146 Chem. Commun., 2013, 49, 146--148 This journal is c The Royal Society of Chemistry 2013

Cite this: Chem. Commun.,2013, 49, 146

Switchable 3D networks by light controlled p-stackingof azobenzene macrocycles†

Raphael Reuter and Hermann A. Wegner*

Azobenzene macrocycles were designed for switchable p-stacking

interaction. After efficient preparation and characterization

of azobenzene macrocycles containing electron rich as well as

electron poor elements a dimeric analogue was synthesized, which

formed reversibly 3D-networks. Gel formation was observed with

aromatic solvents representing the first example of this type based

on switchable azobenzene macrocycles.

Functionality in molecules is governed by their structure andtheir spatial arrangement. In most cases the interactions ofmultiple molecular components on a supramolecular level arecrucial for the successful fulfilment of a given task.1 Thereversible control of such supramolecular interactions on amolecular basis will, therefore, give the power to control theassociated function.2 The azobenzene scaffold is one of themost prominent molecular entities, which can be reversiblyaltered in its spatial arrangement upon irradiation.3–5 Azobenzenescan be changed between the Z and the E conformation uponirradiation by light with appropriate wavelength. This feature hasbeen beautifully applied in a number of functional systems.6,7

Azobenzenes have also been used to control supramolecularinteractions,8 such as hydrogen bonds,9,10 metal complexformation11 or hydrophilic/hydrophobic interactions. Addition-ally, the azobenzene moiety itself can participate in the arrange-ment, which upon isomerization is inhibited.12 In this case thetype of intermolecular interaction is mainly limited to p–pinteractions.13 In general, the aggregation of p-stacks is adistinct property of large aromatics and, in particular, ofshape-persistent macrocycles.14–16 The incorporation of azobenzenesinto such disc-like shape-persistent macrocycles offers theunique opportunity to change the spatial arrangement fromthe two-dimensional flat structure to a three-dimensional geo-metry allowing alteration of their supramolecular assembly.17

This principle has been beautifully applied by Norikane and

coworkers for a switchable liquid crystal system.18 The detailedmolecular interactions were described on the basis of stacking inthe solid-state structure,19 which we also observed for cyclo-trisazobenzenes.20,21 However, this phenomenon has not mani-fested in solution so far.

In this report we add an additional dimension to the conceptof switchable p-stacking of azobenzene macrocycles in order tocontrol 3D networks (Fig. 1). If two macrocycles, capable ofswitchable p-stacking, are connected, these building blocks willnot only form columnar assemblies, but also allow connectionsbetween the stacks to build horizontal as well as lateral net-works. With this approach reversibly porous structures can becreated, which are attractive for storage of small molecules withthe advantage of optional release upon light irradiation.

To realize such a light responsive three-dimensional net-work based on switchable building blocks, first, an appropriate

Fig. 1 Schematic representation of 3D-networks built from dimeric switchableazobenzene macrocycles. In the all-E conformation linked p-stacks are formed(left). Irradiation induces isomerization to a mixture of Z-isomers all deviatingfrom planarity, which impedes the supramolecular interaction (right).

Fig. 2 p-Stacking interaction of two macrocycles with CO2Bu residues as EWGs.

University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056 Basel,

Switzerland. E-mail: hermann.wegner@unibas.ch; Fax: +41-61-267-0976

† Electronic supplementary information (ESI) available: Experimental proceduresand analytical data; UV of isomerization of 1. See DOI: 10.1039/c2cc35974j

Received 17th August 2012,Accepted 1st November 2012

DOI: 10.1039/c2cc35974j

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This journal is c The Royal Society of Chemistry 2013 Chem. Commun., 2013, 49, 146--148 147

monomeric azobenzene macrocycle was designed to investigatethe crucial switchable p-stacking. The incorporation of phenylrings with alternating electron density should enable thenecessary molecular interaction leading to the target macro-cyclic structure 1 (Fig. 2).22 Phenyl moieties substituted withester groups should be less electron rich compared to theunsubstituted rings.

The synthesis relied on the established strategy developed inour laboratory using Suzuki cross-coupling as well as Millsreactions.23,24 Aniline 2 was accessed by known procedures(Scheme 1).25–27 For the introduction of the boronic esterrequired for the Suzuki cross-coupling Miyaura borylation wasemployed.28 Other methods such as lithiation followed by Li–Bexchange were not suitable as the ester is probably not stable tothe harsh lithiation conditions with BuLi. After Suzuki cross-coupling of the boronic ester 4 with bromide 2, biphenyl 5 wasobtained. The next step, the Mills reaction with 3-bromonitroso-benzene (6), proceeded with a good yield of 73%. The Suzukireaction as well as the final oxidative cyclization with leadtetraacetate furnished the desired macrocycle 1 in eight linearsteps in an overall yield of 10%.

As anticipated, the NMR shifts showed a strong concen-tration dependence suggesting significant p-stacking inter-action (Fig. 3). Upon irradiation (365 nm, room temperature)the UV as well as the NMR changed significantly indicating theisomerization from the all-E to a mixture of the Z-isomers. TheNMR of the mixture of Z-isomers did not show any shift atdifferent concentrations proving the effective inhibition of thearomatic p-interaction. Interestingly, an attempt to inhibit thep-stacking by using benzene as solvent led to an even strongershift of the NMR-signals at the same concentration.

