Pillar[5]arene derivatives with three different kinds of repeating units: first examples, crystal structures and selective preparation

Abstract

Based on a new strategy of selective modification, pillar[5]arenes incorporating three different kinds of repeating units were first synthesized.

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In host–guest chemistry, synthesis and functionalization of macrocyclic hosts, such as crown ethers,¹ cyclodextrins,² calixarenes,³ and cucurbitirils,⁴ is a fundamental and challenging topic. Pillararenes,⁵ as a new class of macrocycles, whose repeating units are connected by methylene bridges at the para- position, have received much attention in recent years. Great efforts have been devoted to decorating pillar[5]arenes with different functional groups, which provide their potential applications in the fabrication of (pseudo)rotaxanes,⁶ supramolecular polymers,⁷ vesicles,⁸ transmembrane proton channels,⁹ gold nanoparticles,¹⁰ and other functional materials.¹¹ To the best of our knowledge, all the modification of pillar[5]arenes so far endow their derivatives with one kind of repeating units or two different kinds of repeating units. Pillar[5]arenes with three or more different kinds of repeating units, however, have never been explored, although such derivatives may largely facilitate and expand their host–guest complexation and self-assembly property.

In our recent research, a new method for the synthesis of pillar[5]arenes with two different kinds of repeating units was reported via a partial oxidation/reduction strategy.¹² Based on this procedure, a series of 1,4-dimethoxypillar[m]arene[n]quinines (DMP[m]A[n]Q) and 1,4-dimethoxypillar[m]arene[n]hydroquinones (DMP[m]A[n]HQ) were designed and synthesized in moderate yields. The reported procedure provides a useful method for position-selective modification of pillar[5]arenes.

In the present study, we show that for DMP[3]A[2]HQ 1, if appropriate substituents are used to functionalize the hydroquinone units, the other three dimethoxybenzene units can be further partially oxidized, which provides an opportunity to obtain pillar[5]arenes with three different kinds of repeating units. For this purpose, methoxycarbonyl-methoxy groups were chosen due to the active function of carboxyl units. First, we investigated the oxidative resistance of 1,4-methoxycarbonylmethoxybenzene and 1,4-dimethoxybenzene. When the methoxycarbonyl-methoxy-substituted pillar[5]arene 2 (Scheme 1) was oxidized under the same oxidizing condition as 1,4-dimethoxypillar[5]arene (DMP[5]) by using (NH₄)₂[Ce(NO₃)₆] in a molar ratio of 1 : 1.5 at 20 °C, almost no reaction took place. Even with a molar ratio equal to 1 : 5 at 30 °C, a large amount of 2 remained unchanged, suggesting that 1,4-methoxycarbonylmethoxybenzene units exhibit enhanced oxidative resistance (harder to be oxidized to benzoquinone) compared with 1,4-dimethoxybenzene. Based on this finding, pillar[5]arene 3 with four methoxycarbonyl-methoxy groups was prepared, and the following partial oxidation of 3 allowed for the formation of pillar[5]arene derivatives 4–6. Further reduction of 4 could lead to pillar[5]arene 7. In the pillar structures of 4, 5 and 7, three different kinds of repeating units are present: 1,4-dimethoxybenzene units, benzoquinone or hydrobenzoquinone units, and 1,4-dimethoxycarbonylmethoxybenzene units. This is the first time to obtain pillararene derivatives with three different kinds of repeating units. The subsequent modification of benzoquinone, hydrobenzoquinone and 1,4-dimethoxycarbonylmethoxybenzene units may expand such type of pillar[5]arenes.

Scheme 1 Chemical structures of compounds used in this study.

Pillar[5]arene 3 was synthesized by etherification of DMP[3]A[2]HQ 1^12b with methyl chloroacetate. Subsequent oxidation of 3 by using (NH₄)₂[Ce(NO₃)₆] afforded products 4–6. In these reactions, oxidation of the 1,4-dimethoxybenzene units of 3 to benzoquinone occurred, while the 1,4-dimethoxycarbonylmethoxybenzene units were hardly affected. The synthetic route and main products are outlined in Scheme 2 and Table 1. Different molar ratios of 3 to (NH₄)₂[Ce(NO₃)₆] gave different oxidation compounds. Upon addition of 2 equiv. of (NH₄)₂[Ce(NO₃)₆] to 1 equiv. of 3, one main product was isolated by column chromatography in 44% yield (Table 1, entry 1). ESI-MS analysis showed a peak at m/z 975.3, corresponding to [M + Na]⁺ for compound 4 with one dimethoxybenzene unit oxidized. The ¹H NMR spectrum in CDCl₃ indicated an unsymmetrical structure of this product (Fig. S4†), which suggested that this compound had the benzoquinone unit arranged between one 1,4-dimethoxybenzene unit and one 1,4-dimethoxycarbonylmethoxybenzene unit. The isomer of 4 with the benzoquinone unit arranged between two dimethoxycarbonylmethoxybenzene units (4′, Scheme 3) was isolated in trace amounts, which indicated regioselectivity of the oxidation reaction. When the molar ratio of 3 to (NH₄)₂[Ce(NO₃)₆] was 1 : 3, the yield of compound 4 was decreased to 32%, while product 5 was obtained in 22% yield. This compound comprises two benzoquinone units replacing two dimethoxybenzene units of 3, and its structure and was confirmed by ¹H NMR and ¹³C NMR spectra as well as ESI-MS analysis. 5′, another isomer of 5, with two benzoquinone units adjacent to each other (Scheme 3) was quite a few through the silica gel column, which was consistent with our earlier study.^12b In order to synthesize 6 containing three benzoquinone units, 4 or 6 equiv. of (NH₄)₂[Ce(NO₃)₆] were used, and compound 6 was isolated in yield of 37% or 43%, respectively. Furthermore, temperature was also an important factor for controlling the products. For example, in an almost equal molar ratio of 3/(NH₄)₂[Ce(NO₃)₆] (about 1 : 6), the main product was 5 (Yield = 38%) at 20 °C, but 6 (Yield = 43%) at 30 °C (Table 1, Scheme S3 and S4†). Compounds 5 and 6 were obtained as red solids but 4 as a yellow red solid. According to the TLC analysis, the order of their polarity is 4 < 5 < 6, with melting points of 81.4 °C, 176.3 °C, and 118.2 °C, respectively. These novel pillararene derivatives are soluble in a wide range of organic solvents, such as dichloromethane, chloroform, tetrahydrofuran, dimethylformamide, acetone, acetonitrile, and dimethylsulfoxide. In order to validate the possibility of further functionalization, compound 4 was reduced by using Na₂S₂O₄ as a reductant. Pillar[5]arene 7 was successfully obtained, which was confirmed by NMR, ESI-MS and single crystal diffraction analysis (Fig. S13–S16†).

