, A.; Ozawa, M.; Li, X.; Saigo, K.; Kitazawa, K.
J. Chem. Soc., Chem. Commun. 1993, 1784.
(4) (a) Chiang, L. Y.; Wang, L.-Y.; Swirczewski, J. W.; Soled, S.;
Cameron, S. J. Org. Chem. 1994, 59, 3960. (b) Chen, B.-H.; Huang, J.-P.;
Wang, L. Y.; Shiea, J.; Chen, T.-L.; Chiang, L. Y. J. Chem. Soc., Perkin
Trans. 1 1998, 1171. (c) Chen, B.-H.; Canteenwala, T.; Patil, S.; Chiang,
L. Y. Synth. Commun. 2001, 31, 1659.
(7) Husebo, L. O.; Sitharaman, B.; Furukawa, K.; Kato, T.; Wilson, L. J.
J. Am. Chem. Soc. 2004, 126, 12055.
(5) Chiang, L. Y.; Bhonsle, J. B.; Wang, L.; Shu, S. F.; Chang, T. M.;
Hwu, J. R. Tetrahedron 1996, 52, 4963.
(8) Birkett, P. R.; Avent, A. G.; Darwish, A. D.; Kroto, H. W.; Taylor,
R.; Walton, D. R. M. J. Chem. Soc., Chem. Commun. 1996, 10, 1231.
(9) Al-Matar, H.; Hitchcock, P. B.; Avent, A. G.; Taylor, R. Chem.
Commun. 2000, 35, 1071.
(6) Schneider, N. S.; Darwish, A. D.; Kroto, H. W.; Taylor, R.; Walton,
D. R. M. J. Chem. Soc., Chem. Commun. 1994, 463.
10.1021/ol900110g CCC: $40.75
Published on Web 03/05/2009
2009 American Chemical Society

hydrolysis.10 Starting from fullerene peroxides with multiple
OOtBu groups, Gan and co-workers have prepared a variety
of closed-cage and open-cage fullerenols with at least one
hydroxy group and/or hemiketal moiety.11 The simplest
fullerene diols C60(OH)2 and C70(OH)2 were prepared by the
reaction of C60 and C70 with RuO4 followed by acid
hydrolysis.12
reaction of C60 (36.0 mg, 0.05 mmol) with 4-substituted
phenylhydrazine hydrochlorides 1a-d (0.1 mmol) and
NaNO2 (6.9 mg, 0.1 mmol) in a mixture of toluene (25 mL)
and H2O (1 mL) at 50 °C under air atmosphere afforded
fullerenols 1,4-C60ArOH, instead of C60ArN3 or 1,2-C60ArH.
The reaction conditions and yields for the reaction of C60
with 4-substituted phenylhydrazine hydrochlorides 1a-d and
NaNO2 leading to 1,4-C60ArOH 2a-d are listed in Table 1.
Monohydroxylated fullerenols with the general form of
C60ROH are much less investigated, and only a few such
compounds have been isolated and characterized until
now.13-17 Iyoda and co-workers synthesized C60RFOH by
the reaction of C60 with (RFCO)2O.13 Irngartinger et al.
prepared 1,2-C60(CN)OH via N-O bond cleavage of
[60]fullereno[1,2d]isoxazole,14 which was generated by the
addition of fulminic acid to C60.18 Kitagawa et al. described
the formation of fullerenols 1,4-C60ROH (R ) CHCl2,
CCl2CH2Cl) from the hydrolysis of chlorofullerenes.15
Tajima and co-workers recently reported the synthesis of 1-
hydroxyl-2-(1,3,5-trimethylphenyl)-1,2-dihydro[60]fullerene
(1,2-C60ArOH) by the nucleophilic substitution of C60O in
the presence of BF3·Et2O.16 More recently, Tuktarov et al.
