Synthesis, photophysical and redox properties of the 2,5,7-tri(het)aryl-[1,2,4]triazolo[1,5-a ]pyrimidines

A number of Y-type push-pull compounds based on the [1,2,4]triazolo[1,5-a ]pyrimidine core, namely 5,7-di(het)aryl-substituted 2-phenyl-[1,2,4]triazolo[1,5-a ]pyrimidines, were obtained by transition metal free nucleophilic C–H functionalization. Substituents at both the C-5 and C-7 positions were introduced by successive treatment of the starting 6-bromo-2-phenyl-[1,2,4]triazolo[1,5-a ]pyrimidine with Grignard reagents. In addition, the optical and electrochemical properties of the synthesized push-pull systems were studied.


Introduction
Over the past few decades pyrimidine-cored compounds have gained considerable attention due to their promising application in designing different types of organic electronic devices. 1 For instance, pyrimidinebased π-conjugated compounds are widely and successfully used as active layers of thin-film (opto)electronic devices, including polymer solar cells, 2,3 different types of OLEDs (e.g., compounds 1 4 and 2 5 ), [4][5][6][7][8][9] or even portable detectors of explosives (e.g., compound 3) 10 (Figure 1).Such popularity of pyrimidines is explained by their highly π-deficient nature and ability to be an electron acceptor in various push-pull scaffolds providing an internal charge transfer upon excitation, and, therefore, inducing luminescence properties. 1 In this context, the electron-deficient system of the pyrimidine derivative [1,2,4]triazolo [1,5-a]pyrimidine (TAP) can also be of interest for the elaboration of donor-acceptor molecules.Indeed, substituted TAPs show good fluorescence features, especially in the blue region of spectra. 11Since there is still a great demand for blue emitting materials with high efficiency, 12,13 TAPs seem to be an attractive object for the further research.
One of the main routes to substituted pyrimidines is the direct C-H functionalization, 1,14 otherwise known as nucleophilic aromatic substitution of hydrogen (S N H ). 15,16 This approach can also be applied to the TAPsystem, as already demonstrated by Jie Wu and colleagues who synthesized 2,7-diaryl-substituted TAPs using direct copper-catalyzed CH functionalization. 17However, in general, S N H method requires the prefunctionalization of substrates with auxiliary groups, e.g.halogens, and the catalysis by expensive transition metals, which does not satisfy the atom-economy principle in terms of green chemistry and increases the process cost.As such, we have attempted to improve the C-H functionalization approach to substituted TAPs using organomagnesium compounds as nucleophilic species, thus avoiding the above-mentioned disadvantages and obtaining 5,7-di(het)aryl-substituted TAPs with promising luminescence features. 11ontinuing our previous work 11 on the functionalization of TAPs by Grignard reagents, we present below the synthesis and study of more π-extended 2,5,7-tri(het)aryl-substituted TAPs, obtained with the aim of improving the optical properties.

