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Article

Synthesis and Photophysics of 5-(1-Pyrenyl)-1,2-Azoles

by
María-Camila Ríos
,
Alexander Ladino-Bejarano
and
Jaime Portilla
*
Bioorganic Compounds Research Group, Department of Chemistry, Universidad de los Andes, Carrera 1 No. 18A-10, Bogotá 111711, Colombia
*
Author to whom correspondence should be addressed.
Chemistry 2025, 7(4), 120; https://doi.org/10.3390/chemistry7040120
Submission received: 29 June 2025 / Revised: 22 July 2025 / Accepted: 24 July 2025 / Published: 27 July 2025
(This article belongs to the Special Issue Modern Photochemistry and Molecular Photonics)
Browse Figures
Versions Notes

Abstract

Two pyrene derivatives, substituted at position 1 with isoxazole or NH-pyrazole, were synthesized in 85–87% yield starting from 1-acetylpyrene and via the cyclocondensation reaction of a β-enaminone intermediate with hydroxylamine or hydrazine. The photophysics of the two 5-(1-pyrenyl)-1,2-azoles were explored, revealing that only the isoxazole derivative exhibits good emission properties (ϕF ≥ 74%) but without solvatofluorochromism behavior. However, both probes exhibited noticeable photophysics in the aggregated state (in the presence of H2O and/or in the solid state) and through acid–base interactions (using TFA and TBACN), leveraging the basic and acidic character of the analyzed 1,2-azoles, which was also investigated by 1H NMR spectroscopy. Therefore, the selective incorporation of N-heteroaromatic units into the pyrene scaffold effectively modulates the photophysics and environmental sensitivity of the corresponding probes.

1. Introduction

The pyrene ring belongs to the family of polycyclic aromatic hydrocarbons (PAHs) that possess dual ability to act as both an electron-donating group (EDG) and an electron-withdrawing group (EWG); this scaffold is part of a diverse set of fluorophores that exhibit high fluorescence quantum yields in solution, which endow it with excellent photophysical properties [1,2,3]. In solution, it can exist in both monomeric and excimeric forms (excited dimer), depending on the molecular environment [4,5]; pyrene excimers display distinct spectroscopic features compared to the monomeric species, most notably a redshift in the emission wavelength and changes in fluorescence lifetimes. The formation of these excited-state species is susceptible to environmental conditions, including temperature, viscosity, pressure, pH, solubility, and molecular confinement [4,5,6]. Due to these characteristics, the development of optical probes based on pyrene derivatives has increased significantly in recent years. These molecular systems have demonstrated great applicability in time-resolved fluorescence studies [7,8,9], bioimaging [10,11,12], electro-optical devices [13], and environmental sensing of ions [14,15,16]. Representative examples include fluorescent probes for the detection of biomolecules such as cysteine; anions like cyanide (CN−); and metal ions including Hg2+, Cu2+, Al3+, and so on (Figure 1a) [14,15,16,17,18,19].
It should be noted that most pyrene-based dyes require special ring substitutions and functionalizations for their derivatives to function efficiently, as this scaffold belongs to the family of PAHs that are not functional on their own [1,2,3,20,21]. From this perspective, recent studies have focused on conjugating pyrene with heteroaromatic rings onto the backbone of various dyes, as this structural modification represents a promising strategy for enhancing their photophysics [21,22,23]; as a result, dyes with noticeable electronic properties and synthetic viability have been obtained due to the presence of the heterocyclic unit, particularly by those containing nitrogen atoms [21,24,25,26,27]. The N-heterocyclic core incorporation as an EDG or EWG not only extends π-electron delocalization but can also promote intramolecular charge transfer (ICT), aggregation-induced emission/quenching (AIE/AIQ), or energy transfer (ET) processes by facilitating spatial interactions in the excited state [24,25,26,27,28,29]. As a result, these fluorophores typically exhibit red-shifted emission, higher fluorescence quantum yields, and improved photostability [24,25,26,27,28,29,30,31]. However, examples with 1,2-oxazole (isoxazole) and 1,2-diazole (1H-pyrazole) rings are scarce, with some dyes featuring the pyrazole ring diversely substituted (large molecules) [32,33,34,35] and an example that instead featured a 1,3-oxazole (oxazole) ring [36] (Figure 1b).
Chemistry 07 00120 g001
Figure 1. Pyrene derivatives as (a) chemosensors and (b) fluorophoric azoles [16,17,19,26,29,34]. (c) The three possible 5-(pyren-1-yl)-1,2-azoles, of which two (X:O, NH) are explored in this work.
Figure 1. Pyrene derivatives as (a) chemosensors and (b) fluorophoric azoles [16,17,19,26,29,34]. (c) The three possible 5-(pyren-1-yl)-1,2-azoles, of which two (X:O, NH) are explored in this work.
Chemistry 07 00120 g001
Isoxazole and 1H-pyrazole are five-membered N-heteroaromatic rings with a sp2 hybridized nitrogen atom (pyridine-like, =N–) bonded to an oxygen (furane type –O–) or nitrogen atom (pyrrole type, –NH–), respectively; thus, isoxazole is a ring slightly π-deficient in character, while 1H-pyrazole is slightly π-excessive [37,38]. Isoxazole and pyrazole derivatives are typically obtained via [3 + 2] cycloadditions or cyclocondensation reactions of 1,3-bis-electrophiles with hydroxylamine or hydrazines, respectively. These rings are part of biologically relevant compounds and have recently proven to be applicable in developing fluorophores, primarily for pyrazole derivatives, which is likely due to the restricted electronic properties, stability, and reactivity of isoxazoles (owing to the highly electronegative oxygen atom) versus pyrazoles [37,38,39,40,41,42,43,44,45]. However, most of the studied dyes are large molecules, and today it is crucial in probe discovery to obtain fluorophores based on small molecules with simple structures [37,46,47,48,49,50,51]. Therefore, we aimed to extend our previous work on fluorescent 5-(coumarin-3-yl)isoxazoles (Scheme 1a) [37] to obtain 5-(pyren-1-yl)isoxazole (3), starting from 1-acetylpyrene (1) and by the β-enaminone intermediate 2; similarly, we proposed to prepare 5-(pyren-1-yl)-1H-pyrazole (4) [52] to search its photophysics and compare the results with those of 3, from only an O/NH change. The presence of the pyrene ring in 1,2-azoles would offer dyes with exceptional properties, which act via AIE, ET, or ICT optical phenomena [26,29,34] (Scheme 1b, Figure 1c).