described the preparation of 1,2-C60HOH by the reaction of
C60 with water catalyzed with Cp2MCl2.17 Evidently, much
more monohydroxylated fullerenols C60ROH with different
functional groups and addition patterns are demanded due
to their scarcity and the utility of the hydroxy group.14-17
In our earlier work, we reported that the reaction of C60
with 4-substituted phenylhydrazine hydrochlorides in reflux-
ing chlorobenzene afforded 1-(4-substituted phenyl)-1,2-
dihydro[60]fullerenes (1,2-C60ArH).19 Interestingly, we re-
cently found that upon the addition of sodium nitrite (NaNO2)
the above reaction under moisture and aerobic conditions
unexpectedly afforded 1-hydroxyl-4-(4-substituted phenyl)-
1,4-dihydro[60]fullerenes (1,4-C60ArOH). In this letter, we
report this novel result and further transformation of the 1,4-
C60ArOH into other versatile fullerene derivatives by esteri-
fication, etherification, and arylation.
Table 1. Reaction Conditions and Yields for the Reaction of C60
with 1a-d and NaNO2
a
product
R
reaction time (h)
yieldb
recovered C60
2a
2b
2c
2d
CH3
CH3O
H
6
6
6
18%
19%
14%
20%
59%
69%
50%
64%
Cl
12
a All reactions were performed in toluene-H2O solution (v/v, 25:1) in
air at 50 °C; molar ratio of C60:1:NaNO2 ) 1:2:2. b Isolated yield.
As can be seen from Table 1, 4-substituted phenylhydrazine
hydrochlorides with both electron-donating and electron-
withdrawing groups on the phenyl ring could be employed
in this reaction. Higher reaction temperature resulted in
decreased product yields.
1,4-Fullerenols 2a-d were fully characterized by HRMS,
1H NMR, 13C NMR, FT-IR, and UV-vis spectra. The 1,4-
addition pattern was established by the typical broad peak
at around 440 nm in their UV-vis spectra. Further evidence
for the assignment of 2a-d as 1,4-adducts came from the
13C NMR spectra, which had at least 46 peaks for the sp2-
carbons of the C60 skeleton, consistent with their C1 sym-
metry.
Our recent work on the solvent-free reaction of C60 with
an arylhydrazine hydrochloride and NaNO2 under mechanical
milling conditions, which led to the formation of a fullero-
triazoline compound (C60ArN3),20 promoted us to investigate
the corresponding liquid-phase reaction. Surprisingly, the
1,2-Fullerenols C60ArOH carrying only bulky aryl groups
could be isolated from the nucleophilic substitution of C60O
with a bulky arene such as 1,3,5-trimethylbenzene in the
presence of BF3·Et2O.16 In contrast, our synthesized fullere-
nols are another type of products, i.e., 1,4-adducts, and a
bulky aryl group was not required.
(10) Al-Matar, H.; Abdul-Sada, A. K.; Avent, A. G.; Fowler, P. W.;
Hitchcock, P. B.; Rogers, K. M.; Taylor, R. J. Chem. Soc., Perkin Trans.
2. 2002, 53.
(11) For selected examples, see: (a) Huang, S.; Xiao, Z.; Wang, F.; Gan,
L.; Zhang, X.; Hu, X.; Zhang, S.; Lu, M.; Pan, Q.; Xu, L. J. Org. Chem.
2004, 69, 2442. (b) Xiao, Z.; Yao, J.; Yang, D.; Wang, F.; Huang, S.; Gan,
L.; Jia, Z.; Jiang, Z.; Yang, X.; Zheng, B.; Yuan, G.; Zhang, S.; Wang, Z.
J. Am. Chem. Soc. 2007, 129, 16149. (c) Yao, J.; Xiao, Z.; Gan, L.; Yang,
D.; Wang, Z. Org. Lett. 2008, 10, 2003.
