An efficient comparison of methods involving conventional, grinding and ultrasound conditions for the synthesis of fulleroisoxazolines

Article abstract of DOI:10.1016/j.ultsonch.2014.08.004

In this research, an efficient comparison between conventional, grinding and sonication methods for the synthesis of fulleroisoxazolines was investigated. Compared to the conventional methods, ultrasound procedure showed several advantages including mild reaction conditions, high yields, short reaction times and environmental friendliness.

Full text of DOI:10.1016/j.ultsonch.2014.08.004

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An efficient comparison of methods involving conventional, grinding and ul-
trasound conditions for the synthesis of fulleroisoxazolines
Javad Safaei-Ghomi, Reihaneh Masoomi
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DOI:
http://dx.doi.org/10.1016/j.ultsonch.2014.08.004
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Ultrasonics Sonochemistry
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Please cite this article as: J. Safaei-Ghomi, R. Masoomi, An efficient comparison of methods involving conventional,
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An efficient comparison of methods involving conventional, grinding and
ultrasound conditions for the synthesis of fulleroisoxazolines
Javad Safaei-Ghomi*, Reihaneh Masoomi
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan,
51167, I. R. Iran
Corresponding author Tel.: +98 361 5912385; fax: +98 361 5552935;
*E-mail: safaei@kashanu.ac.ir.(J. Safaei-Ghomi).
Abstract
In this research, an efficient comparison between conventional, grinding and sonication
methods for the synthesis of fulleroisoxazolines was investigated. Compared to the conventional
methods, ultrasound procedure showed several advantages including mild reaction conditions,
high yields, short reaction times and environmental friendliness.
Keywords: Fullerene; Cycloaddition reaction; Fulleroisoxazoline; Ultrasound irradiation; Grinding method.
1. Introduction
Since their discovery, fullerenes in general and buckminsterfullerene C60 in particular,
became a subject of great interest for scientific researches [1, 2]. Extensive studies on the
chemical functionalization of fullerenes have become one of the main challenges in organic
chemistry. Surface functionalization of fullerenes is an attractive approach in the physics,
chemistry, material science, biological and biomedicine fields [3-10]. Fullerenes behave as 2π
electron-deficient dienophiles and 1,3-dipolarophiles undergoing a variety of cycloaddition
reactions [11-15]. Four main types of cycloaddition involving [1+2], [2+2], [3+2] and [4+2]
1

cycloadditions on C60 have been largely investigated [16-19]. All reactions typically take place
on the 6-6 ring double-bond junctions of the fullerene skeleton. The 1,3-dipolar cycloaddition
reaction is one of the most common synthetic approaches for the construction of heterocycle
five-membered rings on the fullerene surface. The main driving force for addition to fullerene is
the relief of strain due to a change in hybridization at the reacting carbons on the spherical
surface from sp2 to sp3. Various types of fullerene derivatives involving fulleropyrrolidines [20],
fulleroindolines [21], fullerene-fused lactones [22], pyrazolo- and oxazolo- fullerenes [23-31]
have been reported in the literature.
In this research we investigated the efficient application of ultrasonic irradiation as a green,
efficient and convenient technique for the synthesis of several fulleroisoxazolines via 1,3-dipolar
cycloaddition reaction.
During last three decades, ultrasound has interestingly been applied in organic synthesis [32,
33]. This technique is more easily controlled in comparison with the conventional methods such
as oil baths, heating jackets and sand baths. These heating sources can increase temperature
gradients within the sample which results in the decomposition of substrates, reagents and
products. In the recent years, a large amount of efforts have been made to replace conventional
energy sources with other modern techniques such as ultrasound. Furthermore, various
sonochemical synthesis of fullerene derivatives have been reported in the literatures [34-37].
This method as an effective and virtually innocuous means of activation in synthetic chemistry
has been applied for various purposes [38-40]. The unique effect of ultrasound in organic
synthesis is duo to the cavitation which is a physical process that creates, enlarges, and implodes
gaseous and vaporous cavities in an irradiated liquid, thus leading the turbulent flow, enhancing
mass transfer and allowing chemical reactions to promote includes shorter reaction times and
2

