Reaction of [60]fullerene with α-alkoxyl/acyloxyl/phenolyl ketoxime: Unusual C-C and C-O bond cleavag

Article abstract of DOI:10.1016/j.tetlet.2012.12.123

Reaction of [60]fullerene with α-alkoxyl/phenolyl/acyloxyl ketoxime in the presence of sodium carbonate afforded fulleroisoxazoline or fullerooxazine derivatives via C-C or C-O bond cleavage respectively. O ₂ was proved to be essential to the reaction. Copyright

Full text of DOI:10.1016/j.tetlet.2012.12.123

Tetrahedron Letters 54 (2013) 1428–1431
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reaction of [60]fullerene with a-alkoxyl/acyloxyl/phenolyl ketoxime: unusual
C–C and C–O bond cleavage
⇑
Hai-Tao Yang , Wen-Long Ren, Xiao-Jiao Ruan, Zong-Yong Tian, Xi-Chen Liang, Chen Han,
⇑
Xiao-Qiang Sun , Chun-Bao Miao
School of Petrochemical Engineering, Changzhou University, Changzhou 213164, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of [60]fullerene with a-alkoxyl/phenolyl/acyloxyl ketoxime in the presence of sodium carbonate
afforded fulleroisoxazoline or fullerooxazine derivatives via C–C or C–O bond cleavage respectively. O2
was proved to be essential to the reaction.
Received 5 September 2012
Revised 24 December 2012
Accepted 31 December 2012
Available online 7 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Fullerene
Ketoxime
Fulleroisoxazoline
Fullerooxazine
Since their first discovery, the fullerenes have attracted the
attention of an increasing number of scientists due to their unique
structure. During the last 20 years numerous studies have been
conducted in the field of organic chemistry to elucidate the reactiv-
ity of C60, and various types of reactions are now known to be
applicable to derivatization at the outside of the cage.1 C60 and
its derivatives exhibit a wide variety of uncommon properties,
some of which have found widespread use in chemical, biological,
and materials sciences.2 [60]Fullerene usually behaves as electron-
deficient alkenes. Many unique reactions can occur on the fuller-
ene but did not work on other alkenes compounds.3 The achieve-
ment of fullerene derivatives with specific structure is still
demanded in different research fields.
also be formed if [60]fullerene was treated with 2-ethoxyl-1,2-
diphenylethanone oxime through extrusion of ethanol. When a
mixture of C60 (54.0 mg), 2-ethoxyl-1,2-diphenylethanone oxime
1b (95.6 mg, 5 equiv), and Na2CO3 (40.0 mg, 5 equiv) was stirred
in 30 mL of toluene at room temperature for 24 h no reaction oc-
curred. While the temperature was raised to 110 °C, to our sur-
prise, the unexpected fulleroisoxazoline product 2a5 was
obtained in 24% yield (57% based on consumed C60) via C–C bond
cleavage. The C–C bond cleavage of ketoxime is very common in
Beckmann rearrangement6 and Beckmann fragmentation.7 Amide
and nitrile were generated from the two kinds of reactions, respec-
tively. Nevertheless, to the best of our knowledge, this kind of C–C
bond cleavage and generation of the isoxazoline compound have
never been reported. In the context of our general interest in fuller-
ene chemistry,8 herein we reported an unusual C–C and C–O bond
cleavage of ketoxime in their reaction with [60]fullerene.