It should be noted that all of the sodium nitrite, water,
and oxygen in the system played crucial roles for the
successful synthesis of 1,4-fullerenols 2a-d. In an attempt
to neutralize the HCl in phenylhydrazine hydrochlorides,
other bases such as NEt3, pyridine, 4-dimethylaminopyridine,
aq NaOH, and aq K2CO3 were used to replace NaNO2 in
the above reaction. However, none or only trace amounts of
1,4-C60ArOH along with some unidentified products could
be obtained in any of these cases. The reaction in anhydrous
toluene at 50 °C under air atmosphere afforded only 1,2-
C60ArH, with the products just the same as those at higher
temperature19 yet in much lower yields. Nevertheless, the
(12) Meier, M. S.; Kiegiel, J. Org. Lett. 2001, 3, 1717.
(13) Yoshida, M.; Morinaga, Y.; Iyoda, M.; Kikuchi, K.; Ikemoto, I.;
Achiba, Y. Tetrahedron Lett. 1993, 34, 7629
.
(14) Irngartinger, H.; Weber, A. Tetrahedron Lett. 1997, 38, 2075
.
(15) Kitagawa, T.; Sakamoto, H.; Takeuchi, K. J. Am. Chem. Soc. 1999,
121, 4298
.
(16) Tajima, Y.; Hara, T.; Honma, T.; Matsumoto, S.; Takeuchi, K. Org.
Lett. 2006, 8, 3203
(17) Tuktarov, A. R.; Akhmetov, A. R.; Pudas, M.; Ibragimov, A. G.;
Dzhemilev, U. M. Tetrahedron Lett. 2008, 49, 808
.
.
(18) Imgartinger, H.; Weber, A.; Esther, T. Liebigs Ann. 1996, 1845.
(19) Chen, Z.-X.; Wang, G.-W. J. Org. Chem. 2005, 70, 2380.
(20) Chen, Z.-X.; Zhu, B.; Wang, G.-W. Lett. Org. Chem. 2008, 5, 65.
1508
Org. Lett., Vol. 11, No. 7, 2009

presence of water would lead to 1,4-C60ArOH at the expense
of 1,2-C60ArH. When more than 0.5 mL of water was added,
the formation of 1,2-C60ArH was completely suppressed.
When the reaction was conducted under a nitrogen atmo-
sphere and otherwise the same conditions, no 1,4-C60ArOH
was produced, indicating that oxygen was indispensable.
The thin-layer chromatography (TLC) monitoring of the
reaction showed that a less polar product was formed at the
early stage of the reaction but disappeared at the end of
the reaction. We surmised that this product was probably
the precursor of 1,4-C60ArOH. Fortunately, we managed to
isolate the product (14%) along with 1,4-fullerenol 2a (9%)
from the reaction of C60 with 1a in a shorter reaction time
(2 h). The product proved to be 1-(4-methylphenyl)-2-nitro-
1,2-dihydro[60]fullerene (3a) (Figure 1) by detailed spectral
characterization.
Scheme 1. Proposed Reaction Mechanism
fullerenols 2 were formed as 1,4-adducts from 1,2-adducts
3. The proposed conversion of 3 to 2 was substantiated by
the fact that 2a was obtained in 43% yield by treating 3a in
toluene/water at 50 °C for 36 h. However, other alternative
pathways cannot be ruled out. For example, the first step
•
might also be oxidized by NaNO2; the NO2 radical could be
formed in the reaction mixture and adds to the radical
intermediates 4.
Fullerenols have great synthetic potential due to the
hydroxyl group. Esterification was first attempted by the
reaction of 1,4-fullerenol 2a with acetic acid employing
DCC/DMAP (1:2:2:0.2) under a nitrogen atmosphere.14 The
reaction in toluene/acetonitrile (v/v, 9:1) for 72 h at room
temperature afforded only 25% of the desired 6a. The
DMAP-catalyzed reaction of 2a with acetic anhydride (Ac2O,
100 equiv) in pyridine at 110 °C for 8 h17 gave only a trace
of 6a along with a mixture of polar unidentified products.
The above two conditions14,17 were reported to be effective
for the esterification of 1,2-fullerenols. These results may
indicate that a 1,4-fullerenol is less reactive than a 1,2-
fullerenol.