high yields [41, 42]. In the previous work we proposed the effect of microwave irradiation on the
synthesis of a series of fulleropyrrazolines/fulleroisoxazolines [43].
Herein we investigate a novel and efficient synthesis of fulleroisoxazolines through various
methods such as stirring, thermal, grinding and ultrasound conditions. Among these, ultrasound
procedure can help to reduce reaction time and increase the yields of the products compared to
the other conventional methods.
2. Experimental
2.1. Materials and Apparatus
Fullerene[60] used in this work was over 99.90% purity from Aldrich. All solvents and
chemical reagents were purchased from Aldrich and Fluka and used without further purification.
1
Melting points were determined on Electro thermal 9200, and are not corrected. H NMR and
13C NMR spectra were recorded on Bruker Avance-400 MHz spectrometers in the presence of
tetramethylsilane as internal standard. The IR spectra were recorded on FT-IR Magna 550
apparatus using with KBr plates. EIMS (70 eV) was performed by Finnigan-MAT-8430 mass
spectrometer in m/z. A multiwave ultrasonic generator (Sonicator 3200; Bandelin, MS 73,
Germany), equipped with a converter/transducer and titanium oscillator (horn), 12.5 mm in
diameter, operating at 20 kHz with a maximum power output of 10-60 W, was used for the
ultrasonic irradiation. The ultrasonic generator automatically adjusted the power level.
2.2. General procedure for the synthesis of (diacetoxyiodo)arene
(Diacethoxyiodo) benzene was prepared according to the reported procedures [44].
3

1
(Diacetoxyiodo)benzene: White solid; mp = 161-163, Yield 65%, H NMR (400 MHz,
DMSO-d6): δ (ppm) 1.84 (s, 6H, CH3), 7.2-8.2 (m, 5H, ArH).
2.3. Synthesis of oxime derivatives
The oxime derivatives (1a-g) were synthesized from aldehyde derivatives and hydroxylamine
hydrochloride in the alkali conditions [45].
Scheme 1. Synthesis of oxime derivatives under alkali conditions
2.4. Representative spectral data
2.4.1. 4-Nitrobenzaldehyde oxime (1a)
Cream solid; mp= 132 oC; FT-IR (KBr): 3306, 1603, 1536, 1347, 1214, 1107, 969, 847, 748,
686 cm-1; 1H NMR (400 MHz, acetone-d6): δ (ppm) 7.89 (d, 2H, ArH), 8.26 (d, 2H, ArH), 8.30
(s, 1H, CH), 8.79 (s, 1H, OH).
2.4.2. 4-Chlorobenzaldehyde oxime (1b)
o
White solid; mp= 110 C; FT-IR (KBr): 3299, 3996, 1594, 1398, 1594, 1492, 1313, 1212,
1087, 969, 873, 824, 691, 505 cm-1; 1H NMR (400 MHz, acetone-d6): δ (ppm) 7.43 (d, 2H, ArH),
7.65 (d, 2H, ArH), 8.12 (s, 1H, CH), 10.45 (s, 1H, OH).
2.4.3. 4-(N,N-Dimethylamino)benzaldehyde oxime (1c)
o
White solid; mp= 185 C; FT-IR (KBr): 3239, 2911, 2803, 1605, 1524, 1359, 1303, 1224,
1176, 954, 865, 811, 730, 569 cm-1; 1H NMR (400 MHz, acetone-d6): δ (ppm) 2.97 (s, 6H, CH3),
7.72 (d, 2H, ArH), 7.44 (d, 2H, ArH), 7.99 (s, 1H, CH), 9.74 (s, 1H, OH).
4

