Communication pubs.acs.org/IC
Regioselective Synthesis and Crystallographic Characterization of Isoxazoline-Ring-Fused Derivatives of Sc3N@Ih‑C80 and C60 Lipiao Bao,† Muqing Chen,† Wangqiang Shen,† Changwang Pan,† Kamran B. Ghiassi,‡ Marilyn M. Olmstead,*,‡ Alan L. Balch,*,‡ Takeshi Akasaka,† and Xing Lu*,† †
State Key Laboratory of Materials Processing and Die & Mold Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China ‡ Department of Chemistry, University of California, Davis, California 95616, United States S Supporting Information *
In this work, an isoxazoline ring was fused either to Sc3N@IhC80 for the first time or to C60 to form the corresponding monoadducts [Sc 3 N@I h -C 8 0 (C 1 0 H 9 O 4 NCl 2 ) (2a) or C60(C10H9O4NCl2) (2b)] with high regioselectivity using 3,5dichloro-2,4,6-trimethoxybenzonitrile oxide (1) as a precursor (Figure 1a). The structures of both 2a and 2b were estabilizhed
ABSTRACT: Highly regioselective 1,3-dipolar cycloaddition of 3,5-dichloro-2,4,6-trimethoxybenzonitrile oxide (1) to Sc3N@Ih-C80 or C60 affords the corresponding isoxazoline-ring-fused derivatives Sc3N@Ih-C80(C10H9O4NCl2) (2a) and C60(C10H9O4NCl2) (2b). 2a represents the first example of an endohedral metallofullerene derivative with an isoxazoline ring. Crystallographic and NMR spectroscopic studies reveal a [5,6]-bond addition pattern in 2a but a [6,6]-bond addition manner in 2b.
M
etal atoms or metallic clusters can be encapsulated inside the hollow cages of fullerenes to afford endohedral metallofullerenes (EMFs).1−4 The unique structures and novel properties of EMFs have attracted significant attention in recent years, and potential applications have been proposed in many fields, such as materials science, biomedicine, catalysis, and photovoltaics. It is now obvious that searching for new synthetic methods to create novel materials based on EMFs with high stability is crucial for broadening their applications, and, accordingly, many chemical transformations have been reported for the functionalization of EMFs.3,5,6 Among them, 1,3-dipolar cycloaddition is unique because of its feasibility of attaching various functional groups to afford relatively stable derivatives. Tremendous efforts have been devoted to the 1,3-dipolar reactions of EMFs with azomethine ylides, which gave rise to the corresponding pyrrolidino-ring-fused derivatives. In a recent effort to pursue new compounds of EMFs with a heterocyclic ring other than the pyrrolidines, we found that the reaction of Sc3N@Ih-C80 with nitrilimine afforded a very stable monoadduct in a highly regioselective manner.7 This result has accordingly stimulated our interest in searching for other cycloadditions for EMFs. As an important class of heterocyclic compounds, isoxazoline derivatives are well-known for their biological activities8 and, moreover, their ability to act as convenient intermediates in the synthesis of polyfunctional compounds.9 Nitrile oxides are widely used as the precursors of isoxazolines to react with alkenes, alkynes, and fullerenes. For instance, some isoxazolinefused derivatives of C 60 and C 70 have been reported previously,10−17 but only a few reports have concentrated on their crystal structures.12,18 Even worse, the relevant studies on EMFs have never been reported, although the isoxazoline derivatives of EMFs may show promising biological applications. © 2016 American Chemical Society
Figure 1. (a) Reaction scheme of Sc3N@Ih-C80/C60 with 1 and the corresponding HPLC profiles of the reaction mixtures containing 1 and (b) Sc3N@Ih-C80 or (c) C60 probed at different reaction times. HPLC conditions: Buckyprep column (Φ4.6 mm × 250 mm, Nacalai Tesque, Inc.), 1 mL/min toluene flow, 20 μL injection volume, 330 nm detection wavelength, room temperature.
