Pyrazolo[1,5-a]pyrimidine-dioxaborinine hybrid compounds: effect of phenyl group incorporation on the periphery

Autores

Rios, M.C. (UNIVERSIDAD DE LOS ANDES) ; Tigreros, A. (UNIVERSIDAD DE LOS ANDES) ; Aranzazu, L. (UNIVERSIDAD DE LOS ANDES) ; Portilla, J. (UNIVERSIDAD DE LOS ANDES)

Resumo

Five new pyrazolo[1,5-a]pyrimidine fluorescent dyes (2a-f) bearing boron difluoro/ß-diketonate (dioxaborinine) moiety were successfully synthesized in a one-pot strategy, and their structures were fully characterized. The main objective of the work was to compare the optical properties of the synthesized compounds concerning their precursors without the dioxaborinine moiety (1a-f). The optical properties were studied via UV-VIS, fluorescence spectroscopy, and emission in the solid state. The photophysical properties of the compounds were compared with that of their starting compounds. The synthesized compounds showed high emission efficiencies (φ = 0.04 - 0.69) as a result of an ICT process between pyrazolo[1,5- a]pyrimidine (donor) and dioxaborinine (acceptor).

Palavras chaves

Pyrazolo[1,5-a]pyrimidine; dioxaborinine; fluorescence

Introdução

In recent decades, fluorescent dyes have won the attention of researchers in various fields, and they possess important applications in many areas such as organic electronics (OLED, OFET)(SALEHI e colab., 2019), chemical detection(TIGREROS, Alexis e PORTILLA, 2020), creation of fluorescent biomarkers(GAO e colab., 2021), and as biomaterials in medical diagnostics and photodynamic therapy(MALDONADO-CARMONA e colab., 2020; SHAN e colab., 2018). In this context, it should be noted that the boron β-diketone difluoride complexes, also known as dioxaborinine derivatives, have been extensively studied due to their interesting photophysical properties(COLLOT, 2021) such as large molar absorption coefficients(POLISHCHUK e colab., 2021), size-dependent luminescence(FEDORENKO e MIROCHNIK e colab., 2021), mechanofluorochromic behavior(ZHANG e colab., 2018), two-photon absorption activity(JU e colab., 2019), controllable emission wavelength by polymeric matrices(FEDORENKO e KHREBTOV e colab., 2021) and high fluorescence quantum yields. These properties allow this type of system to have applications in fluorescent sensing of amines(SEENIVASAGAPERUMAL e SHANMUGAM, 2018; ZHAI e colab., 2017) or cyanide(TAMILARASAN e colab., 2020), bioimaging (cells, tissues, and in vivo)(COLLOT, 2021), or electroluminescence devices (OLED) (KIM e colab., 2018). Another exciting family of fluorescent compounds is the based on pyrazolo[1,5-]pyrimidine ring, dyes that have been fascinating in the last few years due to their high fluorescence quantum yields in both solution and solid-phase and excellent photo and thermostabilities,(TIGREROS, Alexis e ARANZAZU e colab., 2020; TIGREROS, Alexis e MACÍAS e colab., 2021) which showed great applications mainly as fluorescent chemosensors(TIGREROS, A. e colab., 2019; TIGREROS, Alexis e CASTILLO e colab., 2020; TIGREROS, Alexis e colab., 2022; TIGREROS, Alexis e ZAPATA-RIVERA e colab., 2021) or biomarkers(YANG e colab., 2020). The extension of the π-conjugation and the electronic coupling of different fluorophores like triphenylamine- fluorene(TIGREROS, A. e colab., 2014), triphenylamine-BODIPY(LEE e colab., 2021), or pyrene- BODIPY(IRMLER e colab., 2019) has allowed the improvement of the optical properties or induced new ones such as solvatofluorochromism, Near Infrared II two-photon absorption(LI e colab., 2020), or FRET(PORCU e colab., 2018). Therefore, combining two or more fluorophores can be a good strategy for designing new compounds with exciting photophysical properties. Based on the abovementioned facts, here we report on the synthesis and the photophysical characterization of a series of pyrazolo[1,5-]pyrimidine–dioxaborinine hybrids, with Friedel-Craft acetylation, followed by subsequent acetylation as the key synthetic steps in the preparation of the target compounds. Their photophysical and thermal properties were also studied. Finally, a relationship was made between the structure (substituents) and the optical and thermostability.