2. Results and Discussion

2.1. Synthesis

Remarkably, the synthesis of 5-(pyren-1-yl)isoxazole (3) and 5-(pyren-1-yl)-1H-pyrazole (4) was efficiently accomplished in two steps under microwave (MW) conditions, starting from 1-acetylpyrene (1). First, the methyl ketone 1 undergoes a microwave-assisted condensation reaction with N,N-dimethylformamide-dimethylacetal (DMF-DMA), giving the β-enaminone 2 in 92% yield; the reaction proceeds via the nucleophilic addition of the methylene active group into 1 and the successive elimination of two methanol molecules (Scheme 2a) [38]. Finally, the 1,3-bis-electrophilic substrate 2 can react in ethanol with either hydroxylamine hydrochloride (HH, NH2O·HCl) or hydrazine monohydrate (HM, N2H4·H2O) as 1,2-bis-nucleophilic reagents to afford the desired 1,2-azoles 3 and 4 in yields of 85–87% (Scheme 2a); these cyclocondensation reactions proceed under microwave conditions or at reflux (for 4 as decomposition products were observed in MW) by an initial attack of the amino group of reagents and subsequent cyclization (by the residual OH or NH2 groups) with elimination of a molecule of dimethylamine and another of water [38,42]. Dyes 2–4 were isolated by removing excess liquids under reduced pressure, and they were then chromatographed (silica gel in DCM) to afford the pure products. Since unfunctionalized pyrene was not available in our laboratory, this dye was obtained by an adapted protocol using a TFA-mediated deacetylation reaction of 1 [53] (Scheme 1a).
The synthesized compounds pyrene, 2, 3, and 4 were characterized by 1H and 13C NMR spectroscopy and HRMS analysis (Figures S2–S16). Unfortunately, it was not possible to obtain crystals of 3 to confirm its structure by single crystal X-ray diffraction, as occurred for 5-(coumarin-3-yl)isoxazoles a–c analogs (Scheme 2a) [37], perhaps due to the nature of interactions associated with the pyrene ring; thus, the regioselectivity of its formation was established by two-dimensional NMR experiments (i.e., COSY, HSQC, and HMBC), and results were compared with those of 4 (Figures S4, S5, S8 and S9). As expected, signals in the 1H and 13C NMR spectra for the isoxazole derivative 3 are shifted downfield compared to 4, supporting the slight π-deficient character of the ring with oxygen versus the pyrazole ring [37,38]. The heteroaromatic nature of both azoles offered signals for H3 and H4 with low coupling constant values (d, J~1.5 Hz), while a characteristic signal of the pyrene ring was evidenced at ~8.50 ppm (d, J~9.5 Hz) for them, matching the H10′ with high anisotropic effect from the heteroaromatic ring (see Characterization data). Finally, the 1H NMR spectrum of 4 in DMSO-d6 showed the two possible tautomers (Figure S7), with a higher proportion (4:1) of the more stable 5-substituted 1H-pyrazole 4 than its 3-substituted 4′ tautomer, due to the better π-conjugation into 4 (Scheme 2b).