2.4.4. 4-Methoxybenzaldehyde oxime (1d)
o
White solid; mp= 45 C; FT-IR (KBr): 3320, 3006, 2968, 1607, 1512, 1307, 1249, 1169,
1028, 960, 871, 825, 698, 591 cm-1; 1H NMR (400 MHz, acetone-d6): δ (ppm) 3.82 (s, 3H, CH3),
6.94 (d, 2H, ArH), 7.55 (d, 2H, ArH), 8.07 (s, 1H, CH), 10.07 (s, 1H, OH).
2.4.5. 2-Pyridinecarboxaldehyde oxime (1e)
o
White solid; mp= 112 C; FT-IR (KBr): 3187, 3002, 2884, 2807, 1625, 1592, 1433, 1320,
1227, 1154, 981, 822, 770, 734, 664, cm-1;1H NMR (400 MHz, acetone-d6): δ (ppm) 7.35 (t, 1H,
ArH), 7.78 (t, 1H, ArH), 7.86 (d, 1H, ArH), 8.15 (s, 1H, CH), 8.58 (d, 1H, ArH), 10.90 (s, 1H,
OH).
2.4.6. 2-Thiophencarboxaldehyde oxime (1f)
o
Yellow solid; mp= 134 C; FT-IR (KBr): 3433, 3016, 2926, 1632, 1431, 1346, 1049, 941,
802, 715 cm-1;1H NMR (400 MHz, acetone-d6): δ (ppm) 7.12 (t, 1H, ArH), 7.48 (d, 1H, ArH),
7.68 (d, 1H, ArH), 7.79 (s, 1H, CH), 10.98 (s, 1H, OH).
2.4.7. 2-Furanecarboxaldehyde oxime (1g)
o
Brown solid; mp= 92 C; FT-IR (KBr): 3165, 3038, 2861, 1643, 1472, 1376, 1184, 1144,
1017, 969, 823, 749, 589 cm-1; 1H NMR (400 MHz, acetone-d6): δ (ppm) 6.53 (d, 1H, ArH), 6.68
(dd, 1H, ArH), 7.62 (d, 1H, ArH), 8.02 (s, 1H, CH), 10.43 (s, 1H, OH).
2.5. General procedure for the synthesis of fulleroisoxazoline derivatives
2.5.1. Typical stirring method (method A and B)
5

A mixture of C60 (36.0 mg, 0.05 mmol), oximes (1a-g) (0.05 mmol), and PhI(OAc)2 (0.05
mmol) were dissolved in 20 mL of toluene and stirred under nitrogen atmosphere at room
temperature (A) and 60° C (B) for the desired time. The course of the reaction was monitored by
TLC with toluene as an eluent. At the end of reaction, the solvent was evaporated in vacuo, and
the residue was separated on a silica gel column using toluene to afford cycloadducts (2a-g).
First, the unreacted C60 was obtained from column chromatography. Then the products (2a-g)
were yielded.
2.5.2. Grinding method (method C)
A mixture of C60 (36.0 mg, 0.05 mmol), oximes (1a-g) (0.05 mmol), and PhI(OAc)2 (0.05
mmol) were ground by mortar and pestle at room temperature for proper time. After completion
of the reaction as monitored by TLC, the mixture was purified by column chromatography with
toluene as an eluent to afford the fulleroisoxazoline derivatives (2a-g).
2.5.3. Ultrasound irradiation (method D)
In the similar process, the mixture was irradiated by ultrasound in various ultrasonic power
(40 W) for the desired times at 25 °C.
2.6. Representative spectral data for the various cycloadducts
2.6.1. 3ʹ-(4-Nitrophenyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2a)
Brown solid, mp > 300 °C; FT-IR (KBr): 3132, 2921, 2852, 1630, 1518, 1340, 848, 526 cm-
1
13
1; H NMR (400 MHz, CDCl3-CS2): δ (ppm); 8.41 (d, 2H, ArH), 8.48 (d, 2H, ArH); C NMR
(100 MHz, CDCl3-CS2): δ (ppm) 85, 95, 110, 124.2 (2C), 126.0, 128.0, 129.08, 129.7 (2C), 135,
6