In our recent report, we developed an efficient method to pre-
pare C60-fused dihydrooxazine derivatives from the hetero-Diels–
Alder reaction of [60]fullerene with nitrosoalkene generated
in situ by extrusion of HBr from the corresponding
ime.4 According to the mechanism of inverse-electron demanded
hetero-Diels–Alder reactions 2-bromo-1,2-diphenylethanone
oxime was predicted to be more active than 2-bromo-1-phenyleth-
anone oxime. When 2-bromo-1,2-diphenylethanone was treated
with hydroxylamine hydrochloride in ethanol, 2-ethoxyl-1,2-
diphenylethanone oxime, instead of 2-bromo-1,2-diphenyletha-
none oxime, was obtained due to the solvolysis reaction. We are
inquisitive about whether the dihydrooxazine derivatives could
a
-bromo ketox-
The influence of base on the reaction was summarized in Ta-
ble 1. As it was demonstrated, the organic base such as Et3N, DAB-
CO, and DMAP was superior to inorganic base and gave higher
yield in shorter time under the same molar ratio of C60:1b:base
as 1:5:5. DMAP gave the best yield of 2a in 1 h (Table 1, entry 4).
Reducing the amount of 1b to 2 equiv and using catalytic amount
of DMAP also gave 2a in 36% yield in 4 h along with more recov-
ered C60 (Table 1, entries 5 vs 4). While the reaction was operated
at 170 °C using 1,2-dichlorobenzen (ODCB) as the solvent low yield
of 2a was obtained (Table 1, entry 6). From the viewpoint of atom-
economy and the yield based on recovered C60 the molar ratio of
⇑
Corresponding authors. Tel.: +86 519 86330257.
E-mail addresses: yanght898@yahoo.com.cn (H.-T. Yang), chemsxq@yahoo.
C60:1b:DMAP as 1:2:0.2 and the reaction temperature as 120 °C
were selected as the optimal condition.
com.cn (X.-Q. Sun).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.12.123

H.-T. Yang et al. / Tetrahedron Letters 54 (2013) 1428–1431
1429
Table 1
Screening of the reaction conditiona
NOH
OEt
O
base
+
N
Ph
1b
2a
Entry
Base
C60:1a:base
T (°C)
Time (h)
Yield (%)
Recovered C60 (%)
1
2
3
4
5
6
Na2CO3
Et3N
DABCO
DMAP
DMAP
DMAPb
1:5:5
1:5:5
1:5:5
1:5:5
1:2:0.2
1:2:0.2
110
110
110
110
110
170
24
12
12
2
4
1
24
31
29
39
36
9
58
49
47
29
43
65
a
A mixture of C60 (54 mg, 0.75 mmol), 1a, and base in 30 mL of solvent was stirred at proper temperature.
8 mL of 1,2-dichlorobenzene was used as solvent.
b
To determine the generality of this kind of unusual C–C bond
as the single product with approximate yield (Table 2, 1a–c). Next,
the influence of the phenyl group at the -position of C@N was
examined (Table 2, 1d). There was no doubt that the C–C bond
cleavage, a variety of ketoxime were employed to react with C60
(Table 2). Firstly, the influence of the alkoxyl group on the reaction
was investigated. The size of the alkoxyl group was not an impor-
tant impact factor to this reaction. Whether the alkoxyl group was
methoxy, ethoxy, or isopropoxy the same product 2a was obtained
a
cleaved off in this reaction. The leaving group might be
a
PhCHÀ(OEt) carbanion and the phenyl group was a benefit to the
stability of carbanion. If the phenyl group (R2) was replaced by
Table 2
The reaction of C60 with
a
-alkoxyl/phenolyl/acyloxyl ketoxime in the presence of base9
NOH
OR3
O
O
N
base
C-C cleavage
base
C-O cleavage
N
1
C60
+
R
R2
1
R1
R1
R2
3
2
Substrate
Product
Temperature (°C)
Time (h)
4
Yield (%)
37a
Recovered C60 (%)
1a
1b
1c
1d
NOH
OCH3
2a
2a
2a
O
N
110
50
NOH
OC2H5
O
N
110
110
4
4
36a
32a
43
41
NOH
OCH(CH3)2
O
N
NOH
OC2H5
2a
2e
O
9b
73
55
N
150
150
12
24
22c
NOH
OC2H5
1e
O
N
110
150
4
39a
39
Me
NO2
CH3
NOH
1f
2f
OC2H5
O
N
22
17c
70
O2N
NO2
(continued on next page)

1430
H.-T. Yang et al. / Tetrahedron Letters 54 (2013) 1428–1431
Table 2 (continued)
Substrate
Product
Temperature (°C)
Time (h)
22
Yield (%)
20c
Recovered C60 (%)
NOH
OC2H5
1g
2g
O
O
N
MeO
150
60
OCH3
NOH
1h
1i
2h
OC2H5
18c
21a
58
61
N
170
110
26
20
C(CH3)3
NOH
OC2H5
2i
O
N
CH3
NOH
OC2H5
3j
1j
O
O
N
N
170
16
16c
53
NOH
3k
1k
1l
O
CH3
80
110
27
4
19d
26d
70
66
O
NOH
O
—
170
24
NRc
—
All reactions were performed with 54 mg of C60 under air condition.