2.2. Photophysical Properties

The hydrocarbon pyrene is a rigid π-extended fused ring that exhibits neutral or amphoteric (donor/acceptor) electronic character, offering fluorescent dyes governed by the stability of the excited state, with a focus on conformational or π-conjugation factors [1,2,3]; thus, in the varied fluorescence pyrenes, optical mechanisms of ET and AIE by the ring, or charge transfer (CT) [26,29,34] or others (e.g., excited-state intramolecular proton transfer (ESIPT) [54]) by substituents, should dominate. In this way, compounds 3 and 4 are relevant fluorophoric small molecules, despite not being functionalized, due to the notable electronic properties of isoxazole and 1H-pyrazole rings [37,38]; thus, their photophysics (solvatofluorochromism and acidochromism) and aggregation properties were explored by UV–VIS and fluorescence spectroscopy. First, the spectra for the compound 3 were measured at ~20 °C and a concentration of 10 μM in fourteen solvents of varying polarities (Table 1 and Figure 2), including toluene, tert-butyl methyl ether (TBME), tetrahydrofuran (THF), ethyl acetate (AcOEt), dioxane, acetone, dichloromethane (DCM), 1,2-dichloroethane (DCE), chloroform (CHCl3), acetonitrile (MeCN), N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), ethanol, and methanol (MeOH).
The fluorophore 3 exhibited absorption bands at wavelengths (λabs) between 279–283 and 350–456 nm, attributed to π–π* and n–π* transitions, characteristic of an N-heterocyclic core conjugated to the pyrene scaffold [24,25,26,27,28,29,30,31,32,33,34,35,36]. It was found that the absorptivity coefficient (ε) values of this dye in the different solvents are, in general, greater for the absorption bands of π–π* transitions (7900–12,300 M–1cm−1) than for n–π* transitions (6110–10,800 M–1cm−1); these results are due to the high π-conjugation of the pyrene ring, which in addition governs the photophysics of this dye (Table 1 and Figure 2a). Additionally, dye 3 exhibited emission bands (λem) between 396 and 402 nm, with two shoulders (shs) due to excimer species formation (at ~422 and ~445 nm), typical of pyrene derivatives [55]. This dye exhibited moderate Stokes shifts (2916–3496 cm−1) and high fluorescence quantum yield (ϕF) values (≥74%) with no dependency on the solvent’s polarity; however, it was not possible to calculate the ϕF in three solvents due to the compound’s precipitation. In addition, no significant spectral changes were observed with the solvent polarity; that is, no solvatofluorochromic behavior is exhibited by 3 (Figure S17, Lippert–Mataga plot [56,57]). Consequently, the microenvironment of the fluorophoric molecule is not significantly affected in either the basal or excited state [37] (Table 1 and Figure 2b).
On the other hand, to evaluate the influence of the isoxazole ring on the photophysics of 3, brief studies were conducted using the starting ketone 1, the pyrazole 4, and pyrene (Figures S18–S20). Ketone 1 exhibited absorption and emission bands at ~282/357 nm and 403 nm, respectively, and these properties remained unaffected by the solvent’s properties. Like for dye 3, 1 had Stokes shifts (3043–3345 cm−1) and ε with similar tendence, but with doubled ε values (14,670–25,150 M–1cm−1/π–π* and 10,980–21,580/n–π*) and even a shoulder for the n–π* band; likewise, the emission bands showed the typical shoulders, with a secondary pick at 514 nm in TBME due to the exciplex species formation [58]. Pyrene exhibited absorption and emission bands at ~262/273/319/335 nm and ~377 nm, respectively, properties that remained unchanged by the solvent’s properties; these results are consistent with the reported data for this dye [59,60]. Due to ketone 1 and pyrene being weakly (ϕF ≤ 0.2%) and moderately (ϕF of 16–33%, but non-functional dye) fluorescent, respectively, these results confirm that the introduction of the isoxazole ring favorably affects the photophysics of 3 (ϕF of 74–96%, functional dye), perhaps due to an ICT process towards the isoxazole ring with slight π-deficient character [37]. This assumption was confirmed with the weak fluorescence of 4 (ϕF ≤ 6.9%) with π-excessive character and tautomerism [61]; however, 4 showed the best electronic nature (25,570–39,240 M–1cm−1/π–π* and 21,500–31,310/n–π*) due to the donor ring, with a similar tendency in properties to those of 3 (i.e., in π–π*/n–π*, Stokes shifts, and shoulders), and absorption and emission bands of ~280/346 nm and 440 nm (Table 1).

2.3. Properties in the Aggregate State

Although 5-(pyren-1-y)-1H-pyrazole (4) did not fluoresce in solution, it did so in the solid state under UV light, as does isoxazole 3 (Figure 3), validating our assumption that the tautomerism of 4 to 4′ turns off the fluorescence in solution (Figure S20). Perhaps, similarly to an ESIPT process that only occurs in solution, and the caveat that tautomerism is an intermolecular equilibrium [62]; thus, fluorescence quenching of tautomers due to an ESIPT-induced intersystem crossing is revealed [61]. Accordingly, solid-state emission measurements for fluorophores 3 and 4 were also carried out (Figure 3 and Table 1), revealing similar emissions between them (ϕF~23%), with redshifts in the spectra compared to results in solution, e.g., from 394/398 in TBME (Table 1) to 490/504 nm in the solid state. This behavior is likely associated with the similar structure of these dyes, which features two coplanar rings, and due to molecular packing through π···π stacking interactions [37]; as a result, an AIE process [8] with conformational restrictions that increase and direct intermolecular charge transfer was induced (Figure 3b). It should be noted that 5-(pyren-1-yl)-1H-pyrazole (4) exhibited an emission spectrum redshifted versus 5-(pyren-1-yl)isoxazole (3), which also confirms the π-excessive character of the pyrazole ring [38].
Based on the good results of solid-state experiments for 3 and 4, we decided to evaluate the photophysical influence of H2O addition to their MeCN solutions due to aggregation phenomena resulting from the loss of solubility. Experiments were conducted with water additions up to 50%, as higher percentages cause precipitation. For the isoxazole 3, the absorption decreased by 33% upon the addition of 10% H2O and then slightly decreased with 20% H2O, after which the spectra stopped changing, no matter the quantity of water added (Figure 4a); however, the absorption only notably decreased (by 48%) upon the addition of 40% H2O to 4, since it slightly increased at lower percentages or to 50% of water, maybe due to the bets solubility of 4 (bear NH) versus 3 and its tautomerism (Figure S21a). Moreover, the emission of 3 increased gradually with a redshift upon the addition of water, evidencing favorable interactions in the aggregated state that lead to an expected redshift AIE process (Figure 4b); likewise, 4 increased its emission but slightly and without redshift, with a decreasing also at 40% H2O (Figure S21b), confirming the assumption of its bets solubility in the water presence but with poor photophysics in solution.