Material e métodos

All starting materials were weighed and handled in air at room temperature. The reactions were monitored by TLC and visualized by UV (254 nm). All compounds were synthetized via Microwave Assisted Organic Synthesis using a sealed reaction vessel (10 mL, max pressure = 300 psi) containing a Teflon-coated stirring bar (obtained from CEM). Microwave-assisted reactions were performed in a CEM Discover focused microwave (ν = 2.45 GHz) reactor equipped with a built-in pressure measurement sensor and a vertically focused IR temperature sensor; controlled temperature, power, and time settings were used for all reactions. Compounds were purified through flash chromatography on silica gel. NMR spectra were recorded at 400 MHz (1H) and 100 MHz (13C) at 298 K. NMR spectroscopic data were recorded in CDCl3 or DMSO. DEPT spectra were used for the assignment of carbon signals. Chemical shifts (δ) are given in ppm and coupling constants (J) are given in Hz. The following abbreviations are used for multiplicities: s = singlet, d = doublet, t = triplet, and m = multiplet. Melting points were collected using a Stuart SMP10 melting point apparatus, and the acquired data are uncorrected. High-resolution mass spectra (HRMS) were recorded using an Agilent Technologies Q-TOF 6520 spectrometer by electrospray ionization (ESI). The electronic absorption and fluorescence emission spectra were recorded in quartz cuvettes having a path length of 1 cm. UV–vis and emission measurements were achieved at room temperature (20 °C). For fluorescence measurements, both the excitation and the emission slit widths were 5 nm.