a
C60:1:DMAP = 1:2:0.2, toluene.
C60:1:DMAP = 1:2:0.2, ODCB.
C60:1:Na2CO3 = 1:5:5, ODCB.
C60:1:Na2CO3 = 1:5:5, toluene.
b
c
d
hydrogen atom, the reactivity might be decreased and the reaction
perhaps did not work. When a mixture of C60 (54.0 mg), 2-ethoxyl-
1-phenylethanone oxime 1d (26.9 mg, 2 equiv), and DMAP
(1.9 mg, 0.2 equiv) was stirred under the same conditions, no reac-
tion was observed after stirring for 12 h. Increasing the tempera-
ture to 150 °C and amount of 1d to 5 equiv 2a was produced in
13% yield. However, using Na2CO3 instead of DMAP, 2a was iso-
lated in higher yield (22%). The result proved our conjecture. Also,
we can see that organic base is not suitable at high temperature
(Table 1, entry 6; Table 2, 1d) maybe due to the decomposition
of tertiary amine at high temperature.10 Subsequently, the influ-
ence of electronic effect of the substituent group on the phenyl ring
(R1) on the reaction was investigated (Table 2, 1f and 1g). Either
electron-withdrawing or electron-donating group on the phenyl
ring could give the desired product 2f or 2g. Substrate 1i was also
investigated and the reaction of C60 with 2 equiv of 1-ethoxy-1-
phenylpropan-2-one oxime 1i in the presence of 0.2 equiv of DMAP
at 110 °C for 20 h provided 2i in 21% yield. When R1 changed from
aromatic ring to alkyl group such as tertiary butyl group (Table 2,
1h), the similar reaction occurred in company with a little uniden-
tified byproduct at higher temperature (170 °C). To investigate the
mechanism of this kind of reaction 2-ethoxy-3,4-dihydronaphtha-
len-1(2H)-one oxime was synthesized to react with C60 (Table 2,
1j). We envisaged that the leaving group would remain in the
molecular structure of the product after C–C bond cleavage, which
could be detected by NMR analysis. Unexpectedly, when a mixture
NO2
NOH
O
DMAP (0.2 equiv)
N
+
o
toluene, 110 C, N
6 h
2
OEt
1e (2 equiv)
H3C
2e,
trace
NO2
NOH
DMAP (20% mol)
H3C
CN
+
O2N
CO2Et
o
toluene, 110
air, 4 h
C
OEt
1e
H3C
NOH
OMe
O
Na CO (5 equiv)
2
3
N
+
o
ODCB, 150 C, air, 16 h
1m
(5 equiv)
2m, 12%
CO2Me
Scheme 1.

H.-T. Yang et al. / Tetrahedron Letters 54 (2013) 1428–1431
1431
O
respectively. We have no definitive answers so far why the reaction
of 1j and C60 gave the fullerooxazine derivatives.
