Since the discovery of fullerenes1 and their isolation in bulk,2 the research of suitable procedures for their functionalization has become an important challenge in organic chemistry.3 In particular, the most numerous member of the fullerene family, C60, has obtained the highest interest as C60-based molecules. Fullerene-based nanomaterials exhibit a broad range of interesting features in material science and biological application.4 – 10 The double bonds between two hexagons in the structure of C60 are dienophilic, which enables the molecule to undergo a variety of addition reactions including cycloaddition,11 , 12 cyclopropanation,13 addition of organometallic reagents14 and photoinduced electron transfer reaction.15 Among the different types of cycloaddition reactions16 – 19 available for the preparation of heterocyclic fullerene derivatives, 1,3-dipolar cycloaddition demonstrates a powerful tool due to the fact that C60 behaves as an electron-deficient olefin. Synthesis of fivemembered cycles via the addition of 1,3-dipoles to alkenes is a typical organic reaction. In fact, 1,3-dipolar cycloaddition reactions are beneficial for the construction of carbon–carbon bonds and for the preparation of heterocyclic compounds.20 Thus, different 1,3-dipoles, including azomethine ylides, diazo compounds, azides, nitrile oxides, nitrile ylides, nitrile imines, pyrazolinium ylides, and carbonyl ylides, have been reported to react with fullerenes.21 – 30 Fullerene-based heterocyclic rings such as fulleroisoxazolines and fulleropyrazolines with attractive chemical, electrochemical, and photophysical properties31 can be readily synthesized through various procedures such as addition of nitrile imine and nitrile oxide to C60.32 – 37 These reactive intermediates can be easily produced from arylhydrazones/oximes as suitable and accessible substrates. However, the organic addends are good donors to fullerene when they join to C60. Electrochemical studies demonstrate that the cycloadducts show better electron acceptor properties than the parent C60. Hence they can be used as a donor-accepting dyads in photovoltaic devices and improve their performance.38

Green chemistry concentrates on research that can help to reduce or eliminate the negative environmental effects and the amount of undesired hazardous chemicals (including solvents) and increases the selectivity of the product formation.39 Solvent-free syntheses have recently obtained much consideration. These procedures have many advantages including high efficiency and selectivity, easy separation, purification, and mild reaction conditions. Moreover, they are not only environmentally safe but also economically beneficial because toxic wastes can be minimized or eliminated, so the costs of waste treatment are also reduced.40 Various types of mechanochemical devices have been used to provide mechanical activation energy. They differ in their capacity and efficiency and can be mostly categorized into two classes such as grinding devices and milling devices. Grinding is an effective instrument that allows a highly efficient mixing of substrates under solventfree conditions. This method is applied as the most suitable and simple tool for a mechanochemical reaction using a mortar and a pestle, which promotes the reactions through grinding mixing and triturating. Grinding procedure has been widely used by Toda et al. to study several solvent-free organic reactions.41 , 42 In organic chemistry various applications of grinding procedure including C–C bond formation,43 , 44 synthesis of nanocrystallines45 and nanoparticles,46 synthesis of heterocycles,47 and fullerene modifications48 have been reported.

Herein, we wish to report an efficient, eco-friendly, and facile physical grinding approach for the synthesis of fullerene derivatives via 1,3-dipolar cycloaddition of fullerene with arylhydrazones/oximes under solvent-free conditions.

In this research, cycloaddition reactions of C60 and substituted arylhydrazones 1a–i and oximes 3a–g mediated by (diacetoxyiodo)benzene under conventional and grinding conditions is studied to prepare the corresponding fulleropyrazolines 2a–i and fulleroisoxazolines 4a–g. Under grinding conditions, synthesis of fulleropyrazoline and fulleroisoxazoline derivatives is discussed as an ecofriendly and efficient procedure to promote 1,3-dipolar cycloaddition reactions (Scheme 1).

scheme 1

Scheme 1

As an example, a mixture of equimolar amounts of C60, benzaldehyde phenylhydrazone (1a), and PhI(OAc)2 was ground by mortar and pestle at room temperature (Table 1, entry 1). The desired fulleropyrazoline 2a was obtained in 34% yield. In order to extend the range of various cycloadducts, we carried out the reaction using different kinds of arylhydrazones and oximes under this green approach. The heterocyclic fullerene derivatives 2b–i, 4b–g were prepared in the same manner by reaction of the arylhydrazones 1b–i and oximes 3b–g with C60 in the presence of PhI(OAc)2 at room temperature.

