Highly Luminescent 4H-1,2,4-Triazole Derivatives: Synthesis, Molecular Structure and Photophysical Properties

An alternative approach to the Suzuki cross-coupling reaction is used to synthesize a series of new luminophores based on 4-alkyl-4H-1,2,4-triazole cores conjugated via 1,4-phenylene linker to fused-bicyclic and tricyclic aromatic, or heteroaromatic arrangements. The described methodology allows one to conduct the coupling reaction with the use of commercially available boronic acids in the presence of conventional solvents or ionic liquids and produced excellent yields. It was found that the use of ultrasounds or microwaves significantly accelerates the reaction. The obtained compounds exhibited high luminescent properties and a large quantum yield of emitted photons. The X-ray molecular structures of three highly conjugated 4H-1,2,4-triazole representatives are also presented.


Introduction
In recent decades, organic compounds containing both donor and acceptor moieties connected through π-conjugated linkages have been widely investigated due to the possibility of their application in optoelectronic devices [1-3], such as organic light-emitting diodes (OLEDs), photovoltaic cells and organic field-effect transistors (OFETs). However, a potential luminophore should contain not only an extended π-conjugated system, but also other features including the proper electron-hole transporting properties, a high external quantum efficiency, as well as thermal and chemical stabilities [4,5]. Heterocyclic arrangements with highly electronegative nitrogen atoms perfectly fit the requirements for such systems. The presence of nitrogen in the aromatic ring considerably affects the electron distribution within the molecule, and also improves the intramolecular electron transport.

Results and Discussion
Four basic 4-alkyl-3,5-bis(4-bromophenyl)-4H-1,2,4-triazole (5a-d) substrates were synthesized starting from 4-bromobenzoic acid (1), using our previously elaborated methodologies [58] (Scheme 1). For each reaction, triazole precursors (5a-d) containing substituents, differing in their alkyl chain length at the nitrogen atom (position 4), were coupled with 4-(N,N-diphenylamino)phenylboronic acid (6a) in a Suzuki reaction. Transformations were completed using a two-phase solvent system with conventional heating in an oil bath over a sufficiently long period (7 h, TLC) using Pd(PPh 3 ) 4 as a catalyst, and potassium carbonate as a base which gives the desired products in high yields (Scheme 2). Three (8a-10a) of the final products form single crystals in the solid-state (Figure 1), enabling the determination of their molecular structures (Table S1). Compounds 8a and 9a crystallize as ethanol solvates ( Figure S1), while 10a forms a solventless compound. This is caused by the presence of an nhexyl substituent on the triazole ring of 10a. The n-hexyl terminal methyl and methylene atoms (-CH2-CH3) are located in the space occupied by ethanol molecules in 8a and 9a ( Figures S2-S4). The shorter n-butyl and n-propyl substituents cannot fill the crystal net space and leave empty voids with volumes of 153-216 Å 3 , which are accessible for solvent molecules. Due to discrepancy between the volume of the solvent molecules (~97 Å 3 for one ethanol molecule) and voids, these molecules are disordered in the crystal net ( Figures S1 and S5). This affects the neighboring parts of alkyl substituents, which are also disordered in 9a and 10a due to the relative freedom of their packing ( Figure S1). Compounds 8a and 9a in the solid-state are effectively isostructural, whilst 10a adopts a different packing pattern. In all compounds (8a-10a), the molecules extend in one direction of the crystal net, but their mutual shifts are different. In 8a and 9a, the subsequent molecules are shifted to approximately half of the preceding molecule length, i.e., the terminal N,N-diphenylamino group of one molecule is located near the central triazole ring of the neighboring molecule ( Figures S2 and S3). In 10a, the terminal N,N-diphenylamino groups of the neighboring molecules are adjacent ( Figure  S4). The overall conformation of molecules 8a-10a is similar, such that the molecules extend along axes going through the N(triazole)-C(phenylene) bonds due to the presence of 1,4-phenylene moieties. The mutual arrangement of the ring groups is different in all compounds (8a-10a), including clearly visible differences in the isostructural 8a and 9a. The