Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
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Synthesis and Isomerization Behavior of a Macrocycle with Four Photoresponsive Moieties Toru Amaya,* Hayato Fujimoto,† Takahiro Tanaka,† and Toshiyuki Moriuchi Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan S Supporting Information *
ABSTRACT: The macrocycle 1 containing four photoresponsive fluorenylidene moieties was designed. The EZEZ form of 1, 1EZEZ, was selectively produced. Reversible photochemical isomerization between 1EZEZ and 1ZZZZ was achieved, the extent of which was dependent on the light source used. Furthermore, the intermediate 1EZZZ was selectively isomerized to 1ZZZZ thermally and photochemically.
R
esearch on stimuli-responsive molecular machines using light and heat has attracted considerable interest.1,2 For the further evolution of nanotechnology, constructing complex molecular machines that can be precisely controlled at the molecular level is critical. For example, if it were possible to control the isomerization of molecules containing multiple photoisomerization units, a significant structural change could be induced, thus permitting multistep operations to be possible. Such changes have been reported for macrocycles that contain multiple azobenzene moieties as a photoresponsive unit.3 As an example of this, Norikane, Tamaoki, and co-workers4a,c reported the synthesis of a hinge-type molecule containing two azobenzene units that underwent a large, reversible photoinduced dynamic structural transformation. In addition, it has been reported that in macrocycles incorporating four azobenzene units, the molecular recognition behavior for alkali metal ions changes when they are subjected to photoisomerization.4b Wegner and co-workers also reported the preparation of macrocyclic azobenzenes.3a,c They revealed that the photochemical and thermal isomerization of cyclotetraazocarbazole show an integrated molecular logic gate, including OR, NOT, and AND functions.5 Easton and coworkers reported a reversible light-driven molecular muscle based on E/Z isomerization of two stilbene units incorporated in a pseudomacrocycle consisting of two α-cyclodextrin rotaxanes.6 In recent years, Zhu, Steigerwald, Nuckolls, and co-workers reported the synthesis of macrocycles with four stilbene units and their photochemical properties, but reversible isomerization was not described.7 Some representative examples of photoresponsive macrocycles were introduced briefly above. However, selective photoisomerization of a specific alkene moiety in the presence of multiple alkenes is still difficult. In this context, we report the design and preparation of macrocycle 1 containing four photoactive fluorenylidene moieties (Figure 1). We found that the EZEZ form of the © XXXX American Chemical Society
Figure 1. Structures of macrocycle 1 containing four photoactive fluorenylidene moieties.
macrocycle, 1EZEZ, was produced selectively. When it was subjected to irradiation with a white LED, it underwent photoisomerization to the ZZZZ form, 1ZZZZ (Scheme 1). We also report the reverse process, i.e., the photoisomerization of Received: February 19, 2018
A
DOI: 10.1021/acs.orglett.8b00598 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
subjected to X-ray crystallographic analysis. In the crystal structure, there are two independent molecules of 1ZZZZ and four independent molecules of CHCl3 in the asymmetric unit (Figure S2).9 The structure of 1ZZZZ was revealed to be the S4symmetric ZZZZ isomer, in which the adjacent fluorene units are facing in opposite directions (Figure 2b). In view 1, the 20membered ring has the shape of a parallelogram. The C126− C170 distance is 5.6 Å. Cavities are formed by opposing fluorene rings, and the C137−C181 distance is 8.9 Å. A molecule of CHCl3 is included in one of the two cavities (views 4−6). In the packing structure, each molecule is connected by intermolecular CH−π interactions (Figure S3). The NMR spectrum of 1ZZZZ shows eight nonequivalent peaks, which is consistent with the S4-symmetric structure. On the other hand, the major isomer shows 16 nonequivalent peaks, suggesting a twofold-symmetric structure. DFT calculations indicated that 1EZEZ has a C2-symmetric structure. On the other hand, 1EEZZ did not show a C2-symmetric structure (Figure 3). The strain
Scheme 1. Scheme for the Isomerization of 1 in This Work
1ZZZZ to 1EZEZ via the intermediate 1EZZZ, under irradiation with a high-pressure Hg lamp. It was revealed as well that 1EZZZ can be selectively isomerized to 1ZZZZ both thermally and photochemically (Scheme 1). Macrocycle 1 was synthesized in a one-step reaction via basecatalyzed self-condensation of fluorene-2-carboxaldehyde (2) in the presence of aqueous NaOH and Bu4NBr (Figure 2a).8 The
Figure 2. (a) Synthesis of 1. (b) X-ray crystal structure of 1ZZZZ. Extra molecules have been omitted for clarity (views 1−3). The molecular structure with an included CHCl3 is shown in views 4−6. Figure 3. Optimized structures of isomers of 1 based on DFT calculations [B3LYP/6-31G(d,p)] and their strain energies [in kcal/ mol, B3LYP/6-31G(d,p)] relative to that for the most stable isomer, 1ZZZZ.
