Hollow and Solid Spheres Assembled from Functionalized

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Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX

Hollow and Solid Spheres Assembled from Functionalized Macrocycles Containing Adamantane Masahide Tominaga,*,† Nobuto Kunitomi,† Kazuaki Ohara,† Masatoshi Kawahata,†,∥ Tsutomu Itoh,‡ Kosuke Katagiri,§ and Kentaro Yamaguchi*,†

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Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan ‡ Center for Analytical Instrumentation, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan § Department of Chemistry, Faculty of Science and Engineering, Konan University, 8-9-1 Okamoto, Higashinada-ku, Kobe, Hyogo 658-8501, Japan S Supporting Information *

ABSTRACT: An adamantane-based macrocycle possessing eight hydroxyl groups (1) was synthesized, in which the macrocyclic framework comprises two disubstituted adamantane molecules bearing phenyl derivatives connected to two biphenylene spacers by oxygen atoms. Furthermore, functionalized macrocycles containing methyl (2) and methoxycarbonylmethyl (3) groups were prepared. From the X-ray crystallographic analysis, the backbone of the macrocycles in all crystals had a nearly hexagonal shape with a cavity and these macrocycles could be arranged into different tubular structures dependent on the substituents. In acetone, macrocycle (1) formed stable hollow spherical aggregates with multilayer membranes. In contrast, macrocycle (3) exhibited no production of self-assembled materials in chloroform. The addition of hexane into the solution caused the generation of solid spheres and their fused network aggregates, which were finally transformed into crystals owing to the solvent effects.

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tures30−32 and are formed from amphiphilic macrocycles, such as modified calixarenes and pillararenes, bearing hydrophilic and lipophilic functionalities through hydrophobic interactions in water.28,33 However, examples of spherical aggregates built from nonamphiphilic macrocycles having diverse substituents, in place of the hydrophilic or lipophilic groups, in organic media are scarce. Incorporating multiple substituents on macrocycles may modulate the sizes, stability, and inner structures of the spherical aggregates, which may lead to an alternation of their chemical and physical properties. Recently, we demonstrated that the macrocycles containing adamantane and aromatic parts in their frameworks produced hollow spherical aggregates in aqueous and organic solutions, where the aliphatic and rigid adamantane parts in these molecules were of importance for the generation of the hollow spheres, because they are partly involved with CH···π interactions between adamantane and aromatic units and dispersive forces between adamantane parts in addition to solvophobic interactions.34−36 Accordingly, the incorporation of adamantane moieties into a macrocyclic skeleton consisting of phenol derivatives, which enables the introduction of substituents, was a reasonable approach to construct spherical aggregates

INTRODUCTION Synthetic macrocyclic structures are very important receptor molecules because they offer the opportunity to interact with diverse guest compounds through the binding sites of the repeated component units and the well-defined and tunable cavities within their frameworks. Additionally, by the attachment of various functional groups on the macrocyclic skeletons, these substituted macrocycles provide self-assembled nanostructures, including vesicles, tubes, helices, and fibers.1−7 Among the research on these materials, calixarenes, resorcinarenes, pyrogallolarenes, and others constituted of phenol derivatives as component units have been shown to be applicable macrocyclic building blocks to construct supramolecular nanoarchitectures, because several functional groups can be readily incorporated onto the macrocyclic skeletons.8−15 For instance, pillar[n]arenes have recently been receiving considerable attention as a cyclophane host, where n hydroquinone parts are alternately linked by methylene bridges in their 2- and 5-positions.16−25 The family of pillar[n]arenes has rigid and symmetrical cylindrical structures with tunable cavities, whereas hydroxyl groups are placed at the upper and lower rim positions. A wide variety of modified pillar[n]arenes have been synthesized by introducing substituents, and these are directed into self-assembled nanostructures.26−29 Vesicles and micelles are fundamental and general spherical architec© XXXX American Chemical Society