2.4. Acid/Base Properties

Dyes 3 and 4 are azole derivatives with potential basic and acidic behavior, respectively, due to their azolic nature—as they bear a basic sp2 nitrogen atom [39]—and in addition, 4 has an acidic, highly downfield-shifted NH group in its 1H NMR spectra (Figures S6 and S7). In this context, the acid/base behavior of 3 and 4 was preliminarily investigated by absorption and emission spectroscopy using 10 µM solutions of them in acetonitrile; thus, trifluoroacetic acid (TFA, 0.1 M) was added to the solution of 3 in varying quantities, while tetrabutylammonium cyanide (TBACN, 0.1 M) was used by probe 4. It can be observed that the absorption band of 3 at 351 nm decreased, and a new band gradually appeared at 409 nm with a limit of detection (LOD) of 7.41 µM; similarly, the emission band at 398 nm dramatically decreased, accompanied by a band emerging at 350 nm, showing a LOD of 2.41 µM (Figure 5). The limits of detection were determined using the 3σ/slope relationship, where σ is the standard deviation of ten measurements of 3 and the slope of the linear relationship of dyes. On the other hand, we expected that the deportation of the NH group in probe 4 would lead to changes in the absorption or emission properties; however, no significant spectral changes were observed, with an emission slightly enhanced from 3.5% to 4% (Figure S22). Although these preliminary results are not promising, there is some interaction of 4 with CN– (a weak base). Therefore, the use of probes 3 and 4 for colorimetric and fluorometric chemodetection of acids and/or bases is a perspective.
The interaction of dyes 3 and 4 with 1 equiv of TFA or KCN (the spectrum is bad with TBACN), respectively, was studied by 1H NMR experiments in DMSO-d6 (Figures S10–S12), in which the signals corresponding to the heterocyclic core were shifted compared to the molecule alone, according to the respective acid/base medium; for example, the presence of TFA provoked these signals of probe 3 to be shifted downfield. In contrast, the KCN offered signals shifted upfield for 4. However, the results were more pronounced using probe 3, which is consistent with the photophysical experiments. Additionally, a stabilizing cation–π interaction (i.e., K+-pyrene/pyrazole, Figure S13) may prevent the pyrazyl anion from becoming free and its signals from appearing significantly shifted upfield [63,64]. Notably, the suppression of the pyrazole NH signal was also observed upon addition of KCN to the solution of probe 4, supporting the perspective discussed above. As several dyes have been discovered, a comparison was conducted between 3 and 4 and the most related and recently published dyes (Table 2). These works demostrate that 3 and 4 exhibit desirable properties, featuring a simpler synthetic protocol and molecular structure compared to other dyes [35,37,65,66]. In general, although most reported pyrene-based fluorophores have exceptional photophysics, those with simpler structures have limitations in reported photophysical data and applications. Therefore, we hope that these results will encourage different researchers to develop new work using increasingly simpler dyes.

3. Conclusions

In summary, two pyrene derivatives bearing isoxazole and pyrazole were synthesized by simple condensation reactions starting from 1-acetylpyrene, through a β-enaminone intermediate, and using inexpensive reagents. Both compounds were characterized by NMR spectroscopy and HRMS analysis, and their photophysical properties were evaluated in both solution and the solid state. Unlike the pyrazole derivative, the isoxazole-based compound exhibited high fluorescence quantum yields in various solvents (≥80%) and noticeable acidochromism with LOD up to 2.41 μM; however, both probes showed significant redshifted emission in the solid, particularly the pyrazole derivative bearing the more donor azolic core, with quantum yields of ~23%, attributed to AIE phenomena. Although no solvatofluorochromic behavior was observed, the high photoluminescence efficiency of 3 in solution and spectral stability against polarity changes suggest a rigid and unperturbed molecular environment in the excited state. Therefore, the obtained results demonstrate that the selective incorporation of N-heteroaromatic rings effectively modulates the electronic and photophysical properties of the pyrene core, enabling the fine-tuning of parameters such as quantum efficiency, environmental sensitivity, and solid-state behavior. Therefore, the novel obtained fluorophores are small molecules that represent versatile and tunable structures with high potential for applications in optoelectronics, molecular sensing, and solid-state emissive materials.