136.7, 138, 139, 140.4, 140.5, 141.8, 142.04, 142.3, 142.5, 142.9 (2C), 143.1 (2C), 143.6, 143.7
(2C), 144, 144.4, 144.6,145.2, 145.3 (2C), 145.8, 146.0 (2C), 146.1, 146.4, 146.5.
2.6.2. 3ʹ-(4-Chlorophenyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2b)
Brown solid; mp > 300 °C; FT-IR (KBr): 3136, 3050, 2922, 1630, 1459, 1095, 810, 526 cm-
1
13
1; H NMR (400 MHz, CDCl3-CS2): δ (ppm) 7.53 (d, 2H, ArH), 8.16 (d, 2H, ArH); C NMR
(100 MHz, CDCl3-CS2): δ (ppm) 79, 92, 104.16, 128.87, 129.03, 129.09, 130.61, 136.65, 137.02,
140.30, 140.33, 141.70, 142.09, 142.27, 142.32, 142.46 (2C), 142.84 (2C), 142.98 (2C), 144.07,
144.39, 144.47, 144.72 (2C), 144.76, 145.13, 145.21, 145.39, 145.61, 145.83, 145.92, 145.97,
146.23, 146.25, 146.38, 147.24, 147.74, 153.28.
2.6.3. 3ʹ-(4-N,N-Dimethylaminophenyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2c)
Brown solid; mp > 300 °C; FT-IR (KBr): 3125, 2923, 1728, 1603, 1459, 1274, 1122, 1076,
814, 525 cm-1; 1H NMR (400 MHz, CDCl3-CS2): δ (ppm) 3.66 (s, 6H, CH3), 6.78 (d, 2H, ArH),
8.09 (d, 2H, ArH); 13C NMR (100 MHz, CDCl3-CS2): δ (ppm) 49, 60, 85, 96, 102, 104, 105.2,
109, 112 (2C), 116 (2C), 130, 137 (2C), 137.2, 139 (2C), 140.5 (2C), 142.6, 142.7 (2C), 143.1
(2C), 144.0 (2C), 145.2, 145.4 (2C), 145.8, 146.2 (2C), 146.5 (2C), 148.0, 150.2, 151.8.
2.6.4. 3ʹ-(4-Methoxyphenyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2d)
Brown solid; mp > 300 °C; FT-IR (KBr): 3132, 2924, 1727, 1603, 1459, 1263, 1117, 1030,
800, 740, 669 cm-1; 1H NMR (400 MHz, CDCl3-CS2): δ (ppm) 3.89 (s, 3H, OCH3), 7.04 (d, 2H,
13
ArH), 8.15 (d, 2H, ArH); C NMR (100 MHz, CDCl3-CS2): δ (ppm) 54.9, 78.8, 103.6, 114.2
(2C), 121.1, 130.08, 136.3 (2C), 136.7, 140.0, 141.40 (2C), 141.8, 142.0, 142.06, 142.19 (2C),
7

142.56, 142.7 (2C), 143.8, 144.14, 144.52, 144.70 (2C), 144.84 (2C), 144.92, 145.12, 145.30,
145.62 (2C), 145.68, 145.9, 146.09, 146.9, 147.31, 152.01, 161.07.
2.6.5. 3ʹ-(2-pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2e)
Brown solid; mp > 300 °C; FT-IR (KBr): 3134, 3100, 2922, 2852, 1725, 1630, 1574, 1263,
1
1094, 863, 799, 735, 525 cm-1; H NMR (400 MHz, CDCl3-CS2): δ (ppm); 8.62 (d, 1H, ArH),
8.47 (d, 1H, ArH); 7.93 (t, 1H, ArH), 7.40 (t, 1H, ArH);. MS (EI, 70 eV): m/z (%) = 841 (M+,
10), 120 (36), 91 (99), 78 (18), 57 (100).
2.6.6. 3ʹ-(2-Thienyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2f)
Brown solid; mp > 300 °C; FT-IR (KBr): 3134, 2921, 2851, 1738, 1738, 1630, 1426, 1234,
724, 699, 572, 525 cm-1; 1H NMR (400 MHz, CDCl3-CS2): δ (ppm); 7.60 (t, 2H, ArH), 8.10 (d,
1H, ArH).
2.6.7. 3ʹ-(2-Furyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene (2g)
1
Brown solid; mp > 300 °C; H NMR (400 MHz, CDCl3-CS2): δ (ppm); 7.65 (d, 1H, ArH),
7.38 (d, 1H, ArH), 6.64 (dd, 1H, ArH).
3. Results and discussion
In this study, an efficient comparison between conventional, grinding and ultrasound
conditions for the synthesis of fulleroisoxazolines from C60, substituted oximes and PhI(OAc)2
was investigated (Scheme 2).
8

