Hetero-Diels-Alder reaction of [60]fullerene with nitrosoalkene

Article abstract of DOI:10.1016/j.tetlet.2009.10.060

A new type of stable C₆₀-fused dihydrooxazine derivatives was successfully prepared by the hetero-Diels-Alder reaction of C₆₀ with nitrosoalkene generated in situ by extrusion of HBr from the corresponding α-bromooxime.

Full text of DOI:10.1016/j.tetlet.2009.10.060

Tetrahedron Letters 50 (2009) 7337–7339
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Tetrahedron Letters
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Hetero-Diels–Alder reaction of [60]fullerene with nitrosoalkene
*
*
Hai-tao Yang , Xiao-Jiao Ruan, Chun-bao Miao, Hai-tao Xi, Yan Jiang, Qi Meng, Xiao-qiang Sun
Faculty of Chemistry and Chemical Engineering, Jiangsu Polytechnic 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:
A new type of stable C60-fused dihydrooxazine derivatives was successfully prepared by the hetero-
Diels–Alder reaction of C60 with nitrosoalkene generated in situ by extrusion of HBr from the correspond-
ing a-bromooxime.
Received 10 July 2009
Revised 8 October 2009
Accepted 13 October 2009
Available online 30 October 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Since [60]fullerene, the most abundant representative of the
fullerene family, was produced in macroscopic quantities for the
first time in 1990,1 a wide variety of reactions of fullerenes have
been developed to synthesize a great diversity of fullerene com-
pounds,2 some of which have found widespread use in chemical,
biological, and materials sciences.3 Cycloaddition reaction is
among the most outstanding and expeditious methods for the
functionalization of C60 and has been applied to a variety of
[n+2]cycloadditions (n = 1–4). Diels–Alder reaction has been par-
ticularly useful in the chemical modification of C60 to construct
six-membered fullerocycles. However, many of the Diels–Alder
cycloadducts of C60 were found to be thermally unstable and un-
dergo cycloreversion to give the component molecules. Stable
Diels-Alder adducts of C60 were first explored by Müllen and Rubin
in their pioneering work using o-quinodimethane and its ana-
logues as reactive dienes.4
Although the Diels–Alder reaction has been widely explored in
the functionalization of C60, the hetero-Diels–Alder reaction was
seldom investigated. For example, the reaction of C60 with the
oxo,5 thia,6 selenium,7 and aza8 heterologs of o-quinodimethanes,
and with a 1,3-disubstituted-2-aza-1,3-diene,9 has been reported
to date. C60-fused tetrahydropyridazine has been synthesized
through heterocycloaddition of thermally generated 1,2-diaza-
1,3-butadienes with [60]fullerene.10 The reaction of C60 with
1,2,3-triazine11 or 1,2,4,5-tetrazine12 gave azacyclohexadiene-
fused fullerene derivative through [4+2] cycloaddition/nitrogen-
extrusion. There are also other methods to construct six-mem-
bered fulleroheterocycles such as the photochemical addition reac-
tion of fullerene with 1,2-ethylenediamine and piperazine, which
could give a derivative directly bonded to two nitrogen atoms.13
Recently a novel protocol for the preparation of C60-fused d-lac-
tones from benzenediazonium-2-carboxylates controlled by or-
ganic bases has been explored.14
We aimed at developing a new method to prepare fullerene
derivatives with yet unknown novel structure. To the best of our
knowledge, 5,6-dihydro-4H-oxazines are easily accessible from
a-halolximes and olefinic substrates such as enol ethers, enamines,
alkenes, and allenes.15 These processes have been identified as in-
verse-electron demanded hetero-Diels–Alder reactions involving
transient nitrosoalkenes,16 that is, with electron-deficient hetero-
dienes and electron-rich alkenes. However, C60 usually behaves
as an electron-deficient dienophile and reacts with numerous elec-
tron-rich dienes in Diels–Alder reactions. The direct Diels–Alder
reaction of fullerene C60 with nitrosoalkene should be a rather
unfavorable one. We were wondering whether this kind of reaction
could be applied to the functionalization of C60
.