cyclic tetramer was the main product in a mixture of nonpolar products obtained by filtration through a silica gel column, although the formation of cyclic tri- to 11-mers was observed in MALDI-TOF MS analyses (Figure S1). After purification by silica-gel column chromatography, macrocycle 1 was obtained in 11% yield as a mixture of two isomers, although there are six possible isomers, as shown in Figure 1. The two isomers were separated by recycling preparative HPLC with gel-permeation chromatography (GPC) columns. The minor isomer was crystallized from CHCl3 and MeOH, and a single crystal was
energy of 1EEZZ is much larger than that of 1EZEZ (Figure 3). Furthermore, the 1H NMR chemical shifts calculated for 1EZEZ using the GIAO method at the B3LYP/6-31G(d,p) level were similar to the experimentally found values (Table S1). On the basis of these data, we conclude that the major isomer 1EZEZ has the EZEZ configuration. B
DOI: 10.1021/acs.orglett.8b00598 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
in Figure 5. The 1EZEZ isomer absorbs at a longer wavelength compared with 1ZZZZ. The emission of the white LED used
In the course of these studies, we discovered that the ratio of these two isomers of 1 changed with each experiment as a result of photoisomerization caused by the ambient light in the room. Therefore, the reaction, workup, and purification with silica gel column chromatography were performed in the dark. When this was done, 1EZEZ was produced as the sole isomer among the possible cyclic tetramers (Figure 2a).10 Thermal isomerization was not observed for 1ZZZZ and 1EZEZ, even at high temperatures (250 °C in mesitylene-d12 under microwave irradiation). It is likely that this selective formation of 1EZEZ is kinetically controlled. The strain energies of the optimized structures for the six possible isomers of 1 were estimated on the basis of DFT calculations at the B3LYP/6-31G(d,p) level, and the energy gaps relative to the most stable isomer are shown in Figure 3. The most stable isomer is 1ZZZZ, in which steric repulsion is avoided by the twist, as the torsion angle between the planes of the fluorene skeleton is nearly 50° or 120° (Figure S4). The calculated structure is similar to the X-ray crystal structure. The next most stable form is 1EZEZ. The energy gap between them is 1.3 kcal/mol. The above findings indicate that the two synthetically prepared isomers are much more stable than the other isomers. The most highly strained isomer is 1EEEE, the high strain energy of which is probably due to steric repulsion derived from the fluorene skeletons that are nearly on the same plane. Photoisomerization was investigated using 1H NMR spectroscopy (Figure 4). A CD2Cl2 solution of 1EZEZ was irradiated with a white LED at room temperature. After a 30 min period of irradiation, the reaction reached a photostationary state. Almost 90% of 1EZEZ had been isomerized to 1ZZZZ (Figure 4a). The UV−vis absorption spectra of 1EZEZ and 1ZZZZ are shown
Figure 5. Absorption spectra of 1EZEZ and 1ZZZZ (1.0 × 10−5 M in CH2Cl2). The inset shows an expanded view of the 440−480 nm region.
