ORGANIC LETTERS
Synthesis of Coumarin/Pyrrole-Fused Heterocycles and Their Photochemical and Redox-Switching Properties
2013 Vol. 15, No. 11 2802–2805
Chi-Hui Lin and Ding-Yah Yang* Department of Chemistry, Tunghai University, No. 181, Section 3, Taichung Port Road, Taichung City 40704, Taiwan, Republic of China
[email protected] Received April 23, 2013
ABSTRACT
Two coumarin/pyrrole-fused heterocycles were synthesized to investigate their photochemical and redox-switching properties. Photooxidation of the colorless diphenyl-substituted pyrrolocoumarin resulted in a distinct change to red and a sharp decrease in fluorescence intensity. The photooxidized product can be swiftly reverted to the original form by NaCNBH3 reduction or hydrogenation.
Coumarin and its derivatives represent an important class of heterocycles that have wide applications in the areas of medicinal chemistry1 and functional materials.2 When coumarins are fused with other molecular scaffolds, the resulting compounds may generally exhibit promising or even unprecedented properties. For instance, coumarin/ phenanthridine-fused heterocycles have been found to possess unique negative thermochromic properties,3 whereas coumarin/pyran-fused heterocycles have been reported to exhibit molecular switching properties.4 Since some pyrrole derivatives have been documented to be light-sensitive and (1) (a) James, C. A.; Coelho, A. L.; Gevaert, M.; Forgione, P.; Snieckus, V. J. Org. Chem. 2009, 74, 4094–4103. (b) Thasana, N.; Worayuthakarn, R.; Kradanrat, P.; Hohn, E.; Young, L. R.; Ruchirawat, S. J. Org. Chem. 2007, 72, 9379–9382. (c) Kostova, I. Curr. HIV Res. 2006, 4, 347–363. (d) Yao, T. L.; Yue, D. W.; Larock, R. C. J. Org. Chem. 2005, 70, 9985–9989. (e) Borges, F.; Roleira, F.; Milhazes, N.; Santana, L. Curr. Med. Chem. 2005, 12, 887–916. (f) Yu, D. L.; Suzuki, M.; Xie, L. Med. Res. Rev. 2003, 23, 322–345. (2) (a) Goguen, B. N.; Aemissegger, A.; Imperiali, B. J. Am. Chem. Soc. 2011, 133, 11038–11041. (b) Hori, Y.; Ueno, H.; Mizukami, S.; Kikuchi, K. J. Am. Chem. Soc. 2009, 131, 16610–16611. (c) Chen, L.; Hu, T. S.; Yao, Z. J. Eur. J. Org. Chem. 2008, 6175–6182. (d) Komatsu, K.; Urano, Y.; Kojima, H.; Nagano, T. J. Am. Chem. Soc. 2007, 129, 13447– 13454. (e) Lee, M. T.; Yen, C. K.; Yang, W. P.; Chen, H. H.; Liao, C. H.; Tsai, C. H.; Chen, C. H. Org. Lett. 2004, 6, 1241–1244. (f) Hara, K.; Kurashige, M.; Dan-oh, Y.; Kasada, C. New J. Chem. 2003, 27, 783–785. (g) Quanten, E.; Adriaens, P.; Deschryver, F. C.; Roelandts, R.; Degreef, H. Photochem. Photobiol. 1986, 43, 485–492. (3) Chen, J. J.; Li, K. T.; Yang, D. Y. Org. Lett. 2011, 13, 1658–1661. (4) Li, K. T.; Lin, Y. B.; Yang, D. Y. Org. Lett. 2012, 14, 1190–1193. 10.1021/ol401138q r 2013 American Chemical Society Published on Web 05/28/2013
are prone to undergo oxidation upon UV irradiation,5 we speculate that coumarin/pyrrole-fused heterocycles may also reveal intriguing functional properties. In our continuing efforts to develop novel coumarin-based functional materials, we report the synthesis of two 7-dimethylaminocoumarin/ pyrrole-fused derivatives and subsequent evaluation of their photochemical and redox-switching properties. Our studies indicate that both compounds are highly sensitive to light, and one may potentially function as an organic redox switch with color change and emission variation as two output properties. Scheme 1 shows the preparation of the pyrrolocoumarins 1 and 2. The microwave-promoted coupling of 3-acylcoumarins 36 or 47 with 1-amino-1-phenylpropan-2-one hydrochloride (5)8 using diisopropylethylamine (DIPEA) as a base in dichloroethane (DCE) generated the 4-aminosubstituted coumarin 6 or 7. The subsequent refluxing 6 and 7 in the presence of a catalytic amount of p-TsOH in methanol for 0.5 h afforded the target pyrrolocoumarins 1 and 2 almost quantitatively. (5) Leete, E. J. Am. Chem. Soc. 1961, 83, 3645–3653. (6) Majumdar, K. C.; Bhattacharyya, T. Tetrahedron Lett. 2001, 42, 4231–4233. (7) Kuo, P. Y.; Yang, D. Y. J. Org. Chem. 2008, 73, 6455–6458. (8) Fitton, A. O.; Muzanila, C. N.; Odusanya, O. M.; OppongBoachie, F. K.; Duckworth, S. J.; Hadi, A. H. A. J. Chem. Res 1988, 11, 352–353.