To our satisfaction, when a mixture of C60 (54.0 mg), 2-bromo-1-
phenylethanone oxime 1a (80.0 mg, 5 equiv), and Na2CO3 (40.0 mg,
5 equiv) in 30 mL toluene was stirred at room temperature for 15 h
the desired dihydrooxazine-fused C60 derivative 2a was obtained in
26% (67% based on consumed C60) yield (Scheme 1).
To examine the scope and limitation of the used substrates, var-
ious
a-bromooximes 1a–g were synthesized by the reactions of a-
bromoketone with hydroxylamine hydrochloride and applied to
17
the hetero-Diels–Alder reactions of C60
.
The reaction times and
isolated yields along with recovered C60 for the reactions of C60
O
NOH
O
N
Na2CO3
-HBr
C60
N
Br
R
R
R
R'
R'
R'
1a 2a: R = Ph, R' = H
1
,
2
1b 2b: R = 4-CH
,
3OC6H4, R' = H
C6H4, R' = H
1c 2c: R = 4-NO
,
3,2R' = H
1d 2d: R = CH
,
1e 2e: R, R' = -(CH
2)4-
,
R
R'
1f 2f:
,
* Corresponding authors. Tel./fax: +86 519 86330257.
E-mail address: yanght898@yahoo.com.cn (H. Yang).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.10.060

7338
H. Yang et al. / Tetrahedron Letters 50 (2009) 7337–7339
with
a
-bromooximes compounds 1a–f and Na2CO3 in a molar ratio
characterized by 13C NMR because of its very low solubility, were
characterized in the same way.
of 1:5:5 in toluene at proper temperature are listed in Table 1. The
effect of other bases such as triethylamine, pyridine, and sodium
ethoxide was also examined. The result showed that triethylamine
and pyridine did not work because they could react with the bro-
mooxime to form an organic salt which could not react with C60. In
addition, sodium ethoxide could not initiate the reaction either.
As far as we know the electron-rich alkene was widely used in
the hetero-Diels–Alder reaction of nitrosoalkene; however, there
are few reports that the electron-deficient alkenes were used as
dienophiles in this kind of reversed-electron demanded reaction.18
As can be seen from Table 1, 1a–f reacted well with C60. When R
was an aromatic group and R0 was hydrogen (1a–c) the yields were
higher and the electronic property of the substituent on the phenyl
had little influence on the reaction. While R was an aliphatic group
(1d–e) the reaction needed higher temperature and proceeded
much slower and the yields decreased notably. The possible expla-
nation was that the nitrosoalkene generated from 1a–c might be
formed easily and might have higher stability due to the conjuga-
tion of aromatic cycle with the C@C and N@O double bonds when R
was an aromatic group, thus benefitting the reaction. It is to be
noted that when R was CO2Et group and R0 was hydrogen no prod-
uct was obtained at 100 °C in spite of prolonging the reaction time
to 48 h. Because fullerene is an electron-deficient alkene, the in-
crease of electron-withdrawing ability of nitrosoalkene would de-
crease the reactivity. From this result we predicted that the
nitrosoalkene with R being a phenyl group and the R0 being an alkyl
or a phenyl group would be formed easily and had higher stability,
and the reaction would proceed easier than 1a–c. Firstly, we syn-
thesized 1f which reacted with C60 in shorter time (1.5 h) and gave
higher yield (47%). That 1f had higher reactivity than 1a–c proved
our prediction. But we failed in synthesizing the substrate with R
and R0 being all phenyl group because the solvolysis reaction oc-
curred. All new compounds 2a–f were very stable. There was not
any decomposition in solid state at room temperature even when
placed for two months or in toluene solution at 110 °C for 24 h.
