Synthesis and Photophysical Properties of 2-Aryl-6,8-bis(arylethenyl)-4-methoxyquinolines

Iodine-methanol mediated oxidative-aromatization of 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones afforded the corresponding 2-aryl-6,8-dibromo-4-methoxy-quinolines in high yield and purity. The isomeric 1-(2-amino-3,5-dibromophenyl)-3-aryl-2-propen-1-ones reacted with iodine in methanol afford in a single pot operation the corresponding 2-aryl-6,8-dibromo-4-methoxyquinoline (major) and 2-aryl-6,8-dibromoquinolin-4(1H)-one (minor) products that were separated in sequence by column chromatography on silica gel. Suzuki-Miyaura cross-coupling of the 6,8-dibromo-4-methoxyquinoline derivatives with excess arylvinylboronic acids afforded the corresponding 2-aryl-6,8-bis(2-arylethenyl)-4-methoxyquinolines. The absorption and fluorescence properties of these compounds were also determined.

Application of dichlorobis-(triphenylphosphine)palladium(II) (PdCl 2 (PPh 3 ) 2 as Pd(0) catalyst source, on the other hand, led to incomplete conversion of 4a to afford the cross-coupled product 6a in 55% yield after 18 h. The prolonged reaction times and reduced yield prompted us to use PdCl 2 (PPh 3 ) 2 -tricyclohexylphosphine catalyst complex in DMF-water (3:1, v/v) and an excess of arylboronic acid (2.5 equiv.) in the presence of K 2 CO 3 as a base in analogy with the literature precedents [23,24,27] and we achieved complete conversion of 4a to 6a within 3 h. Alkylphosphine ligands, are known to coordinate with palladium and increase its electron density more so than arylphosphines and, in turn, accelerate the oxidative addition and reductive elimination steps in the catalytic cycle [28,29]. Extension of these reaction conditions to other dibromoquinolines 4 using 4-substituted phenyvinylboronic acids as coupling partners afforded the corresponding 2-aryl-6,8-bis(2-arylethenyl)-4-methoxyquinolines 6a-l in high yield without the need for column chromatography (Scheme 4).   Reagents and conditions: (i) ArCH = CHB(OH) 2 (2.5 equiv.), PdCl 2 (PPh 3 ) 2 , PCy 3 , K 2 CO 3 , dioxane-water The analogous aryl, alkenyl and alkynyl substituted quinoline derivatives have been found to serve as potent inhibitors of tyrosine kinase PDGF-RTK [30], and anti-retroviral agents [31] or LTD 4 receptor antagonists [32]. The 4-alkoxy-3,6-diarylquinolines, on the other hand, are reported to exhibit potent and selective agonism of the somatostatin receptor subtype 2 (sst 2 ) and to represent promising agents for the treatment of diabetic retinopathy and proliferative diseases [33]. Likewise, the 6-or 8-aryl substituted 2,4-dimethoxyquinolines were found to exhibit high activity against the agriculturally important nematode, Haemonchus contortus with potency comparable to that of the commercially available levamisole [34]. Systems 6a-l are also analogues of the 2-aryl-3,4-bis(phenylethenyl) quinolines and the 3,4-bis(alkynyl)-2-arylquinolines with potential to serve as molecular organic materials in nanomaterials or building blocks for polyquinolines or quinoline-based copolymers with enhanced photonic and electronic properties [35].

Photophysical Property Studies of Systems 6
Polysubstituted quinolines 6a-l comprise an electron-deficient quinoline framework as an electron-acceptor linked to the 4-substituted aryl ring via a π-conjugated spacer to comprise a donor-π-acceptor system. Preliminary absorption and fluorescence properties of systems 6a-l were determined in chloroform at room temperature.