dihedral angles between the least-squares plane of the diphenylene moiety rings vary from 12.3(1)° to 31.95(6)°, while the angles between the N,N-diphenylamino moiety rings differ from 52.80(5)° to 66.52(6)° (Table S3). The C-N and N-N bonds with the triazole ring possess similar lengths (Table S2) and respective values are between the length of single and double bonds C-N and N-N, [59] what proves the electron delocalization within the ring. The C(triazole)-C(phenylene) bonds exhibit shortening observed Three (8a-10a) of the final products form single crystals in the solid-state (Figure 1), enabling the determination of their molecular structures (Table S1). Compounds 8a and 9a crystallize as ethanol solvates ( Figure S1), while 10a forms a solventless compound. This is caused by the presence of an n-hexyl substituent on the triazole ring of 10a. The n-hexyl terminal methyl and methylene atoms (-CH 2 -CH 3 ) are located in the space occupied by ethanol molecules in 8a and 9a (Figures S2-S4). The shorter n-butyl and n-propyl substituents cannot fill the crystal net space and leave empty voids with volumes of 153-216 Å 3 , which are accessible for solvent molecules. Due to discrepancy between the volume of the solvent molecules (~97 Å 3 for one ethanol molecule) and voids, these molecules are disordered in the crystal net ( Figures S1 and S5). This affects the neighboring parts of alkyl substituents, which are also disordered in 9a and 10a due to the relative freedom of their packing ( Figure S1). Compounds 8a and 9a in the solid-state are effectively isostructural, whilst 10a adopts a different packing pattern. In all compounds (8a-10a), the molecules extend in one direction of the crystal net, but their mutual shifts are different. In 8a and 9a, the subsequent molecules are shifted to approximately half of the preceding molecule length, i.e., the terminal N,N-diphenylamino group of one molecule is located near the central triazole ring of the neighboring molecule ( Figures S2 and S3). In 10a, the terminal N,N-diphenylamino groups of the neighboring molecules are adjacent ( Figure  S4). The overall conformation of molecules 8a-10a is similar, such that the molecules extend along axes going through the N(triazole)-C(phenylene) bonds due to the presence of 1,4-phenylene moieties. The mutual arrangement of the ring groups is different in all compounds (8a-10a), including clearly visible differences in the isostructural 8a and 9a. The dihedral angles between the least-squares plane of the diphenylene moiety rings vary from 12.3(1) • to 31.95(6) • , while the angles between the N,N-diphenylamino moiety rings differ from 52.80(5) • to 66.52(6) • (Table S3). The C-N and N-N bonds with the triazole ring possess similar lengths (Table S2) and respective values are between the length of single and double bonds C-N and N-N, [59] what proves the electron delocalization within the ring. The C(triazole)-C(phenylene) bonds exhibit shortening observed typically in exocyclic bonds connected to aromatic rings [59], which results in the redirecting of the electron density toward the C-C bond. The complete hydrogen bonding scheme of compounds 8a and 9a could not be resolved due to the disorder in the solvent molecules' positions. Nevertheless, the studied molecules possess only two classical hydrogen bonds acceptors and non-classical hydrogen bonds donors [60]. The N1 and N2 atoms participate in weak C-H···N hydrogen bonds (Table S4). The isostructural forms of 8a and 9a have the same π···π stacking interaction motifs due to the similarity of their crystal packing [61]. One of the phenyl rings from each terminal N,N-diphenylamino substituent interacts with their symmetry generated equivalent rings. Additionally, one of these rings interacts with the symmetry generated ring of the N,N-diphenylamino moiety located on the opposite end of the molecule (Table S5). Consequently, one of the four rings belonging to N,N-diphenylamino substituents interacts with two rings, meaning two interact with one ring, and one does not form any π···π stacking interactions. In 10a, only two different π···π stacking interactions exist. The first one is formed between the neighboring triazole rings and the second one between one at the phenyl rings of each terminal N,N-diphenylamino moiety, i.e., similarly to 8a and 9a, the phenyl ring of one terminal moiety interacts with the symmetry generated ring of the oppositely located terminal moiety (Table S5).