Resultado e discussão

1. Synthesis of compounds 2a-f The synthetic route for compounds 2a-f is shown in Scheme 1. The pyrazolo[1,5-a]pyrimidine starting materials 1a-f were obtained according to previous procedures. The synthesis of compounds 2a-f was accomplished by using BF3OEt2 and acetic anhydride in DCE solution at 90ºC for 24h in good yields (49-70 %) in a one-pot strategy. First, an electrophilic aromatic substitution reaction occurs to afford acetylated intermediates. Next, a second acetylation reaction occurs in the acetyl group due to the excess of acylating agent (Ac2O-BF3OEt2). Finally, the formation of boron difluoro β-diketonate 2 is obtained in the presence of BF3OEt2 as reported before by many authors(NAGAI e colab., 2008). Absorption and emission properties The UV-vis absorption and fluorescence spectroscopic data in THF solution and emission in the solid-state of compounds 1a-f and 2a-f are shown in Figures 1 and 2 and the corresponding photophysical properties are summarized in Table 1. Compounds 1a-f exhibit the typical dual-bands spectra of pyrazolo[1,5-a]pyrimidine derivates observed in the ranges of 300-400 nm and 400-550 nm, corresponding to the π-π* and n-π* and, in less extension, to an intramolecular charge transfer (ICT) transition between the pyrazole (donor) and pyrimidine (acceptor) units(TIGREROS, Alexis e ARANZAZU e colab., 2020). As expected, the absorption coefficient values (ε) increase with the sequential introduction of phenyl groups in the pyrazolo[1,5-a]pyrimidine core. On the other hand, the introduction of electron-withdrawing group (dioxaborine) results in a slight red shift of the absorption band of less energy with an important increase of the absorption coefficient in compounds 2a-f. Therefore, the good electronic communication between two units is evident. However, the ICT process is slightly enhanced after a good acceptor group was incorporated, reflecting the low electron donating capability of the pyrazole unit when compared with other electron donating groups (e. g., triphenylamine: ICT band λ= 425 nm)(TAMILARASAN e colab., 2020). In general, as the number of phenyl groups increase the absorption coefficient of the ICT transition decrease. Fascinatingly, the highest ε value was found in compound 2a (37378 Lmol-1cm-1) which has the less π- conjugation. Therefore, the ICT transition is the main responsible of the absorption spectrum. Thanks to the high coplanarity between aryl groups and pyrazole moiety(PORTILLA e colab., 2005, 2007), good absorption coefficient values were observed in compound 2c. However, compounds with phenyl groups at position 7 (2b and 2e) display the lower ε values for the ICT bands. Meanwhile, as expected compounds with phenyl groups at position 2 and 7 (2d and 2f) display intermediate values. In summary, the tendency found (2a > 2c > 2d > 2f > 2b > 2e) indicates that substitution pattern and the electronic communication with the periphery rings is critical for the absorption capability. When excited at 300 nm, derivatives 1a-f exhibited fluorescence emission in the blue-green region (441–491 nm), where the number and position of phenyl substituents did not play an important role in the excited state energy of these fluorophores, Figure 2a. Meanwhile, the efficiency of the emission (φ) ranges from 0.03 (1a) to 0.30 (1f). The coplanarity expected between phenyl groups and pyrazole moiety at position 2 in compounds 1c, 1d and 1f could explain the better quantum yield observed in these cases. Probes 2a-f exhibited fluorescence emission in the blue-green region (400-479 nm) under excitation at λ = 300 nm, Figure 2b. As already observed with compounds 1a-f, for these compounds, the number and position of phenyl substituents present on the pyrazolo[1,5-a]pyrimidine unit slightly affect the fluorescence maximum location. Furthermore, compounds 2a-f show a considerable increase in their fluorescence quantum yield in THF compared to 1a-f, with φ values as high as 0.69 for 2f. Thus, the extension of the π-conjugation and the ICT character of the transition cause by a dioxaborinine moiety significantly affect the emission from the excite state in solution. These results can be explained by the restricted motion in 2a-f as a result of ICT process, avoiding the non-radiative process due to rotation of phenyl groups in compounds 1a-f(XU e colab., 2022). 3. Solid-phase emission properties Figure 3a shows the results from the photophysics in the solid-state for compounds 1a-f, where the samples were treated as a powder. The solid-phase slightly affects the emission maximum location in substituted pyrazolo[1,5-a]pyrimidine from 417 nm (1c) to 488 nm (1e). The emission efficiency of these compounds appeared to be quite different from those observed in solution with values as high as 0.51 (1a) The introduction of dioxaborinine moiety, except by 2e λEm = 530 nm, did not affect substantially the emission maximum location (448 nm in 2a to 480 nm in 2f). The emission behavior in 2e could be ascribed to a micro-crystalline disposition that induces a better donor-acceptor interaction as reported before in pyrazolo[1,5-a]pyrimidine with nitrobenzene as a substituent group.(TIGREROS, Alexis e colab., 2022) Importantly, compounds containing dioxaborinine unit 2a-f show a considerable decrease in their fluorescence quantum yield at solid-phase when compared to solutions in THF, with quantum yields as low as 0.02 for 2a and 2d. Therefore, these results indicate that the dioxaborinine moiety afforded higher interactions such as π-stacking between the heterocyclic rings present in the hybrid chemical structures. Those interactions could deactivate the excited state and decrease the quantum yield through the formation of H-aggregates(WITTE e colab., 2021).

Conclusões

In conclusion, we have synthesized a set of pyrazolo[1,5-a]pyrimidine-dioxaborinine hybrid compounds 2a-f in a one-pot manner using Friedel-Craft acylation conditions as the key step and using easily available pyrazolo[1,5-a]pyrimidine 1a-f as starting substrates. From results obtained, the best candidates for optical applications in solid-phase such as OLED or solid-state laser are dioxaborinine-free pyrazolo[1,5- a]pyrimidines 1a-f. Meanwhile, those applications requiring high fluorescence intensities like sensing or bioimages may use derivates 2a-f which display quantum yields as high as 0.69. The relatively easy availability by synthesis together with favorable photophysical properties make some of these compounds promising candidates for future application in optical devices, sensing or bioimages.

Agradecimentos

The authors wish to thank Universidad de los Andes for financial support.

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