O2
R2-C-OR3
R2-CH-OR3
7
O
C60
R1
N
5
N
C
O
Acknowledgments
R1
OH
O
N
N
OR3
R2
2
Na2CO3
NaHCO3
OR3
The authors are grateful for the financial support from the Na-
tional Natural Science Foundation of China (Nos. 20902039 and
21202011), and the Priority Academic Program Development of
Jiangsu Higher Education Institutions.
R1
R1
R2
4
O
1
N
O
C60
N
R1
R1
R2
R3O
R2
6
Supplementary data
3
Supplementary data (experimental details for the preparation
of 1a–k, 2, 3 and spectra of 1a–k, 2a, 2h, 2i, 2m, 3i, and 3j) associ-
ated with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2012.12.123.
Scheme 2.
of C60 (54.0 mg), 1j (77.0 mg, 5 equiv), and Na2CO3 (40.0 mg,
5 equiv) was stirred in 30 mL of o-dichlorobenzene at 170 °C for
16 h the dihydrooxazine derivative 3j, instead of fulleroisoxazo-
lines derivatives, was obtained in 16% yield through C–O bond
cleavage. Then 1e was chosen as a substrate in order to facilitate
the detection of the leaving group. When 1e was treated with C60
and DMAP, 2e was obtained in 39% yield along with the formation
of ethyl 4-nitrobenzoate, which might be generated from the oxi-
dation of 1-(ethoxymethyl)-4-nitrobenzene by oxygen. All the re-
sults mentioned above demonstrated that the oxime with R1 and
R2 being both aryl group had a high reactivity.
To understand the effect of O2, the reaction of C60 with 1e and
DMAP was performed under N2 atmosphere. Only a trace of 2e
was observed on TLC after 6 h. It proved that the O2 is crucial to
this reaction. In the absence of C60, 1e was treated with DMAP in
toluene at 110 °C for 4 h. The generation of 4-methyl benzonitrile
and ethyl 4-nitrobenzoate was detected through GC–MS analysis
and ethyl 4-nitrobenzoate also could be isolated in 31% yield
(Scheme 1). The nitrile might be generated though Beckmann frag-
mentation. When 2-methoxycyclohexanone oxime 1m was per-
formed in this reaction, unlike the cyclic ketone oxime 1j,
fulleroisoxazoline derivative 2m was afforded in 12% yield after
stirring in ODCB at 150 °C for 16 h.
References and notes
1. (a) Hirsch, A.; Brettreich, M. Fullerenes: Chemistry and Reactions; Wiley-VCH:
Weinheim, Germany, 2005; (b) Langa, F.; Nierengarten, J.-F. Fullerenes:
Principles and Applications; RSC Publishing: Cambridge, UK, 2007.
2. (a) Martin, N.; Sánchez, L.; Llescas, B.; Pérez, I. Chem. Rev. 1998, 98, 2527; (b)
Prato, M.; Maggini, M. Acc. Chem. Res. 1998, 31, 519; (c) Nakamura, E.; Isobe, H.;
Tomita, N.; Sawamura, M.; Jinno, S.; Okayama, H. Angew. Chem., Int. Ed. 2000,
39, 4254; (d) Nakamura, E.; Isobe, H. Acc. Chem. Res. 2003, 36, 807; (e) Guldi, D.
M.; Zerbetto, F.; Georgakilas, V.; Prato, M. Acc. Chem. Res. 2005, 38, 38; (f)
Cremer, J.; Bauerle, P.; Wienk, M. M.; Janssen, R. A. J. Chem. Mater. 2006, 18,
5832.