Scheme 1. Preparation of Pyrrolocoumarins 1 and 2
water to yield the 9. The subsequent [1,5]-acyl migration from the C-2 to C-3 position of 9 furnishes the 10.11 Final methanolysis of 10 in methanol releases the target 2. The aforementioned mechanism is strongly supported by the isolation and characterization of the rearranged intermediate 109 during the reaction (Figure S1 in the SI). We believe this acid-catalyzed sequence of cyclization, dehydration, rearrangement, and methanolysis of 3-acyl-4-amino-substituted coumarins may provide an alternate route to the preparation of valuable multisubstituted pyrrole heterocycles.
Scheme 2. Proposed Mechanism for the Formation of 2 from 7
The molecular structures of 6, 7, 1, and 2 were verified by H and 13C NMR spectroscopy as well as the X-ray crystallography as depicted in Figure 1.9 Note that the 1H NMR spectra of 7 and 6 show a broad absorption peak at chemical shifts of 13.42 and 8.57 ppm, respectively, indicating the presence of an intramolecular H-bonding between the carbonyl oxygen and amino hydrogen in solution. Indeed, this H-bonding is clearly observed in the crystal data of 7 (Figure 1). Interestingly, no H-bonding between the 3-carbonyl oxygen and 4-amino hydrogen was found in the crystal structure of 6. Instead, it shows that the two phenyl groups lie parallel to each other with the distance between ˚ , and are nearly orthogonal to them measured to be ∼3.40 A the coumarin moiety. This observation suggests that 6 mainly exists in a stable aromatic ππ stacking conformation in the solid state, presumably due to the favored crystal packing during crystallization.10 1
Figure 1. ORTEP crystal structures of 6, 7, 1, and 2.
Scheme 2 depicts the proposed mechanism for the formation of 2 from 7. It begins with acid-catalyzed intramolecular cyclization of 7 to give the tertiary alcohol 8, which is followed by 1,4-elimination to lose a molecule of Org. Lett., Vol. 15, No. 11, 2013
With the availability of 1 and 2, their photochemical properties and redox-switching behaviors were then investigated. Both pyrrolocoumarins were found to be highly sensitive to light and change colors when exposed to UV light. For instance, upon UV irradiation (352 nm, 8 W each 8), the colorless 1 turned red within seconds. Figure 2 shows the UVvis absorbance changes of 1 in methylene chloride prior to and after irradiation. With the increase of exposure time, a new broad absorption band with the peak wavelength around 504 nm gradually emerged, along with the appearance of three isosbestic points at 265, 299, and 387 nm. To our delight, the photogenerated product of 1 was stable enough to be isolated and characterized to be the alcohol 11 (Scheme 3), although the photogenerated product of 2 was not. Figure 3 depicts the crystal structure of 11,9 which clearly reveals a disrupted aromatic pyrrole ring along with a tertiary alcohol at the C-3 position. To explore the role of the 7-amino group in this photooxidation, 12, which lacks the 7-dimethylamino group on the coumarin moiety, (9) Crystallographic data (excluding structure factors) for 1, 2, 6, 7, 10, and 11 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC-930377, 930378, -930379, -930380, -930381, and -930382, respectively. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336033. (10) Lin, C. H.; Chuang, R. R.; Kuo, P. Y.; Yang, D. Y. Tetrahedron Lett. 2013, 54, 2431–2434. (11) Tsuge, O.; Uneo, K.; Oe, K. Chem. Lett. 1979, 11, 1407–1410. (12) Joshi, S. D.; Sakhardande, V. D.; Seshadri, S. Indian J. Chem., Sect. B 1984, 23, 206–208. 2803
Figure 3. ORTEP crystal structure of 11. 5
Figure 2. Absorption spectra of 1 (3.1 10 M in CH2Cl2) obtained with different exposure times (352 nm), 0 to 60 s, in increments of 10 s. Scheme 4. Photooxidation of 12
Scheme 3. Redox Switching between 1 and 11
was prepared12 and subjected to irradiation under the same conditions as those for 1. No photooxidation product was observed even when 12 was under prolonged irradiation (Scheme 4). The fact that 12 is light-insensitive and does not respond to UV light suggests that the 7-dimethylamino group of 1 plays a crucial role in its photochemical properties, presumably owing to the amine’s strong electrondonating properties. This assumption was supported by the cyclic voltammetry (CV) of 1 and 12 (Figure S5 in the SI). The CV data indicate that the presence of the dimethylamino group on the 7-position of the coumarin ring of 1 drastically decreases the oxidation potential of the pyrrole ring from þ1.338 to þ0.769 V, which renders 1 susceptible to oxidation upon UV irradiation. In addition to color change, 1 also exhibited a second output property upon UV irradiation, that is, emission variation. Figure 4 shows the time-dependent fluorescence spectra of 1 obtained with different exposure times (352 nm). While 1 was highly fluorescent in CH2Cl2 (λmax = 410 nm, Φf = 0.65), the fluorescence intensity at 410 nm decreased substantially with the increase in exposure time. The resulting oxidized 11 is essentially nonfluorescent in CH2Cl2 (Φf = 0.03) with up to a 21-fold decrease in fluorescence quantum yield after photooxidation. The quenching of the intrinsic 7-dimethylaminocoumarin fluorescence in 11 is probably caused by the efficient electronic coupling between the 7-dimethylaminocoumarin donor and the N-benzylideneimine acceptor. 2804
Figure 4. Fluorescence spectra of 1 (2.5 106 M in CH2Cl2) obtained with different exposure times (352 nm), 0 to 21 s, in increments of 3 s.
