Synthesis and functionalization of [60]fullerene-fused imidazolines

Article abstract of DOI:10.1021/ol400319w

The silver carbonate promoted reaction of [60]fullerene with (Z)-N-arylbenzamidines afforded the unprecedented C₆₀-fused imidazoline derivatives in high yields. Substrates with both electron-donating and -withdrawing groups on aromatic rings co

Full text of DOI:10.1021/ol400319w

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Synthesis and Functionalization of
[60]Fullerene-Fused Imidazolines
Cheng-Lin He,† Rui Liu,† Dan-Dan Li,† San-E Zhu,† and Guan-Wu Wang*,†,‡
CAS Key Laboratory of Soft Matter Chemistry, 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, and State Key Laboratory of
Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, P. R. China
gwang@ustc.edu.cn
Received February 3, 2013
ABSTRACT
The silver carbonate promoted reaction of [60]fullerene with (Z)-N-arylbenzamidines afforded the unprecedented C60-fused imidazoline
derivatives in high yields. Substrates with both electron-donating and -withdrawing groups on aromatic rings could be employed. In addition,
the electrochemistry and further selective functionalization of the obtained C60-fused imidazolines were investigated.
3
Owing to potential applications in materials, medical
chemistry, and nanotechnology,1 various methodologies
have been explored to functionalize fullerenes, and a large
number of fullerene products have been prepared over the
past two decades.2 Transition-metal-mediated reactions
of [60]fullerene (C60) have attracted increasing attention.
Although various reactions of C60 mediated by Mn(OAc)3
and Fe(ClO4)34 have been reported, the utilization of other
transition metal salts including silver salts in the radical
reactions of fullerenes is underdeveloped.5 In our previous
work, we found that Fe(ClO4)3 could efficiently promote
the radical reactions of C60 and afforded C60-fused
oxazolines,6 dioxolanes,7 and dioxaborolanes,8 where an
oxygen and a nitrogen atom or two oxygen atoms are
connected to the C60 cage. Herein, we disclose that silver
carbonate can promote the radical reaction of C60 with
† University of Science and Technology of China.
‡ Lanzhou University.
(1) For selected reviews, see: (a) Nakamura, E.; Isobe, H. Acc. Chem.
Res. 2003, 36, 807. (b) Guldi, D. M.; Illescas, B. M.; Atienza, C. M.;
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Y.; Komatsu, K. Chem. Commun. 2008, 6083.
(5) AgOAc has been employed in the catalytic enantioselective 1,3-
dipolar cycloadditions of fullerenes; see: (a) Filippone, S.; Maroto, E. E.;
ꢀ
n-Domenech, A.; Suarez, M.; Martı
Martı
´
´
n, N. Nat. Chem. 2009, 1, 578.
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n-Domenech, A.;
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(6) Li, F.-B.; Liu, T.-X.; Wang, G.-W. J. Org. Chem. 2008, 73, 6417.
(7) Li, F.-B.; Liu, T.-X.; You, X.; Wang, G.-W. Org. Lett. 2010, 12,
3258.
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1800.
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55, 2009.
r
10.1021/ol400319w
XXXX American Chemical Society

(Z)-N-arylbenzamidines to provide C60-fused imidazolines,
in which two nitrogen atoms are attached to the fullerene
moiety. In addition, further selective functionalization of
the obtained C60-fused imidazolines by a Grignard reagent
and 3-chloroperbenzoic acid (mCPBA) is demonstrated.
At the outset of our studies, the Ag2CO3-promoted
reaction of C60 with (Z)-N-phenylbenzamidines (1a) was
chosen to screen the reaction conditions. The reaction of
Shortening or prolonging the reaction time led to a lower
yield (Table 1, entries 11 and 12). The efficiency of other
silver salts was also examined. Ag2O and AgOAc could
promote the reaction, but both of them gave an inferior
yield compared to Ag2CO3 (Table 1, entries 13 and 14).
Disappointingly, when Mn(OAc)3 2H2O, Cu(OAc)2 H2O,
3
3
or FeCl3 6H2O was employed as the oxidant, 2a was
3
isolated in much lower yields (Table 1, entries 15ꢀ17).