The final products were tested for their luminescent properties, displaying strong fluorescent properties (Table 1, Figure 2). The compounds have a relatively large Stokes shift (∆λ =~90 nm) and a near-unity quantum yield (Φ > 0.98). From these results, an alternative approach to the Suzuki reaction was investigated ( Table 2).
Materials 2020, 13, x FOR PEER REVIEW 9 of 21 typically in exocyclic bonds connected to aromatic rings [59], which results in the redirecting of the electron density toward the C-C bond. The complete hydrogen bonding scheme of compounds 8a and 9a could not be resolved due to the disorder in the solvent molecules' positions. Nevertheless, the studied molecules possess only two classical hydrogen bonds acceptors and non-classical hydrogen bonds donors [60]. The N1 and N2 atoms participate in weak C-H···N hydrogen bonds (Table S4). The isostructural forms of 8a and 9a have the same π···π stacking interaction motifs due to the similarity of their crystal packing [61]. One of the phenyl rings from each terminal N,Ndiphenylamino substituent interacts with their symmetry generated equivalent rings. Additionally, one of these rings interacts with the symmetry generated ring of the N,N-diphenylamino moiety located on the opposite end of the molecule (Table S5). Consequently, one of the four rings belonging to N,N-diphenylamino substituents interacts with two rings, meaning two interact with one ring, and one does not form any π···π stacking interactions. In 10a, only two different π···π stacking interactions exist. The first one is formed between the neighboring triazole rings and the second one between one at the phenyl rings of each terminal N,N-diphenylamino moiety, i.e., similarly to 8a and 9a, the phenyl ring of one terminal moiety interacts with the symmetry generated ring of the oppositely located terminal moiety (Table S5). The final products were tested for their luminescent properties, displaying strong fluorescent properties (Table 1, Figure 2). The compounds have a relatively large Stokes shift (Δλ = ~90 nm) and a near-unity quantum yield (Φ > 0.98). From these results, an alternative approach to the Suzuki reaction was investigated ( Table 2).   Wavelength determined from the 3D emission spectrum for C = 5.0 × 10 −6 M CH 2 Cl 2 solution (nm). c quinine sulfate was used as a standard [62]. d trans,trans-1,4-diphenyl-1,3-butadiene was used as a standard [63]. e exact value cannot be determined due to nonlinearity of standard/sample dependence in the Φ region of 0.97-1.00 [64]. Table 2. An alternative ionic liquids (IL) Suzuki cross-coupling reaction of the 4-alkyl-3,5-bis(4bromophenyl)-4H-1,2,4-triazole moiety (7a-10a).
Materials 2020, 13, x FOR PEER REVIEW 10 of 21 plotted as spheres with arbitrary radii. The disordered solvent molecules of 8a and 9a, as well as a minor contribution from the distorted alkyl chains of 9a and 10a, are omitted for clarity. . Wavelength determined from the 3D emission spectrum for C = 5.0 × 10 −6 M CH2Cl2 solution (nm). c quinine sulfate was used as a standard [62]. d trans,trans-1,4-diphenyl-1,3-butadiene was used as a standard [63]. e exact value cannot be determined due to nonlinearity of standard/sample dependence in the Φ region of 0.97-1.00 [64]. The use of ionic liquids in the Suzuki cross-coupling reaction opens up the possibility for the additional acceleration of the reaction with the use of ultrasound or microwaves. These variants (  2, 7, 8, 13, 14, 19 and 20) in an oil bath while maintaining a high coupling efficiency. The most beneficial aspects from an economic point of view is the use of a small addition of a classical solvent (toluene, 1 mL) and conducting the reaction in a microwave reactor, where the complete conversion of substrates takes place after only 6 min (TLC), and the products are obtained in high yields ( Table 2, entries: 6, 12, 18 and 24, 62-97%).