Synthesis of TAP compounds
As previously highlighted, TAPs have electron deficient character, so they tend to enter into addition reactions with nucleophiles.Previously, we reported that the reaction of 6-bromo-TAP 4 with (het)aryl magnesium bromides proceeds regioselectively at the C-7 position.The resulting σ H -adducts can undergo an eliminative aromatization, thus giving 7-substituted TAPs 5a-d, which can be further treated with additional Grignard reagents to afford the 5,7-disubstituted TAPs 6aa-dd (Scheme 1). 11Scheme 1.General pathway to 5,7-disubstituted TAPs.
In accordance with our approach, we tried to construct 2,5,7-tris(het)aryl-TAPs by attacking the C-2 position of 5,7-di(het)aryl-TAP with Grignard reagents as well as stronger nucleophiles -aryllithium compounds, but in both cases the attempts failed (Scheme 2).Thus, we decided to synthesize the desired 2,5,7-tri(het)aryl-TAPs by the successive functionalization of 2-aryl-substituted TAP at its C-5 and C-7 positions using Grignard reagents, similar to the manner described above.Scheme 2. Interaction 5,7-di(het)aryl-TAPs with aryl lithium reagents.
To this end, 2-phenyl-TAP 8, formed from 3-phenyl-1,2,4-triazol-5-amine (7), obtained by earlier reported procedure, 18 and 1,1,3,3-tetramethoxypropane, was selected as a model compound to realize our strategy and treated with Grignard reagents prepared in situ from the corresponding aryl bromides and magnesium in THF.However, in the course of this reaction the regioselectivity was not observed, thus giving the mixture of products of the C-5 and C-7 addition.Thus, we turned our attention to another TAP derivative, namely 6bromo-2-phenyl-TAP 9. Substrate 9 was prepared by the condensation of 3-phenyl-1,2,4-triazol-5-amine (7)  with 2-bromomalonaldehyde in glacial acetic acid solution (Scheme 3) in 87% yield.Compound 9 can also be obtained by the direct bromination of 2-phenyl-TAP 8 but only in 44% yield.The first addition of (het)aryl magnesium bromides to compound 9 proceeded regioselectively at low temperatures and afforded σ H -adducts 10a-d in 68-91% yields.The latter adducts were aromatized by dehydrobromination with triethylamine, resulting in 2,7-disubstituted TAPs 11a-d (Table 1).The second attachment of Grignard reagents to derivatives 11a-d led to the formation of 2,5,7trisubstituted TAPs 12aa-dd after the one-pot oxidation of addition intermediates (Table 2), which, however, proceeded slowly and required prolonged bubbling of oxygen through the reaction mixture.
It is worth noting that the synthesized compounds, due to the presence of an additional phenyl group in the azole moiety, have poorer solubility compared to the substances described in our previous article.However, this did not prevent us to obtain analytically pure forms of these compounds in the all cases.Nevertheless, it is clear, that to construct similar TAP molecules with bulk (hetero)aromatic moieties, fragments bearing long-chain or branched alkyl or alkoxy groups should be inserted to improve solubility of the desired final TAPs.

Optical and electrochemical measurements
The UV-vis absorption and photoluminescence spectra of compounds 11 and 12 were recorded in CH 2 Cl 2 solution (2 × 10 −5 mol • L −1 ) at ambient temperature (Table 3).E HOMO/LUMO values were estimated from the corresponding onset potentials in electrochemical studies, E gap = E LUMO − E HOMO (for additional data see SI).Measurements of E g opt were carried out by the optical method 19 in a solid form.The quantum yields were determined by the relative method; 19 the comparison sample was quinine bisulfate.All obtained substituted TAPs exhibit a very strong light absorption in violet and near UV regions of the spectrum (Figure 4).The luminescence of compounds 11 and 12 varies from near UV (11a-c) and violet (12aa-12cd) to blue (11d) and green (12da, 12dc, 12dd).Compound 11a with the simplest structure has a minimum quantum yield among the studied 2,7-disubstituted TAPs.Replacement of the C-7 phenyl group by 4methoxyphenyl or 4-(N,N-dimethylamino)phenyl groups leads to significant increase in quantum yields to above 60%.All TAPs containing 2-thienyl-group show average quantum yields with maximum value of 45% for 11c and 12cb.TAPs 11b and 12bb containing 4-methoxyphenyl group show significant quantum yields of 62%.At the same time, there is a small bathochromic and significant bathofluoric shift.The greatest bathofluoric effect is achieved by introducing 4-(N,N-dimethylamino)phenyl at C-5 and C-7 positions (compound 12dd).The emission maximum shifts to 538 nm (Figure 4).A similar effect can be achieved by replacing the substituent at C-5 position on thienyl as in 12dc (emission maximum at 530 nm).At the same time, quantum yields of these compounds are relatively low, 15 and 24%, respectively.Compound 12db, containing 4-methoxyphenyl and 4-(N,N-dimethylamino)phenyl substituents, shows good quantum yield, which is higher than the group average (41%), as well as strong bathofluoric shift with emission maximum at 497 nm.The swap of substituents in compound 12db gives compound 12bd with an almost minimum quantum yield in the group (17%) and an insignificant bathofluoric shift (emission maximum at 416 nm).
Comparing the series of compounds 11 and 12 with the previous one of compounds 6, 11 it should be noted that entering additional phenyl at C-2 position of TAP led to some increase in quantum yields, however, the luminescence maxima are on average shifted to the region of shorter wavelengths.If comparing 5-phenyl-7-(het)aryl-and 2-phenyl-7-(het)aryl TAPs, a significant increase of quantum yields is observed, in the case of 5phenyl-7-[4-(N,N-dimethylamino)phenyl]-TAP 6da and corresponding compound 11d -twofold.