Table 1 Synthesis of heterocyclic fullerene derivatives under conventional and grinding conditions*
Full size table

According to Table 1, grinding approach is more convenient in the yields and the reaction time than conventional conditions.49 Under grinding, the transformations with moderate to good yields were carried out without any significant amounts of unsuitable side product.

Since fullerene C60 is a polyalkene with less reactivity than other alkenes, about half of the unreacted fullerene can be recovered using extraction with toluene after completion of the reaction.

Mildness, short reaction times, work-up easiness, high efficient, and convenient conditions are the superiorities of this green protocol for the synthesis of fulleropyrazolines and fulleroisoxazolines compared to the previously described methods.20 , 38 , 49 Also one of the most prominent advantages of grinding method is the absence of toxic solvent.

The plausible mechanism for the efficient synthesis of heterocyclic fullerene derivatives under grinding conditions was suggested (Scheme 2).

scheme 2

Scheme 2

At the beginning step, the reactive intermediates A, nitrile imines or nitrile oxides, were formed in situ by the interaction of arylhydrazones or oximes and (diacetoxyiodo) benzene. Then the desired cycloadducts were synthesized via 1,3-dipolar cycloaddition between dipoles A and fullerene. Under grinding approach, the great improvement in the reaction conditions is due to the introducing effective mechanochemical energy resulted in the suitable contacts of substrates. Under these conditions, nitrile imines or nitrile oxides A as very reactive chemical intermediates are formed very fast, so speeding 1,3-dipolar cycloadditions.

The structures of new products were studied using 1H, 13C NMR, IR, and mass-spectroscopy data as well as by elemental analysis. The mass spectra of the heterocyclic cycloadducts 2a–i, 4a–g show the [M]+ peak. The signals corresponding to the organic addend of these compounds appear in the 1H NMR spectra. The chemical shifts of these signals are observed at lower field compared with the corresponding starting arylhydrazone or oxime. The 1H NMR spectra of cycloadducts 2a–i are characterized by absence of the imine proton signal, which is present in the 1H NMR spectra of starting arylhydrazones 1a–i (for example, in the spectra of compound 1h it appears at ~9.50 ppm, see Fig. 1). This change also confirms the proposed structure of the reaction products.

Figure 1
figure 1

1H NMR spectrum of a) 2-thiophencarboxaldehyde phenylhydrazone (1h); b) 1'-phenyl-3'-(2-thienyl)pyrazolino[4',5':1,2]-[60]fullerene (2h)

Full size image

The signals of aromatic protons, which appear at 6.7–7.3 ppm in the 1H NMR spectra of arylhydrazones 1a–i, are shifted down field in fulleropyrazolines 2a–i and appear at 7.1–8.0 ppm (Fig. 1). This shift has been attributed in other fullerene derivatives to the existence of a charge transfer complex between the organic addend and the C60 cage.50

In conclusion, the effective method for the grindingmediated solvent-free synthesis of fulleropyrazolines and fulleroisoxazolines is described. The application of this technique does not involve any hazardous organic solvent and has various advantages including design of safe reaction conditions, moderate to good yields, shorter reaction times, and environmentally friendly procedure.

Experimental

FT-IR spectra were recorded on a Nicolet Magna-IR 550 spectrometer in KBr pellets. 1H and 13C NMR spectra were recorded on a Bruker DRX-400 Avance spectrometer (400 and 100 MHz, respectively) in CDCl3–CS2, 1:1, TMS as internal standard. Mass spectra were recorded by Finnigan-MAT-8430 mass spectrometer (EI, 70 eV). Elemental analysis was performed on a Carlo Erba EA 1108 analyzer. Melting points were determined on an Electro thermal 9200 apparatus. TLC analysis was performed on TLC plastic plates (Sigma-Aldrich), eluent PhMe. Silica gel 60 (highpurity grade, pore size 60 Å, 70–230 mesh, 63–200 μm, Merck) was used for column chromatography, eluent was PhMe. Crystalline C60 powder (99.9%) was purchased from Sigma-Aldrich company. All solvents and reagents were purchased from Sigma-Aldrich and Fluka and used without further purification. (Diacetoxyiodo)benzene was synthesized according to the literature method.51 Substituted arylhydrazones 1a–i and oximes 3a–g were synthesized according to the literature methods.52

Grinding experiments were performed on a typical mortar and pestle.