Received: January 9, 2019

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DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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mass spectrometry. The results of these identifications were in full agreement with the proposed structures. Numerous modified macrocyclic compounds have been synthesized by incorporating substituents to exploit new host-guest properties and their self-assembled materials in addition to the change of their solubility, shapes, and conformations. Thereby, a modified adamantane-based macrocycle with the methoxycarbonylmethyl group (3) as a representative example was designed, because this functional group has been used to modify calixarenes and pillararnes.38,39 The adamantane-based macrocycle 1 was reacted with methyl bromoacetate in the presence of potassium carbonate to afford fully substituted macrocycle 3 in yield of 62%. The molecular structures of macrocycles 1−3 were clearly established by X-ray crystallographic analysis of a single crystal (Figure 1). Colorless crystals (1a−3a) were obtained from the vapor diffusion of chloroform into an acetone solution of 1, the vapor diffusion of hexane into a chloroform solution of 2, and slow evaporation of a mixture of hexane and chloroform of 3, respectively. In crystals 1a and 2a, the compounds 1 and 2 revealed that the macrocyclic structures had a hexagonal shape, where the distance between the centroids of phenyl rings in the biphenylene spacers was 11.3 Å for 1 and 11.5 Å for 2. The distance between the centroids of the adamantane moieties was 18.5 Å for 1 and 18.2 Å for 2. The four phenyl derivative moieties lay almost perpendicular to the macrocyclic plane, whereas the two biphenylene linkers were almost horizontal (Figure 1a,b). In crystal 3a, the backbone of the macrocycle exhibited a similar shape and size to those of 1 and 2 (Figure 1c). The entire shape of 3 was a tubular structure, where the average distance between the carbon atoms of the methyl group in the substituents was 13.1 Å. In crystal 1a, individual macrocycles 1 were aligned into tubular structures with rectangular channels through two pairs of hydrogen bonds between hydroxyl groups directly along c axis (Figure 2a), which were assembled into a threedimensional network structure through OH···O, CH···O, and CH···π interactions between adamantane, dihydroxyphenyl, and biphenylene moieties (Figure 2b). Solvent molecules were included within the cavity of tubular structures. In crystal 2a, macrocycles 2 were arranged into tubular structures along the a axis, which were assembled into network structures through CH···π and CH···O interactions between adamantane, dimethoxyphenyl, and biphenylene moieties (Figure 3a,b). Another channel was observed in the crystalline lattices along the b axis (Figure 3c). Chloroform molecules were entrapped in the spaces of the network structures and interacted with the oxygen atoms of methoxy groups through CH···O interactions. In the packing of the macrocycles, two types of one-dimensional pores were formed. In crystal 3a, macrocycle 3 was assembled into tubular structures with small rectangle channels directly along the a axis (Figure 4a), which were produced in the network structures through CH···π and CH···O interactions between adamantane, phenyl derivative, and biphenylene parts (Figure 4b). In the tubular structures, two of the substituents on the macrocycle were mutually included within the cavity of the neighboring macrocycles to form one-dimensional polymers bearing pseudorotaxane structures, where the substituents interacted with the biphenylene spacer through CH···π and CH···O interactions. We investigated the self-assembly behaviors of the adamantane-based macrocycles in organic solution to obtain

bearing numerous functional groups. Herein, we report on the synthesis and structural analysis of three adamantane-based macrocycles bearing eight substituents. X-ray crystallographic analysis revealed that the backbone of all macrocycles was nearly hexagonally shaped with a cavity, which could be arranged into diverse tubular structures. The macrocycles supplied hollow spheres with multilayer membranes or spherical particles depending on the substituents in organic media.

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RESULTS AND DISCUSSION We previously presented the synthesis of an adamantane-based oxacyclophane, where two disubstituted adamantanes bearing dimethoxyphenyl moieties were connected by two pyrazine linkers through oxygen atoms.34 Its macrocycle gave hollow spherical aggregates in aqueous solution. Thus, we designed an adamantane-based macrocycle (1) with eight hydroxyl groups to introduce the functional groups, which comprised two disubstituted adamantane units bearing phenyl derivatives connected to two biphenylene spacers by oxygen atoms. We synthesized the macrocycle 1 according to Scheme 1. Scheme 1. Adamantane-Based Macrocycles Bearing Eight Substituents 1−3

Compound 4 was synthesized from 1,3-adamantanediol as the starting material according to a published procedure,37 and then the Ullmann coupling reaction with 4 and 1,4diiodobenzene by using CuI/N,N-dimethylglycine in the presence of cesium carbonate afforded compound 5 in yield of 71%. The homocoupling of 5 gave macrocycle 2 by nickelpromoted coupling under the high-dilution conditions in yield of 30%. The treatment of 2 with boron tribromide in dichloromethane gave the demethylated macrocycle 1 in yield of 90%. The structures of the two macrocycles 1 and 2 were characterized by 1H and 13C NMR spectroscopy and B

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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Figure 1. Molecular structures of macrocycles 1−3 in (a) crystal 1a, (b) crystal 2a, and (c) crystal 3a with top and side views. Solvent molecules and disordered atoms are omitted for clarity.

Figure 2. Packing diagram of macrocycle 1 in crystal 1a: (a) side view of the tubular structure and (b) top view of the network structures. Solvent molecules and disordered atoms are omitted for clarity.

the morphological information by using field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The macrocycle 1 bearing hydroxyl groups was dissolved in acetone (0.1 mM) at 50 °C for 1 h and allowed to stand for 3 days at 25 °C. SEM images exhibited planar disklike objects with a diameter of approximately 450 nm after drying on a solid surface (Figure 5a). Under high vacuum, the removal of solvents within the

hollow spheres resulted in planarized structures.40,41 The hollow nature of the spherical assemblies was evidenced by TEM experiment, which exhibited a defined contrast between the center and border of the spheres (Figure 5b). Hollow spherical aggregates possessed a multilayer film with a shell thickness of 20−30 nm. The macrocycle 1 had hydrophobic aliphatic and aromatic parts and polar hydroxyl groups. Thus, the polar hydroxyl groups on the macrocycle were exposed to C

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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Figure 3. Packing diagram of macrocycle 2 in crystal 2a: (a) side view of the tubular structure and (b) top and (c) side views of the network structures. Solvent molecules are omitted for clarity.