4. Materials and Methods

4.1. General Information

All precursors and reagents were purchased from MERCK (Darmstadt, Germany), used without further purification, and weighed and handled in the air at room temperature (r.t., ~20 °C). By thin-layer chromatography (TLC) on silica gel (60 F254) from MERCK and using a UV lamp (254 or 365 nm) as a visualization agent, the progression of reactions and purification processes was performed. Flash chromatography was performed on silica gel (230–400 mesh) from MERCK. Reactions under microwave (MW) irradiation were carried out in a sealed reaction vessel (10 and 35 mL, Pmax = 300 psi) bearing a Teflon-coated stir bar (obtained from CEM) and a CEM Discover SP (Matthews, NC, USA) 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.
NMR spectroscopic data were recorded on a Bruker Avance (Karlsruhe, Germany) 400 MHz (1H) and 101 MHz (13C) in CDCl3 or DMSO-d6, using the residual non-deuterated signal (1H: 7.26 or 2.50) and the deuterated solvent signal (13C: 77.06 ppm) as internal standards [67]. DEPT-135 experiments were used for the carbon signals assignment (CH and CH3). Chemical shifts (δ) are reported in parts per million (ppm), and the coupling constants (J) in Herz (Hz). Abbreviations used for multiplicities were s = singlet, d = doublet, and m = multiplet. High-resolution mass spectra (HRMS) were obtained on an Agilent Technologies Q-TOF 6520 spectrometer (Santa Clara, California, USA) through electrospray ionization (ESI). Melting points were determined in capillary tubes using a Stuart SMP10 melting point apparatus (Stone, UK) and were not corrected. The UV–VIS absorption (on a Varian Cary 100 Conc) and fluorescence emission (on a CARY Eclipse) spectra were recorded in quartz cuvettes with a path length of 1 cm using spectrophotometers of Agilent Technologies (Santa Clara, California, USA). UV–VIS absorption and fluorescence emission measurements were accomplished at room temperature (~20 °C). Both the excitation and emission slit widths were 5 nm for fluorescence measurements.
The fluorescence quantum yields (ϕF) were determined using Prodan (ϕF = 94% in DCM) as a reference standard, as described in Equation (1).
ϕ f , x = ϕ f , s t F x F s t A s t A x n x 2 n s t 2
where F is the integral photon flux, A is the absorption factor, and n is the refractive index of the solvent. Index x and st denote the sample and standard, respectively [68].

4.2. Synthesis and Characterization Data

4.2.1. Synthetic Protocols

The β-enaminone intermediate 2 and 5-(pyren-1-yl)isoxazole (3) were prepared by adapting conditions of protocols previously developed in our laboratory [69]. In this context, a mixture of 1-actylpyrene (1, 1.5 mmol, 97%, 355 mg) and DMF-DMA (1.18 equiv, 94%, 250 μL) was irradiated with microwave at 150 °C (160 W, monitored by an IR temperature sensor) and maintained at this temperature for 30 min in a sealed tube containing a Teflon coated magnetic stirring bar. The resulting reaction mixture was quickly cooled to 50 °C by airflow, and the excess DMF-DMA was removed under reduced pressure; the residue was then purified by flash chromatography on silica gel (eluent: DCM) to afford (E)-3-(dimethylamino)-1-(pyren-1-yl)prop-2-en-1-one (2) in 92% yield. Likewise, 3 was synthesized by reacting 2 (0.5 mmol, 100 mg) with NH2OH·HCl (1.5 equiv, 99%, 52 mg) in ethanol (0.5 mL) under microwave irradiation (60 W) for 20 min; the resulting reaction mixture was purified by flash chromatography (eluent: DCM) to deliver the desired isoxazole 3 [37]. In contrast, 3(5)-(pyren-1-yl)-1-H-pyrazole (4) was obtained under reflux in ethanol (3 mL) by reacting 2 (0.5 mmol, 100 mg) with N2H4·H2O (1.5 equiv, 97%, 40 μL) for 2 h; the excess ethanol was removed under reduced pressure and the residue was chromatographed on silica gel (eluent: DCM) to afford 4 in 87% yield.
On the other hand, pyrene was obtained by an adapted protocol using a water/TFA-mediated deacetylation reaction of 1-acetylpyrene (1) under reflux conditions for 2 h [53]. A solution of 1 (65 mg, 0.266 mmol) in TFA (0.85 mL) and water (0.15 mL) was refluxed for 2 h and then cooled to ~20 °C. The reaction mixture was poured over ice and extracted with DCM (3 × 4 mL). The combined organic layers were washed with water and dried over anhydrous sodium sulfate. Finally, the residue was chromatographed on silica gel (eluent: DCM/pentane 1:1) to afford the pure product in 56% yield (30 mg).