Scheme 2. Synthesis of fulleroisoxazolines under various conditions
At first a mixture of C60 (36.0 mg), 4-Nitrobenzaldehyde oxime 1a (1 equiv) and PhI(OAc)2
(1 equiv) was chosen as a model reaction. It was stirred in 20 mL toluene for 90 min at room
temperature, the desired fulleroisoxazoline 2a was obtained with yield of 36%. Then the reaction
was investigated under thermal, grinding and ultrasound conditions. The synthesis of
fulleroisoxazolines under ultrasound irradiation was discussed as an efficient and green
procedure to promote 1, 3-dipolar cycloaddition reactions with good yields and shorten reaction
times. In our initial study, the effects of irradiation power on the efficiency of the reaction were
discussed in detail. Various rang of irradiation powers (10-60 W) were studied in the model
reaction and the results were summarized in Table 1.
<Table 1>
As shown in Table 1, when the irradiation power was 10 and 20 W (Table 1, entry 1-2), no
reaction was occurred within 10 minutes. However, the reaction could not improve well in the
irradiation power of 60 W (Table 1, entry 6). Then other various irradiation times were studied
under 60 W. In the power of 40 W irradiation the yield of 2a was better than that with 30 W
within 10 min (45%, Table 2, entry 3). Increasing the irradiation power from 40 to 50 W (Table
1, entries 4, 5) the reaction yield did not change a considerable amount (46 % in the similar
time). Finally the results indicated that there is an optimum power for effective synthesis of 2a in
the power of 40 W. It was studied with increasing the reaction time from 2 min to 15 min, the
yields were also improved (Table 2, entry 1–7). Finally an optimum time was specified for the
reaction under irradiation power (40 W) (Table 2, entry 4).
<Table 2>
9

However, all effective conditions in the ultrasound method were optimized. After
optimization of the irradiation power and time, we carried out the reaction using different kinds
of oxime derivatives under this condition. Considering all methods for synthesis of
fulleroisoxzolines, it was approved that under thermal conditions the times and the yields of the
reaction did not considerably improve while in the grinding procedure, only the rate of the
reaction was increased. The absence of toxic solvent is one of the advantages of grinding
method. Under grinding conditions the reaction time decreased compared to the conventional
methods, but the yields of the products were moderate. According to Table 3, it was found that
the sonication was a simple, mild and convenient method of constructing oxazoline cycle on
fullerene through 1,3-dipolar reaction compared to the other methods and the previous reported
results based on the application of microwave irradiation in synthesis of fullerene derivatives
[43].
<Table 3>
It is observed that under microwave and ultrasound irradiations not only the reaction times
are reduced but also the yields are increased. Microwave and ultrasound techniques as very
efficient and eco-friendly alternative to traditional for introducing energy in organic reactions has
substantially been increased and can be replaced the conventional methods such as stirring,
thermal, and grinding. In fact microwave [43] and ultrasound procedures have various operations
in improvement of the cycloaddition reactions. According to the previous reported literature [43]
and the present data in Table 3 about the synthesis of fullerene derivatives, it is demonstrated
that under ultrasound irradiation the time and yields of the reactions are surprising improved
compared to the microwave and other methods. Thus application of ultrasonic irradiation for
improvement of the reactions are more efficient and convenient than that of microwave.
10

Under sonication, in all cases spectacular accelerations and great improvements in yields and
reaction conditions are obtained through a special operation (Fig. 1).
Fig. 1. Comparison of the reaction times of the final products in various conditions
This finding is due to the phenomenon of cavitation that is grown by reducing the ambient
pressure by static or dynamic means under ultrasound irradiation. Under sonication the reaction
mixture is activated by inducing high local temperatures and pressure generated inside the
cavitation bubble and its interfaces when it collapses and speeds up the reaction rate and shortens
the reaction time [46, 47]. Ultrasound procedure as a green and effective method can replace the
conventional method, because in many reactions the straight heating can disturb the starting
materials and the related products and sometimes generate by-products.
The possible mechanism for rapid and efficient synthesis of fulleroisoxazolines under
ultrasound was proposed (Scheme 3). At first nitril oxides as the reactive intermediates were
generated in situ from the suitable contact of oximes and (diacetoxy)iodobenzene. Then the
desired cycloadducts were prepared by 1,3-dipolar cycloadditions between these dipoles and
fullerene. Under ultrasound irradiation great improvements in yields and reaction conditions is
due to the introducing the effectiveness energy resulted the cavitation. Under these conditions,
nitril oxides as very reactive chemical intermediates are generated very fast, thus facilitating 1,3-
dipolar cycloadditions.
Scheme 3. Proposed mechanism for the synthesis of fulleroisoxazoline derivatives mediated by PhI(OAc)2
11

