Multicomponent Synthesis of New Fluorescent Boron Complexes Derived from 3-Hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde

Novel fluorescent pyrazole-containing boron (III) complexes were synthesized employing a one-pot three-component reaction of 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-aminobenzenecarboxylic acids, and boronic acids. The structures of the novel heterocyclic compounds were confirmed using 1H-, 13C-, 15N-, 19F-, and 11B-NMR, IR spectroscopy, HRMS, and single-crystal X-ray diffraction data. The photophysical properties of the obtained iminoboronates were investigated using spectroscopic techniques, such as UV–vis and fluorescence spectroscopies. Compounds display main UV–vis absorption maxima in the blue region, and fluorescence emission maxima are observed in the green region of the visible spectrum. It was revealed that compounds exhibit fluorescence quantum yield up to 4.3% in different solvents and demonstrate an aggregation-induced emission enhancement effect in mixed THF–water solutions.

Over the years, many methods have been used to synthesize pyrazole derivatives, including ring formation via the cyclocondensation of hydrazines, with carbonyl systems and dipolar cycloadditions being the most relevant [21,22].Another approach to synthesizing pyrazole derivatives is related to the functionalization of pyrazole ring, and a number of reported synthetic late-stage pyrazole functionalizations rely on (pseudo)halogenation and following transition-metal catalysis or direct C-H functionalization [23,24].A multicomponent reaction (MCR) approach has also been successfully applied to synthesize pyrazole-containing heterocyclic systems [25,26].Multicomponent reactions can be highlighted as one of the most valuable tools used by researchers to synthesize heterocyclic compounds, as they meet the principles of sustainable chemistry, are cost-and timeeffective, and are atom-and bond-economic [27,28].Recent examples of multicomponent reactions for synthesizing pyrazole-containing compounds include the synthesis of biheterocyclic pyrazole-linked thiazole or imidazole derivatives from appropriate aryl glyoxal, aryl thioamide, and pyrazolones [29] or the formation of stable pyrazole amides via a Ugi four-component reaction [30].A multicomponent synthesis approach was applied to obtain multisubstituted pyrazole derivatives from alkynes, nitriles, and titanium imido complexes [31].We have also reported the synthesis and structural elucidation of several series of novel biheterocyclic pyrazole-containing compounds by employing different types of multicomponent reactions, starting from 3-alkoxy-1H-pyrazole-4-carbaldehydes [32].

Chemistry
The synthesis of iminoboronates is usually achieved via a one-pot, three-component reaction of salicylaldehydes and anthranilic acids condensing to corresponding imines and double condensation with boronic acids.The reaction requires no catalyst, and usually, target products are formed while refluxing the reaction mixture in methanol [45], ethanol [46], acetonitrile [44,47,48], carbon tetrachloride [49], or water [50] media.
The synthesis of the pyrazole-containing organoboron compounds 4a-k was accomplished by starting from 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde (1) [58], 2-aminobenzenecarboxylic acids (2a-c), and boronic acids (3a-d), and employing an MCR approach (Scheme 1).Refluxing the reaction mixture in ethanol for 48 h, cooling, filtrating, and washing the formed solid provided the target products 4a-k.Efforts to obtain a higher yields by stirring the reaction mixture under MW irradiation [45] or switching the reaction solvent to methanol [47], acetonitrile [44,47,48], or carbon tetrachloride [49] did not improve the results.The scope of the reaction was evaluated using 2-aminobenzenecarboxylic acids substituted with 5-chloro or 5-methyl moieties as well as a variety of boronic acids containing both electron-donating (methyl, methoxy) and electron-withdrawing (fluoro, trifluoromethyl) substituents.The substituents of the reacting materials did not influence the result of the reaction outcome, and the products were formed in a 47-72% yield.All the compounds were obtained as yellow solids stable at ambient conditions.Attempts to obtain an analogous boron complex by employing 4-(diethylamino)phenylboronic acid were unsuccessful, as only unreacted starting materials could be observed in the reaction mixture.The complexes bore a chiral boron center and were obtained as a racemic mixture [45].

NMR Spectroscopic Investigations
The structure of compounds 4a-k was unambiguously assigned based on the HRMS, IR, and NMR spectral data analysis.We have carried out detailed NMR studies for the obtained novel compounds to fully map 1 H, 13 C, 15 N, 19 F, and 11 B signals.A detailed analysis of the representative compound 4a is given in Figure 1a-c.The formation of the N → B coordination bond was evidenced via NMR spectroscopy.The 11 B NMR spectrum of 4a displays one broad resonance signal at δ 6.1 ppm, which agrees with the data of other tetracoordinated boron-atom-bearing Schiff bases [44,47].In addition, the remaining key information for structure elucidation was obtained using two-dimensional NMR spectroscopy techniques such as 1 H-1 H ROESY, 1 H- 13 C HMBC, 1 H-13 C H2BC, 1 H-15 N HMBC, and 1,1-ADEQUATE (Figure 1c).For instance, the most downfield methine proton in the 1 H NMR spectrum (singlet, δ 9.65 ppm) was assigned to the new (-CH=N + -) bond from the iminoboronate moiety, while another distinct methine signal (singlet, δ 9.24 ppm) was assigned to the pyrazole 5-H proton from the 1H-pyrazol-4-yl moiety.   C NMR (regular) and 11 B NMR (underlined) chemical shifts [ppm; ref.TMS] of compound 4a in DMSO-d6; (c) relevant 1,1-ADEQUATE, 1 H- 13 C HMBC, 1 H- 15 N HMBC, 1 H-13 C H2BC, and ROE correlations.