Fortunately, we found that the acetylation of 1,4-fullerenol
2a as well as its analogues 2b-d worked very well with
Ac2O in the presence of p-toluenesulfonic acid (TsOH). The
reaction conditions and product yields for acetoxylated
fullerenes 6a-d along with recovered fullerenols 2a-d are
listed in Table 2. The esterification reaction was efficient
and gave products 6a-d in 64-82% yields after 6 h. The
identities for products 6a-d were evidently confirmed by
comparing their spectral data with the reported ones.19
The etherification of fullerenols 2a-d with methanol could
be realized by TsOH in a mixture of solvents. The reaction
conditions and product yields for methoxylated fullerenes
7a-d along with recovered fullerenols 2a-d are listed in
Table 3. It is noteworthy that 7a could also be obtained in
71% yield by treating 3a with methanol at 50 °C for 36 h,
further supporting the last two steps in Scheme 1.
Figure 1. Structure of 3a.
The HRMS (+ESI) of 3a gave a peak at 880.0387 for
+
C67H7NNaO2 , corresponding to the [M + Na]+ peak. In
the IR spectrum of 3a, the strong absorptions at 1556, 1341,
and 805 cm-1, which were close to 1572, 1328, and 815
cm-1 for the nitro group in polynitrofullerenes,5 exhibited
the existence of the nitro group rather than the nitrite group.
In the 13C NMR spectrum of 3a, there were 25 peaks with
some overlapping ones in the range of 153-134 ppm for
the sp2 carbons of the fullerene skeleton, accompanied with
the peaks at 106 and 69 ppm for the two sp3 carbons of the
fullerene cage. These 13C NMR data are fully consistent with
its molecular structure with a Cs symmetry. The 1,2-addition
pattern of product 3a was obvious in its UV-vis spectrum,
which showed a characteristic sharp peak at 420 nm.
Nitrofullerene 3a represents the first example of the fully
characterized and structurally defined fullerene compounds
with the nitro group directly attached to the fullerene cage,
even though polynitrofullerenes C60(NO2)n as a mixture5 and
a multiadduct of C60 bearing a ONO2 group11a have been
reported.
On the basis of the above experimental results, a plausible
reaction mechanism for the formation of 1,4-C60ArOH is
shown in Scheme 1. The first two steps leading to fullerenyl
radicals 4 are the same as the previously proposed ones.19
The addition of the nitrite anion to radicals 4 results in radical
anions 3-•, which are oxidized, presumably by oxygen, to
the neutral products 3. The attack of H2O at the C4 position
of 3 with the leaving of the nitrite anion via a SN2′
mechanism gives intermediates 5, and subsequent loss of
proton generates 1,4-fullerenols 2. Similar SN2′ processes
on the fullerene cage have been reported.4a,21 The proposed
mechanism shown in Scheme 1 perfectly explains why
The arylation of fullerenols 2a-d with toluene could also
be successfully achieved in the presence of TsOH. The
reaction conditions and product yields of the arylated
fullerenes 8a-d along with recovered 2a-d are listed in
Table 4. It should be pointed out that the two aryl groups
(21) Avent, A. G.; Abdul-Sada, A. K.; Clare, B. W.; Kepert, D. L.; Street,
J. M.; Taylor, R. Org. Biomol. Chem. 2003, 1, 1026.
Org. Lett., Vol. 11, No. 7, 2009
1509

Table 2. Reaction Conditions and Yields for the Acetylation of
Fullerenols 2a-d in the Presence of TsOHa
Table 4. Reaction Conditions and Yields for the Arylation of
Fullerenols 2a-d in the Presence of TsOHa
product
R
reaction time (h) yieldb recovered fullerenol
reaction
time (h)
recovered
fullerenol
product
R
yieldb
6a
6b
6c
6d
CH3
CH3O
H
6
6
6
6
74%
70%
82%
64%
11%
23%
7%
8a
8b
8c
8d
CH3
CH3O
H
10
12
2
71%
53%
62%
66%
7%
16%
11%
13%
Cl
23%
a All reactions were performed in CS2 at an oil bath temperature of 80
Cl
2
°C; molar ratio of 2:Ac2O:TsOH ) 1:2:2. b Isolated yield.