here has a strong peak around 465 nm as a component of blue emission. In this region, both 1EZEZ and 1ZZZZ absorb weakly, but the absorbance of 1EZEZ is stronger than that of 1ZZZZ (Figure 5 inset). This finding is one of the reasons for the selective isomerization of 1EZEZ to 1ZZZZ. Irradiation of 1ZZZZ with a high-pressure Hg lamp through Pyrex glass led to the regeneration of 1EZEZ in 20% yield, together with the generation of the 1EZZZ isomer in 20% yield (Figure 4b). Both isomers can absorb 365 nm light, but 1ZZZZ has a stronger absorption band than 1EZEZ. 1EZZZ was isolated by recycling preparative HPLC with GPC columns. The 1H NMR spectrum of the isolated product indicated that the four fluorenylidene units are nonequivalent, which is consistent with the structure of 1EZZZ.11 Irradiation of 1EZZZ with a white LED also gave 1ZZZZ and 1EZEZ in a 9:1 ratio (Scheme 2a). This is Scheme 2. Isomerization of 1EZZZ under (a) White LED Irradiation and (b) Microwave Irradiation at 100 °C in the Dark
consistent with the experiment involving the photoisomerization of 1EZEZ to 1ZZZZ under white LED irradiation, as described above. Interestingly, 1EZZZ underwent thermal isomerization at 100 °C under microwave irradiation to provide 1ZZZZ and 1EZEZ in a 9:1 ratio (Scheme 2b). Such thermal isomerization was not observed for 1ZZZZ and 1EZEZ even at higher temperatures (250 °C), as described above. Therefore, the thermal isomerization of 1EZZZ can be attributed to strain-derived instability. In conclusion, the macrocycle 1EZEZ containing four photoactive fluorenylidene moieties was selectively synthesized in the dark via the base-catalyzed self-condensation reaction of 2. Selective photoisomerization of 1EZEZ to 1ZZZZ under white LED irradiation was also revealed. The regeneration of 1EZEZ
Figure 4. 1H NMR experiments (400 MHz) in CD2Cl2 for the photoisomerization of (a) 1EZEZ under white LED irradiation and (b) 1ZZZZ under irradiation with a high-pressure Hg lamp. C
DOI: 10.1021/acs.orglett.8b00598 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
68, 8291. (c) Norikane, Y.; Katoh, R.; Tamaoki, N. Chem. Commun. 2008, 1898. (5) (a) Schweighauser, L.; Wegner, H. A. Chem. Commun. 2013, 49, 4397. (b) Schweighauser, L.; Häussinger, D.; Neuburger, M.; Wegner, H. A. Org. Biomol. Chem. 2014, 12, 3371. (6) Dawson, R. E.; Lincoln, S. F.; Easton, C. J. Chem. Commun. 2008, 3980. (7) Chen, Q.; Trinh, M. T.; Paley, D. W.; Preefer, M. B.; Zhu, H.; Fowler, B. S.; Zhu, X.-Y.; Steigerwald, M. L.; Nuckolls, C. J. Am. Chem. Soc. 2015, 137, 12282. (8) For a related condensation reaction, see: Amaya, T.; Mori, K.; Wu, H.-L.; Ishida, S.; Nakamura, J.; Murata, K.; Hirao, T. Chem. Commun. 2007, 1902. (9) Crystal data for 1ZZZZ: triclinic, space group P1̅ (No. 2), a = 14.5297(3) Å, b = 15.2227(3) Å, c = 23.9525(5) Å, β = 95.5948(16)°, V = 5039.38(19) Å3, Z = 2, R1 = 0.1194, wR2 = 0.3495. The data have been deposited with the Cambridge Crystallographic Data Centre (CCDC1812923). (10) The 1H NMR spectrum is shown in Figure S5. It should be noted that although the spectrum was measured after silica gel column chromatography, it was revealed beforehand that 1ZZZZ and 1EZEZ cannot be separated under the conditions employed here. (11) Isolated 1EZZZ contained a small amount of 1ZZZZ (ca. 5%) after purification.
from 1ZZZZ was possible under irradiation with a Hg lamp, although the conversion was not high. The isomer 1EZZZ was formed as an intermediate in the photoisomerization and was then selectively isomerized to 1ZZZZ both photochemically and thermally. Such reversible isomerization can induce a large change in molecular shape. A study regarding the development of stimuli-responsive molecular machines is currently underway.
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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.orglett.8b00598. Experimental procedures and detailed characterization data for the compounds (PDF) Accession Codes
CCDC 1812923 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by e-mailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] (T. Amaya). ORCID
Toru Amaya: 0000-0002-7716-0630 Author Contributions †
H.F. and T.T. contributed equally.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank Dr. Norimitsu Tohnai at Osaka University for the single-crystal X-ray structural analysis. REFERENCES
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DOI: 10.1021/acs.orglett.8b00598 Org. Lett. XXXX, XXX, XXX−XXX