With a suitable molecular system for columnar p-stacking inhand the preparation of a dimeric variation was commenced.The general strategy was chosen according to the synthesis of

macrocycle 1. It was envisioned to combine two macrocycles bya click-reaction, a Cu-catalysed [2 + 3] dipolar cycloaddition.29,30

Such a transformation required the incorporation of a suitablecoupling partner. For this purpose an alkyne moiety wasincorporated into one of the biphenyl moieties (Scheme 2).Additionally, the design has been modified by increasing thelength of the alkyl chain in the ester moiety, which should havebeneficial effects on the stacking as well as on the solubility.The aromatic alkyne part was prepared via Sonogashira cross-coupling with tri-iso-propylsilyl (TIPS) acetylene (9) and phenol8. This synthetic intermediate 10 was connected with thebenzylic alcohol 12 using the Mitsunobu protocol. Reductionof the nitro functionality followed by Suzuki cross-couplingyielded the desired biphenyl building block 14.

The final transformation to build up the macrocycles beganwith a Mills reaction. The following Suzuki cross-couplingreaction delivered the precursor for the macrocyclization inquantitative yield. Ring closure and deprotection led to the

Scheme 1 Synthesis of butyl ester substituted trisazobiphenyl macrocycles 1.

Fig. 3 1H-NMR spectra of 1 at different concentrations in CDCl3 before irradiationand after irradiation.

Scheme 2 Assembly of the macrocycle and connection via click reaction to bis-macrocycle 17.

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148 Chem. Commun., 2013, 49, 146--148 This journal is c The Royal Society of Chemistry 2013

macrocyclic alkyne 15, which was then converted to the bis-macrocycle 17 by click reaction with the diazide 16. Thearomatic peaks of the dimeric macrocycle 17 showed a signifi-cantly larger high field shift compared to the monomer 1 atsimilar concentrations indicating an even stronger p–p-stackingfor the dimer 17.

Already before the workup of the click reaction, it wasobserved that product 17 formed a gel with the solvent toluene,which could be attributed to the incorporation of solventmolecules inside the 3D p-stacking network. The process ofgel formation was further explored with different solvents(Table 1). The effect was only observed for aromatic solvents.For ortho-xylene gel formation was detected at a concentrationof 1.25% (m/v) (Table 1, entry 2). In other solvents like CHCl3 orCH2Cl2 this property was not observed (Table 1, entries 3 and4). Also in THF no gelification took place (Table 1, entry 5). Thepreference for aromatic solvents could originate from thecavities spanned from the aromatic gelator, which supportp-stacking with the solvent. The gel was stable for at least oneday at room temperature.

Finally, the switching behaviour was investigated. When thesample was irradiated with UV light at 365 nm the gel slowlyliquefied and after three hours a clear orange liquid wasobtained supporting the anticipated dissociation of the 3Dnetworks (Fig. 4). Although there have been numerous reportson switchable gel systems based on azobenzenes,31,32 as well asa recent non-switchable example based on shape-persistentmacrocyles,33 the scaffold displayed above is to the best ofour knowledge the first one, which combines these two princi-ples. Compared to the other examples of switchable azobenzenegels where a group attached to the azobenzene is responsiblefor the network formation required for gelation, it is in thiscase the p-stacking of the azobenzene macrocycles, whichprovides the necessary non-covalent interaction. Therefore,the macrocyclic structure is essential for the network–gelformation. The long alkyl chains might serve as spacersto provide the necessary cavities for solvent incorporation.

A derivative of 17 with butyl instead of hexyl chains did notshow any gelation ability.

In summary, a new molecular system based on dimerictrisazobiphenyl macrocycles has been prepared, which displaysswitchable p-stacking interaction upon UV irradiation.This property has been utilized to build up light-controlledthree-dimensional networks, which form switchable gels witharomatic solvents. The basic principle should also be applicableto bind other small molecules and release them on demand justwith light. Further studies on the structure and formation of thegel are ongoing.

The authors thank the Swiss National Science Foundationand SystemsX.ch for financial support. H. A. W. is indebted tothe Fonds der Chemische Industrie for a Liebig fellowship.

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1071–1090.4 H. Bouas-Laurent and H. Durr, Pure Appl. Chem., 2001, 73, 639–665.5 J. F. Rabek, Photochemistry and Photophysics, CRC, 1991.6 R. S. Stoll and S. Hecht, Angew. Chem., Int. Ed., 2010, 49, 5054–5075.7 M.-M. Russew and S. Hecht, Adv. Mater., 2010, 22, 3348–3360.8 S. Yagai and A. Kitamura, Chem. Soc. Rev., 2008, 37, 1520–1529.9 Y. Matsuzawa and N. Tamaoki, J. Phys. Chem. B, 2010, 114,

1586–1590.10 F. Rakotondradany, M. A. Whitehead, A.-M. Lebuis and

H. F. Sleiman, Chem.–Eur. J., 2003, 9, 4771–4780.11 M. Yamamura, Y. Okazaki and T. Nabeshima, Chem. Commun.,

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N. Stingelin and P. Smith, J. Mater. Chem., 2011, 21, 4339–4345.13 M. Shimomura and T. Kunitake, J. Am. Chem. Soc., 1987, 109,

5175–5183.14 C. Grave and A. Schluter, Eur. J. Org. Chem., 2002, 3075–3098.15 W. Zhang and J. S. Moore, Angew. Chem., Int. Ed., 2006, 45,

4416–4439.16 S. Hoger, Chem.–Eur. J., 2004, 10, 1320–1329.17 R. Reuter and H. A. Wegner, Chem. Commun., 2011, 47,

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Fig. 4 Solution of 17 in ortho-xylene [c = 1.25% (m/v)]. Left: gel beforeirradiation. Right: solution after irradiation at 365 nm for 3 h.

Table 1 Gel formation of bis-macrocycle 17 in different solvents

Entry Solvent Concentrationa Gel

1 Toluene 10 Yes2 o-Xylene 1.25 Yes3 CHCl3 5 No4 CH2Cl2 5 No5 THF 5 No

a In % m/v.

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