Synthesis of heterocyclic fullerene derivatives 2a–i and 4a–g by conventional method (General Method).49 Fullerene C60 (36 mg, 0.05 mmol), arylhydrazone 1a–i or oxime 3a–g (0.05 mmol), and PhI(OAc)2 (16 mg, 0.05 mmol) were dissolved in PhMe (20 ml). The mixture was stirred under nitrogen atmosphere at room temperature for proper time. After completion of the reaction as monitored by TLC, the mixture was purified by column chromatography to afford the cycloadducts 3a–i, 4a–g.

Grinding-based synthesis of heterocyclic fullerene derivatives 2a–i and 4a–g (General Method). A mixture of fullerene C60 (36 mg, 0.05 mmol), arylhydrazone 1a–i or oxime 3a–g (0.05 mmol), and PhI(OAc)2 (16 mg, 0.05 mmol) was ground using 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 to afford the cycloadducts 3a–i, 4a–g. 1H, 13C NMR and IR spectral data of the known compounds 2a–e, 4a–d,f,g match the reported in the literature.34 , 38 , 49

3'-(4-Chlorophenyl)-1'-phenylpyrazolino[4',5':1,2]-[60]fullerene (2f). Brown powder. IR spectrum, ν, cm–1: 3100 (=C–H s), 1626 (C=N s), 1600, 1453 (C=C s), 1094 (C–Cl s), 872 (=C–H oop. bend, Ar), 753, 692 (=C–H oop. bend, Ph). 1H NMR spectrum, δ, ppm (J, Hz): 6.91–7.27 (2H, m, H Ph); 7.32 (2H, d, J = 8.0, H Ar); 7.36–7.40 (1H, m, H Ph); 7.48 (2H, d, J = 8.0, H Ar); 7.69–8.25 (2H, m, H Ph). 13C NMR spectrum, δ, ppm: 86.1; 90.5; 110.3; 112.6; 113.0; 115.9; 116.5 (2C); 117.2; 118.8; 119.6; 122.7; 124.5; 125.1 (2C); 127.9 (2C); 128.1 (2C); 131.4; 133.2 (2C); 134.8; 136.1; 137.5 (2C); 137.9; 138.6; 141.2 (2C); 142.6; 145.7; 146.5 (2C); 152.8; 155.2 (2C); 163.1; 165.4; 169.1 (2C). Mass spectrum, m/z (I rel, %): 949 [M]+ (5), 91 (100). Found, %: C 92.45; H 1.06; N 3.12. C73H9ClN2. Calculated, %: C 92.36; H 0.96; N 2.95.

1'-Phenyl-3'-(2-pyridyl)pyrazolino[4',5':1,2][60]-fullerene (2g) . Brown powder. IR spectrum, ν, cm–1: 3150 (=C–H s), 1629 (C=N s), 1600, 1462 (C=C s), 1566, 1491 (C=C s, Py), 881 (=C–H oop. bend, Py), 753, 689 (=C–H oop. bend, Ph) 1H NMR spectrum, δ, ppm (J, Hz): 7.17 (1H, t, J = 7.5, H Ar); 7.27 (2H, d, J = 8.0, H Ar); 7.36 (1H, t, J = 7.5, H Ar); 7.47 (1H, t, J = 7.5, H Ar); 7.76–7.90 (2H, m, H Ar); 8.38–8.60 (2H, m, H Ar). 13C NMR spectrum, δ, ppm: 75.1; 85.9; 111.4; 112.3; 113.4; 114.9 (2C); 116.5; 117.1; 119.2; 121.7; 123.6; 125.2 (2C); 127.1 (2C); 129.0 (2C); 130.2; 133.5; 135.4 (2C); 136.2; 137.1; 138.7 (2C); 140.2 (2C); 141.7; 143.1; 145.0; 146.5; 150.9 (2C); 152.2; 153.7 (2C); 155.1; 157.5; 160.0; 162.2; 164.0; 166.9; 168.0 (2C). Mass spectrum, m/z (I rel, %): 915 [M]+ (5), 91 (100). Found, %: C 94.54; H 0.91; N 4.66. C72H9N3. Calculated, %: C 94.42; H 0.99; N 4.59.