The identities of compounds 2a–e were fully established by
their MS, 1H NMR, 13C NMR, FT-IR, and UV–vis spectra. Taking 2a
as an example, the APCI mass spectrum of 2a showed the molecu-
lar ion peak at m/z 853. The 1H NMR spectrum of 2a displays a sin-
glet at 4.57 ppm for methylene and peaks of the five hydrogens for
the phenyl ring. In the 13C NMR spectrum of 2a, there are 30 peaks
due to the sp2-C of the C60 skeleton in the range of 153.09–
136.45 ppm and two sp3-C of the C60 cage at 95.57 and
65.25 ppm along with 4 peaks for the phenyl rings in the range
of 133.4–126.9 ppm, 1 peak at 175.15 ppm for the ON@C moiety,
and 1 peak at 35.56 ppm for the CH2 group, consistent with the
Cs symmetry of its molecular structure. The resonance of the sp3-
In conclusion, the hetero-Diels–Alder reaction of C60 with nitro-
soalkene generated in situ from the corresponding a-bromooximes
by treatment with Na2CO3 was explored, and led to the formation
of a new type of stable C60-fused dihydrooxazine derivatives. These
fullerene products may be further functionalized by the manipula-
tion on the C@N double bond and weak N–O bond. Further work is
underway to investigate functionalization of the C@N double bond
and N–O bond on the dihydrooxazine ring.
Acknowledgments
The authors are grateful for the financial support from the Na-
tional Natural Science Foundation of China (Nos. 20902039 and
20872051) and Foundation of Jiangsu Provincial Key Laboratory
of Fine Petrochemical Technology (KF0807).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.10.060.
References and notes
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M.; Zerbetto, F.; Georgakilas, V.; Prato, M. Acc. Chem. Res. 2005, 38, 38; (f)
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H.; Nagase, S.; Akasaka, T. Tetrahedron Lett. 2008, 47, 2302.
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14. Wang, G.-W.; Zhu, B. Chem. Commun. 2009, 1769.
C of C60 cage was close to that directly attached to an oxygen atom
15. (a) Wabnitz, T. C.; Saaby, S.; Jørgensen, K. A. Org. Biomol. Chem. 2004, 2, 828; (b)
Gallos, J. K.; Sarli, V. C.; Varogli, A. C.; Papadoyanni, C. Z.; Papaspyrou, S. D.;
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Czerwonka, R.; Hain, U.; Reissig, H.-U. Synthesis 2008, 237.
19,14
in the recent report of 1,2-adducts of C60
.
Other dihydroox-
azine-fused C60 derivatives (2b–e) except 2f, which could not be
16. (a) Gilchrist, T. L. Chem. Soc. Rev. 1983, 53; (b) Arnold, T.; Orschel, B.; Reissig,
H.-U. Angew. Chem., Int. Ed. Engl. 1992, 31, 1033; (c) Yoon, S. C.; Kim, K.; Park, Y.
J. J. Org. Chem. 2001, 66, 7334.
Table 1
Yields and reaction time for the reaction of C60 with 1a–e using Na2CO3 as a base
17. Typical procedure for the synthesis of 2a–f:
A mixture of C60 (54.0 mg,
R0
Temperature
(°C)
Time
(h)
Product
Yielda
(%)
0.075 mmol), 1 (0.375 mmol), and Na2CO3 (0.375 mmol) was dissolved in
30 mL of toluene and stirred at proper temperature for a desired time. The
product was separated on a silica gel column with CS2 or CS2-toluene as the
eluent to afford unreacted C60 and adduct 2.
Substrate
R
1a
1b
1c
1d
1e
Ph
H
H
H
H
25
25
25
100
80
15
15
15
25
24
2a
2b
2c
2d
2e
26 (67)
26 (59)
31 (86)
18 (60)
16 (53)
Compound 2a: 1H NMR (500 MHz, CS2–CDCl3) d 8.11 (dd, J = 6.5, 2.1 Hz, 2H),
7.61–7.55 (m, 2H), 4.57 (s, 2H); 13C NMR (125 MHz, CS2–CDCl3, all 2C unless
indicated) d 175.15 (1C, C@N), 153.09, 148.30 (1C), 148.07, 147.76 (1C), 146.64,
146.55, 146.42, 146.27, 146.18, 145.71, 145.63, 145.44, 145.42, 145.34, 144.71,
144.58, 144.50, 142.81, 142.70, 142.69, 142.46, 142.37, 142.07, 142.06, 141.58,
141.52, 140.22, 139.95, 137.94, 136.45, 133.37 (1C, aryl C), 131.58 (1C, aryl C),
129.20 (aryl C), 126.87 (aryl C), 95.57 (1C, sp3-C of C60), 65.25 (1C, sp3-C of C60),
4-CH3OC6H4
4-NO2C6H4
CH3
–(CH2)4–
R
R'
1f
25
1.5
48
2f
47 (75)
—
35.56 (1C, CH2);) UV–vis (CHCl3) kmax nm 256, 316, 690; FT-IR m
/cmꢀ1 (KBr)
2920, 2850, 1462, 1425, 1347, 1181, 1114, 1104, 967, 918, 767, 759, 687, 575,
1g
COOEt
H
100
—
a
563, 554, 526; MS (+APCI) m/z 853.