Experimental Section
General.All reagents, except for 3-phenyl-1,2,4-triazol-5-amine, and solvents were purchased from commercial sources and dried by using standard procedures before use.3-Phenyl-1,2,4-triazol-5-amine was prepared according to the literature. 11Analytical studies were carried out using equipment of the Center for Joint Use "Spectroscopy and Analysis of Organic Compounds" at the Postovsky Institute of Organic Synthesis of the Russian Academy of Sciences (Ural Division).Melting points were determined on Boetius combined heating stages and are uncorrected.Elemental analysis was carried on a Eurovector EA 3000 automated analyzer. 1H and 13 C NMR spectra were recorded on AVANCE-400 and AVANCE-500 instruments in DMSO-d 6 or CDCl 3 with TMS as an internal standard.The GC-MS analysis of all samples was carried out using an Agilent GC 7890A MS 5975C Inert XL EI/CI GC-MS spectrometer with a quadrupole mass-spectrometric detector with electron ionization (70 eV), and scan over the total ionic current in the range m/z 20-1000 and a quartz capillary column HP-5MS (30 m × 0.25 mm, film thickness 0.25 mm).Column chromatography was carried out using Alfa Aesar silica gel 0.040-0.063mm (230-400 mesh), eluting with ethyl acetate/hexane (50:50) or ethyl acetate containing 0.5% of triethylamine.The progress of the reactions and the purity of compounds were checked by TLC on Sorbfil plates (Russia), in which the spots were visualized with UV light (λ 254 or 365 nm).Optical spectra were obtained using a Shimadzu UV-2600 double-beam UV-vis spectrophotometer, a Varian Cary Eclipse fluorescence spectrophotometer and a Hêllma QS-101 high precision quartz cell in CH 2 Cl 2 solution.Solutions of compounds with 4-(N,N-dimethylaminophenyl) substituents were made with the addition of Me 4 NOH base.Bi-quinine sulfate was used as the standard for relative quantum yield measuring.
Cyclic voltammetry was carried out on a Metrohm Autolab PGSTAT128N potentiostat with a standard threeelectrode configuration.Typically, a three electrodes cell equipped with a glass carbon working electrode, a Ag/AgNO 3 (0.01 M) reference electrode, and a glass carbon rod counter electrode was employed.The measurements were done in dichloromethane with tetrabutylammonium hexafluorophosphate (0.1 M) as the supporting electrolyte under an argon atmosphere at a scan rate of 100 mV/s.The potential of Ag/AgNO 3 reference electrode was calibrated by using the ferrocene/ferrocenium redox couple (Fc/Fc + ).

2,5,7-Trisubstituted [1,2,4]triazolo[1,5-a]pyrimidines (12aa-dd) (General procedure).
Grignard reagent solution was prepared from magnesium powder (36 mg, 1.5 mmol) and the appropriate bromo(het)arene (1.5 mmol) in THF (10 mL).It was cooled to -78 °C and the corresponding 7-substituted-TAP 6 (1 mmol) was added.After 1 h the bath temperature was elevated to 50 °C, and the reaction mixture was stirred for another 2 h.Then the oxygen atmosphere was created and kept for 2 h.When the reaction was completed, the flask was cooled, and the reaction mixture was charged with cold water (2-3 mL) and ammonium chloride (107 mg, 2 mmol).The volatiles were then distilled off in vacuo, the residue was filtered, washed with cold water and hexane, dried and recrystallized to afford the desired products 12aa-dd.
triazolo[1,5-a]pyrimidines based on the nucleophilic aromatic substitution of hydrogen (S N H ) in the 2-aryl-substituted TAP substrate has Successive nucleophilic addition of Grignard reagents on 6-bromo-2-phenyl-TAP enables substitution first at C-7 and then at C-5 via direct C-H functionalization.Basic optical and electrochemical properties of 2,7-di(het)aryl-and 2,5,7-tri(het)aryl-substituted derivatives have been also investigated.Most of the studied compounds exhibit strong fluorescence with high quantum yields up to 61%.