Letter pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Air-Stable N,N′‑Dihydroporphycene: A Quinoxaline-Fused Tetrapyrrolic Macrocycle That Detects Fluoride Anion via Deprotonation Ying Yin,†,‡ Tridib Sarma,† Fei Wang,† Ningning Yuan,†,‡ Zhiming Duan,*,† Jonathan L. Sessler,*,† and Zhan Zhang*,†,‡ †
Center for Supramolecular Chemistry and Catalysis, Shanghai University, 99 Shangda Road, Shanghai 200444, China College of Chemistry & Material Science, South-Central University for Nationality, Wuhan, Hubei 430074, China
‡
Org. Lett. Downloaded from pubs.acs.org by WEBSTER UNIV on 02/27/19. For personal use only.
S Supporting Information *
ABSTRACT: An air-stable N,N′-dihydroporphycene, the twoelectron reduced form of porphycene, possessing two quinoxaline moieties fused at meso positions, was prepared and characterized. Nuclear magnetic resonance (NMR) and ultraviolet−visible light (UV-vis) spectroscopic studies and single-crystal X-ray diffraction analyses support its formulation as a nonaromatic species. Upon treatment with tetrabutylammonium fluoride (TBAF) in chloroform, a color change is produced that is consistent with deprotonation. Selective detection of this anion is readily achieved.
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N,N′-Dihydroporphycene (Figure 1) is the cannonical twoelectron reduced form of porphycene. N,N′-Dihydroporphycenes resemble isophlorins, their analogues in the porphyrin series, and are typically unstable being oxidized spontaneously to porphycene upon exposure to air.8 Generally, N,N′dihydroporphycenes serve as nonisolated, direct precursors to porphycenes in the classic McMurry coupling-based synthesis introduced by Vogel.2 The lack of stability associated with these intermediates is readily understandable, not only because the corresponding porphycenes are energetically favored aromatic species, but because oxidation will reduce the repulsion among the inner hydrogen atoms in the reduced form. Perhaps not surprisingly, efforts to prepare and study N,N′-dihydroporphycenes as stand-alone synthetic targets have been limited. Vogel and co-workers employed catalytic hydrogenation to produce a meso-substituted N,N′-dihydroporphycene 2 and characterized the resulting structure by means of NMR and UV−vis absorption spectroscopy, as well as via single-crystal X-ray structural analysis (Figure 2).8 Hayashi et al. also reported a N,N′-dihydroporphycene 3 bearing CF3 groups at the β-pyrrolic positions.9 In the presence of an oxidant (air or 2,3-dichloro-5,6-dicyanoquinone (DDQ)), these N,N′-dihydroporphycenes were found to convert to the corresponding porphycenes. This provided important support for the notion that N,N′-dihydroporphycenes were, in fact, key intermediates in the synthesis of
orphycene is the most venerable and best studied constitutional isomer of porphyrin (Figure 1).1 Since
Figure 1. Relationship between N,N′-dihydroporphycene and porphycence (left) and isophlorin and porphyrin (right).
the first report by Vogel and co-workers,2 great efforts have been made to synthesize and functionalize porphycenes and to prepare new derivatives. These studies have been motivated in part by an appreciation that porphycenes possess Q-like absorption features in the ultraviolet−visible light (UV-vis) spectral region that are red-shifted and more intense, relative to those typically seen for porphyrins.1,3 Such optical characteristics, combined with efficient triplet-state generation, have made porphycenes attractive for use in certain biological applications, including photodynamic therapy.4 It has been found that adding synthetically fused benzene/aromatic ring(s) at the meso position(s) can further shift the Q-like transitions into the near IR region (λmax = 800−1000 nm).5 Expanding the porphycene core by embedding benzene units also leads to a dramatic bathochromic shift in the absorption features.6 These findings provide an incentive to generate new structures related to porphycenes.6,7 © XXXX American Chemical Society
Received: February 1, 2019
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DOI: 10.1021/acs.orglett.9b00445 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
condensation with o-diaminobenzene 1 was obtained in moderate yield. N,N′-Dihydroporphycene 1 was characterized initially via 1 H NMR spectroscopy. The chemical shift pattern (see the Supporting Information) was fully consistent with the assignment of 1 as a nonaromatic species, despite the presence of a formal 20 π-electron circuit within the system. Both the peripheral alkyl C−H protons and the quinoxaline C−H protons resonate in the region expected for a nonaromatic species (i.e., in the normal alkyl and aromatic regions, respectively). The inner NH protons resonate at 7.2 ppm as expected. An integration of the NH signals proved consistent with the presence of four inner NH protons. Further MALDITOF mass analysis of 1 proved consistent with the molecular formula of C46H51N8. Taken in concert, we conclude that 1 as isolated is at the N,N′-dihydroporphcene oxidation state and is not converted spontaneously to the corresponding porphycene, as is true for most other analogous species. In fact, target 1 proved so stable that, as yet, we have been unable to isolate the corresponding porphycene, either by exposure to air or treatment with standard oxidants, such as tetrachloroquinone (chloranil), DDQ, and FeCl3. The single-crystal X-ray diffraction analysis of 1 provided support for the inferences drawn from the 1H NMR spectroscopic experiments (vide supra; see also Figure 3).
Figure 2. N,N′-Dihydroporphycences 1−4 and calix[4]pyrrole.
porphycene. In contrast to Vogel and Hayashi, Yamada and coworkers reported a dodecasubstituted dihydroporphycene 4 and claimed that it resisted oxidation when exposed to air or DDQ.10 However, this finding has yet to be generalized. Moreover, the chemical properties of this and other reduced porphycene species have not been studied in detail. Here, we report a meso-quinoxaline-fused N,N′-dihydroporphycene 1 and show that, in chloroform solution, this air stable species can differentiate fluoride out of a series of test anions via an anion-specific deprotonation mechanism. In an effort to produce a stable reduced porphycene potentially suitable for detailed study, we designed the quinoxaline-fused N,N′-dihydroporphycene 1. The quinoxaline subunits were embedded into 1 for two reasons. First, they were expected to extend the π-electron periphery and shift the absorption bands further into the red portion of the spectral region. Second, they would increase the rigidity of the system, thereby enhancing the air stability of the system. The synthesis of compound 1 is shown in Scheme 1. Briefly, the known bipyrrole 511 was subject to partial hydrolysis to Scheme 1. Synthesis of N,N′-Dihydroporphycene 1
Figure 3. Single-crystal structure of 1: front view (top) and side view (bottom) (CCDC No. 1874161).
Bond lengths consistent with C−C single bonds are observed for the intrapyrrolic linkages within the bipyrrole subunits (average = 1.466 Å), as well as between the pyrrolic and diazine moieties (C−C bond average = 1.470 Å). The meso C−C bonds are also elongated, relative to what is seen in porphycenes (1.462 Å on average in 1 vs ≤1.400 Å in porphycene2,12 or 1.454 Å in meso-dibenzoporphycene5). In contrast to porphycene, macrocycle 1 is highly ruffled and is characterized by an alternating up−down−up conformation. The dihedral angle between the neighboring pyrrole rings is 89° while that between the pyrrole and diazine rings is 41°. This distortion is ascribed to steric interactions between the inner hydrogen atoms, as well as perhaps repulsions between the peripheral alkyl groups. The nonplanarity of 1 is considered likely to reduce the efficiency of π-orbital overlap within the system as a whole and likewise make the pyrrole NH protons more accessible for interaction with Lewis bases. The structure of 1, in particular the existence of four acidic NH groups, bears resemblance to that of calix[4]pyrrole (Figure 2), a system well-known for its anion recognition features. Therefore, we tested the response of N,N′dihydroporphycene 1 toward anions. This was done by adding
give the bipyrrole carboxylic acid 6. Subsequent decarboxylation afforded the mono-α-free bipyrrole 7. Linking two molecules of 7 through consecutive acylation with oxalyl chloride, followed by condensation with o-diaminobenzene, resulted in the quinoxaline-fused tetrapyrrole 8. Heating 8 at reflux in ethylene glycol, in the presence of excess sodium hydroxide, led to the α-free tetrapyrrole 9, which is the key precursor to 1. Following macrocyclization involving another sequence of acylation with oxalyl chloride and in situ B
DOI: 10.1021/acs.orglett.9b00445 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters tetrabutylammonium (TBA+) salts of representative test anions, including those of F−, Cl−, Br−, NO3−, H2PO4−, and ClO4−, to chloroform solutions of 1. As can be seen from an inspection of Figure 4, a clear color change was observed only
low temperature and those of NHs protons at room temperature were consistent with the proposed deprotonation. 19 F NMR spectroscopic analyses of samples treated with TBAF were also performed (see the Supporting Information); again, evidence of deprotonation of 1 by the fluoride anion was seen. Specifically, a bifluoride anion resonance (δ = −155 ppm) was seen whether the spectrum was recorded in DMSOd6 at room temperature or in DCM-d2 at low temperature. Consistent with the 1H NMR spectral studies, the 19F signal of the bifluoride anion was not readily apparent at room temperature when the spectrum was recorded in DCM-d2; however, a new peak with a chemical shift of ca. −10 ppm was seen. The lack of readily observable bifluoride anion signal in DCM-d2 (as well as in chloroform-d) at room temperature is rationalized in terms of the relatively nonpolar properties of these solvents (as compared to DMSO-d6) and their commensurately lower ability to stabilized charged species. When considered in aggregate, the NMR spectroscopic evidence thus provides support for the conclusion that the spectroscopic and colorimetric response produced by the fluoride anion is due to deprotonation, rather than NH-Lewis base binding per se. Since deprotonation dominated this anion recognition process, compound 1 was also treated with tetrabutylammonium hydroxide (TBAOH). As expected, a significant color change was observed upon the addition of TBAOH. However, the resulting solution was blue, rather than orange, as seen for the samples treated with TBAF. This is ascribed to differing degrees of deprotonation being engendered by these two anions (F− vs OH−). However, it could also reflect differences in the host−guest interactions, including those involving the bifluoride anion produced as the result of fluoride anionmediated NH deprotonation. Efforts to distinguish between these two limiting mechanistic scenarios are ongoing. In summary, we report the synthesis and fluoride recognition features of an air-stable N,N′-dihydroporphycene 1. In analogy to what has been seen in the case of the dodecasubstituted porphycene 4, this N,N′-dihydroporphycene is nonaromatic, in terms of its electronic features. This proposed lack of aromaticity is reflected in a highly nonplanar structure, as seen in the solid state. On the basis of NMR spectral studies, it was concluded that the reduced porphycene 1 could recognize the fluoride anion with high selectivity, but does so via a deprotonation, rather than an anion recognitionbased mechanism.
Figure 4. Photograph of chloroform solutions of 1 seen in the absence and presence of various anions (studied as their tetrabutylammonium (TBA+) salts).
in the case of the fluoride anion salt. The same phenomena were observed when dichloromethane was used as the solvent. Since pseudohalogens, such as the cyanide anion, often produce a response with hydrogen-bond-based anion receptors, the interaction of cyanide anion with 1 was further examined, but little appreciable color change was observed. It is well-known that fluoride is a relative strong base that can deprotonate acidic hydrogens to generate bifluoride anion (HF2−).13 However, it can also interact with pyrrolic NH groups through hydrogen bonding interactions, as in the case with calix[4]pyrrole under many conditions.14 These two distinct mechanisms could independently or jointly lead to the observed changes in the UV-vis absorption features and account for the color differences. In order to obtain insight into which mechanism, if either, is predominant in our case, we performed room-temperature and variable-temperature (VT) 1 H NMR spectral studies, as well as 19F NMR spectral analyses in several deuterated solvents. Signals corresponding to the bifluoride anion, the expected product of deprotonation by fluoride, were clearly seen in the 1 H NMR spectrum in the range of 15−17 ppm in DMSO-d6 at room temperature (see the Supporting Information). When CD2Cl2 (DCM-d2) or CDCl3 (chloroform-d) were used as the NMR solvents, bifluoride signals were not observed at room temperature. However, they were observed at lower temperatures while the NH signals were seen to flatten and broaden (see Figure 5). Although subject to error (i.e., limited precision) the integrals of the bifluoride proton signals at
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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.9b00445. Synthetic experimental, additional spectroscopic information, and structural data (PDF) Accession Codes
CCDC 1874161 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 emailing
[email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Figure 5. Partial VT 1H NMR spectra of 1 recorded with 2 equiv of TBAF in DCM-d2. C
DOI: 10.1021/acs.orglett.9b00445 Org. Lett. XXXX, XXX, XXX−XXX
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(8) Vogel, E.; Grigat, I.; Köcher, M.; Lex, J. A PyrrolophanedienePorphycene Redox System. Angew. Chem., Int. Ed. Engl. 1989, 28, 1655−1657. (9) Matsuo, T.; Ito, K.; Kanehisa, N.; Hayashi, T. A Structural Isomer of Nonaromatic Porphyrin: Preparation of 20π-Conjugated Porphycene Based on Electronic Perturbation. Org. Lett. 2007, 9, 5303−5306. (10) Kuzuhara, D.; Yamada, H.; Yano, K.; Okujima, T.; Mori, S.; Uno, H. First Synthesis of Dodecasubstituted Porphycenes. Chem. Eur. J. 2011, 17, 3376−3383. (11) (a) Shevchuk, S. V.; Davis, J. M.; Sessler, J. L. Synthesis of sapphyrins via a ‘3+1+1’ procedure. Tetrahedron Lett. 2001, 42, 2447−2450. (b) Brö ring, M.; Link, S. First Synthesis of a Conformationally Restricted 2, 2’-Bipyrrole. Synthesis 2002, 2002, 67−70. (12) Sarma, T.; Panda, P. K.; Anusha, P. T.; Rao, S. V. Dinaphthoporphycenes: Synthesis and Nonlinear Optical Studies. Org. Lett. 2011, 13, 188−191. (13) Ghosh, S. K.; Ishida, M.; Li, J.; Cha, W.-Y.; Lynch, V. M.; Kim, D.; Sessler, J. L. Synthesis and anion binding studies of ophenylenevinylene-bridged tetrapyrrolic macrocycle as an expanded analogue of calix[4]pyrrole. Chem. Commun. 2014, 50, 3753−3756. (14) Gale, P. A.; Sessler, J. L.; Král, V.; Lynch, V. Calix[4]pyrroles: Old Yet New Anion-Binding Agents. J. Am. Chem. Soc. 1996, 118, 5140−5141.
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected] (Zhan Zhang). *E-mail:
[email protected] (Jonathan L. Sessler). *E-mail:
[email protected] (Zhiming Duan). ORCID
Zhiming Duan: 0000-0002-8332-6131 Jonathan L. Sessler: 0000-0002-9576-1325 Author Contributions
Z.Z., J.L.S., and Z.D. designed the study and supervised the work. Y.Y. synthesized the macrocycle and carried out the property studies with the help of T.S., F.W., and N.Y. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The work was supported by the National Natural Science Foundation of China (Grant No. 21672141 to Z.Z.) and Shanghai University (J.L.S.).
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REFERENCES
(1) (a) Waluk, J. Spectroscopy and Tautomerization Studies of Porphycenes. Chem. Rev. 2017, 117, 2447−2480. (b) Anguera, G.; Sánchez-García, D. Porphycenes and Related Isomers: Synthetic Aspects. Chem. Rev. 2017, 117, 2481−2516. (c) Sánchez-García, D.; Sessler, J. L. Porphycenes: synthesis and derivatives. Chem. Soc. Rev. 2008, 37, 215−232. (2) Vogel, E.; Köcher, M.; Schmickler, H.; Lex, J. Porphycene, a new type of porphine isomer. Angew. Chem., Int. Ed. Engl. 1986, 25, 257− 259. (3) Starukhin, A.; Vogel, E.; Waluk, J. Electronic Spectra of Porphycenes in Rare Gas and Nitrogen Matrices. J. Phys. Chem. A 1998, 102, 9999−10006. (4) (a) Braslavsky, S. E.; Müller, M.; Mártire, D. O.; Pörting, S.; Bertolotti, S. G.; Chakravorti, S.; Koç-Weier, G.; Knipp, B.; Schaffner, K. Photophysical properties of porphycene derivatives (18 π porphyrinoids). J. Photochem. Photobiol., B 1997, 40, 191−198. (b) Stockert, J. C.; Canete, M.; Juarranz, A.; Villanueva, A.; Horobin, R. W.; Borrell, J. I.; Teixido, J.; Nonell, S. Porphycenes: facts and prospects in photodynamic therapy of cancer. Curr. Med. Chem. 2007, 14, 997−1026. (c) Arnbjerg, J.; Jiménez-Banzo, A.; Paterson, M. J.; Nonell, S.; Borrell, J. I.; Christiansen, O.; Ogilby, P. R. Two-Photon Absorption in Tetraphenylporphycenes: Are Porphycenes Better Candidates than Porphyrins for Providing Optimal Optical Properties for Two-Photon Photodynamic Therapy? J. Am. Chem. Soc. 2007, 129, 5188−5199. (5) (a) Oohora, K.; Ogawa, A.; Fukuda, T.; Onoda, A.; Hasegawa, J.y.; Hayashi, T. meso-Dibenzoporphycene has a Large Bathochromic Shift and a Porphycene Framework with an Unusual cis Tautomeric Form. Angew. Chem., Int. Ed. 2015, 54, 6227−6230. (b) Sarma, T.; Panda, P. K. Annulated Isomeric, Expanded, and Contracted Porphyrins. Chem. Rev. 2017, 117, 2785−2838. (6) Anguera, G.; Cha, W.-Y.; Moore, M. D.; Brewster, J. T., II; Zhao, M. Y.; Lynch, V. D.; Kim, D.; Sessler, J. L. An Expanded Porphycene with High NIR Absorptivity That Stabilizes Two Different Kinds of Metal Complexes. Angew. Chem., Int. Ed. 2018, 57, 2575−2579. (7) (a) Ono, T.; Koga, D.; Yoza, K.; Hisaeda, Y. The first synthesis of meso-dicycloalkylporphycenes: ring strain effects on structural and optical properties of isomeric porphyrins. Chem. Commun. 2017, 53, 12258−12261. (b) Kuzuhara, D.; Sakaguchi, M.; Furukawa, W.; Okabe, T.; Aratani, N.; Yamada, H. Synthesis, Characterization and Protonation Behavior of Quinoxaline-Fused Porphycenes. Molecules 2017, 22, 908−823. D
DOI: 10.1021/acs.orglett.9b00445 Org. Lett. XXXX, XXX, XXX−XXX