4.2.2. Characterization Data

(E)-3-(Dimethylamino)-1-(pyren-1-yl)prop-2-en-1-one (2): Yellow solid (428 mg, 92%); mp 115–116 °C (Lit. [52] 114 °C). 1H NMR (400 MHz, CDCl3): δ = 2.89 (s, 3H, CH3), 3.03 (s, 3H, CH3), 5.66 (d, J = 12.7 Hz, 1H, Hb), 7.99–8.20 (m, 9H, 1-pyrenyl ring (1-pyr)), 8.54 (br d, J = 12.7 Hz, 1Hc). 13C{1H} NMR (101 MHz, CDCl3): δ = 37.3 (CH3), 45.1 (CH3), 99.1 (CHb), 124.3 (CH), 124.7 (C), 124.9 (C), 125.2 (CH), 125.3 (CH), 125.4 (CH), 125.4 (CH), 126.1 (CH), 127.3 (CH), 128.0 (CH), 128.1 (C), 128.3 (C), 130.9 (C), 131.3 (C), 131.8 (C), 137.4 (C), 155.5 (CcH), 193.8 (Ca=O) ppm. HRMS (ESI+): calcd. for C21H18NO+ 300.1383 [M + H]+; found 300.1387. These experimental data matched those previously reported [52].
5-(1-Pyrenyl)isoxazole (3): White solid (229 mg, 85%); mp 125–126 °C. 1H NMR (400 MHz, CDCl3): δ = 6.69 (d, J = 1.4 Hz, 1H4), 7.96–8.20 (m, 8H, 1-pyr), 8.47 (d, J = 1.4 Hz, 1H3), 8.50 (d, J = 9.5 Hz, 1H10′) ppm. 13C{1H} NMR (101 MHz, CDCl3): δ = 103.0 (CH4), 121.5 (C), 123.9 (CH), 124.3 (C), 124.6 (CH), 124.7 (C), 125.7 (CH), 126.0 (CH), 126.3 (CH), 126.6 (CH), 127.1 (CH), 128.4 (C), 128.8 (CH), 129.0 (CH), 130.5 (C), 131.1 (C), 132.5 (C), 150.7 (CH3), 169.9 (C5) ppm. HRMS (ESI+): calcd. for C19H12NO+ 270.0913 [M + H]+; found 270.0908.
3(5)-(1-Pyrenyl)-1H-pyrazole (4). Yellow solid (300 mg, 87%); mp 175–176 °C (Lit. [52] 178 °C). 1H NMR (400 MHz, CDCl3): δ = 6.67 (d, J = 1.5 Hz, 1H4), 7.66 (d, J = 1.5 Hz, 1H3), 7.85 (d, J = 8.9 Hz, 1H,1-pyr), 7.92–8.02 (m, 5H, 1-pyr), 8.09 (m, 2H, 1-pyr), 8.48 (d, J = 9.3 Hz, 1H10′) ppm; 1H NMR in DMSO-d6 (a tautomers mixture was observed): δ = 6.85 (br s, 1H, H4/4′), 7.77 (d, J = 1.4 Hz, 0.2H, H3′), 8.00–8.32 (m, 9H, 1-pyr), 9.04 (J = 1.4 Hz, 0.8H, H3), 13.26 (br s, 0.8H, NH), 13.47 (br s, 0.2H, NH’) ppm.13C NMR (100 MHz, CDCl3): δ = 106.8 (CH4), 124.4 (CH), 124.5 (C), 124.7 (C), 124.8 (CH), 125.0 (CH), 125.2 (CH), 125.9 (CH), 126.9 (C), 127.0 (CH), 127.2 (CH), 127.6 (CH), 127.8 (CH), 128.6 (C), 130.8 (C), 131.0 (C), 131.3 (C), 133.8 (CH3), 147.7 (C5) ppm. HRMS (ESI+): calcd. for C19H13N2+ 269.1073 [M + H]+; found 269.1061. These experimental data matched those previously reported [52].
Pyrene: this compound was obtained by the general protocol as a pale yellow solid (30 mg, 56%). Mp 150–151 °C (Lit. [70] 146–147 °C). 1H NMR (400 MHz, CDCl3): δ = 8.02 (t, J = 7.6 Hz, 2H), 8.09 (s, 4H), 8.20 (d, J = 7.7 Hz, 4H) ppm. 13C NMR (101 MHz, CDCl3): δ = 124.7 (C), 125.0 (CH), 125.9 (CH), 127.4 (CH), 131.2 (C) ppm. These experimental data matched those previously reported [70].