a All reactions were performed in toluene at an oil bath temperature of
80 °C; molar ratio of 2:TsOH ) 1:5. b Isolated yield.
must be the same in the 1,4-C60(Ar)2 products prepared by
the Lewis acid-assisted nucleophilic substitution of C60O.16
However, the 1,4-C60(Ar)Ar′ products with two different aryl
groups could be achieved by our protocol.
ppm), but the corresponding sp3 carbon was upfield shifted
by more than 14 ppm in 8a-d (ca. 60 ppm) because of the
addend change to an aryl group.
The structures of products 7a-d and 8a-d were fully
Fullerenyl cation intermediates have been produced by
dissolving 1,4-C60ROH (R ) CHCl2, CCl2CH2Cl) in
CF3SO3H15 or by treating 1,2-C60ArOH with BF3·Et2O.16 We
believe that the esterification, etherification, and arylation
of fullerenols 2a-d in the presence of TsOH should also
proceed through the formation of the corresponding fullerenyl
carbocations, followed by the reaction with Ac2O, MeOH,
and toluene. TsOH was preferred in our protocol because it
was cheap and environmentally friendly and showed high
efficiency for all three transformations.
In summary, 1,4-fullerenols C60ArOH were synthesized
via the reaction of [60]fullerene with 4-substituted phenyl-
hydrazine hydrochlorides and sodium nitrite under moisture
and aerobic conditions at 50 °C. The key and unprecedented
intermediate C60Ar(NO2) was isolated and characterized. A
possible mechanism for the formation of 1,4-fullerenols
involving C60Ar(NO2) via a SN2′ pathway was proposed.
Further transformations of the 1,4-fullerenols through es-
terification, etherification, and arylation were also carried out
in the presence of p-toluenesulfonic acid.
1
established by their MS, H NMR, 13C NMR, FT-IR, and
UV-vis spectra. All etherified and arylated fullerenes 7a-d
and 8a-d are 1,4-adducts, which are supported by the peak
at ca. 440 nm in their UV-vis spectra and the C1 molecular
symmetry deduced from their 13C NMR spectra except for
8a. Due to the same two addends, 1,4-adduct 8a showed
much fewer peaks (31 peaks) for the sp2 carbons along with
one peak at 60 ppm for the two sp3 carbons of the C60 cage
in its 13C NMR spectrum, agreeing with its C2 symmetry. It
is noteworthy that the δc value for the sp3 carbon of C60
attached to the oxygen atom was close to each other in 2a-d
(ca. 74 ppm), 6a-d (76-78 ppm19), and 7a-d (79-80
Table 3. Reaction Conditions and Yields for the Methoxylation
of Fullerenols 2a-d in the Presence of TsOHa
Acknowledgment. The authors are grateful for the finan-
cial support from the National Natural Science Foundation
of China (Nos. 20572105 and 20621061) and the National
Basic Research Program of China (2006CB922003).
reaction
time (h)
recovered
fullerenol
product
R
yieldb
7a
7b
7c
7d
CH3
CH3O
H
60
60
60
50
26%
46%
37%
44%
47%
39%
50%
46%
Supporting Information Available: Detailed experimen-
1
tal procedures and characterization data, as well as the H
Cl
NMR and 13C NMR spectra of 2a-d, 3, 7a-d, and 8a-d.
This material is available free of charge via the Internet at
http://pubs.acs.org.
a All reactions were performed in 1,4-dioxane-CS2-MeOH solution (v/
v/v, 2:1:1) at an oil bath temperature of 100 °C; molar ratio of 2:TsOH )
1:5. b Isolated yield.
OL900110G
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Org. Lett., Vol. 11, No. 7, 2009