Scheme 2 Synthesis of 4–6 from pillar[5]arene 3.

Table 1 Yields of main products for different molar ratio of 3 to (NH₄)₂[Ce(NO₃)₆] at 30 °C

Molar ratio (3/(NH4)2[Ce(NO3)6])	Yields of main products
1 : 2	4 (44%)
1 : 3	4 (32%), 5 (22%)
1 : 4	6 (37%)
1 : 6	6 (43%)

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Scheme 3 Chemical structures of 4′ (another isomer of 4) and 5′ (another isomer of 5).

Single crystals of 3 were obtained by slow evaporation of a dichloromethane–isopropyl ether mixture (1 : 1, v/v) at room temperature (Fig. 1). The compound 3 has crystallographically imposed twofold symmetry. The X-ray crystal structure of 3 confirmed the successful synthesis of this methoxycarbonylmethoxy-substituted pillar[5]arene. Furthermore, single crystals of 4–6 grew under the same condition as that used for 3 (Fig. 2). It was found that the pillar structure still remained after oxidation, which was particularly important for further functionalization. On the other hand, it was very difficult to confirm the chemical structure of 4 or 5 based on NMR spectra and ESI-MS analysis as it had another isomer (4′ or 5′). Fortunately, the precise conformations of 4 and 5 were further confirmed by single crystal X-ray analysis in accordance with ¹H NMR experiments.

Fig. 1 Ball-and-stick views of the crystal structure of 3. Solvent molecules are omitted for clarity. C, black; H, white; O, red.

Fig. 2 Ball-and-stick views of the crystal structures of 4 (a and b), 5 (c and d) and 6 (e and f). Solvent molecules are omitted for clarity. C, black; H, white; O, red.

Furthermore, we studied the cavity properties of 4–6. There is one dichloromethane molecule in the cavity of 4 and 5 (Fig. 3a and b). Interestingly, there exist two C–H⋯π interactions between dichloromethane and 4 with C–H⋯π plane distances of 2.83 Å and 2.85 Å, and between dichloromethane and 5 with C–H⋯π plane distances of 2.69 Å and 2.73 Å. The crystal structure of 6 (Fig. 3c) features two dichloromethane molecules located outside of the cavity.

Fig. 3 Capped-stick views of the crystal structures of 4 (a), 5 (b), and 6 (c). C, black; H, white; O, red; Cl, green; N, blue. The yellow dotted lines denote C–H⋯π interactions.

Self-assembly of the macrocycles 4–6 in the solid state was also studied. The methoxycarbonyl groups, benzoquinone units, and the methoxy groups are able to act as hydrogen bonding donors and acceptors and cause the molecules to self-assemble. From the crystal packing of 4 and 5, it can be seen that pillar host molecules stack on top of each other to form a tubular assembly in the solid state (Fig. 4a and b). The tubes further arranged honeycomb-like in rows. The packing in the crystal structure of 6 showed two overlapping tubes (Fig. 4c).

Fig. 4 Tubular assemblies of 4 (a), 5 (b), and 6 (c). For clarity, one tubular assembly is depicted in purple and the other in green.

In summary, partial oxidation of pillar[5]arene 3 substituted with methoxycarbonylmethoxy and methoxy groups was carried out under mild conditions. The reactions were functional group-selective, leading to partially oxidized dimethoxybenzene units and unaffected dimethoxycarbonylmethoxybenzene units. The distribution of reaction products 4–6 containing one, two or three benzoquinone units depends on the molar ratio of 3 to (NH₄)₂[Ce(NO₃)₆]. Compounds 4 and 5 comprise three different kinds of repeating units in the macrocyclic structure. They represent a new type of pillar[5]arene derivatives. With the same thought, if the methoxycarbonylmethoxy group of 3 was changed to other functional groups, such as alkyl bromide, propargyl or allyl groups, did the selective modification still work out? This attempt will help to find out a law for functional groups-selectivity. Further functionalization of such compounds, e.g., reduction of benzoquinone units (to afford compound 7), etherification of hydroquinone units, or hydrolysis of methoxycarbonyl groups to active carboxyl groups, will provide a wide platform for their potential applications in host–guest chemistry, self-assembly, biosensors, drug delivery and so on.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (31002701).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Synthetic procedures, characterizations. CCDC reference numbers 950515–950518 and 953388. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3ra44581j

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