Therefore, the molar ratio of 1:3:2 for the regents C60, 1a,
and Ag2CO3 and the temperature of 110 °C in chloro-
benzene under a nitrogen atmosphere were chosen as the
optimized reaction conditions (Table 1, entry 4).
C60 with 1a and Ag2CO3 in a molar ratio of 1:1:1 at 110 °C
for 10 h gave 2a in 10% yield (Table 1, entry 1). Increasing
the amount of Ag2CO3 to 2 equiv provided 2a in 24% yield
(Table 1, entry 2). An additional increase of 1a to 2 equiv
resulted in a 42% yield (Table 1, entry 3). When the molar
ratio was enhanced to 1:3:2, the product yield could be
further improved to 56% (Table 1, entry 4). It was found
that an inert atmosphere was important, as the reaction in
open air or an oxygen atmosphere significantly decreased
the product yield (Table 1, entries 5 and 6).
With the optimized conditions in hand, we started to
investigate the scope of the reaction. We were pleased to
find that (Z)-N-arylbenzamidines (1aꢀg) with both electron-
donating and -withdrawing groups could be employed
and furnished the desired [60]fullereoimidazolines 2aꢀg
in 42ꢀ59% isolated yields, higher than those of most
monoadducts. (Z)-N-Arylbenzamidines bearing a methyl,
chlorine, or methoxy group in both aryl rings could
undergo the Ag2CO3-promoted cycloaddition reaction
to C60. Intriguingly, ortho-substituted substrates pro-
ceeded well and even provided higher product yields
(Table 2, entries 3 and 5). In addition, the chlorine group
in products 2c, 2d, and 2g (Table 2, entries 3, 4, and 7) may
be used as a handle for coupling reactions.
Table 1. Optimization oftheReactionConditionsof C60 with 1aa
The structures of C60-fused imidazolines 2aꢀg were
1
fully established by their MALDI-TOF MS, H NMR,
molar
ratiob
temp
time
(h)
yield
(%)c
13C NMR, IR, and UVꢀvis spectra. All products 2aꢀg
exhibited correct molecular weights in their mass spectra.
The 13C NMR spectra of 2aꢀg except 2c clearly exhibited
no more than 30peaks in the range of 134ꢀ149 ppm for the
sp2-carbons of the fullerene cage and two peaks at 85ꢀ87
and 93ꢀ94 ppm for the two sp3-carbons of the fullerene
skeleton, consistent with the Cs symmetry of their mole-
cular structures. However, because of the steric hindrance
of Cl at the ortho position, the 13C NMR spectrum of 2c
exhibited 45 peaks for the sp2-carbons of the fullerene
skeleton, along with two peaks for the two sp3-carbons of
C60 cage, agreeing with its C1 symmetry. The chemical
shiftsfor the two C60 sp3-carbons of 2aꢀg are close tothose
of fullerene derivatives with the nitrogen atom attached
to the C60 skeleton.6,9 The typical chemical shifts at
163ꢀ164 ppm in the 13C NMR spectra indicated the
presence of the amidine moiety. The UVꢀvis spectrum
of all products showed a peak at 427ꢀ428 nm, which is the
characteristic peak for 1,2-adducts of C60.
entry
oxidant
(°C)
1
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
AgOAc
Ag2O
1:1:1
1:1:2
1:2:2
1:3:2
1:3:2
1:3:2
1:3:3
1:4:2
1:3:2
1:3:2
1:3:2
1:3:2
1:3:2
1:3:2
1:3:2
1:3:2
1:3:2
110
110
110
110
110
110
110
110
90
10
10
10
10
10
10
10
10
10
10
8
10 (100)
24 (92)
42 (75)
56 (95)
18 (50)
17 (37)
55 (72)
54 (66)
18 (100)
54 (63)
46 (87)
51 (67)
8 (38)
2
3
4
5d
6e
7
8
9
10
11
12
13
14
15
16
17
130
110
110
110
110
110
110
110
12
10
10
10
10
10
40 (75)
12 (71)
14 (50)
4 (80)
Mn(OAc)3 2H2O
3
Cu(OAc)2 H2O
3
FeCl3 6H2O
3
a All reactions were carried out under a nitrogen atmosphere unless
otherwise indicated. b Molar ratio refers to C60/1a/oxidant. c Isolated yield;
the values in parentheses were based on consumed C60. d The reaction was
carried out in open air, and 1a was recovered in 96% yield when C60 was
omitted from the system under the same conditions. e The reaction was
carried out under an oxygen atmosphere, and 1a was recovered in 98%
yield when C60 was omitted from the system under the same conditions.
