Synthesis, regioselective aerobic Pd (II)-catalyzed C-H bond alkenylation and the photophysical properties of pyrenylphenylpyrazoles

Synthesis, regioselective aerobic Pd (II)-catalyzed C-H bond alkenylation and the photophysical properties of pyrenylphenylpyrazoles Rafał Flamholc, Janusz Zakrzewski, Anna Makal, Arnaud Brosseau, Rémi Métivier, 1 Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland Uniwersity of Warsaw, Biological and Chemical Research Center, Żwirki i Wigury 101, 02089 Warszawa, Poland PPSM, ENS Cachan, CNRS, UniverSud, 61 av President Wilson, 94230 Cachan, France

Compounds 2a and 2b were characterized by 1 H and 13 C NMR spectroscopy and elemental analyses. Their structures were unambiguously established by single-crystal X-ray diffraction (vide infra).
The reaction afforded selectively, after 6 h of heating, the product of ortho-alkenylation of the phenyl ring 3 in an acceptable isolated yield (42%). The structure of 3 was confirmed by spectroscopic and analytical data. In particular, its 1 H NMR spectrum contained four one-proton signals (2 doublets and 2 triplets) in the 7.4-7.85 ppm region, which is a characteristic pattern of a 1,2-disubstituted benzene. The signals of the pyrene moiety (8.0-8.9 ppm) correspond to 9 protons and the splitting pattern is closely similar to that observed for 2a.
Finally, the olefinic protons give rise to two doublets (7.95 and 6.48 ppm) with J = 16 Hz confirming a trans configuration.
To the best of our knowledge, the reported reaction constitutes the first example of the alkenylation of a compound bearing the 1-phenylpyrazole moiety under Fujiwara-Moritani conditions (i.e. Pd(II) catalyst and oxidant for the recovery of Pd(II) reduced to Pd(0) in the catalytic cycle). It is worth noting that our system is environmentally benign (acetic acid is one of the solvents that is recommended by the Solvent Selection Guide 33 ) and inexpensive dioxygen is the sole oxidant (aerobic reaction). Furthermore, in our earlier work on alkenylation of pyrene using the same catalytic system 32 we found that this reaction also works when oxygen is replaced by air, but the yields of the products were lower.
We also attempted to perform the alkenylation of 2b, but we found that under the aforementioned conditions no reaction took place. In our opinion, this lack of reactivity of 2b may be explained by larger distortions from the planarity of the phenylpyrazole moiety in this compound in comparison with 2a. The generally accepted mechanism of directed C-H activation involves the formation of a cyclometalated intermediate i.e. a compound bearing the Pd atom bridging nitrogen and an ortho-carbon. We believe that the formation of such an intermediate from 2b would be less favorable than from 2a due the larger twist of the phenyl ring from the pyrazole plane in the former compounds (according to X-ray data 46°as compared with 27°found in 2a).

Photophysical properties of 2a-b and 3
The electronic absorption spectra of 2a-b and 3 in CHCl 3 (10 −5 M, Fig. 1a and Table 1) display features typical for a monomeric pyrene chromophore. They reveal only a weak solvent effect (see ESI †) suggesting a small transition moment. The absorption spectra of 2a and 3 are very similar. The absorption spectrum of 2b shows a more pronounced vibrational structure than 2a and 3, which may suggest a more rigid structure of the former compound in solution. A comparison of the λ max values of 2a and 3 (352 nm and 353 nm, respectively) shows that the introduced electron-poor alkenyl group practically does not influence the excitation energy of the fluorophore.
Compounds 2a-b and 3 emit fluorescence in solution and in the solid state. Fig. 1b shows their emission spectra recorded in deaerated, diluted (10 −6 M) chloroform solutions. The spectroscopic data are gathered in Table 1.
The more or less resolved vibrational structure of the absorption and emission bands of 2a-b may be due to various reasons such as different conformational rigidity, different deviations from planarity, different solvatation (e.g. formation of hydrogen bonds to pyrazole nitrogens). These bands may be attributed to a local excitation (LE) of the pyrenyl fluorophore. In contrast, 3 displays dual fluorescence. Its emission spectrum in CHCl 3 displays a structured band that is similar to that of 2a and a broad, featureless band with a maximum at 495 nm. Dual fluorescence is a phenomenon that is encoun- tered for some donor-acceptor π-systems, and is usually interpreted as a result of emission from an LE state and an excited state with intramolecular charge transfer (ICT). 34 It was observed for some biphenyl pyrene derivatives bearing electron withdrawing ester groups. 35 ICT emission was also observed for some pyrene-heterocycle systems and their metal complexes. [36][37][38][39] This means that the introduction of the lateral acrylic ester chain endowed 3 with an emissive low-lying ICT excited state. As expected, the relative contributions of the LE and ICT bands strongly depend on the polarity of the solvent (Fig. 2).
In a nonpolar solvent, hexane, only the LE band is observed with maxima at 395 and 405 nm. The emission quantum yield in this solvent reaches 0.59. In more polar solvents (chloroform and dichloromethane) the intensity of the LE band decreases and the ICT band appears. A careful analysis of the