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/chemistry7040120/s1. Figure S1: Molecular structure of (a) reagents, (b) intermediate 2, and products 3 and 4.; Figure S2: 1H, 13C{1H}, and DEPT-135 of (E)-3-(dimethylamino)-1-(pyren-1-yl)prop-2-en-1-one (2); Figure S3. 1H, 13C{1H}, and DEPT-135 of 5-(pyren-1-yl)isoxazole (3); Figure S4. COSY and HSQC of 5-(pyren-1-yl)isoxazole (3); Figure S5. HMBC of 5-(pyren-1-yl)isoxazole (3); Figure S6. 1H, 13C{1H}, and DEPT-135 of 5-(pyren-1-yl)-1H-pyrazole (4); Figure S7. 1H NMR of 5-(pyren-1-yl)-1H-pyrazole (4) in DMSO-d6; Figure S8. COSY of 5-(pyren-1-yl)-1H-pyrazole (4); Figure S9. HSQC and HMBC of 5-(pyren-1-yl)-1H-pyrazole (4); Figure S10. 1H, 13C{1H}, and DEPT-135 of pyrene; Figure S11. 1H NMR of the pyrenylisoxazole 4 upon the addition of 1 equiv of TFA in DMSO-d6; Figure S12. 1H NMR of 5-(pyren-1-yl)-1H-pyrazole (4) upon the addition of 1 equivalent of TFA or 1 equivalent of KCN in DMSO-d6; Figure S13. Expanded 1H NMR of 5-(pyren-1-yl)-1H-pyrazole (4) upon the addition of 1 equivalent of TBACN in DMSO-d6; Figure S14. HRMS analysis of (E)-3-(dimethylamino)-1-(pyren-1-yl)propen-1-one (2); Figure S15. HRMS analysis of 5-(pyren-1-yl)isoxazole (3); Figure S16. HRMS analysis of 5-(pyren-1-yl)-1H-pyrazole (4); Figure S17. Lippert-Mataga plot for 5-(pyren-1-yl)isoxazole (3); Figure S18. (a) UV-vis absorption and (b) fluorescence emission (λexc = 300 nm) spectra for 1-acetylpyrene (1) in TBME, DCM, and MeOH at 10 μM and ~20 °C; Figure S19. (a) UV-vis absorption and (b) fluorescence emission (λexc = 300 nm) spectra for pyrene in TBME, DCM, and MeOH at 10 μM and ~20 °C; Figure S20. (a) Absorption and (b) emission (λexc = 300 nm) spectra for 4 in three solvents at 10 μM and ~20 °C. Photograph of 4 in DCM under natural light and using a UV lamp of 395 nm; Figure S21. (a) Absorption and (b) emission (λexc = 300 nm) spectra upon the addition of different %H2O to the solutions of 4 in MeCN (10 μM ) at ~20 °C; Figure S22. (a) Absorption and (b) emission (λexc = 300 nm) spectra upon the addition of TBACN to the solutions of 4 in MeCN (10 μM ) at ~20 °C.

Author Contributions

Three individuals listed as authors contributed significantly to the development of this manuscript, and no other person was involved with its composition. The authors’ contributions are as follows: literature review, experimental, and result analysis, M.-C.R. and A.L.-B.; conceptualization, analysis of results, writing, manuscript review and editing, supervision, and resources, J.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the science faculty at the Universidad de los Andes, project INV-2025-213-3467.

Data Availability Statement

The data supporting the findings of this study are available within the article and its Supporting Information (SI).† Supporting data for this article are provided in the SI, which includes HRMS analysis with spectra copies, as well as 1H NMR, 13C NMR, DEPT-135, COSY, HSQC, and HMBC spectra copies. In addition, photophysical details are also presented in the Supporting Information† of this investigation.

Acknowledgments

We thank the Chemistry Department and Vicerrectoría de Investigaciones at the Universidad de los Andes for financial support. We also acknowledge Sandra Ortiz of Universidad de Los Andes for acquiring the mass spectra (for the HRMS analysis).

Conflicts of Interest

The authors declare no conflicts of interest to report with this manuscript.