3. For example: (a) Zhang, W.; Swager, T. M. J. Am. Chem. Soc. 2007, 129, 7714; (b)
Wang, G.-W.Chen, X.-P.;Cheng, X. Chem. Eur. J. 2006, 12, 7246; (c) Gan, L.; Huang, S.;
Zhang, X.;Zhang, A.;Cheng, B.; Cheng, H.;Li,X.; Shang, G.J.Am. Chem.Soc. 2002, 124,
13384; (d) Zhong, Y.-W.; Matsuo, Y.; Nakamura, E. Org. Lett. 2006, 8, 1463; (e)
Iwamatsu, S.-I.; Stanisky, C. M.; Cross, R. J.; Saunders, M.; Mizoroge, N.; Nagase, S.;
Murata, S. Angew. Chem., Int. Ed. 2006, 45, 5337; (f) Stanisky, C. M.; Cross, R. J.;
Saunders, M.; Murata, M.; Murata, Y.; Komatsu, K. J. Am. Chem. Soc. 2005, 127, 299;
(g) Zheng, M.; Li, F.-F.; Ni, L.; Yang, W.-W.; Gao, X. J. Org. Chem. 2008, 73, 3159.
4. Yang, H.-T.; Ruan, X.-J.; Miao, C.-B.; Xi, H.-T.; Jiang, Y.; Meng, Q.; Sun, X.-Q.
Tetrahedron Lett. 2009, 50, 7337.
5. Meier, M. S. Tetrahedron 1996, 52, 5043.
6. (a) Hashimoto, M.; Obora, Y.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2008, 73, 2894;
(b) Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 3599; (c)
Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9, 73; (d) Sardarian,
A. R.; Shahsavari-Fard, Z.; Shahsavari, H. R.; Ebrahimi, Z. Tetrahedron Lett. 2007,
48, 2639.
7. (a) Krishna, U. M. Tetrahedron Lett. 2010, 51, 2148; (b) Furuya, Y.; Ishihara, K.;
Yamamoto, H. Bull. Chem. Soc. Jpn. 2007, 80, 400; (c) Cao, L.; Sun, J.; Wang, X.;
Zhu, R.; Shi, H.; Hu, Y. Tetrahedron 2007, 63, 5036; (d) Ishihara, K.; Furuya, Y.;
Yamamoto, H. Angew. Chem., Int. Ed. 2002, 41, 2983; (e) Hori, K.; Nomura, K.;
Mori, S.; Yoshii, E. J. Chem. Soc., Chem. Commun. 1989, 712; (f) Biju, P. J.;
Laxmisha, M. S.; Rao, G. S. R. S. J. Chem. Soc., Perkin Trans. 1 2000, 4512.
8. (a) Yang, H.-T.; Ruan, X.-J.; Miao, C.-B.; Sun, X.-Q. Tetrahedron Lett. 2010, 51,
6056; (b) Yang, H.-T.; Tian, Z.-Y.; Ruan, X.-J.; Zhang, M.; Miao, C.-B.; Sun, X.-Q.
Eur. J. Org. Chem. 2012, 4918; (c) Miao, C.-B.; Tian, Z.-Y.; Ruan, X.-J.; Sun, X.-Q.;
Yang, H.-T. Heterocycles 2011, 83, 1615.
On the base of these results, the possible mechanism for the for-
mation of fulleroisoxazolines and fullerooxazines was proposed in
Scheme 2. The oxime anion 4, generated from the deprotonation of
1, underwent two different routes to afford nitrile oxide 5 and
nitrosoalkene 6, followed by cycloaddition reaction with C60 to af-
ford fulleroisoxazolines 2 and fullerooxazines 3, respectively. Oxi-
dation of cabanion 7 by O2 would generate the ester. Aryl group
was a benefit to the stability of carbanion 7. Therefore, 1a–c, 1e,
and 1i needed a lower reaction temperature (110 °C).