Compound Absorption
Emission (λ excit = 345 nm) ICT band observed in chloroform and dichloromethane reveals the presence of two contributions, located at ∼500 and 550 nm, respectively. They can be tentatively assigned to two distinct conformations of the ICT excited state of 3. Finally, in highly polar solvents (methanol, acetonitrile) fluorescence is weak and the ICT band becomes very broad and hardly detectable. Since the largest difference is observed between hexane and chloroform we also measured the fluorescence of 3 in mixed hexane-chloroform solvents. The spectra are shown in Fig. 3. It can be observed that addition of up to 30% of chloroform to hexane brings about sharp changes in the emission spectra of 3. The intensity of the LE band drops down and the broad ICT band appears. However, the intensity of the ICT band decreases and the two relative contributions of the ICT bands evolve at higher chloroform contents which may be due to the decrease of the fluorescence quantum yield (0.59 in hexane and 0.42 in chloroform) and a change of the relative proportion of the different conformations of the ICT state.
We also performed a time-resolved study of fluorescence of the synthesized compounds in CHCl 3 solution. The fluorescence decay curves are shown in Fig. 4.
The fitting of these curves ( Table 2) revealed multiexponential decays, which is not surprising when taking into account the various possible conformations of the excited 2a-b and 3.
Interestingly, compound 2a showed a fast rise (τ ∼ 0.39 ns) of fluorescence following the laser pulse, which was observed at 390, 420 and 450 nm, thus suggesting that the emissive  state is formed by a fast relaxation of the initial Franck-Condon state. In our opinion, the rise time of 2a is probably due to some geometry reorganisation of the molecule in the excited state (such as planarisation of some conjugated substituent in the excited state).
At a longer time period two emissive components are clearly distinguishable with lifetimes of 2.68 and 4.68 ns. Two main decay times, 6.56 and 14.78 ns, were observed for 2b at 385 nm. However, at longer emission wavelengths (400 and 430 nm) a third component at 2.86 ns became important ( f 1 = 0.10-0.30).
Fitting of the fluorescence decay of 3 revealed three decay components. The two main ones ( f 2 + f 3 > 0.95) have been determined to be τ 2 = 3.75 and τ 3 = 8.38 ns. The contribution of the faster component τ 2 increased along with the increase in the monitoring wavelength and reached f 2 = 0.92 at 520 nm. Therefore, this component can be identified as corresponding to the ICT excited state. On the other hand, the slower component had the largest contribution in emission observed at 420 nm, thus corresponding to emission originating mainly from the LE state. The above data suggest the formation of both LE and ICT excited states of 3 during the laser pulse. The lifetime of the LE state is longer than that of the ICT state.
The data presented here show that dual fluorescence of 3 is sensitive to the polarity of the environment surrounding the fluorophore and, therefore, that this compound can be used as a fluorescent micropolarity probe, especially in weakly polar media.
The solid-state emission spectra of 2a, 2b and 3 are shown in Fig. 5. The emission maxima are at 503, 484 and 513 nm, and the emission quantum yields are respectively 0.05, 0.05 and 0.07.
The spectra are closely similar to the maxima in the region of the ICT transition of 3 in solution. The presence of the unsaturated substituent in 3 has only a slight influence on the emission maximum. The vibrational structure that is present in the spectrum of 2b suggests emission originating from the monomers, whereas the broad structureless bands observed for 2a and 3 may be assigned to solid-state aggregates or excimers. This hypothesis was confirmed by X-ray data, which reveal different crystal packings in 2a and 2b (unfortunately all of our attempts to obtain crystals of 3 that would be suitable for the X-ray diffraction study failed).

X-ray diffraction study of 2a and 2b
Compounds 2a and 2b crystallize from dichloromethanehexane in the centrosymmetric P2(1)/c space group in the monoclinic system, unattended by solvent molecules. Their molecular structures are shown in Fig. 6. In terms of molecular geometry, both compounds show great similarity. The only significant difference in the bond lengths is visible in the C17-C18 bond in the pyrazole moiety, which in the case of 2a is longer by ∼0.05 Å. The relative orientations of the pyrene moiety, the pyrazole ring and the phenyl ring are, however, quite different. In particular, the twist of the phenyl ring with respect to the pyrazole moiety is much more pronounced in the case of 2b (as stated above). The values of the important dihedral angles are reported in Table 3. In the case of 2b, a short C1-C20 contact (3.101(2) Å) between the anchor atoms of the pyrene moiety and the phenyl ring is present. This is in fact the minimal possible distance for these two atoms among all