by single-crystal X-ray diffraction (XRD), which shows a [5,6]bond addtion on Sc3N@Ih-C80 and a [6,6]-bond addition on C60 with an unexpected difference of the conformation of the pmethoxy group in the substituent. Typically, an anhydrous toluene solution containing both Sc3N@Ih-C80 and 1 (see the Supporting Information for details) was heated at reflux under argon (Figure 1a). As shown in the high-performance liquid chromatography (HPLC) profiles in Figure 1b, the reaction proceeded smoothly, and only one new peak was observed, as a consequence of high regioselectivity. The Received: March 13, 2016 Published: April 21, 2016 4075
DOI: 10.1021/acs.inorgchem.6b00631 Inorg. Chem. 2016, 55, 4075−4077
Communication
Inorganic Chemistry
it shows almost no effect on C60, which is most probably because of the existence of a metallic cluster in Sc3N@Ih-C80. The molecular structures of 2a and 2b were unambiguously determined by single-crystal XRD crystallographic studies. Black crystals suitable for data collection were obtained by slow diffusion of n-hexane into a carbon disulfide solution of 2a or 2b at room temperature over 2 weeks. There are four disordered cage orientations (occupancy values: 0.39, 0.21, 0.21, and 0.19) and eight disordered scandium positions (occupancy values: 0.94, 0.50, 0.42, 0.40, 0.34, 0.20, 0.12, and 0.07) in the crystal structure of 2a. The major conformer of 2a is depicted in Figure 3a. It is obvious that the
same procedure performed on C60 shows that it has reactivity similar to that of Sc3N@Ih-C80 (Figure 1c). The reaction mixtures were then subjected to further HPLC separations, which afforded 2a and 2b in 45% and 35% yield, respectively. Visible−near-IR measurements were carried out to characterize the electronic properties of 2a and 2b (Figure 2). The
Figure 2. Visible−near-IR spectra of Sc3N@Ih-C80, 2a, C60, and 2b in toluene. The four curves are vertically shifted to ease comparison.
absorption spectrum of 2a shows broad absorption bands from 650 to 1114 nm, which is apparently different from that of pristine Sc3N@Ih-C80. Besides, the addition position is proposed to be at a [5,6]-bond junction on the cage because of the absence of the absorption band at 800−820 nm, which is characteristic for the [6,6]-adducts.19 For 2b, three strong new absorption peaks are found at λ = 429, 460, and 690 nm compared to the spectrum of pristine C60. Undoubtedly, the electronic structures of both 2a and 2b have been perturbed by chemical modification. The electrochemical behaviors of 2a and 2b were characterized by cyclic voltammetry and differential pulse voltammetry (Figure S3), and the redox potentials are summarized in Table 1
Figure 3. ORTEP drawing showing the structures of (a) 2a and (b) 2b with thermal ellipsoids at the 50% probability level. The C−O bonds of the p-methoxyl groups in both compounds are marked by solid red lines. Only the major scandium sites and the major cage orientation in 2a are presented, and solvent molecules are omitted for clarity.
isoxazoline ring is fused to the cage at a [5,6]-bond junction rather than at a [6,6]-bond junction as a consequence of thermodynamic selectivity.22−27 In agreement with that, the solution 1H NMR spectrum of 2a (Figure 4) contains three
Table 1. Redox Potentials (V vs Fc/Fc+) of Sc3N@Ih-C80, 2a, C60, and 2ba ox
compound Sc3N@Ih-C80 2a C60c 2b
b
E1
+0.59 +0.46
red
E1
−1.26 −1.02 −1.13 −1.12
red
E2
−1.62 −1.34 −1.50 −1.50
red
E3
−2.37 −1.71 −1.95 −1.96
a
Determined by differential pulse voltammetry in 1,2-dichlorobenzene with 0.1 M (n-Bu)4NPF6 at a platinum working electrode. bReference 20. cReference 21.