The effects of ultrasound irradiation observed during organic reactions are due to cavitations
[39, 42]. The bubbles which are made by compression of the liquid are rapidly collapse, they can
be seen as microreactors that offer the opportunity of speeding up certain reactions [41]. Since
the volatile molecules can enter the micro bubbles, high temperature and pressure can be
produced during cavitations through breaking the chemical bonds and reacting with other
species, consequently. The desired products can be obtained in good yields and very short
reaction times. We increased the scope of the present study by the reaction of several oxime
derivatives with C60 in the presence of PhI(OAc)2 under ultrasound irradiation. According to
Table 3, the reaction of various oxime derivatives with C60 was accelerated by sonication
compared to the other conventional methods. The corresponding products were prepared in good
yields and excellent reaction times under ultrasonic irradiation (Fig. 2).
Fig. 2. Comparison of the reaction yields of the isolated products in various conditions
It seems this method for preparation of fulleroisoxazolines has some advantages including
one-pot reaction, very short times, high efficient, appropriate, mild and useful conditions in
comparison to other methods [48, 49]. The structure of products identified by spectroscopic data
1
such as: MS (EI, 70 eV), H NMR, 13C NMR and FT-IR. As an exact discussion (2e), the
molecular ion peak was shown at m/z 841. In the IR spectra, the stretching frequency of aromatic
C=C and C=N of oxazoline ring is formed in the region between m = 1461–1650 and 1630 cm-1,
respectively. Also the stretching vibration of C–H in the aromatic ring was appeared at region
between m = 3100 cm-1 (Fig. 3).
12

Fig. 3. IR spectrum of 3ʹ-(2-pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene
In 1H NMR spectra of oxime derivative (1e), the signals around δ= 7.30–8.60 are assigned by
protons of CH of aromatic rings while these protons are deshilded in fulleroisoxazoline (2e) and
the related signals appear in δ= 7.4-8.7 (Fig. 4). These results in fulleroisoxazolines and other
fullerene derivatives are related to the creation of a charge transfer complex between the organic
addend and the fullerene [50]. Also the signal related to imine and hydroxy protons appeare in
the δ = 8.15 and 10.90 ppm, respectively, while this signal disappear in the fulleroisoxazoline
(2e) spectrum because of junction of oxime derivative (1e) to C60.
Fig. 4. 1H NMR spectrum of (a): 2-Pyridinecarboxaldehyde oxime; (b) 3ʹ-(2-
pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene
In summary, synthesis of several fulleroisoxazolines was investigated under the various
methods including stirring, thermal, grinding and ultrasound conditions. Ultrasound irradiation
provides an effectiveness procedure to synthesis fullerene derivatives with high yields and short
reaction times.
4. Conclusion
In this research we provide an efficient alternative method to make fulleroisoxazolines from
oxime derivatives and C60 mediated by PhI(OAc)2. Compared with the conventional methods,
ultrasound procedure provides several advantages including mild and controllable reaction
conditions, reducing the extent of decomposition of both the starting materials and the reaction
13

products, rapid reaction rates, shorter reaction times, good yields, and environmental
friendliness. We expect this approach will disclose extensive purposes in the field of fullerene
chemistry, sonochemistry and green synthesis.
Acknowledgment
The authors are grateful to University of Kashan for supporting this work by Grant NO:
159196/XVI.
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16