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Photochemical & Photobiological Sciences of the possible conformations of 2b. The C-C bonds between the pyrene and pyrazole fragments and the C-N bond between the pyrazole and the phenyl group are essentially single, when judged by their lengths, thus suggesting no strong conjugation between these fragments. The pyrene moiety is essentially flat in the case of 2a, while in the case of 2b it is slightly bent.
However, the compounds differ significantly in terms of the intermolecular interactions. In the case of 2a the molecules display close and extensive π⋯π stacking interactions between the pyrenyl moieties related by crystallographic inversion (Fig. 7a). In addition, the phenyl rings of the molecules related by the other crystallographic inversion are also showing Table 2 Fitting parameters for fluorescence decays of 2a-b and 3 in CHCl 3 at various emission wavelengths λ em (nm) τ 1 (ns) τ 2 (ns) τ 3 (ns) a A fourth time-constant τ 4 ∼ 0.008 ns with a fraction of intensity lower than 0.01 was necessary to obtain satisfactory fitting curves, probably due to residual scattering signal; therefore, we have neglected this very small contribution here.  π⋯ interactions (there is a short contact of 3.394(4) Å). On the other hand, N2 is effectively shielded from any C-H⋯N interactions. The dimers of 2a interact in the crystal lattice mainly by C-H⋯π contacts; in particular, the phenyl moieties are oriented in such a way as to form short C-H⋯π interactions with the pyrenyl moieties.
There are no π⋯π interactions in the crystal lattice of 2b. On the other hand, N2 is involved in the C-H⋯N interaction with the aromatic C-H group from the pyrenyl group in an adjacent molecule (the H⋯N distance is relatively short, 2.659(6) Å). A network of such short contacts stretches along the crystallographic [001] direction (Fig. 7b). The only other types of interactions present in the case of 2b are numerous  C-H⋯π interactions of the pyrenyl moieties with one another and with the phenyl moieties.

Conclusions
We have synthesized new fluorophores having a 1-phenylpyrazole moiety attached to the pyrenyl group and we demonstrated feasibility of regioselective C-H functionalization (alkenylation) of the phenyl ring in these compounds. The introduction of the electron-withdrawing acrylic substituent endowed the ( phenylpyrazolyl)pyrene fluorophore with polarity-sensitive dual fluorescence, tentatively explained as originating from LE and ICT excited states. Therefore, it appears that directed C-H functionalization offers an easy route for tuning the emissive properties of this fluorophore.

Experimental
Solvents were purified before use by reported methods. All reagents were purchased from Sigma-Aldrich and used without further purification. Column chromatography was carried out on silica gel 60 (0.040-0.063 mm, 230-400 mesh, Fluka

Synthesis of 2a and 2b
A suspension of 1 (254 mg, 1 mmol) and phenylhydrazine hydrochloride (288 mg, 2 mmol) in methanol (95 ml) containing conc. aq. HCl (5.5 ml) was stirred for 5 h at room temperature. The mixture was poured into water and extracted several times with dichloromethane. The extracts were washed with aqueous NaHCO 3 , water, dried over Na 2 SO 4 and evaporated to dryness. Compounds 2a and 2b were separated by column chromatography (eluent : hexane-dichloromethane 1 : 1).  Alkenylation of 2a with n-butyl acrylate A suspension of 2a (344 mg, 1 mmol), n-butyl acrylate (2 mmol), 4,5-diazafluoren-9-one (18.2 mg, 10% mol) and Pd(OAc) 2 (11.2 mg, 5% mol) in acetic acid (5 ml) was refluxed for 6 h under 1 atm of oxygen (balloon). The reaction mixture was poured into water and extracted several times with dichloromethane. The extracts were washed with aqueous NaHCO 3 , water, dried over Na 2 SO 4 and evaporated to dryness.  13  X-ray diffraction study X-ray diffraction analysis of 2a and 2b. The single crystalsclear light yellow prismsof 2a and 2b suitable for X-ray analysis were obtained by slow diffusion of n-hexane into their respective chloroform solutions.
The data for crystals of 2a and 2b were collected on an Agilent Supernova 4 circle diffractometer system equipped with a copper and molybdenum microsource and an Atlas CCD detector. The data were collected using molybdenum radiation for 2a and copper radiation for 2b with CrysAlis171 software and integrated with the CrysAlisPRO software. Data were corrected for absorption effects using the multi-scan method (SCALE3 ABSPACK).
The structures were solved by direct methods using SXELXS and refined by a full-matrix least squares procedure with SHELXL within OLEX2 graphical interface. Figures were produced with Ortep3v2 and Mercury_3.3 software.
For further details of the X-ray diffraction study, see ESI. †