The highest yields were obtained for derivatives with two and four carbon alkyl chains, the subsequent reactions were carried out for these two series of triazole precursors, 5a and 5c (Scheme 3), and then their emission properties were tested (Table 3). Generally, compounds containing a 4H-1,2,4-triazole core substituted with an ethyl group at the position 4 were synthesized with a slightly smaller range of yields (70-99% for 7a-k, Tables 1 and 3) than their counterparts with the butyl substituent (62-99% for 9a-k, Tables 1 and 3). The use of ionic liquids in the Suzuki cross-coupling reaction opens up the possibility for the additional acceleration of the reaction with the use of ultrasound or microwaves. These variants ( Table 2, entries: 3-6, 9-12, 15-18 and 21-24) have a shorter reaction time compared to conventional heating ( Table 2, entries: 1, 2 , 7, 8, 13, 14, 19 and 20) in an oil bath while maintaining a high coupling efficiency. The most beneficial aspects from an economic point of view is the use of a small addition of a classical solvent (toluene, 1 mL) and conducting the reaction in a microwave reactor, where the complete conversion of substrates takes place after only 6 min (TLC), and the products are obtained in high yields ( Table 2, entries: 6, 12, 18 and 24, 62-97%).

Product
Yield a (%)  Three-dimensional fluorescence characteristics were determined for all the final products from the outlined reactions. The spectra of compounds 7a-7e, 8a, 9a-9e and 10a possess a single fluorescence maximum, while compounds 7f-7k and 9f-9k have two maxima (Figures 2-4). Almost all of the synthesized compounds emit strong fluorescence upon irradiation with UV light. The only exceptions are the compounds 7k and 9k containing the thianthrene substituent (Table 3). This is due to the presence of two sulfur atoms in the thianthrene moiety. Typically, the presence of one sulfur atom in a molecule causes the severe quenching of fluorescence [65,66]. In each molecule of compound 7k and 9k, four sulfur atoms are present, thus, the almost total quenching of fluorescence is observed (Figures 3  and 4). Similarly, the existence of two sulfur atoms per one molecule in 7f and 9f distinctly decreases the number of emitted photons in comparison to the other studied compounds without a sulfur atom in the structure. The change in the aliphatic substituent length at the triazole nitrogen N atom does not affect the position and shape of the three-dimensional emission maxima. The effect of increased emission wavelengths for aliphatic substituents with even number of carbon atoms (in comparison to these with odd number of carbon atoms) is not observed in the studied case [58]. This suggests that the presence of substituents containing a single ring at the ends of the 4-alkyl-3,5-bis(phenyl)-4H-1,2,4-triazole core is necessary for the aforementioned even/odd number of carbon atoms and its influence on fluorescence. In the studied compounds, the terminal substituents consists of two up to four rings (in the subsequent or fused arrangement) and this completely diminishes the effect of the aliphatic substituent parity at the triazole nitrogen N atom. Table 3. 4-Alkyl-3,5-bis(4-arylphenyl)-4H-1,2,4-triazoles 7b-k and 9b-k prepared using the Suzuki cross-coupling reaction a .