Figure captions:
Scheme 1. Synthesis of oxime derivatives under alkali conditions
Scheme 2. Synthesis of fulleroisoxazolines under various conditions
Scheme 3. Proposed mechanism for the synthesis of fulleroisoxazoline derivatives mediated by PhI(OAc)2
Fig. 1. Comparison of the reaction times of the final products in various conditions
Fig. 2. Comparison of the reaction yields of the isolated products in various conditions
Fig. 3. IR spectrum of 3ʹ-(2-pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene
Fig. 4. 1H NMR spectrum of (a): 2-Pyridinecarboxaldehyde oxime; (b) 3ʹ-(2-
pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene
17

a
Table 1. Effects of ultrasound irradiation power on the reaction of oxime 1a, phI(OAc)2 and C60
Entry
Ultrasound
Time
(min.)
10
Yield
(%)b
NRc
NRc
23
power (W)
1
2
3
4
5
6
10
20
30
40
50
60
10
10
10
45
10
46
10
48
aOxime 1a, phI(OAc)2 and C60 : 1 : 1 : 1.
bIsolated yields.
CNo reaction.
18

a
Table 2. Effects of ultrasound irradiation time on the reaction of oxime 1a, phI(OAc)2 and C60
Entry
ultrasound
Time
Yield
(%)b
NRc
12
power (W)
(min.)
1
2
3
4
5
6
7
40
40
40
40
40
40
40
2
4
6
20
8
32
10
12
15
45
47
46
aoxime 1a, phI(OAc)2 and C60 : 1 : 1 : 1.
bIsolated yields.
CNo reaction.
19

Table 3. Synthesis of fulleroisoxazoline derivatives under various conditions (A, B, C, D, E methods)
Aa
Bb
Cc
Dd
Ee
Time
Entry
Oxime
Products
Time
(min)
Yields (%)f/
Recovered
C60(%)
Time
(min)
Yields (%)f/
Recovered
C60(%)
Time
(min)
Yields (%)f/
Recovered
C60(%)
Time
(min)
Yields (%)f/
Recovered
C60(%)
Yields (%)f/
Recovered
C60(%)
(min)
1a
1b
1c
1d
1e
1f
2a[31]
2b[31]
2c[27]
2d[31]
2e
90
90
60
90
40
50
90
36/41
30
35
20
30
15
20
30
34/40
15
15
10
15
15
10
15
25/45
10
10
6
45/29
15[43]
15[43]
10[43]
15[43]
10
41/47
1
2
3
4
5
6
7
41/42
32/40
34/45
15/49
20/51
17/53
35/45
30/42
29/47
20/51
22/48
20/49
38/39
30/45
29/45
17/49
23/48
20/51
50/26
46/28
42/31
38/38
41/40
42/39
45/39
41/42
42/38
31/43
34/38
33/40
10
5
2f[27]
2g[27]
5
15
1g
10
10
aStirring; bThermal (60° C); cGrinding; dUltrasound (40 W), eMicrowave irradiation (200W).
fIsolated yields.
20

OH
NH2OH.HCl
NaOH
R-CHO
R
N
c)
d)
Me2N
Cl
H3CO
b)
O2N
R: a)
e)
f)
g)
N
S
O
Scheme 1. Synthesis of oxime derivatives under alkali conditions
21

N
R
O
R
N
OH
PhI(OAc)2
Me2N
c)
Cl
H3CO
O2N
b)
d)
R: a)
e)
f)
g)
N
S
O
Scheme 2. Synthesis of fulleroisoxazoline derivatives under various conditions
22

N
R
O
CH3
O
I
H
H
C
AcO
OAc
O
I
O
O
H
R
N
C60
+
R
N
R
C
N
O
-HOAc
Ph
- HOAc
-PhI
Ph
Scheme 3. Proposed mechanism for the synthesis of fulleroisoxazoline derivatives mediated by PhI(OAc)2
23

Fig. 1. Comparison of the reaction times of the final products in various conditions
24

Fig. 2. Comparison of the reaction yields of the isolated products in various conditions
25

Fig. 3. IR spectrum of 3ʹ-(2-pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene
26

Fig. 4. 1H NMR spectrum of (a): 2-Pyridinecarboxaldehyde oxime; (b) 3ʹ-(2-
pyridyl)isoxazoline[4ʹ,5ʹ:1,2][60]fullerene
27

Graphical Abstract:
28

Sonochemically cycloaddition of C60 with oximes was mediated by PhI(OAc)2
Fulleroisoxazolines were synthesized in high yields and short times under sonication
Sonication is an efficient method in the synthesis of fullerene derivatives
29