Figure 4. Packing diagram of macrocycle 3 in crystal 3a: (a) side view of the tubular structure and (b) top view of the network structures. The substituents within cavities are shown in the CPK model.

the outside of the sphere owing to a relatively polar environment (Figure 6a). By adding chloroform into this solution, the crystals were generated. Therefore, the membrane structures were possibly constituted of tubular assemblies built

from hydrogen bonds between the hydroxyl groups of the macrocycles, as revealed by X-ray analysis. The hollow spheres retained their shapes and sizes after 3 weeks, which suggested stable self-assembled architectures. In contrast, in the selfD

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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network aggregates were mainly observed other than the plateshaped crystals. Under this condition, solid spheres could not retain their shapes, which displayed the dynamic phenomena of the morphological change and phase transformation (Figure 6b). From these experimental results, the inner structures of spherical aggregates crucially relied on the substituents on the backbone of macrocycles. Stable hollow spheres were generated from 1 through hydrogen bonds between the hydroxyl groups. Meanwhile, macrocycle 3, which bore multiple and polar methoxycarbonylmethyl groups, exhibited the amphiphilic propensity, thus leading to the formation of solid spheres by the solvent effect in a relatively apolar circumstance. It is noteworthy that macrocycles were aligned to give the tubular structures in the crystalline states, which may be partly involved in producing the self-assembled materials. To investigate self-assembly behaviors and crystal structures of the two components,42 we performed the experiments using various guest molecules and adamantane-based macrocycles. Among them, pale-yellow single crystals (3b), which possessed 1:1 host-guest complexation stoichiometry, were generated from a mixture of chloroform and hexane solution of 3 with 1,3,5-trinitrobenzene in a 1:1 ratio.43,44 The macrocyclic framework of 3 in crystal 3b was almost similar to that in crystal 3a, whereas the orientation of substituents was in a different fashion (Figure 7a). Macrocycle 3 was assembled into columnar structures directly along the a axis (Figure 7b), which were fabricated to produce the network structures through CH···O interactions between the substituents. In the void space between macrocycles, 1,3,5-trinitrobenzene was enclathrated to interact with the phenyl ring of the macrocycle through a donor−acceptor interaction, where the centroid− centroid distance and the dihedral angle between the planes of the aromatic rings were 3.54 Å and 9.61°, respectively. It is noteworthy that the guest molecules were located not at the interior but at the exterior of the macrocycle,45,46 because the incorporated functional groups may be partly and preferentially positioned within the cavity of the macrocycles in the crystalline state.

Figure 5. (a) SEM and (b) TEM images obtained from an acetone solution of 1 (0.1 mM) after 3 days. (c) SEM and (d) TEM images obtained from a hexane/chloroform mixture (1:1, v/v) of 3 (0.1 mM) after 3 h.

Figure 6. Schematic representation of the self-assembly of macrocycles (a) 1 and (b) 3.

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assembly behavior of macrocycle 2, SEM images exhibited mainly the generation of the microsized crystalline materials due to their prominent crystal packing, indicating that hydroxyl groups in macrocycle 1 are essential for the formation of hollow spheres. Macrocycle 3 was dissolved in chloroform (0.1 mM) and allowed to stand for 3 d at 25 °C. SEM micrographs displayed no support for the generation of well-defined self-assembled materials and the formation of unordered aggregates. The macrocycle was soluble in chloroform but only slightly soluble in hexane. The addition of hexane into a chloroform solution of 3 (hexane/chloroform = 1:1, v/v, 0.1 mM) gave the crystals after 18 h. The molecular assembly of macrocycle 3 until crystal occurrence was monitored as a function of time by FESEM. SEM images showed globular objects with a diameter of approximately 450 nm after 3 h (Figure 5c). From TEM experiments, the images exhibited a wholly black color, which suggested that the spherical aggregates were solid structures (Figure 5d). With duration, fused assemblies of the spheres, such as fibrous and network aggregates with a width of approximately 500 nm, were confirmed and progressively increased with the decrease of spherical aggregates (Figure S1, Supporting Information). In the early stage after crystal occurrence of 3,

CONCLUSIONS In summary, we have described the synthesis, crystal structures, and molecular assembly of three functionalized adamantane-based macrocycles. All macrocyclic backbones had the similar hexagonal shape and were arranged into tubular structures in the crystalline states. The macrocycles containing the adamantane units were useful building blocks for constructing spherical aggregates. Furthermore, chemical modification of the multiple substituents on the rigid macrocyclic frameworks could tune the inner structures of the spherical architectures. The preparation of adamantanebased macrocycles linked with π-aromatic molecules, with their self-assembly behavior and photophysical properties is currently in progress in our laboratory.47

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EXPERIMENTAL SECTION

General Information. All solvents and reagents were obtained from commercial suppliers and were used without further purification. All air-sensitive reactions were carried out under an argon atmosphere. Melting points were determined by using the ATM-01 device. Elemental analyses were performed with a PerkinElmer 2400 elemental analyzer. IR spectra were recorded with a Jasco FT/IR6300 instrument. 1H and 13C NMR spectra were recorded on a E