Although the exact pathway leading to 2aꢀg remains to
be clarified, a plausible mechanism is outlined in Scheme 1.
First, the reaction of N-arylbenzimidamide 1 with Ag2CO3
generates 3, which undergoes homolytic cleavage of
the nitrogenꢀsilver bond to provide radical species 4.
A similar Cu-catalyzed process was recently reported.10
Increasing the amount of either 1a or Ag2CO3 further
was not beneficial to achieve a higher yield, yet more C60
was consumed (Table 1, entries 7 and 8). When the tem-
perature was lowered to 90 °C, 2a was obtained in only
18% yield (Table 1, entry 9). When the temperature was
increased to 130 °C, the yield dropped slightly to 54%
accompanied by more byproducts (Table 1, entry 10).
(9) (a) Zheng, M.; Li, F.-F.; Ni, L.; Yang, W.-W.; Gao, X. J. Org.
Chem. 2008, 73, 3159. (b) Zhu, B.; Wang, G.-W. J. Org. Chem. 2009, 74,
4426. (c) Zhu, B.; Wang, G.-W. Org. Lett. 2009, 11, 4334. (d) Chuang,
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B
Org. Lett., Vol. XX, No. XX, XXXX

Table 2. Reaction Conditions and Yields for the Reaction of C60
with 1aꢀg in the Presence of Ag2CO3
Scheme 1. Proposed Reaction Mechanism for the Formation of
2aꢀg
a
C60/1a/Ag2CO3 = 1:3:2 was used to achieve higher con-
versions and product yields. However, the concerted
[3 þ 2] annulation process of amidines to C60 via a nitrene
intermediate cannot be excluded.10
Table 3 shows the half-wave reduction potentials of
products 2aꢀg together with C60. The first reduction
potentials are generally shifted anodically by ca. 100 mV
for most monoadducts of C60. However, the E1 of 2aꢀg
showed a smaller negative shift (30ꢀ50mV) relativeto that
of C60, due to the two attached heteroatoms.9d,12 There-
fore, fullereoimidazolines 2aꢀg may be utilized as low-
lying LUMO acceptors in organic photovoltaic devices by
choosing appropriate donor material.12
a
Table 3. Half-Wave Reduction Potentials of 2aꢀg Along with C60
compd
E1
E2
E3
C60
2a
2b
2c
2d
2e
2f
ꢀ1.077
ꢀ1.117
ꢀ1.119
ꢀ1.114
ꢀ1.111
ꢀ1.114
ꢀ1.124
ꢀ1.116
ꢀ1.456
ꢀ1.493
ꢀ1.493
ꢀ1.493
ꢀ1.485
ꢀ1.490
ꢀ1.504
ꢀ1.498
ꢀ1.911
ꢀ2.013
ꢀ2.013
ꢀ2.016
ꢀ1.997
ꢀ2.010
ꢀ2.026
ꢀ2.018
a All reactions were carried out at 110 °C under a nitrogen atmo-
sphere with a molar ratio of C60/1/Ag2CO3 = 1:3:2. b Isolated yield; the
2g
values in parentheses were based on consumed C60
.
a Potential in V versus a ferrocene/ferrocenium couple. Experiment
conditions: 0.20 mM of 2aꢀg/C60 and 0.1 M of n-Bu4NClO4 in
anhydrous o-dichlorobenzene; reference electrode: SCE; working elec-
The radical addition of 4 to C60 will give fullerenyl radical 5.
Alternatively, the intermediate 5 may also be formed by the
homolytic addition of 3 to C60.6 Intramolecular cyclization
of 5 produces radical 6.
trode: Pt; auxiliary electrode: Pt wire; scanning rate: 50 mV sꢀ1
.