UV-Vis Absorption Properties of 4-Methoxyquinoline Derivatives 6
The electronic absorption spectra of the 4-methoxyquinoline derivatives 6a-l were acquired in CHCl 3 and the compounds absorb in the region μ 310-390 nm ( Figure 1). The absorption spectra of these compounds are characterized by intense absorption peaks near 310-350 nm and the less intense ones around 360-380 nm. The band in the region 310-350 nm is due to π-π* transition attributed to the conjugated quinoline ring of the molecule in analogy with the assignment for π-styrylquinolines [36], whereas the lowest energy band which is largely of charge transfer character is due to the 2-aryl group.
Both the absorption maxima and wavelength are influenced by the variation of substituents on the arylvinyl and the 2-aryl groups. Compounds 6d, 6f, 6i and 6k showed strong UV-vis absorption intensities at around 340 nm reflecting the following trend in intensity: 6d > 6k > 6i > 6f. A combination of the strong electron donating 2-(4-methoxyphenyl) group and moderately donating 4-fluorophenylvinyl substituents in 6d seem to increase the electron density of the quinoline ring thus the π-π* transition. A combination of the relatively less donating 2-(4-chlorophenyl) group or 2-phenyl group and the two 4-methoxyvinyl substituents on the fused benzo ring also enhance the absorptivities for 6f and 6i, respectively. Enhanced intensity comparable to that of 6f but at different wavelength is also observed for 6h bearing the 2-(4-methoxyphenyl) group and the two 4-chlorophenylvinyl groups. Except for the 2-(4-methoxyphenyl) substituted derivative 6d, it seems the presence of 4-fluorophenyl moieties in 6a, b and c led to reduced absorption intensities than for derivatives bearing chloro atoms on the styryl groups. It appears the presence of the chloro atoms increase the electron affinity of the quinoline ring than the fluoro atoms.  The fluorescence spectra of these compounds show similar pattern and are characterized by a single emission band in the region 410-490 nm, which are attributed to π-π* transition of the conjugated system. The fluorescence patterns of compounds 6a-l are affected by the presence of the halo substituents on the styryl and 2-phenyl groups [37]. Systems 6c and 6f with mixed halides (F and Cl) on either the 2-phenyl or styryl groups show increased emission and slight bathochromic shifts. A combination of the 2-(4-methoxyphenyl) and 4-fluorophenylvinyl derivative 6d significantly reduces the emission intensity than the other derivatives bearing the 4-fluorophenylvinyl substituents. Increased emission and pronounced red shift effect are also observed for 6i bearing the 2-phenyl and 4-methoxystyryl groups. The increased intensities and bathochromic shifts are presumably the result of increased π-electron delocalization along the vinylene bridge and/or the 2-aryl group towards the electron-deficient quinoline ring.

General
Melting points were recorded on a Thermocouple digital melting point apparatus and are uncorrected. IR spectra were recorded as powders using a Bruker VERTEX 70 FT-IR Spectrometer with a diamond ATR (attenuated total reflectance) accessory by using the thin-film method. For column chromatography, Merck kieselgel 60 (0.063-0.200 mm) was used as stationary phase. NMR spectra were obtained as CDCl 3 solutions using Varian Mercury 300 MHz NMR spectrometer and the chemical shifts are quoted relative to the solvent peaks. Low-and high-resolution mass spectra were recorded at an ionization potential of 70eV using Micromass Autospec-TOF (double focusing high resolution) instrument. The synthesis and characterization of substrate 1 have been described elsewhere [38]. The UV-vis spectra were recorded on a Perkin Elmer Lambda 35 UV/vis spectrometer while emission spectra were taken using a Perkin Elmer LS 45 fluorescence spectrometer.

Crystal Structure Solution and Refinement
X-ray quality crystals of the title compound 3b were obtained by slow crystallization from ethanol solution. Intensity data were collected on a Bruker APEX II CCD area detector diffractometer with graphite monochromated Mo K  radiation (50 kV, 30 mA) using the Bruker APEX 2 [39] data collection software. The collection method involved -scans of width 0.5° and 512 × 512 bit data frames. Data reduction was carried out using the program Bruker SAINT+ [40]. The crystal structure was solved by direct methods using Bruker SHELXTL [41]. Non-hydrogen atoms were first refined isotropically followed by anisotropic refinement by full matrix least-squares calculations based on F 2 using SHELXTL. Hydrogen atoms were first located in the difference map then positioned geometrically and allowed to ride on their respective parent atoms. Diagrams and publication material were generated using SHELXTL, PLATON [42] and ORTEP-3 [43]. Crystallographic parameters are summarized in Table 1.

Conclusions
The generality, brevity and operational simplicity of iodine/methanol-mediated oxidative aromatization reaction of the 2-aminochalcones or their 2,3-dihydroquinolin-4(1H)-one isomers and the accompanying high yields make this methodology a suitable alternative to metal-catalyzed aromatization and subsequent methylation or oxidative aromatization-dechloromethoxylation of related derivatives. Elaboration of the 6,8-dibromoquinoline scaffold via Suzuki-Miyaura cross-coupling with arylvinylboronic acids, on the other hand, afforded polysubstituted quinoline derivatives that would not be easily accessible via the known classical methods such as the Skraup, Friedlander and Doebner-von Miller reactions. The absorption and fluorescent properties of these compounds showed a strong correlation with the substituent groups on the styryl and the 2-phenyl groups with the halo substituents shifting both the absorption and emission maxima to shorter wavelengths. Many styrylquinolines prove to be dyes with enhanced photo-and electroluminescent properties and they find application in medicine and pharmacology [44]. The preliminary photophysical properties of compounds 6 serve as a prelude to compounds with potential photonic or electronic properties.