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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Figure 7. (a) Molecular structure and (b) network structure of macrocycle 3 and 1,3,5-trinitrobenzene in crystal 3b. Disordered atoms are omitted for clarity. Bruker AV400 spectrometer in CDCl3 and dimethyl sulfoxide (DMSO)-d6 using tetramethylsilane as an internal standard at 298 K. High-resolution mass spectroscopy measurements were carried out using Exactive (Thermo Fisher Scientific) consisting of the Orbitrap analyzer and electrospray ionization (ESI) source. X-ray crystallographic data were acquired using a Bruker SMART APEX II diffractometer with Mo Kα radiation and a Bruker D8 VENTURE diffractometer with Cu Kα radiation. Column chromatography was performed by using Wakogel C-200, and thin-layer chromatography was carried out on 2.0 mm precoated silica gel glass plates (Merck). SEM images were obtained with a Hitachi S-4800 microscope at an accelerating voltage of 1.6 kV. A drop of the solution of 1 or 3 was placed on an aluminum foil and dried in vacuo at room temperature for 12 h. The sample was then coated with Pt/Pd in an ion coater for 40 s. Transmission electron microscopy was performed at 120 kV using a JEOL JEM-2100F microscope. A drop of the solution of 1 or 3

was placed on a carbon-coated copper grid and dried in vacuo at room temperature for 12 h. CAUTION! 1,3,5-Trinitrobenzene is highly explosive and should be handled carefully even in small amounts. Synthesis of 5. A mixture of 1,3-bis(4-hydroxy-3,5dimethoxyphenyl)adamantane (4)37 (0.44 g, 1.0 mmol), 1,4diiodobenzene (2.64 g, 8.0 mmol), CuI (0.38 g, 2.0 mmol), N,Ndimethylglycine (0.21 g, 2.0 mmol), and cesium carbonate (1.30 g, 4.0 mmol) in anhydrous N,N-dimethylformamide (20.0 mL) was stirred at 120 °C for 3 days under an argon atmosphere. After cooling to room temperature, the reaction mixture was suspended with chloroform, which was then washed with water and brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The crude residue was purified by silica gel column chromatography (eluent: chloroform/hexane = 1:1, v/v) and gel permeation chromatography (eluent: chloroform) to afford the title compound (5) as a white solid F

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry (0.60 g, 0.71 mmol) in a yield of 71%. mp 241−242 °C. Fourier transform infrared (FT-IR) (attenuated total reflection (ATR), cm−1): 2899, 2846, 1591, 1478, 1330, 1237, 1130, 998, 819, 754. 1 H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.4 Hz, 4H), 6.68 (s, 4H), 6.64 (d, J = 8.8 Hz, 4H), 3.78 (s, 12H), 2.39 (br s, 2H), 2.06−1.97 (m, 10H), 1.82 (br s, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 158.6, 152.7, 148.6, 138.0, 129.8, 117.3, 102.6, 83.7, 56.3, 49.7, 42.3, 37.8, 35.7, 29.5. HRMS (ESI, m/z) calcd for C38H39I2O6 [M + H]+ 845.0831, found 845.0807. Anal. calcd for C38H38I2O6: C, 54.04; H, 4.54. Found: C, 54.35; H, 4.65. Synthesis of Macrocycle 2. A mixture of 2,2′-bipyridine (125 mg, 0.80 mmol), 1,5-cyclooctadiene (86.5 mg, 0.80 mmol), and bis(1,5cyclooctadiene)nickel(0) (220 mg, 0.80 mmol) in anhydrous and degassed N,N-dimethylformamide (25.0 mL) was stirred at 80 °C for 30 min in the absence of light under an argon atmosphere. A solution of compound 5 (169 mg, 0.20 mmol) in anhydrous and degassed N,N-dimethylformamide (25.0 mL) was added dropwise to the reaction mixture during 1 h, and the resulting mixture was stirred at 80 °C for 1 h and further at room temperature for 2 h. The reaction was stopped by adding aqueous 1 M HCl. Chloroform was added into the crude mixture, which was washed with water and brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The crude residue was purified by silica gel column chromatography (eluent: chloroform) and gel permeation chromatography (eluent: chloroform) to afford the title compound (2) as a white solid (36 mg, 0.03 mmol) in yield of 30%. mp > 300 °C (decomposed). FT-IR (ATR, cm−1): 2899, 2835, 1593, 1490, 1461, 1329, 1238, 1131, 864, 823, 754. 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.8 Hz, 8H), 6.85 (d, J = 8.4 Hz, 8H), 6.69 (s, 8H), 3.80 (s, 24H), 2.44 (br s, 4H), 2.23 (br d, J = 12.0 Hz, 8H), 1.93 (br d, J = 11.2 Hz, 8H), 1.86 (br s, 4H), 1.80 (br s, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ 157.7, 152.9, 148.2, 134.0, 130.3, 127.4, 114.9, 102.8, 56.4, 53.3, 41.5, 37.9, 35.7, 29.5. HRMS (ESI, m/z) calcd for C76H77O12 [M + H]+ 1181.5410, found 1181.5382. Anal. calcd for C76H76O12: C, 77.27; H, 6.48. Found: C, 77.03; H, 6.62. Synthesis of Macrocycle 1. To a solution of 2 (118 mg, 0.10 mmol) in anhydrous dichloromethane (80 mL), a dichloromethane solution of boron tribromide (4.0 mmol) was added at 0 °C under an argon atmosphere and was stirred under an argon atmosphere for 3 h. The reaction mixture was quenched with water and evaporated under reduced pressure. The residue was dissolved in ethyl acetate, and then the solution was washed with water and brine, dried with anhydrous sodium sulfate, and filtered. The filtrate was concentrated to dryness to afford the title compound (1) (96 mg, 0.09 mmol) as a white solid in yield of 90%. mp > 300 °C (decomposed). FT-IR (ATR, cm−1): 2961, 2897, 2846, 1592, 1492, 1328, 1261, 1232, 1103, 1040, 807, 726. 1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 8H), 7.41 (d, J = 8.4 Hz, 8H), 6.76 (d, J = 8.4 Hz, 8H), 6.44 (s, 8H), 2.29 (br s, 4H), 2.01 (br d, J = 10.8 Hz, 8H), 1.75 (br d, J = 11.2 Hz, 8H), 1.68 (br d, J = 11.2 Hz, 8H). 13C{1H} NMR (100 MHz, DMSO-d6) δ 157.4, 150.4, 147.6, 132.9, 127.2, 126.9, 115.0, 104.2, 52.7, 40.9, 36.6, 35.3, 29.0. HRMS (ESI, m/z) calcd for C68H61O12 [M + H]+ 1069.4158, found 1069.4138. Synthesis of Macrocycle 3. To a mixture of 1 (53.5 mg, 0.05 mmol) and potassium carbonate (111 mg, 0.80 mmol) in anhydrous N,N-dimethylformamide (20.0 mL), methyl bromoacetate (184 mg, 1.20 mmol) was added at room temperature and stirred under an argon atmosphere for 1 week. The reaction mixture was quenched with water and evaporated under reduced pressure. The resultant residue was suspended in chloroform, which was then washed with water and brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The crude residue was subjected to silica gel column chromatography (eluent: chloroform) and gel permeation chromatography (eluent: chloroform) to afford the title compound (3) (51 mg, 0.031 mmol) as a white solid in yield of 62%. mp > 300 °C (decomposed). FT-IR (ATR, cm−1): 2898, 2839, 1758, 1593, 1491, 1330, 1238, 1210, 1131, 1031, 822, 809, 724. 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.8 Hz, 8H), 6.89 (d, J = 8.8 Hz, 8H), 6.72 (s, 8H), 4.63 (s, 16H), 3.69 (s, 24H), 2.38 (br s, 4H), 2.08 (br d, J = 11.6 Hz, 8H), 1.85 (br d, J = 11.2 Hz, 8H), 1.74 (br s, 8H). 13C{1H} NMR

