Azacalix[2]arene[2]carbazoles: synthesis, structure and properties

Abstract

A new type of –NH– bridged azacalix[2]arene[2]carbazoles has been synthesized by aromatic nucleophilic substitution reaction via one pot and/or fragment coupling strategy. Both symmetric and unsymmetric macrocycles are obtained. X-ray single crystal analysis reveals 1,3-alternation conformation of the macrocycle. The spectroscopic and electrochemical properties of the macrocycles are also explored.

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Though recorded in the literature as early as the 1960s,¹ azacalixarenes,² in which the –CH₂– bridging groups in classic calixarenes³ are replaced by –NH– (or –NR–) groups, remained quiet until the turn of the century. The pioneering and intensive work by the groups of Ito,⁴ Wang,⁵ Tsue,⁶ Yamamoto,⁷ and Rajca⁸ et al. have woken up the field. Their strategy for synthesis of the macrocycle skeletons was based on metal-catalyzed aryl amination reaction between halogen substituted benzene and amino (or N-substituted amino) substituted benzene via fragment coupling strategy. Almost at the same time, a high efficient fragment coupling strategy based on nucleophilic substitution reaction (S_NAr) was reported from Wang's group for the synthesis of oxygen and/or nitrogen bridged calix[2]arene[2]triazines,⁹ followed by Katz's one-pot strategy for the construction of macrocycle skeletons of oxacalixarenes.¹⁰ Subsequent work by Seri,¹¹ Katz,¹² Chen,¹³ Wen,¹⁴ and Konishi¹⁵ demonstrated that this powerful method could also light up the field of azacalixarenes. Metal catalyst does not need for this method. High dilute conditions, which are usually necessary for macrocycle synthesis, are not needed either. The reaction conditions are much milder and the yields are greatly improved. Various nucleophilic and electrophilic components can be conveniently incorporated. The breakthrough in synthesis opens new applications for this type of fascinating macrocycles.

Usually there are two ways of expanding the cavity of the azacalixarenes. First one is to incorporate more benzene rings into the skeleton, i.e., to synthesize azacalix[n]arenes (n > 4). But with the increase of n, the construction efficiency of macrocycle drops dramatically. Usually azacalix[4]arene is the most abundant product. Furthermore, the conformational flexibility of large macrocycles (n > 4) leads to collapse or twist of the cavity, which greatly limits the range of applications of the macrocycles. The other way is to adapt rigid or semirigid poly-aromatic rings as components to expand the cavity. For example, iptycene,¹⁶ tetraphenylethylene,¹⁷ 1,8-naphthyridine,¹⁸ diphenyl-adamantane,¹⁹ terphenylene,²⁰ naphthalene,²¹ BINOL,²² diphenylketone,²³ adamantane,²⁴ etc. have been used for expanding the cavity of oxacalixarene family. However, to the best of our knowledge, there are few examples of this strategy for the azacalixarene family.^13,14

Carbazole molecules are quite interesting due to their unique photophysical and redox properties: they exhibit relatively intense luminescence and undergo reversible oxidation processes which make them suitable as hole carriers. Thus carbazole-based materials have gained great attention in chemical and materials community for applications in organic light emitting diodes (OLEDs), photovoltaic cells, and field effect transistors.²⁵

Based on the powerful method developed by Wang⁹ and Katz¹⁰ et al., here we use 3,6-diaminocarbazole derivatives as nucleophilic components and 1,5-difluoro-2,4-dinitrobenzene as electrophilic component to construct a new type of azacalix[2]arene[2]carbazoles. On the one hand, incorporation of the rigid carbazolyls into the macrocycle skeleton will expand the noncollapsable cavity; one the other hand, the carbazolyls will endow the macrocycle with novel spectroscopic and/or electrochemical properties, which will expand the range of applications of this fascinating macrocycle. Both one-pot and fragment coupling methods were used for the synthesis of symmetric and unsymmetric macrocycles respectively.