Further functionalization of the synthesized fullereoimi-
dazolines was also attempted by using 2a as a representa-
tive compound. After 2a was treated with CH3MgBr
in chlorobenzene at 0 °C for 5 min and subsequently
quenched by NH4Cl, the regioselective product 7a with a
Although the addition of a carbon-centered radical
to the N-terminus of the CdN bond is rare, the formed
radical in 6 is stabilized by two nitrogen substituents and
a phenyl group.11 Oxidation of radical 6 by another Agþ
species with the loss of Hþ affords 2. Therefore, 2 molar
equiv of Ag(I) were required, and the molar ratio of
(12) Hashiguchi, M.; Obata, N.; Maruyama, M.; Yeo, K. S.; Ueno,
T.; Ikebe, T.; Takahashi, I.; Matsuo, Y. Org. Lett. 2012, 14, 3276.
(11) Friestad, G. K. Tetrahedron 2001, 57, 5461.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 2. Further Functionalization of 2a
Figure 2. Optimized structures and relative energies of 7a and its
regioisomer 7a-1.
The protonation of the formed fullenenyl anion could
afford 7a or its regioisomer 7a-1. The introduction of an
unfavorable [5,6] double bond in isomeric 7a-1 would
increase its formation energy.
Indeed, theoretical calculations at the B3LYP/3-21G*
level showed that 7a was more stable than 7a-1 by
28.6 kJ molꢀ1 (Figure 2). It should be pointed out that
3
although the amidino carbon atom had the largest positive
charge of þ0.628, the Grignard reagent did not attack the
CdN bond. The addition mode of CH3MgBr to C60-fused
imidazolines here is different from that to C60-fused lac-
tones, which underwent either a reductive ring opening14
or addition to the CdO bond of the lactone moiety.15
Furthermore, the nitroxide 8a could be prepared in 44%
yield after treatment of 2a with mCPBA at 60 °C for 3 h.
Product 8a was also fully characterized. The addition of
the oxygen atom to 2a lowered the symmetry from Cs
to C1, and thus the 13C NMR of 8a exhibited 52 peaks
for the sp2-carbons of the fullerene cage in the range of
149ꢀ135 ppm. The δC of the amidino carbon that was
located at 162.96 ppm indicated that the oxygenation did
not occur at the CdN bond. This result was supported by
the calculated larger negative density at the nitrogen atom
bearing the phenyl group (ꢀ0.765) compared to the imino
nitrogen atom (ꢀ0.476) (Figure 1).
Figure 1. Partial NBO charge distribution of 2a.
1,2,3,4-configuration was isolated in 70% yield (Scheme 2).
In the 1H NMR spectrum of 7a, two singlets for the methyl
group and fullerenyl proton were located at 2.71 and
5.94 ppm besides those for the two phenyl groups. The
13C NMR of 7a exhibited 53 peaks in the 152ꢀ129 ppm
range for the sp2-carbons of the fullerene skeleton and
four peaks at87.46, 82.98, 59.58, and 57.39 ppm for the four
sp3-carbons of the C60 cage. The amidino carbon showed
little chemical shift compared to that of 2a, suggesting
that it remained unchanged. The UVꢀvis spectrum of 7a
exhibited the typical feature of fullerene products with a
1,2,3,4-configuration (see Figure S1 in the Supporting
Information).13 To better understand the regioselectivity
for the Grignard addition reaction, the NBO charge dis-
tribution of 2a was calculated at the B3LYP/3-21G* level.
As shown in Figure 1, the fullerenyl carbon with a positive
charge of þ0.125 should be the site of attack by CH3MgBr.
In summary, Ag2CO3 has been successfully applied to
the radical reaction of C60 with (Z)-N-arylbenzamidines
affording unprecedented C60-fused imidazolines. [60]-
Fulleroimidazolines can be further functionalized to give
regioisomeric products with a 1,2,3,4-configuration or
nitroxide products, which would be difficult to synthesize
by existing methods.
Acknowledgment. We are grateful for financial sup-
port from NSFC (21132007) and Specialized Research
Fund for the Doctoral Program of Higher Education
(20123402130011).
Supporting Information Available. Experimental pro-
cedures, spectral data, spectra, and computation details.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(13) (a) Kordatos, K.; Bosi, S.; Ros, T. D.; Zambon, A.; Lucchini, V.;
Prato, M. J. Org. Chem. 2001, 66, 2802. (b) Izquierdo, M.; Osuna, S.;
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The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX