The C18 macro-aromatic carbo-benzene core is a strong chromophoric unit resembling the porphine ring which is prone to quench the emission of fluorophoric substituents. Within the aim of preparing fluorescent carbo-benzenes (and carbo-cyclohexadiene parents) for measurement of their two-photon absorption cross-section by the TPEF method, several indole derivatives were devised and anchored to the C18 macrocycle either directly, p-phenylogously or ethynylogously. Synthesis methodology and spectroscopical measurements are presented in a comparative prospec

Baglai, Iaroslav

Chauvin, Remi

Maraval, Valérie

Voitenko, Zoia

Volovenko, Yulian

English

French-Ukrainian Journal of Chemistry

FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY (2013, VOLUME 1, ISSUE 1)  48  Towards fluorescent indolyl-carbo-benzenes  Iaroslav Baglaia,b, Valérie Maraval*b, Zoia Voitenkoa , Yulian Volovenkoa, Remi Chauvin*b a Kiev National Taras Shevchenko University, 60 Volodymyrska St, 01033 Kiev, Ukraine. b CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France. Université de Toulouse, UPS, INPT, F-31077 Toulouse, France. vmaraval@lcc-toulouse.fr, chauvin@lcc-toulouse.fr  The C18 macro-aromatic carbo-benzene core is a strong chromophoric unit resembling the porphine ring which is prone to quench the emission of fluorophoric substituents. Within the aim of preparing fluorescent carbo-benzenes (and carbo-cyclohexadiene parents) for measurement of their two-photon absorption cross-section by the TPEF method, several indole derivatives were devised and anchored to the C18 macrocycle either directly, p-phenylogously or ethynylogously. Synthesis methodology and spectroscopical measurements are presented in a comparative prospect.    Introduction Most recent efforts in carbo-mer chemistry[1] focused on the synthesis of p-disubstituted carbo-benzenes[2], essentially because of promising theory-predicted third-order non-linear optical (NLO) properties, and more particularly Two-Photon Absorption (TPA) properties which can be more generally anticipated for generic quadrupolar pi-extended systems[3]. As the measurement of TPA cross-section is classically performed by the Two-Photon Excited Fluorescence (TPEF) method applicable to fluorescent molecules only, the synthesis of fluorophore-p-disubstituted carbo-benzenes was envisaged. The p-dianisyl-carbo-benzene 1[2a], which is the central ring carbo-mer of the terphenyl fluorophore 2[4], was first targeted and synthesized, but appeared to exhibit almost no fluorescence (Figure 1). Anchoring of indolyl fluorophores to a carbo-benzene core was then envisaged, either directly, or through different conjugated linkers. The synthesis and properties of such p-bis-indolyl-carbo-benzenes are described hereafter. The influence of both the linker (simple bond,   Figure 1. Targeted fluorophore-p-disubstituted carbo-benzenes.  p-phenylene or ethynylene), and the anchoring atom in the indole unit (N or C3) on the FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY (2013, VOLUME 1, ISSUE 1)  49 spectroscopic and optical properties of the carbo-chromophores are then considered.   Results and discussion  The synthesis of fluorophore-p-disubstituted carbo-benzenes was performed from a common [6]pericyclynedione key precursor 3 (Scheme 1), whose preparation in 9 steps and 7 % overall yield had been optimized[5]. The Grignard reactant of commercially available p-bromophenyl-N-indole 4 and the lithium derivatives of the 3-bromoindole 5[6] and indol-3-ylacetylene 6[7] were added to the same [6]pericyclynedione 3. The obtained [6]pericyclynediol products 7, bearing p-N-indolylphenyl substituents, and 9, bearing C-indolylacetylene substituents, could be isolated in 66 and 61 % yield respectively, while the bis-C-indolyl-substituted macrocycle 8 was found to be poorly stable and could not be purified[8]. In view of performing the macro-aromatization step to the bis-indolyl-carbo-benzene targets, the [6]pericyclynediols 7-9 were then treated with SnCl2/HCl in DCM, followed by aqueous NaOH. The bis-indolyl precursors 7 and 8 thus gave the expected carbo-benzenes 10 (in 71 % yield from 7) and 11 (in 3 % yield from 3 over 2 steps) respectively, but the bis-alkynyl- substituted substrate 9 did not furnish the expected carbo-benzene 12 upon such acidic reductive conditions (Scheme 2). Indeed, the OOMePh PhMeOOOMeMeOPh Ph 1) 22) H+NEtPhBrPhOMeOMePhOMePhOMePhHOOH53+ 2 n-BuLi1) 22) H+Br N+ MgPhOMeOMePhOMePhOMePhHOOHN EtPhPhEt N1) 22) H+NEtPh 6+ 2 n-BuLi4HPhOMeOMePhOMePhOMePhHOOHN EtPhPhEtNNN7, 66 %89, 61 %Scheme 1. Double nucleophilic addition of indolyl substituents to the [6]pericyclynedione 3.  process of reductive aromatization of 9 appeared to be poorly selective, giving three highly colored spots on TLC plates of the reaction mixture, and after treatment, none of the chromophoric products were found to correspond to the targeted bis-alkynyl-carbo-benzene 12. The main product isolated by flash chromatography was the bis-chloroalkenyl-  Scheme 2. Reductive aromatization of the bis-indolyl- [6]pericyclynediol substrates 7-9 (Scheme 1). carbo-benzene 13 resulting from the regio- and stereo-selective addition of HCl onto the two FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY (2013, VOLUME 1, ISSUE 1)  50 external triple bonds of 9, likely induced by the combined pi-donor effect of both the electron-rich C18 ring and the adjacent indole moieties (Scheme 3). This situation has been termed as a “pi-frustration” between facing pi-electron rich moieties in a given molecule[2c,7b]. The carbo-chromophore 13 was found to react with traces of water on silicagel to give two other carbo-benzenes 14 and 15. These two products result from mono- and di-hydrolysis of one or both the chloroalkenyl groups of 13, respectively, during purification on silicagel. The sensitivity of the chloroalkenyl groups of 13, giving methylene ketone motifs in the presence of traces of acids, can be ascribed again to the combined pi-donor effects, or pi-frustration, of the neighboring indole and C18 aromatic rings. Hydrolysis of chloroalkenes into methylene ketones indeed generally requires the use of much harsher conditions[9]. Scheme 3. Synthesis of the bis-chloroalkenyl-carbo-benzene 13 and its hydrolysis products 14 and 15.  The three carbo-benzenes 13-15 were obtained in a global 7 % yield from 9 and, in spite of their low stability, could be well characterized by MS and NMR spectroscopy. Full NMR studies (including 2D experiments) allowed confirmation of the proposed structures[7b]. It is noteworthy that the ethylenic protons of 13 and 14, resonating at 8.4 and 8.5 ppm respectively in 1H NMR, are quite deshielded because of their proximity with the strong diatropic ring current of the aromatic macrocycle. The structures of the carbo-benzenes 11 and 13 were confirmed by X-ray diffraction analysis of single crystals deposited from DCM solutions (Figure 2).  As compared to the bis-indolylphenyl-carbo-benzene 10, the poor stability of the bis-chloroalkenyl-carbo-benzene 13 (where the indole moieties are separated from the C18 ring by conjugated bridges of similar lengths) was explained by an enhanced pi-frustration in 13 resulting from the more efficient conjugation through the linear ethylenic linkers of 13 than through the cyclic, aromatic, and thus insulating, phenylene linkers of 10[7b]. The two hydrolyzed carbo-benzenes 14 and 15 also appeared to be poorly stable despite the loss of direct conjugation between the indole moieties and the macrocycle through methylene ketone linkers. A possible explanation for this sensitivity could be the persistence of a conjugation (and so of a pi-frustration) through the enolic form of the methylene ketone groups, and/or the enhanced reactivity of the oxygen  FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY (2013, VOLUME 1, ISSUE 1)  51   Figure 2. XRD molecular views of 11 (top) and 13 (bottom).  atom due to the pi-donor effect of the adjacent indole unit. Alternatively, a prototropic rearrangement of the acidic methylene groups and adjacent butyne/butatriene edges of the carbo-benzene ring, leading to a conjugated keto group, could initiate the de-aromatization and degradation of the former. The absorption spectra of the five indolyl-substituted carbo-benzenes 10, 11, 13-15 were recorded in chloroform solutions (Figure 3)[10]. By comparing the carbo-benzenes 10 and 13 having the same conjugation extent, and the largest in the series, one can see that the λmax value of 13 (515 nm) is much higher than that of 10 (486 nm, ∆λmax = 29 nm), thus showing that the conjugation through a linear ethylenic linker is more efficient than through a cyclic and aromatic phenylene linker. The carbo-benzene  Figure 3.  UV-vis absorption spectra of indolyl-substituted carbo-benzenes 10, 11, 13-14 (in CHCl3).  13, having a large and efficient conjugation path, displays the highest λmax value of the whole series. Upon hydrolysis of a chloroalkenyl group (first from 13 to 14, then from 14 to 15), a 30 nm hypsochromic shift of the λmax value was observed, likely due to the loss of conjugation between the indole and the carbo-benzene moieties, when passing from a chloroalkene linker to a methylene ketone linker (even if a residual conjugation should occur in the enolic form). Finally, the carbo-benzene 11, where the indolyl substituents are directly connected to the aromatic macrocycle by the C3-atom, exhibits the expected hypsochromic shift of the λmax value (503 nm). This is due to the shorter conjugation extent in 11 as compared to 13 (λmax = 515 nm, ∆λmax = 12 nm) bearing the same C3- connected indolyl motifs, but here separated from the macrocycle by chloroalkene linkers.  The poor stability of the bis-indolyl-carbo-benzenes 13-15 prevented the determination of their emission properties. Nevertheless, emission spectra of the two stable representatives of the series (10 and 11) were FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY (2013, VOLUME 1, ISSUE 1)  52 recorded and were found to display quite different patterns. Indeed, while the p-N-indolylphenyl-substituted carbo-benzene 10 was reported to be very weakly fluorescent, exhibiting a unique small emission band at 595 nm, assigned to the residual fluorescence of the carbo-benzene core[2c], the p-bis-C-indolyl-carbo-benzene 11 was found to be strongly emitting at 305 nm upon excitation at 242 nm, this emission being assigned to the fluorescence of the indole moieties. A weak emission at 603 nm was also detected upon excitation at 503 nm and could be attributed to the carbo-benzenic core fluorescence (Table 1, Figure 3). So, the emission of the indole units is quenched in 10 (while its [6]pericyclynic precursor 7 strongly emits at 333 nm), but persists in 11. Such a quenching of the fluorescence was also recently observed in fluorene-substituted carbo-benzenes without p-phenylene linkers[11], but this phenomenon could not be clearly explained to date.  [6]pericyclynediols Carbo-benzenes # λmaxAbs λEm/λexc # λmaxAbs λEm/λexc 7 268(302) 333(481)/302 10 486 595/297 8 ─ ─ 11 503(242) 305/242 603/503 Table 1. Absorption (λmaxAbs) and emission (λEm) wavelengths of stable p-bis-indolyl-carbo-benzenes and precursors (in CHCl3, in nm, secondary bands in brackets).  Figure 3. Emission spectra of 11 in CHCl3 upon excitation at 242 nm (left) and at 503 nm (right: 500 times magnified vertical scale).  An interpretation could be a color quenching (re-absorption of the emitted photons by a strongly colored environment) in 10 due to its very large extinction coefficient (ε = 350 000 L.mol-1.cm-1) while that of 11 is much smaller (ε = 41 000 L.mol-1.cm-1).   Conclusions A series of p-bis-indolyl-carbo-benzenes, where the indole moieties are connected to the C18 macrocycle by different atoms of the fluorophore and through different linkers have been prepared, and their relative stability was interpreted by the proposition of the pi-frustration concept. The absorption and emission properties of the most stable representatives were studied and compared. The carbo-benzene 11, bearing indole units directly connected to the aromatic macrocycle by their C3 atom, appears as the first example of fluorescent carbo-benzene.  Acknowledgments. The purchase of supplies and costs of analyses were supported by the ANR (11-BS07-016-01). I.B. was supported by the French Embassy in Kiev, Ukraine, the FRENCH-UKRAINIAN JOURNAL OF CHEMISTRY (2013, VOLUME 1, ISSUE 1)  53 investigations having been performed within the framework of the GDRI (Groupement Franco-Ukrainien en Chimie Moléculaire).  References [1] (a) R. Chauvin, Tetrahedron Lett. 1995, 397-400; (b) V. Maraval, R. Chauvin, Chem. Rev. 2006, 106, 5317-5343. [2] (a) C. Saccavini, C. Sui-Seng, L. Maurette, C. Lepetit, S. Soula, C. Zou, B. Donnadieu, R. Chauvin, Chem.−Eur. J. 2007, 13, 4914-4931; (b) L. Leroyer, C. Lepetit, A. Rives, V. Maraval, N. Saffon-Merceron, D. Kandaskalov, D. Kieffer, R. Chauvin, Chem.−Eur. J. 2012, 18, 3226-3240; (c) A. Rives, I. Baglai, V. Malytskyi, V. Maraval, N. Saffon-Merceron, Z. Voitenko, R. Chauvin, Chem. Commun. 2012, 48, 8763-8765. [3] O. Mongin, L. Porrès, M. Charlot, C. Katan, M. Blanchard-Desce, Chem.−Eur. J. 2007, 13, 1481-1498. [4] J. M. Kauffman, C. J. Kelley, A. Ghiorghis, E. Neister, L. Armstrong, Laser Chem. 1988, 8, 335-348. [5] (a) C. Saccavini, C. Tedeschi, L. Maurette, C. Sui-Seng, C. Zou, M. Soleilhavoup, L. Vendier, R. Chauvin, Chem.−Eur. J. 2007, 13, 4895-4913; (b) L. Leroyer, C. Zou, V. Maraval, R. Chauvin, C. R. Chim. 2009, 12, 412-429.  [6] D. Kim, M.-S. Kang, K. Song, S. O. Kang, J. Ko, Tetrahedron 2008, 64, 10417-10424. [7] (a) I. Baglai, V. Maraval, C. Duhayon, R. Chauvin, Acta Cryst. 2013, E69, o921-o922; (b) I. Baglai, V. Maraval, C. Bijani, N. Saffon-Merceron, Z. Voitenko, Y. M. Volovenko, R. Chauvin, Chem. Commun. DOI: 10.1039/C3CC43204A.  [8] The instability of 8 was recently proposed to be induced by the pi-donation of the indolic N atom which can expel LiO− and give a reactive iminio enediyne intermediate. (a) M. Shiri, Chem. Rev. 2012, 112, 3508-3549; (b) I. Baglai, V. Maraval, Z. Voitenko, C. Duhayon, Y. M. Volovenko, R. Chauvin, submitted for publication. [9] (a) A. Bhattacharya, T. Vasques, T. Ramirez, R. E. Plata, J. Wu, Tetrahedron Lett. 2006, 47, 5581-5183; (b) H. Nemoto, S. Fujita, M. Nagai, K. Fukumoto, T. Kametani, J. Am. Chem. Soc. 1988, 110, 2931-2938; (c) S. Clough, J. Gupton, A. Ligali, M. Roberts, D. Driscoll, S. Annet, A. Hewitt, M. Hudson, E. Jackson, R. Miller, B. Norwood, R. Kanters, H. Wire, H. Petruzzi, Tetrahedron 2005, 61, 7554-7561. [10] The extinction coefficients of the poorly stable carbo-benzenes 13-15 were not determined. [11] I. Baglai, V. Maraval, R. Chauvin, unpublished results.  

Towards fluorescent indolyl-carbo-benzenes

http://kyivtoulouse.univ.kiev.ua/journal/index.php/fruajc/article/download/38/24

Towards fluorescent indolyl-carbo-benzenes

Abstract

Similar works

Full text

Available Versions

French-Ukrainian Journal of Chemistry