Symmetrically substituted macrocycle 1–3 could be easily achieved by a one-pot approach as described in Scheme 1. 3,6-Diamino-9-isobutylcarbazole 5 was reacted with 1,5-difluoro-2,4-dinitrobenzene 8 via the nucleophilic aromatic substitution (S_NAr) reaction in the presence of triethylamine under refluxing in THF solution. After cooling to room temperature the macrocyclic product 1 precipitated from the solution and the pure product was isolated by filtration with 78% yield. Similarly, the macrocycle 2 modified with more soluble N-(2-ethylhexyl) substituents of 3,6-diaminocarbazole could also be synthesized in 35% yield. However, under the same condition, compound 3 containing 4-(9H-carbazol-9-yl)butyl groups could not be afforded until DMSO was used as the solvent and K₂CO₃ as the base after being heated at 100 °C with a yield of 48%. It is easily found that the yields of 2 and 3 were relative lower compared with that of 1. That may be resulted from different solubility of compound 1 and compounds 2 and 3. Precipitation of less soluble macrocycle product 1 from the reaction mixture greatly shifted the reaction equilibrium to the product; while remaining of the more soluble products of 2 and 3 in the reaction mixture hindered the reaction.

Scheme 1 One-pot syntheses of symmetric macrocycles 1, 2 and 3.

Besides one pot approach as described above, the “3 + 1” fragment coupling approach⁹ was also used to prepare this type of macrocycles (Scheme 2). One pot method shows high efficiency on the macrocycle skeleton construction, but it lacks variability and only symmetric macrocycles can be obtained. Though more synthetic steps are needed for the fragment coupling approach, different functional groups can be introduced into the macrocycle skeleton via this method. For example, the unsymmetrically substituted macrocycle 4 can be obtained via the following two routes. One route started with reaction of one equivalent of 9-(4-(9H-carbazol-9-yl)butyl)-9H-3,6-diamino-carbazole 7 with two equivalents of 1,5-difluoro-2,4-dinitrobenzene 8 in THF and Et₃N under reflux to afford the “2 + 1” fragment 9 in 93% yield. Compound 9 then reacted with N-(2-ethylhexyl) derived 3,6-diaminocarbaozle 6 to give the unsymmetrically substituted macrocycle 4 in 61% yield. A total yield of 57% was achieved via this route. In another route the N-(2-ethylhexyl) substituted carbazole unit was first incorporated into the “2 + 1” fragment 10 via reaction of one equivalent of N-(2-ethylhexyl)-3,6-diaminocarbazole 7 and two equivalents of 1,5-difluoro-2,4-dinitrobenzene 8 under similar conditions as for fragment 9 with a yield of 91%. The cyclization step finished with reaction of fragment 10 and 9-(4-(9H-carbazol-9-yl)butyl)-9H-3,6-diamino-carbazole 7 with a yield of 62%. Both routes showed similar efficiency (total yield over two steps of 57% vs. 56%). The symmetric macrocycle 3 could also be obtained via the fragment coupling strategy. Further reaction of the “2 + 1” fragment 9 with N-carbazolyl derived 3,6-diaminocarbazole 7 in a 1 : 1 molar ratio in DMSO with K₂CO₃ as base at 100 °C gave the macrocycle 3 in 45% yield. As we can see that both one pot route and fragment coupling route show similar efficiency for the synthesis of 3.

Scheme 2 Synthesis of symmetric 3 and unsymmetric 4 via [3 + 1] fragment coupling strategy.

Minimum amount of solvents (soluble for all the reagents except K₂CO₃) were used for all the cyclization steps. Variation of volume of solvents did not affect the cyclization efficiency substantially. High dilute conditions are not needed. The chemical structures for all the macrocycles have been confirmed by NMR and HRMS.

Fortunately, we obtained a single crystal of 2 suitable for X-ray analysis²⁶ by slow evaporation of a dichloromethane/acetonitrile mixture (3 : 1, v/v) at room temperature (Fig. 1). Similar to most oxa- and azacalixarenes, azacalix[2]arene[2]carbazole 2 has a 1,3-alternate conformation.²⁷ The two carbazole rings are almost parallel to each other with a dihedral angle of 19.8° between the two ring planes and a N–N distance of 5.70 Å. While the two benzene rings are almost perpendicular to each other with a dihedral angle of 75.9°. The two benzene rings are isolated with the upper rim distance of 12.8 Å (between two H^bs). This arrangement of conformation puts the interior protons (H^a) just above the carbazole ring planes, the anisotropic shielding zones. This might account for the relatively high field chemical shifts of H^a (5.39 ppm for 1 and 5.41 ppm for 2 in CDCl₃, 4.81 ppm for 3 and 4.94 ppm for 4 in DMSO-d₆). A cavity is surrounded by two carbazole subunits and two nitrobenzene subunits, which provides an opportunity to encapsulate small organic molecules. An average distance of 2.63 Å is observed between NO₂ oxygen atom and the bridging –NH– nitrogen atom, which is much shorter than sum of van der Waals radii of oxygen and nitrogen (3.07 Å). A hydrogen bond must form between NH and O. This is in consistent with the observation that the magnetic resonance signal of NHs (H^c) appear at a very downfield area (9.54 ppm for 1 and 9.55 ppm for 2 in CDCl₃, 9.62 ppm for 3 and 9.67 ppm for 4 in DMSO-d₆).