Isolated yield, that in the parentheses refers to the yield based on consumed C60
.

H. Yang et al. / Tetrahedron Letters 50 (2009) 7337–7339
7339
Compound 2b: 1H NMR (500 MHz, CS2–CDCl3) d 8.03 (d, J = 8.9 Hz, 2H), 7.03 (d,
J = 8.9 Hz, 2H), 4.51 (s, 2H), 3.89 (s, 3H); 13C NMR (125 MHz, CS2–CDCl3, all 2C
unless indicated) d 173.97 (1C, C@N), 162.27 (1C, aryl C), 153.13, 148.17 (1C),
147.65 (1C), 146.52, 146.45, 146.30, 146.16, 146.07, 145.68, 145.52, 145.36,
145.30, 145.23, 144.63, 144.48, 144.45, 142.71, 142.59, 142.58, 142.35, 142.28,
141.97, 141.95, 141.48, 141.44, 140.10, 139.85, 137.83, 136.42, 128.32 (aryl C),
125.55 (1C, aryl C), 114.49 (aryl C), 95.29 (1C, sp3-C of C60), 65.13 (1C, sp3-C of
C60), 55.05 (1C, CH3O), 35.18 (1C, CH2); UV–vis (CHCl3) kmax nm 257, 315, 690;
2848, 1511, 1462, 1424, 1374, 1181, 984, 948, 921, 902, 878, 857, 767, 729,
644, 575, 561, 553, 526; MS (+APCI) m/z 791.
Compound 2e: 1H NMR (500 MHz, CS2 CS2–DMSO-d6) d 4.35 (dd, J = 10.5,
6.3 Hz, 1H), 3.09–3.05 (m, 1H), 2.92–2.85 (m, 1H), 2.52–2.41 (m, 2H), 2.17–2.05
(m, 3H), 1.93–1.90 (m, 1H); 13C NMR (125 MHz, CS2–DMSO-d6, all 1C unless
indicated) d 177.76 (C@N), 151.46, 150.62, 150.50, 147.36, 146.87, 146.41,
145.77, 145.76, 145.73, 145.68, 145.61, 145.42, 145.38 (2C), 145.36, 145.30,
145.27 (2C), 144.76 (2C), 144.71, 144.68, 144.61, 144.56, 144.52, 144.47 (2C),
144.43, 144.07, 143.82, 143.75, 143.70, 142.00 (2C), 141.91, 141.88 (2C),
141.85, 141.67, 141.57, 141.52, 141.36 (2C), 141.30, 141.26, 141.09, 140.82,
140.64, 140.54, 140.53, 139.12, 139.11, 138.78, 138.41, 136.97, 136.64, 136.01,
135.22, 94.93 (1C, sp3-C of C60), 68.44 (1C, sp3-C of C60), 40.10 (1C, CH2); UV–vis
FT-IR m
/cmꢀ1 (KBr) 2925, 2831, 1604, 1511, 1461, 1426, 1349, 1305, 1253,
1176, 1019, 968, 920, 868, 830, 768, 623, 575, 563, 554, 526; MS (+APCI) m/z
883.