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Chemistry 07 00120 sch001
Scheme 1. Synthesis of (a) 5-(3-coumarinyl)isoxazoles [37] and (b) research proposal.
Scheme 1. Synthesis of (a) 5-(3-coumarinyl)isoxazoles [37] and (b) research proposal.
Chemistry 07 00120 sch001
Chemistry 07 00120 sch002
Scheme 2. Synthesis of (a) the β-enaminone 2 and (b) 5-(pyren-1-yl)-1,2-azoles 3 and 4.
Scheme 2. Synthesis of (a) the β-enaminone 2 and (b) 5-(pyren-1-yl)-1,2-azoles 3 and 4.
Chemistry 07 00120 sch002
Chemistry 07 00120 g002
Figure 2. (a) Absorption and (b) emission (λexc = 300 nm) spectra for 3 in fourteen solvents (10 μM) at ~20 °C. Photograph of 3 in DCM (10 μM) under natural light and using a UV lamp of 395 nm.
Figure 2. (a) Absorption and (b) emission (λexc = 300 nm) spectra for 3 in fourteen solvents (10 μM) at ~20 °C. Photograph of 3 in DCM (10 μM) under natural light and using a UV lamp of 395 nm.
Chemistry 07 00120 g002
Chemistry 07 00120 g003
Figure 3. (a) Solid state emission spectra for dyes 3 and 4. Photograph under a UV lamp of 395 nm. (b) Possible supramolecular interactions in the solid state of the two studied dyes.
Figure 3. (a) Solid state emission spectra for dyes 3 and 4. Photograph under a UV lamp of 395 nm. (b) Possible supramolecular interactions in the solid state of the two studied dyes.
Chemistry 07 00120 g003
Chemistry 07 00120 g004
Figure 4. (a) Absorption and (b) emission (λexc = 300 nm) spectra upon the addition of different %H2O to a solution of the 5-(pyren-1-yl)isoxazole (3) in MeCN (10 μM ) at ~20 °C.
Figure 4. (a) Absorption and (b) emission (λexc = 300 nm) spectra upon the addition of different %H2O to a solution of the 5-(pyren-1-yl)isoxazole (3) in MeCN (10 μM ) at ~20 °C.
Chemistry 07 00120 g004
Chemistry 07 00120 g005
Figure 5. (a) Absorption and (b) emission (λexc = 300 nm) spectra upon the addition of TFA to a solution of 5-(pyren-1-yl)isoxazole (3) in MeCN (10 μM) at ~20 °C.
Figure 5. (a) Absorption and (b) emission (λexc = 300 nm) spectra upon the addition of TFA to a solution of 5-(pyren-1-yl)isoxazole (3) in MeCN (10 μM) at ~20 °C.
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Table 1. Spectroscopic properties of 1-acetylpyrene (1) and fluorophores 3 and 4 [a].
Table 1. Spectroscopic properties of 1-acetylpyrene (1) and fluorophores 3 and 4 [a].
CompoundStateλabs (nm)
π–π*,
n–π*shs		ε
(M–1 cm–1)		λem (nm)
maxshs		ϕF (%) [b]Stokes Shift (cm–1)
Chemistry 07 00120 i001Toluene279, 3568660, 6110398418,448882964
TBME279, 3518780, 6300394416/442743109
THF282, 3549330, 7240404416/446923496
AcOEt280, 3517900, 7130396416/442793238
Dioxane281, 3558070, 7810396416/446952916
Acetone282, 3508890, 7920398416/446813446
DCM282, 3528890, 7930400418/448963409
DCE282, 3548060, 6720400420/450ND3249
CHCl3283, 3549560, 8630400420/450863249
MeCN280, 3529150, 8390398416/446913283
DMF282, 3519590, 8470400420/450ND3490
DMSO284, 35612,300, 10,800402422/452903214
EtOH280, 3539923, 8970400418/446ND3329
MeOH279, 35211,270, 9320400418/448953409
Chemistry 07 00120 i002TBME281, 35535920,630, 17,960398438/466 (514434/548) [c]0.13043
DCM285, 35939314,670, 10,980408498/5320.23345
MeOH281, 35638725,150, 21,580402428/4680.13314
Chemistry 07 00120 i003TBME281, 34725,570, 21,510394408/4361.33438
DCM281, 34629,140, 23,430394408/4366.93521
MeOH278, 34539,240, 31,310392408/4361.53475
Chemistry 07 00120 i004TBME262, 272, 319305, 33418,000, 34,095, 21,826, 36,660378389 163487
DCM263, 274, 321306, 337 15,864, 33,546, 24,435, 39,457377392333146
MeOH261, 272, 318309, 334 25,029, 47,577, 29,409, 28,931376390263349
3 **[d]White solidND--49023.4--
4 **[d]Yellow solidND--50422.6--
[a] Spectra were recorded at ~20 °C by solutions* 10 µM (λexc = 300 nm). [b] Quantum yields were calculated using prodan (ϕDCM = 94%) as a standard. * [c] secondary λem. [d] Sodium salicylate as a standard (ϕF = 55%) and λexc = 325 nm. ** ND: not determined.
Table 2. Spectroscopic properties comparison of dyes 3 and 4 with recently reported fluorophores [a].
Table 2. Spectroscopic properties comparison of dyes 3 and 4 with recently reported fluorophores [a].
Fluorophore
(Stages, Overall Yield) [a]		State [b]λabs/λem (nm)ε (M–1 cm–1)ϕF (%)Application, LOD (μM) in SolventRef.
Chemistry 07 00120 i005in DCM
--		327/379
--		30,100
--		39
--		Coordination, NHC-Cu-ClCheng et al., 2023 [65]
Chemistry 07 00120 i006in DCM
Solid state		343/423
--/469		39,000
--		26
33		--Zych et al., 2024 [35]
Chemistry 07 00120 i007in DMSO
--		321/427
--/475		--
--		--
56		Sensor, 0.09/Hg2+ in DMSO/H2OWen et al., 2024 [66]
Chemistry 07 00120 i008in TBME
Solid state		438/473
449/535		38,130
--		21
49		Acidochromism,
3.38/TFA in MeCN		Ríos et al., 2025 [37]
Chemistry 07 00120 i009in TBME
Solid state		351/394
--/490		6300
--		74
23.4		Acidochromism,
2.41/TFA in MeCN		This work
Chemistry 07 00120 i010in TBME
Solid state		347/394
--/504		21,510
--		1.3
22.6		Acidochromism,
--/CN– in MeCN
[a] Starting from commercially accessible and relatively inexpensive reagents; [b] in solution or the aggregated state (powder).
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Ríos, M.-C.; Ladino-Bejarano, A.; Portilla, J. Synthesis and Photophysics of 5-(1-Pyrenyl)-1,2-Azoles. Chemistry 2025, 7, 120. https://doi.org/10.3390/chemistry7040120

AMA Style

Ríos M-C, Ladino-Bejarano A, Portilla J. Synthesis and Photophysics of 5-(1-Pyrenyl)-1,2-Azoles. Chemistry. 2025; 7(4):120. https://doi.org/10.3390/chemistry7040120

Chicago/Turabian Style

Ríos, María-Camila, Alexander Ladino-Bejarano, and Jaime Portilla. 2025. "Synthesis and Photophysics of 5-(1-Pyrenyl)-1,2-Azoles" Chemistry 7, no. 4: 120. https://doi.org/10.3390/chemistry7040120

APA Style

Ríos, M.-C., Ladino-Bejarano, A., & Portilla, J. (2025). Synthesis and Photophysics of 5-(1-Pyrenyl)-1,2-Azoles. Chemistry, 7(4), 120. https://doi.org/10.3390/chemistry7040120

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