Product
Yield a (%) Wavelength determined from the 3D emission spectrum for C = 5.0 × 10 −6 M CH 2 Cl 2 solution (nm). c quinine sulfate was used as a standard [62]. d trans,trans-1,4-diphenyl-1,3-butadiene was used as a standard [63]. e exact value cannot be determined due to the nonlinearity of standard/sample dependence in the Φ region 0.97-1.00 [64].      The number of rings in terminal substituents also affects the excitation and emission wavelengths ( Figure S8). There is a decrease in the excitation wavelength for the first maximum on the spectrum (accompanied by an increase in the excitation wavelength for the second maximum on the spectrum) with an increase in the number of rings ( Figure S8). The difference between the excitation and emission wavelengths at the maxima falls by approximately 70-84 nm (for compounds possessing two fluorescence maxima, at least one fulfills this relation), thus the energy gap between the respective orbitals responsible for the fluorescence is very similar in all studied compounds. The spectra of the compounds with rings separated by a single bond (7a-10a) or with no more than two fused rings (7b-7e and 9b-9e) possess a single maximum in the three-dimensional fluorescence spectrum. The compounds with three fused rings (7f-7k and 9f-9k) possess two more or less shaped maxima at the same emission wavelength and two different excitation wavelengths. Manifestations of these maxima were faintly but unambiguously visible in the compounds with almost completely quenched fluorescence (7k and 9k). All the single maxima possess a considerable degree of asymmetry, with the emission drastically fading with a decrease in the emission wavelengths and/or increase in the excitation wavelengths. In two other directions of the spectra, the emission decreases slowly. This originates from the electronic transitions of the excited state (S 1 ) to the different energy sub-levels (vibrational energy levels 0, 1, 2, . . . ) of the ground state (S 0 ). The asymmetricity increases with the number of electrons in the delocalized system (7b ≈ 7c ≈ 9b ≈ 9c < 7d ≈ 7e ≈ 9d ≈ 9e < 7a ≈ 8a ≈ 9a ≈ 10a), due to the increased number of vibrational energy levels. The presence of two fluorescence maxima in the spectra of compounds 7f-7k and 9f-9k is caused by the presence of ring systems possessing two different heteroatomic rings (central and terminal ones). The intensity of both maxima is similar for compounds 7g-7j and 9g-9j. For compounds 7f and 9f, the first (at lower excitation wavelengths) maxima is stronger than the second one (existing at larger excitation wavelengths), while for compounds 7j and 9j the mutual relation of maxima intensities is reversed. This effect is caused by the presence of a thiophene moiety in the thianthrene ring system of 7f and 9f and an occurrence of an additional phenylene moiety in 7j and 9j (in comparison to the other studied compounds). The conjugation of the triazole ring with appropriately selected substituents containing together more than six aromatic rings (7a-10a, 7g-7j, and 9g-9j excluding 7f, 7k, 9f, and 9k, containing sulfur atoms) leads to reach a nearly 1.00 value of quantum yield (Φ). Such properties are not achieved by triazoles conjugated with four aromatic rings [58]. Their Φ, although high, reaches values maximally around 0.9. The triazoles which are not bonded directly to aryl substituents are characterized by a very low Φ (below 0.01) [67]. To improve the fluorescence properties of triazoles conjugated with a lower number of aromatic rings, the coordination compounds with d 10 transition metals are synthesized [68]. Even then, the zinc compounds of triazoles with one aromatic ring achieve Φ only up to 0.075 [69]. The Φ of the studied compounds correlate well with the fluorescence intensities (larger fluorescence leads to larger Φ, Figure S9), whereas there is no discernible relationship between Φ and absorption ( Figure S10). This suggests that the mechanism of fluorescence is similar in all compounds and the relatively large differences in the absorption values derive from the variations in the amount of electromagnetic energy (photons) transformed directly into internal energy. The above described effects (presence/lack of a correlation) exist also in 4-alkyl-3,5-bis(phenyl)-4H-1,2,4-triazole substituted at the ends by a single ring [58] and there is no such effects in the di(1,3,4-oxadiazol-2-yl)-1,2,4,5-tetrazine and 3,6-di(1,3,4-thiadiazol-2-yl)-1,2,4,5-tetrazine derivatives [70]. In the case of the compounds exhibiting a single fluorescence maximum, the n→π* absorption transition is the main source of the excited states leading to the subsequent emission of the fluorescence photons. The origin of fluorescence in the compounds exhibiting two fluorescence maxima are n→π* (for higher λ ex max ) and π→π* (for lower λ ex max ) absorption transitions [68]. The involved n-type orbital originates from the nitrogen atom of the triazole ring (N1 or N2) and the source of the π-type orbital is also the triazole ring [71]. The lowest unoccupied molecular orbital in similarly conjugated 1,2,4-triazole compounds is antibonding delocalized orbital (π*), which most often is the benzene ring directly attached to the triazole ring [72] or fused π* orbital of triazole and the neighboring benzene [73]. The presence of a single fluorescence maximum or two fluorescence maxima of the same emission wavelength indicates that π*→π transitions are responsible for the fluorescence in the studied compounds [74]. Noteworthy is the fact that upon ultraviolet irradiation, the compounds 7a-10a emit a strong deep-blue fluorescence light visible by the naked eye. The blue-violet color emitted light is clearly visible for compound 7c-7e, 7h-7j, 9c-9e, 9h-9j.