Compound 2c: 1H NMR (500 MHz, CS2–DMSO-d6) d 8.44 (d, J = 8.9 Hz, 2H), 8.38
(d, J = 8.9 Hz, 2H), 4.69 (s, 2H); 13C NMR (125 MHz, CS2–DMSO-d6, all 2C unless
indicated) d 173.36 (1C, C@N), 152.27, 148.74 (1C, aryl C), 147.46 (1C), 147.22,
146.91 (1C), 145.84, 145.74, 145.60, 145.44, 145.37, 144.82, 144.76, 144.61,
144.59, 144.50, 144.06, 143.84, 143.79, 142.00, 141.91, 141.88, 141.61, 141.52,
141.28, 141.25, 140.74, 140.66, 139.24, 139.12, 138.07, 137.04, 135.44, 127.41
(aryl C), 123.37 (aryl C), 94.81 (1C, sp3-C of C60), 64.52 (1C, sp3-C of C60), 34.01
(CHCl3) kmax nm 256, 316, 689; FT-IR m
/cmꢀ1 (KBr) 2932, 2861, 1511, 1462,
1426, 1181, 979, 943, 912, 879, 840, 728, 574, 563, 553, 526; MS (+APCI) m/z
831. Compound 2f: 1H NMR (500 MHz, CS2–CDCl3) d 8.38 (d, J = 7.7 Hz, 1H),
7.50 (t, J = 7.5 Hz, 1H), 7.44 (d, J = 7.4 Hz, 1H), 7.34 (d, J = 7.4 Hz, 1H), 4.77 (dd,
J = 10.7, 6.5 Hz, 1H), 3.20–3.09 (m, 2H), 2.93–2.86 (m, 1H), 2.71–2.63 (m, 1H);
UV–vis (CHCl3) kmax nm 259, 317, 689; FT-IR m
/cmꢀ1 (KBr) 2921, 2853, 1513,
(1C, CH2); UV–vis (CHCl3) kmax nm 256, 316, 690; FT-IR
m
/cmꢀ1 (KBr) 2920,
1462, 1429, 1338, 1181, 1008, 973, 923, 875, 861, 760, 728, 625, 575, 563, 554,
526; MS (+APCI) m/z 879.
2849, 1509, 1463, 1425, 1340, 1181, 1102, 965, 914, 875, 849, 767, 751, 687,
574, 563, 554, 526; MS (+APCI) m/z 898.
18. (a) Venkata, P.P.; Sarala, B.; Sarika, R.; Abhijit, R.; Sunanda, G.D. PCT Int. Appl.
2007, WO 2007046022 A2.; (b) Tret’yakova, E. V.; Flekhter, O. B.; Galin, F. Z.;
Tolstikov, G. A. Chem. Nat. Compd. 2004, 40, 391.
19. (a) Wang, G.-W.; Li, F.-B.; Zhang, T.-H. Org. Lett. 2006, 8, 1355; (b) Wang, G.-W.;
Li, F.-B.; Xu, Y. J. Org. Chem. 2007, 72, 4774; (c) Wang, G.-W.; Li, F.-B.; Chen, Z.-
X.; Wu, P.; Cheng, B.; Xu, Y. J. Org. Chem. 2007, 72, 4779; (d) Li, F.-B.; Liu, T.-X.;
Wang, G.-W. J. Org. Chem. 2008, 73, 6417; (e) Wang, G.-W.; Lu, Y.-M.; Chen, Z.-
X.; Wu, S.-H. J. Org. Chem. 2009, 74, 4841.
Compound 2d: 1H NMR (500 MHz, CS2–CDCl3) d 4.14 (s, 2H), 2.70 (s, 3H); 13C
NMR (125 MHz, CS2–CDCl3, all 2C unless indicated) d 175.62 (1C, C@N), 153.18,
148.32 (1C), 148.05, 147.80 (1C), 146.65, 146.60, 146.42, 146.31, 146.22,
145.75, 145.63, 145.48, 145.44, 145.37, 144.74, 144.61, 144.50, 143.07, 142.86,
142.73, 142.71, 142.47, 142.39, 142.07, 141.60, 141.52, 140.20, 139.96, 137.84,
136.33, 94.98 (1C, sp3-C of C60), 64.63 (1C, sp3-C of C60), 37.81 (1C, CH2), 21.80
(1C, CH3); UV–vis (CHCl3) kmax nm 256, 316, 689; FT-IR m
/cmꢀ1 (KBr) 2917,