The photogenerated compound 11 can be swiftly reverted to the original 1 when treated with reducing agents such as sodium cyanoborohydride (NaCNBH3) or bubbled with H2 under acidic conditions (Scheme 3). The reverse reaction mechanism apparently involves imine reduction/hydrogenation and is followed by acid-catalyzed dehydration to reconstitute the pyrrole ring. While hydrogenation is more atom-economical (both H-atoms are incorporated into the product) than NaCNBH3 reduction, the Pd/C catalyst needs to be removed from the Org. Lett., Vol. 15, No. 11, 2013
Scheme 5. Preparation of Pd/Fe3O4 Magnetic Nanoparticles
system via either filtration or centrifugation before entering the next redox-switching cycle. In an effort to avoid this repeated filtration/centrifugation process, the metal catalyst Pd/C was replaced with the Pd-functionalized Fe3O4 magnetic nanoparticles (Pd-MNPs), which can be magnetically pulled down from the solution with an external magnet. The Pd/Fe3O4 MNPs13 were readily accessed by the coupling of Na2PdCl4 with the commercially available Fe3O4 nanoparticles in aqueous NaOH solution and was followed by reduction with NaBH4 in methanol, as depicted in Scheme 5. The Pd-grafted magnetic materials were further characterized by XRD spectroscopy (Figure S6 in the SI). Figure 5 shows the time-dependent absorption spectra of 11 in CH2Cl2 with different exposure times to the bubbling H2 gas in the presence of catalytic amounts of Pd-MNPs and formic acid. Delightfully, the red 11 turned colorless again with the reappearance of the 354 nm absorption band, which is characteristic for 1. The reversible switching process between 1 and 11 by UV irradiation and hydrogenation was repeated for 10 cycles without significant changes in the UVvis spectra (Figure S8 in the SI). Note that the Pd-MNPs were reused in the next cycle with almost consistent catalytic activity. When Pd-MNPs were replaced with the unfunctionalized MNPs, no reversible switching between 1 and 11 was observed (Figure S9 in the SI). The result suggests that reduction of 11 back to 1 was indeed catalyzed by Pd attached onto the MNPs. Our studies indicate that the pyrrolocoumarin 1 and the tertiary alcohol 11 are interchangeable and can be converted from one to the other using UV light and H2 as two external stimuli with two discernible output properties. In this bistable redox-switching system, O2 is employed as the oxidizing agent and H2 as the reducing agent. Since the former is an ultimate oxidant, as it is virtually unlimited and free, and the latter is an ideal reductant with the smallest molecular weight and generates no waste, we believe that the interconversion between 1 and 11 could be considered as a (13) Liu, J. M.; Peng, X. G.; Sun, W.; Zhao, Y. W.; Xia, C. G. Org. Lett. 2008, 10, 3933–3936.
Org. Lett., Vol. 15, No. 11, 2013
Figure 5. Absorption spectra of 11 (1.5 105 M in CH2Cl2) obtained with different exposure times to bubbling H2 gas, HCO2H (1.0 106 M), and Pd-MNPs (2 mg), 0 to 2 m, in increments of 0.5 m.
“near-perfect” redox-switching reaction, as it proceeds through a highly atom-economical and almost waste-free manner (the only byproduct generated is water). In summary, two new pyrrolocoumarins 1 and 2 were synthesized and characterized via acid-catalyzed intramolecular cyclization of 6 and 7, respectively. Both compounds were found to be highly light-sensitive and change colors upon UV irradiation. We have demonstrated that the reversible switching between the pyrrolocoumarin 1 and the tertiary alcohol 11 can be realized by utilizing photooxidation and chemical reduction as two external stimuli with two easily detectable output properties, that is, color change and emission variation. Further photochemical and redox-switching studies on other related pyrrolocoumarin systems are currently in progress. Acknowledgment. We thank the National Science Council of the Republic of China, Taiwan, for financially supporting this research under Contract No. NSC 100-2113M-029-005-MY2. Supporting Information Available. Synthesis of 1, 2, 6, 7, and 12; experimental details; additional spectra; and X-ray crystal structure details for 1, 2, 6, 7, 10, and 11 (CIF). This material is available free of charge via the Internet at http://pubs.acs.org. The authors declare no competing financial interest.
2805