compared to pristine Sc3N@Ih-C80 and C60. Both 2a and pristine Sc3N@Ih-C80 exhibit one oxidation process and three reduction steps. However, the first oxidation potential of 2a is negatively shifted by 130 mV, while the reduction potentials of 2a are positively shifted by 240−660 mV compared to those of pristine Sc3N@Ih-C80, resulting in a smaller electrochemical gap of 2a (1.48 V) than that of pristine Sc3N@Ih-C80 (1.85 V). However, C60 (−1.13, −1.50, and −1.95 V) and 2b (−1.12, −1.50, and −1.96 V) possess nearly the same reduction potentials. These results indicate that chemical modification has an obvious influence on the electrochemical properties of Sc3N@Ih-C80, but
Figure 4. 1H NMR spectra of 2a and 2b at 600 MHz. Solvent: 1:1 CS2/ CDCl3.
proton signals at 4.18, 4.04, and 3.83 ppm with equal intensity corresponding to three nonequivalent methyl groups, which can only originate from a [5,6]-bond addition pattern. Besides, the bond length between the carbon atoms at the sites of addition (C1A−C2A) is 1.59 Å, which is slightly shorter than the values reported for [5,6]-pyrrolidino-fused Sc3N@Ih-C80 (1.619 Å)23 4076
DOI: 10.1021/acs.inorgchem.6b00631 Inorg. Chem. 2016, 55, 4075−4077
Communication
Inorganic Chemistry and pyrazole-ring-fused C80 (1.61 Å).7 In addition, the C81−N2 bond distance is 1.254 Å, demonstrating its double-bond character. As shown in Figure S4a, the closest interfullerene distances in 2a are very short (3.033 and 3.171 Å), disclosing strong π−π interactions between molecules. As to 2b, there is no solvent molecule present in the structure and the entire system is fully ordered. Figure 3b shows the molecular structure of 2b. The addition occurs at a [6,6]-bond junction, which is more reactive than the [5,6]-bond junction.28 This addition pattern is also confirmed by the solution 1H NMR spectrum of 2b (Figure 4), which shows two proton signals at 4.16 and 3.99 ppm with a 2:1 ratio. Besides, the closest interfullerene distance in 2b is 3.321 Å (Figure S4b), which is longer than the values in 2a (3.033 and 3.171 Å). Unexpectedly, the exohedral unit in 2a employs an up-mode conformation, with the p-methoxyl group far from the cage, while a down-mode conformation is observed in 2b, with the p-methoxyl group approaching the fullerene cages (Figure 3), which most probably derives from crystal packing force. In summary, the first isoxazoline derivative of EMFs and a similar derivative of C60 were synthesized via a highly regioselective reaction of 1 with Sc3N@Ih-C80 and C60, respectively. Studies of crystallography and NMR spectroscopy disclose that the isoxazoline ring is fused to a [5,6]-bond junction on Sc3N@Ih-C80 but to a [6,6]-bond junction on C60. In addition, absorption results reveal that the electronic structures of both C60 and Sc3N@Ih-C80 have been altered markedly by chemical modifications. However, electrochemical results show that the isoxazoline ring has a strong influence on the redox potentials of Sc3N@Ih-C80, but it has no obvious influence on the electrochemical properties of C60. This facile method with high regioselectivity may lead to the potential application of these fullerene derivatives with a bioactive isoxazoline ring.
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to K.B.G. and the Analytical and Testing Center in HUST for all related measurements.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.inorgchem.6b00631. Experimental details and additional spectroscopic information (PDF) CIF data (CIF) CIF data (CIF)
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REFERENCES
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. *E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Financial support from The National Thousand Talents Program of China, NSFC (Grants 21171061 and 51472095), Program for Changjiang Scholars and Innovative Research Team in University (Grant IRT1014), and the U.S. National Science Foundation (Grant CHE-1305125 to A.L.B. and M.M.O.) is gratefully acknowledged. We thank the Advanced Light Source, supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy, under Contract DE-AC02-05CH11231, for beam time and a fellowship 4077
DOI: 10.1021/acs.inorgchem.6b00631 Inorg. Chem. 2016, 55, 4075−4077