Conclusions
Four alternative approaches using palladium-catalyzed Suzuki cross-coupling reactions to synthesize a series of highly-conjugated 4H-1,2,4-triazole derivatives were presented. The reactions of the intermediate 4-alkyl-3,5-bis(4-bromophenyl)-4H-1,2,4-triazoles and boronic acids were conducted using conventional heating in a two-phase solvent system (toluene/EtOH/H 2 O) or using an ionic liquid (choline-OH). For the ionic liquid approach, it was possible to use ultrasound or microwave assistance, which significantly reduces the reaction time. Additionally, this type of methodology removes the need for large amounts of organic solvents and for the addition of auxiliary reagents such as a base or a phase transfer catalyst. Generally, 4-alkyl-4H-1,2,4-triazole derivatives conjugated to different fused-bicyclic and fused-tricyclic systems via a 1,4-phenylene linker were obtained in excellent yields. Almost all compounds are effective fluorophores and emit visible light upon irradiation by ultraviolet electromagnetic waves. The exceptions are the products possessing sulfur atoms within terminal moieties, which cause a large decrease in the fluorescence. The studied compounds produce fluorescence with large quantum yields (up to almost 100%), which depend on a structure of the terminal substituents. The obtained compounds, due to their good emission properties and relatively good solubility in typical organic solvents, seem to be of particular interest for optoelectronic purposes.
Supplementary Materials: The following are available online at http://www.mdpi.com/1996-1944/13/24/5627/s1, copy of 1 H NMR, 13 C NMR and HRMS spectra; X-ray crystallography data; absorption spectrometry data. Figure S1: Complete asymmetric units of the structures of compounds 8a, 9a, and 10a, with atom numbering scheme, plotted with 50% probability of displacement ellipsoids of non-hydrogen atoms. Hydrogen atoms are plotted as spheres of arbitrary radii, Figure S2: Solvent accessible voids within crystal structure of 8a, Figure S3: Solvent accessible voids within crystal structure of 9a, Figure S4: The part of crystal packing in 10a, Figure S5: Disorder model of solvent in 8a, Figure S6: UV-Vis spectra of 7a-10a and 7b-7k, Figure S7: UV-Vis spectra of 9b-9k, Figure S8: Positions of global maxima for studied compounds (divided into groups containing 2 or 3 rings at the ends of 4-alkyl-3,5-bis(phenyl)-4H-1,2,4-triazole core). "1 st max." and "2 nd max." indicate the first (for smaller excitation wavelengths) and the second (for larger excitation wavelengths) maxima on three-dimensional fluorescence spectra, Figure S9: Quantum yield of studied compounds as a function of fluorescence intensity at global and local maximum, Figure S10: Quantum yield of studied compounds in relation to absorption at global and local maximum of fluorescence, Table S1: Crystal data and structure refinement details for 8a, 9a, and 10a. The structures of 8a and 9a were refined twice: against measured and squeezed data, Table S2: Selected structural data of 8a, 9a, and 10a, Table S3: Dihedral angles ( • ) between ring least squares planes in 8a, 9a, and 10a. Each ring is indicated by one atom, which belongs solely to this ring, Table S4: Non-classic hydrogen bonds and the first level graph motifs in the studied compounds (Å, • ), Table S5: Stacking interactions in the studied compounds. Each ring is indicated by one atom, which belongs solely to this ring. The α is a dihedral angle between planes I and J, β is an angle between Cg(I)-Cg(J) vector and normal to plane I, d p is a perpendicular distance of Cg(I) on ring J plane.