(100 MHz, CDCl3) δ 169.3, 157.4, 151.5, 148.1, 134.3, 132.4, 127.4, 115.3, 107.5, 67.2, 52.5, 52.1, 41.2, 37.5, 35.5, 29.3. HRMS (ESI, m/ z) calcd for C92H92O28Cl [M + Cl]− 1679.5469, found 1679.5478. Anal. calcd for C92H92O28: C, 67.14; H, 5.63. Found: C, 66.79; H, 5.68. X-ray Crystallography. X-ray data for crystal 2a were collected on a diffractometer equipped with a charge-coupled device detector (Bruker SMART APEX II) with monochromated Mo Kα (λ = 0.71073 Å) radiation. X-ray data for crystals 1a, 3a, and 3b were collected on a diffractometer equipped with a complementary metal oxide semiconductor detector (Bruker D8 VENTURE PHOTON 100) with monochromated Cu Kα (λ = 1.54178 Å) radiation. Data collection was carried out at 100 K using the Japan Thermal Engineering Co., Ltd. Cryostat system equipped with a liquid nitrogen generator. Structure solution and refinement were performed by using SHELXS97, SHELXT-2014/5, SHELXT-2018/2, SHELXL97, and SHELXL-2018/3.48−50 Crystallographic Data for 1a. C74H76O16, Mr = 1221.34; monoclinic, space group P21/c, Z = 2, Dcalc = 1.149 g cm−3, a = 20.2602(9), b = 18.4745(10), c = 9.7083(5) Å, β = 103.791(4)°, V = 3529.0(3) Å3, 25510 measured and 3161 independent [I > 2σ(I)] reflections, 469 parameters, final R1 = 0.0708, wR2 = 0.1835, S = 1.021 [I > 2σ(I)]. CCDC 1414082. Crystallographic Data for 2a. C82H82Cl18O12, Mr = 1897.58; triclinic, space group P1̅, Z = 1, Dcalc = 1.477 g cm−3, a = 10.7288(19), b = 13.240(2), c = 16.153(3) Å, α = 69.581(2), β = 85.990(2), γ = 83.114(2)°, V = 2133.9(7) Å3, 20346 measured and 6397 independent [I > 2σ(I)] reflections, 509 parameters, final R1 = 0.0943, wR2 = 0.2877, S = 1.059 [I > 2σ(I)]. CCDC 1414083. Crystallographic Data for 3a. C92H92O28, Mr = 1645.65; triclinic, space group P1̅, Z = 1, Dcalc = 1.334 g cm−3, a = 10.6042(3), b = 12.9313(4), c = 16.1150(6) Å, α = 111.1780(19), β = 90.073(3), γ = 95.912(2)°, V = 2047.82(12) Å3, 16888 measured and 3707 independent [I > 2σ(I)] reflections, 545 parameters, final R1 = 0.0823, wR2 = 0.2370, S = 1.053 [I > 2σ(I)]. CCDC 1414084. Crystallographic Data for 3b. C98H95N3O34, Mr = 1858.76; triclinic, space group P1̅, Z = 2, Dcalc = 1.359 g cm−3, a = 9.8426(4), b = 20.6842(7), c = 24.5207(9) Å, α = 113.198(2), β = 97.551(2), γ = 90.007(2)°, V = 4541.3(3) Å3, 61337 measured and 12665 independent [I > 2σ(I)] reflections, 1344 parameters, 8 restraints, final R1 = 0.0847, wR2 = 0.2389, S = 1.039 [I > 2σ(I)]. CCDC 1887418.