Fig. 1 X-ray crystal structure of 2: (a) side view, (b) top view.

The UV-vis absorption spectra for macrocycles 1–4 were recorded in CHCl₃ (Fig. 2). The maximum absorption band appeared at about 340 nm. A shoulder band at about 410 nm and a weak absorption band at about 510 nm were also observed. These absorptions in the longer wavelength regions might come from the partial conjugation of the carbazolyl units with adjacent NH bridges. For macrocycles 3 & 4 with pendent carbazolyls, a sharp absorption band at about 295 nm was observed.

Fig. 2 UV absorption spectra for macrocycles 1–4, recorded in CHCl₃, concentration: 5 × 10⁻⁶ mol L⁻¹.

The electrochemical property of the macrocycle were explored by cyclic voltammetry (CV). All macrocycles showed irreversible traces (Fig. 3). Macrocycle 1 & 2 exhibited similar oxidation waves at about 1.04 V; while two reduction waves at 0.30 V and −0.80 V were observed for macrocycle 1, 0.29 V and −1.12 V for macrocycle 2. For macrocycle 3, no obvious oxidation wave was observed and two reduction waves at 0.06 V and −1.05 V appeared. Macrocycle 4 showed an oxidation wave at 1.01 V and two reduction waves at 0.23 V and −0.76 V.

Fig. 3 Cyclic voltammograms of 1–4 (scan rate: 200 mV s⁻¹; concentration: 0.5 mM; solvent: chloroform; counter electrode: Pt; reference electrode: Ag/Ag⁺; supporting electrolyte: 0.1 M Bu₄NPF₆).

In conclusion a new type of –NH– bridged azacalix[2]arene[2]carbazoles was synthesized via aromatic nucleophilic substitution reaction (S_NAr) between N-substituted-3,6-diaminocarbazole and 1,5-difluoro-2,4-dinitrobenzene. Both one-pot and/or fragment coupling strategy were adapted and thus both symmetric and unsymmetric macrocycles were available. NMR and HRMS confirmed the chemical structures of the macrocycle. X-ray single crystal analysis of one macrocycle revealed 1,3-alternate conformation. The cavity of the macrocycle was expanded by incorporating rigid polyaromatic rings. The spectroscopic and electrochemical properties of the macrocycle were also explored. Because of easy synthesis, expanded cavities and electroactive properties, azacalix[2]arene[2]carbazoles might find wide applications in the field of supramolecular chemistry and material science.

Acknowledgements

This work is supported by the National Natural Science Foundation of China (Grant 91227105 21572208), Zhejiang Natural Science Foundation (Grant LY12B02021 LY15B020007), Open Foundation of Zhejiang Provincial Top Key Academic Discipline of Applied Chemistry and Eco-Dyeing & Finishing Engineering (YR2012009), 521 talent program of Zhejiang Sci-Tech University and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.

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26. Crystal data: C₅₂H₅₄N₁₀O₈, M_w = 947.05, crystal size: 0.48 × 0.45 × 0.42 mm³, crystal system: monoclinic, space group R3̄, a = 32.871(2), b = 32.871(2), c = 24.1978(15) Å, α = β = 90°, γ = 120°, U = 22643(3) ų, Z = 18, D_c = 1.250 Mg m⁻³, T = 293(2) K, μ(Mo-Kα) = 0.705 mm⁻¹, 8615 reflections measured, 3711 unique (R_int = 0.0278), R₁ = 0.1359. ESI.†.
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Footnote

† Electronic supplementary information (ESI) available: Synthesis and characterization data for new compounds, CIF file for X-ray single crystal of 2. CCDC 1444882. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra01197g

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