1'-Phenyl-3'-(2-thienyl)pyrazolino[4',5':1,2][60]-fullerene (2h). Brown powder. IR spectrum, ν, cm–1: 3150 (=C–H s), 1631 (C=N s), 1600, 1489 (C=C s), 1595, 1428 (C=C s, thiophene), 871 (=C–H oop. bend, thiophene), 751, 695 (=C–H oop. bend, Ph). 1H NMR spectrum, δ, ppm (J, Hz): 7.13–7.20 (2H, m, H Ar); 7.24 (1H, t, J = 5.0, H Ar); 7.46–7.52 (3H, m, H Ar); 7.94 (1H, d, J = 8.0, H Ar); 7.98 (1H, d, J = 8.0, H Ar). 13C NMR spectrum, δ, ppm: 52.2; 78.2; 123.9 (2C); 124.1; 124.5; 125.4 (2C); 125.9; 126.0; 126.2; 126.8; 127.6; 128.3 (2C); 128.7; 129.1 (2C); 129.3 (2C); 130.0; 130.5; 131.2; 132.5; 133.4; 135.6; 136.8; 137.0; 138.2; 139.7; 140.2; 141.5; 142.0; 143.1 (2C); 144.0; 145.2. Mass spectrum, m/z (I rel, %): 920 [M]+ (4), 91 (100). Found, %: C 92.50; H 0.92; N 3.10; S 3.82. C71H8N2S. Calculated, %: C 92.60; H 0.88; N 3.04; S 3.48.

3'-(2-Furyl)-1'-phenylpyrazolino[4',5':1,2][60]-fullerene (2i). Brown powder. IR spectrum, ν, cm–1: 3100 (=C–H s), 1628 (C=N s), 1600, 1420 (C=C s), 1454, 1400 (C=C s, Fur), 850 (=C–H oop. bend, Fur), 751, 693 (=C–H oop. bend, Ph). 1H NMR spectrum, δ, ppm (J, Hz): 7.30–7.70 (6H, m, H Ar); 8.90 (2H, d, J = 8.0, H Ar). 13C NMR spectrum, δ, ppm: 76.1; 84.5; 109.6; 111.5; 112.9; 113.1 (2C); 115.6; 116.5; 120.1; 121.3; 123.4; 124.2 (2C); 125.1 (2C); 127.6 (2C); 131.9; 133.2; 134.5 (2C); 135.2; 137.1; 139.6 (2C); 140.1 (2C); 141.0; 143.5; 144.0; 146.1; 151.2 (2C); 152.9; 153.3 (2C); 156.2; 157.5; 159.1; 161.4; 163.6; 165.0; 167.1. Mass spectrum, m/z (I rel, %): 904 [M]+ (10), 91 (100). Found, %: C 94.32; H 0.97; N 3.19. C71H8N2O. Calculated, %: C 94.24; H 0.89; N 3.10.

3'-(2-Pyridyl)isoxazolo[4',5':1,2][60]fullerene (4e). Brown powder. IR spectrum, ν, cm–1: 3001 (=C–H s), 1630 (C=N s), 1600, 1461 (C=C s, Py), 799 (=C–H oop. bend, Py). 1H NMR spectrum, δ, ppm (J, Hz): 7.40 (1H, t, J = 8.0, H Py); 7.93 (1H, t, J = 8.0, H Py); 8.47 (1H, d, J = 7.5, H Py); 8.62 (1H, d, J = 7.5, H Py). 13C NMR spectrum, δ, ppm: 77.5; 86.1; 110.2; 111.5; 113.4; 115.9 (2C); 116.7; 117.2; 119.8; 122.0; 124.3; 125.1 (2C); 128.9 (2C); 129.5; 130.1; 132.7; 135.6; 136.3; 137.8; 138.4; 139.2 (2C); 141.9; 142.3; 144.5; 146.7; 150.2; 151.8; 152.2 (2C); 155.0; 157.1; 160.8; 163.0; 165.2. Mass spectrum, m/z (I rel, %): 840 [M]+ (2), 91 (100). Found, %: C 94.12; H 0.53; N 3.42. C66H4N2O. Calculated, %: C 94.29; H 0.48; N 3.33.