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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.joc.9b00069. NMR spectra, SEM images, and crystal data (PDF) X-ray crystallographic files of 1a (CIF) X-ray crystallographic files of 2a (CIF) X-ray crystallographic files of 3a (CIF) X-ray crystallographic files of 3b (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (M.T.). *E-mail: [email protected] (K.Y.). ORCID

Masahide Tominaga: 0000-0003-3199-1882 Masatoshi Kawahata: 0000-0003-2865-4113 Kosuke Katagiri: 0000-0002-3871-619X Kentaro Yamaguchi: 0000-0002-2629-716X Present Address ∥

Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan (M.K.).

G

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry Notes

(20) Li, C. Pillararene-Based Supramolecular Polymers: from Molecular Recognition to Polymeric Aggregates. Chem. Commun. 2014, 50, 12420−12433. (21) Han, C.; Ma, F.; Zhang, Z.; Xia, B.; Yu, Y.; Huang, F. DIBPillar[n]arenes (n = 5, 6): Syntheses, X-ray Crystal Structures, and Complexation with n-Octyltriethyl Ammonium Hexafluorophosphate. Org. Lett. 2010, 12, 4360−4363. (22) Li, C.; Shu, X.; Li, J.; Chen, S.; Han, K.; Xu, M.; Hu, B.; Yu, Y.; Jia, X. Complexation of 1,4-Bis(pyridinium)butanes by Negatively Charged Carboxylatopillar[5]arene. J. Org. Chem. 2011, 76, 8458− 8465. (23) Ma, Y.; Chi, X.; Yan, X.; Liu, J.; Yao, Y.; Chen, W.; Huang, F.; Hou, J.-L. per-Hydroxylated Pillar[6]arene: Synthesis, X-ray Crystal Structure, and Host−Guest Complexation. Org. Lett. 2012, 14, 1532− 1535. (24) Li, C.; Shu, X.; Li, J.; Fan, J.; Chen, Z.; Weng, L.; Jia, X. Selective and Effective Binding of Pillar[5,6]arenes toward Secondary Ammonium Salts with a Weakly Coordinating Counteranion. Org. Lett. 2012, 14, 4126−4129. (25) Hu, X.-B.; Chen, Z.; Chen, L.; Zhang, L.; Hou, J.-L.; Li, Z.-T. Pillar[n]arenes (n = 8−10) with Two Cavities: Synthesis, Structures and Complexing Properties. Chem. Commun. 2012, 48, 10999−11001. (26) Song, N.; Chen, D.-X.; Qiu, Y.-C.; Yang, X.-Y.; Xu, B.; Tian, W.; Yang, Y.-W. Stimuli-Responsive Blue Fluorescent Supramolecular Polymers Based on a Pillar[5]arene Tetramer. Chem. Commun. 2014, 50, 8231−8234. (27) Zhang, Z.; Luo, Y.; Chen, J.; Dong, S.; Yu, Y.; Ma, Z.; Huang, F. Formation of Linear Supramolecular Polymers That Is Driven by C− H···π Interactions in Solution and in the Solid State. Angew. Chem., Int. Ed. 2011, 50, 1397−1401. (28) Yao, Y.; Xue, M.; Chen, J.; Zhang, M.; Huang, F. An Amphiphilic Pillar[5]arene: Synthesis, Controllable Self-Assembly in Water, and Application in Calcein Release and TNT Adsorption. J. Am. Chem. Soc. 2012, 134, 15712−15715. (29) Yu, G.; Ma, Y.; Han, C.; Yao, Y.; Tang, G.; Mao, Z.; Gao, C.; Huang, F. A Sugar-Functionalized Amphiphilic Pillar[5]arene: Synthesis, Self-Assembly in Water, and Application in Bacterial Cell Agglutination. J. Am. Chem. Soc. 2013, 135, 10310−10313. (30) Lim, Y.-b.; Moon, K.-S.; Lee, M. Recent Advances in Functional Supramolecular Nanostructures Assembled from Bioactive Building Blocks. Chem. Soc. Rev. 2009, 38, 925−934. (31) Liu, T. Hydrophilic Macroionic Solutions: What Happens When Soluble Ions Reach the Size of Nanometer Scale? Langmuir 2010, 26, 9202−9213. (32) Zhang, X.; Wang, C. Supramolecular Amphiphiles. Chem. Soc. Rev. 2011, 40, 94−101. (33) Lee, M.; Lee, S.-J.; Jiang, L.-H. Stimuli-Responsive Supramolecular Nanocapsules from Amphiphilic Calixarene Assembly. J. Am. Chem. Soc. 2004, 126, 12724−12725. (34) Tominaga, M.; Kunitomi, N.; Katagiri, K.; Itoh, T. Adamantane-Based Oxacyclophanes Containing Pyrazines: Synthesis, Crystal Structure, and Self-Assembly Behavior. Org. Lett. 2015, 17, 786−789. (35) Tominaga, M.; Noda, A.; Ohara, K.; Yamaguchi, K.; Itoh, T. Synthesis, Hollow Spherical Aggregation, and Crystallization of an Adamantane-derived Azacyclophane Containing Triazine Rings. Chem. Lett. 2016, 45, 773−775. (36) Tominaga, M.; Takahashi, E.; Ukai, H.; Ohara, K.; Itoh, T.; Yamaguchi, K. Solvent-Dependent Self-Assembly and Crystal Structures of a Salen-Based Macrocycle. Org. Lett. 2017, 19, 1508− 1511. (37) Tominaga, M.; Katagiri, K.; Azumaya, I. Pseudopolymorph and Charge-Transfer Co-Crystal of Disubstituted Adamantane containing Dimethoxyphenol Moieties. Cryst. Growth Des. 2009, 9, 3692−3696. (38) Arnaud-Neu, F.; Collins, E. M.; Deasy, M.; Ferguson, G.; Harris, S. J.; Kaitner, B.; Lough, A. J.; McKervey, M. A.; Marques, E.; Ruhl, B. L.; Schwing-Weill, M. J.; Seward, E. M. Synthesis, X-ray Crystal Structures, and Cation-Binding Properties of Alkyl Calixaryl