9. General procedure for the reaction of C60 with
a-alkoxyl/acyloxyl/phenolyl
We further investigated the reaction of
olyl ketoxime with C60 under a similar condition. When
a
-acyloxyl and
a-phen-
ketoxime: A mixture of C60 (54.0 mg), ketoxime 1 (5 equiv, mixture of the E/Z
isomer) and Na2CO3 (40.0 mg, 5 equiv) in 30 mL of solvent (toluene: 80 or
110 °C; o-dichlorobenzene: 150 or 170 °C) was stirred at proper temperature
for designated time. The mixture was concentrated in vacuo and the residue
was purified on a silica gel column with CS2, CS2–toluene or toluene–ethyl
acetate as the eluent to afford unreacted C60 and adducts 2 or 3. 2h: 1H NMR
(500 MHz, CS2–CDCl3) d 1.73 (s, 9H); 13C NMR (125 MHz, CS2–CDCl3, all 2C
unless indicated) d 160.31 (1C, C@N), 147.67 (1C), 147.25 (1C), 146.35, 146.21,
146.12, 145.97, 145.94, 145.91, 145.63, 145.49, 145.40, 145.31, 145.20, 145.15,
144.87, 144.42, 144.08, 143.02, 142.93, 142.85, 142.53, 142.46, 142.39 (4C),
142.04, 141.62, 140.37, 139.90, 136.41, 136.33, 104.17 (1C, sp3-C of C60), 79.21
(1C, sp3-C of C60), 36.73 (1C, –CMe3), 30.48 (3C, CH3); UV–vis (CHCl3) kmax nm
a-acetoxyl
acetophenone oxime 1k was treated with C60 in the presence of
Na2CO3 at 80 °C for 27 h the dihydrooxazine derivative 3k was ob-
tained in 19% yield through C–O bond cleavage because the AcOÀ is
easier to leave compared to carbanion 7. Increasing the tempera-
ture to 110 °C, higher yield (26%) of 3k was acquired in shorter
time (4 h). Nevertheless,
a-phenonyl acetophenone oxime could
not react with C60 in the presence of Na2CO3 even stirring at
170 °C for 27 h.
256, 317, 430, 677; FT-IR m
/cmÀ1 (KBr) 2922, 2853, 1584, 1509, 1370, 1172,
1152s, 1092, 1004, 831, 765, 606, 571, 526; MS (+APCI) m/z 819. 2m: 1H NMR
(500 MHz, CS2–CDCl3) d 3.63 (s, 3H), 3.03 (t, J = 7.4 Hz, 2H), 2.43 (t, J = 7.3 Hz,
2H), 2.11 (quint, J = 7.5 Hz, 2H), 1.91 (quint, J = 7.5 Hz, 2H); 13C NMR (125 MHz,
CS2–CDCl3, all 2C unless indicated) d 172.23 (1C, COO), 153.44 (1C, C@N),
147.59 (1C), 147.05 (1C), 146.19, 146.07, 146.02, 145.82, 145.71, 145.47,
145.27, 145.12, 145.03, 144.95 (4C), 144.79, 144.22, 143.94, 142.84, 142.64
(4C), 142.26 (4C), 142.14, 142.08, 142.03, 141.65, 140.59, 140.01, 136.76,
136.38, 101.95, (1C, sp3-C of C60), 80.33 (1C, sp3-C of C60), 51.50 (1C, COOCH3),
33.53 (1C), 28.25 (1C), 26.23 (1C), 24.87 (1C).
All of the known compounds were confirmed by comparing
their spectral data with those reported in the literature.4,5,8a,11
The identification of a new compound 2h was fully confirmed by
its MS, 1H NMR, 13C NMR, FTIR and UV–vis spectra.9
In summary, we investigated the reaction of [60]fullerene with
a-alkoxyl/phenolyl/acyloxyl ketoxime in the presence of sodium
carbonate. A kind of unusual C–C and C–O bond cleavage of ketox-
ime was observed. The fulleroisoxazolines or fullerooxazine deriv-
atives could be obtained via C–C or C–O bond cleavage,
10. Wang, G.-W.; Chen, X.-P.; Chen, X. Chem. Eur. J. 2006, 12, 7246.
11. Meier, M. S.; Poplawska, M. J. Org. Chem. 1993, 58, 4524.