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by JSPS KAKENHI Grant Number JP16K05801. HRMS was performed at the Center for Analytical Instrumentation, Chiba University.

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REFERENCES

(1) Ravoo, B. J.; Darcy, R. Cyclodextrin Bilayer Vesicles. Angew. Chem., Int. Ed. 2000, 39, 4324−4326. (2) Jeon, Y. J.; Bharadwaj, P. K.; Choi, S. W.; Lee, J. W.; Kim, K. Supramolecular Amphiphiles: Spontaneous Formation of Vesicles Triggered by Formation of a Charge-Transfer Complex in a Host. Angew. Chem., Int. Ed. 2002, 41, 4474−4476. (3) Seo, S. H.; Chang, J. Y.; Tew, G. N. Self-Assembled Vesicles from an Amphiphilic ortho-Phenylene Ethynylene Macrocycle. Angew. Chem., Int. Ed. 2006, 45, 7526−7530. (4) Yang, W.-Y.; Lee, E.; Lee, M. Tubular Organization with Coiled Ribbon from Amphiphilic Rigid-Flexible Macrocycle. J. Am. Chem. Soc. 2006, 128, 3484−3485. (5) Kim, J.-K.; Lee, E.; Kim, M.-C.; Sim, E.; Lee, M. Reversible Transformation of Helical Coils and Straight Rods in Cylindrical Assembly of Elliptical Macrocycles. J. Am. Chem. Soc. 2009, 131, 17768−17770. (6) Yang, W.-Y.; Ahn, J.-H.; Yoo, Y.-S.; Oh, N.-K.; Lee, M. Supramolecular Barrels from Amphiphilic Rigid−Flexible Macrocycles. Nat. Mater. 2005, 4, 399−402. (7) Kim, Y.; Shin, S.; Kim, T.; Lee, D.; Seok, C.; Lee, M. Switchable Nanoporous Sheets by the Aqueous Self-Assembly of Aromatic Macrobicycles. Angew. Chem., Int. Ed. 2013, 52, 6426−6429. (8) Atwood, J. L.; Barbour, L. J.; Jerga, A. Storage of Methane and Freon by Interstitial van der Waals Confinement. Science 2002, 296, 2367−2369. (9) Dalgarno, S. J.; Thallapally, P. K.; Barbour, L. J.; Atwood, J. L. Engineering Void Space in Organic van der Waals Crystals: Calixarenes Lead the Way. Chem. Soc. Rev. 2007, 36, 236−245. (10) Atwood, J. L.; Barbour, L. J.; Ness, T. J.; Raston, C. L.; Raston, P. L. A Well-Resolved Ice-like (H2O)8 Cluster in an Organic Supramolecular Complex. J. Am. Chem. Soc. 2001, 123, 7192−7193. (11) Hof, F.; Craig, S. L.; Nuckolls, C.; Rebek, J., Jr. Molecular Encapsulation. Angew. Chem., Int. Ed. 2002, 41, 1488−1508. (12) Dalgarno, S. J.; Cave, G. W. V.; Atwood, J. L. Toward the Isolation of Functional Organic Nanotubes. Angew. Chem., Int. Ed. 2006, 45, 570−574. (13) Gerkensmeier, T.; Iwanek, W.; Agena, C.; Fröhlich, R.; Kotila, S.; Näther, C.; Mattay, J. Self-Assembly of 2,8,14,20-Tetraisobutyl5,11,17,23-tetrahydroxyresorc[4]arene. Eur. J. Org. Chem. 1999, 2257−2262. (14) Cave, G. W. V.; Antesberger, J.; Barbour, L. J.; McKinlay, R. M.; Atwood, J. L. Inner Core Structure Responds to Communication between Nanocapsule Walls. Angew. Chem., Int. Ed. 2004, 43, 5263− 5266. (15) Dalgarno, S. J.; Tucker, S. A.; Bassil, D. B.; Atwood, J. L. Fluorescent Guest Molecules Report Ordered Inner Phase of Host Capsules in Solution. Science 2005, 309, 2037−2039. (16) Ogoshi, T.; Kanai, S.; Fujinami, S.; Yamagishi, T.; Nakamoto, Y. para-Bridged Symmetrical Pillar[5]arenes: Their Lewis Acid Catalyzed Synthesis and Host−Guest Property. J. Am. Chem. Soc. 2008, 130, 5022−5023. (17) Xue, M.; Yang, Y.; Chi, X.; Zhang, Z.; Huang, F. Pillararenes, A New Class of Macrocycles for Supramolecular Chemistry. Acc. Chem. Res. 2012, 45, 1294−1308. (18) Strutt, N. L.; Zhang, H.; Schneebeli, S. T.; Stoddart, J. F. Functionalizing Pillar[n]arenes. Acc. Chem. Res. 2014, 47, 2631−2642. (19) Ogoshi, T.; Yamagishi, T. Pillar[5]- and Pillar[6]arene-Based Supramolecular Assemblies Built by Using Their Cavity-Size-Dependent Host−Guest Interactions. Chem. Commun. 2014, 50, 4776−4787. H

DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Esters and Ketones, a New Family of Macrocyclic Molecular Receptors. J. Am. Chem. Soc. 1989, 111, 8681−8691. (39) Yu, G.; Xue, M.; Zhang, Z.; Li, J.; Han, C.; Huang, F. A WaterSoluble Pillar[6]arene: Synthesis, Host−Guest Chemistry, and Its Application in Dispersion of Multiwalled Carbon Nanotubes in Water. J. Am. Chem. Soc. 2012, 134, 13248−13251. (40) Tanaka, Y.; Miyachi, M.; Kokube, Y. Selective Vesicle Formation from Calixarenes by Self-Assembly. Angew. Chem., Int. Ed. 1999, 38, 504−506. (41) Yang, M.; Wang, W.; Yuan, F.; Zhang, X.; Li, J.; Liang, F.; He, B.; Minch, B.; Wegner, G. Soft Vesicles Formed by Diblock Codendrimers of Poly(benzyl ether) and Poly(methallyl dichloride). J. Am. Chem. Soc. 2005, 127, 15107−15111. (42) Tominaga, M.; Kawahata, M.; Itoh, T.; Yamaguchi, K. Spherical Aggregates and Crystal Structure of Naphthalenediimide-Based Macrocycle and Complexation with Perylene. Cryst. Growth Des. 2018, 18, 37−41. (43) Das, A.; Ghosh, S. Supramolecular Assemblies by ChargeTransfer Interactions between Donor and Acceptor Chromophores. Angew. Chem., Int. Ed. 2014, 53, 2038−2054. (44) Shanmugaraju, S.; Mukherjee, P. S. π-Electron Rich Small Molecule Sensors for the Recognition of Nitroaromatics. Chem. Commun. 2015, 51, 16014−16032. (45) Wang, S.; Wang, Y.; Chen, Z.; Lin, Y.; Weng, L.; Han, K.; Li, J.; Jia, X.; Li, C. The Marriage of Endo-Cavity and Exo-Wall Complexation Provides a Facile Strategy for Supramolecular Polymerization. Chem. Commun. 2015, 51, 3434−3437. (46) Gong, H.-Y.; Rambo, B. M.; Lynch, V. M.; Keller, K. M.; Sessler, J. L. “Texas-Sized” Molecular Boxes: Building Blocks for the Construction of Anion-Induced Supramolecular Species via SelfAssembly. J. Am. Chem. Soc. 2013, 135, 6330−6337. (47) Liu, H.-B.; Zhang, Q.; Wang, M.-X. Synthesis, Structure, and Anion Binding Properties of Electron-Deficient Tetrahomocorona[4]arenes: Shape Selectivity in Anion−π Interactions. Angew. Chem., Int. Ed. 2018, 57, 6536−6540. (48) Sheldrick, G. M. A Short History of SHELX. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112−122. (49) Sheldrick, G. M. SHELXTIntegrated Space-Group and Crystal-Structure Determination. Acta Crystallogr., Sect. A: Found. Adv. 2015, 71, 3−8. (50) Sheldrick, G. M. Crystal Structure Refinement with SHELXL. Acta Crystallogr., Sect. C: Struct. Chem. 2015, 71, 3−8.

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DOI: 10.1021/acs.joc.9b00069 J. Org. Chem. XXXX, XXX, XXX−XXX