Single-Crystal X-ray Diffraction Analysis
Suitable crystals of 4a for X-ray diffraction analysis were obtained from tetrahydrofuran.The asymmetric unit of 4a contains two independent molecules, A and B (Figure 2), that are connected to each other via a pseudoinversion center, the coordinates of which, although close to the crystallographic point (¾, ¼, ¼), are still different from it (the real coordinates are 0.7250, 0.2508, and 0.2698).Therefore, it is not possible to increase the symmetry of the crystal structure.Thus, this structure belongs to the triclinic crystal system.The configuration of the asymmetric boron atoms in molecules A and B are S-and R-, respectively.Thus, the substance represents a true racemate.
The heterocyclic system is almost planar; only one boron atom deviates from the plane of the remaining atoms of this system (the deviations are 0.573(7) Å for A and 0.588(7) Å for B).The plane of the phenyl substituent in position 10 makes a dihedral angle with the plane of the heterocycle equal to 17.3(4)° (in A) and 16.1(4)° (in B).The phenyl ring in position 7 is perpendicular to the heterocycle; the dihedral angles are 89.7(4)° in A and 88.8( 4

)° in B.
There is only a slight π-π interaction between molecules A and B, with the shortest atom-atom contact being 3.330( 6) Å (between N10 and C13).At the same time, molecule A forms a strong π-π stacking interaction with the neighboring molecule A in the crystal structure.The distance between the least-squares planes of the heterocyclic systems equals 3.159(6) Å.In turn, the B molecule in the crystal of the compound also binds to the neighboring B molecule through the π-π stacking interaction; in this case, the distance between the least-squares planes of the heterocyclic systems equals 3.278(6) Å. Figure 3 illustrates molecular packing in the unit cell.An unambiguous assignment of the aforementioned methine protons was easily achieved from the long-range HMBC correlation data.The pyrazole 5-H proton solely showed 1 H-15 N HMBC correlations with the neighboring N-1 "pyrrole-like" (δ −168.9 ppm) and N-2 "pyridine-like" (δ −117.9 ppm) nitrogen atoms.While the methine proton from the iminoboronate moiety correlated with the neighboring nitrogen atom (δ −194.3 ppm) only.These findings were further supported by the distinct long-range 1 H- 15 N HMBC and 1 H- 13 C HMBC correlations between the methine protons (phenyl 2 ′ (6 ′ )-H and 3 ′′′ -H) from the neighboring aryl moieties and the corresponding carbon or nitrogen atoms.
The 1 H-1 H ROESY spectrum of 4a further elucidated the connectivities based on through-space correlations.For example, distinct ROEs were observed between the pyrazole ring proton 5-H, the phenyl group 2 ′ (6 ′ )-H protons (δ 7.92-7.95ppm), and the most downfield methine proton from the iminoboronate moiety.The aforementioned methine proton also correlated with the 3 ′′′ -H proton (δ 8.12 ppm), confirming their proximity in space.Having successfully identified all the main 1 H spin systems, the remaining protonated and quaternary carbons were easily assigned from the 1 H-13 C H2BC and 1,1-ADEQUATE spectral data.
The newly formed iminoboronates 4a-k, which contain a pyrazole ring, consist of three nitrogen atoms.The chemical shifts of the N-1 "pyrrole-like" and N-2 "pyridine-like" nitrogen atoms from the 1H-pyrazol-4-yl moiety were in the ranges from δ −168.0 to −169.3 ppm and from δ −117.3 to −117.9 ppm, respectively.The nitrogen atom in compounds 4a-d,f-h, from the iminoboronate moiety (-CH=N + -), resonated from δ −192.9 to −194.3 ppm, while in the case of compounds 4e,i-k, which contained 4 ′′ -CF 3 or 5 ′′′ -Cl groups, it resonated slightly upfield in the range from δ −196.8 to −197.9 ppm.The 11 B NMR spectra of 4a-k exhibited a single broad resonance signal in the range of δ 5.6 to 6.5 ppm.Data analysis showed that the chemical shift values were highly consistent within compounds 4a-k, thus validating the shifts for each position.

Single-Crystal X-ray Diffraction Analysis
Suitable crystals of 4a for X-ray diffraction analysis were obtained from tetrahydrofuran.The asymmetric unit of 4a contains two independent molecules, A and B (Figure 2), that are connected to each other via a pseudoinversion center, the coordinates of which, although close to the crystallographic point (¾, ¼, ¼), are still different from it (the real coordinates are 0.7250, 0.2508, and 0.2698).Therefore, it is not possible to increase the symmetry of the crystal structure.Thus, this structure belongs to the triclinic crystal system.The configuration of the asymmetric boron atoms in molecules A and B are Sand R-, respectively.Thus, the substance represents a true racemate.
Suitable crystals of 4a for X-ray diffraction analysis were obtained from tetra furan.The asymmetric unit of 4a contains two independent molecules, A and B 2), that are connected to each other via a pseudoinversion center, the coordinates of although close to the crystallographic point (¾, ¼, ¼), are still different from it ( coordinates are 0.7250, 0.2508, and 0.2698).Therefore, it is not possible to incre symmetry of the crystal structure.Thus, this structure belongs to the triclinic crys tem.The configuration of the asymmetric boron atoms in molecules A and B are R-, respectively.Thus, the substance represents a true racemate.
The heterocyclic system is almost planar; only one boron atom deviates fr plane of the remaining atoms of this system (the deviations are 0.573(7) Å for 0.588(7) Å for B).The plane of the phenyl substituent in position 10 makes a dihedr with the plane of the heterocycle equal to 17.3(4)° (in A) and 16.1(4)° (in B).The ring in position 7 is perpendicular to the heterocycle; the dihedral angles are 89.7( and 88.8(4)° in B.
There is only a slight π-π interaction between molecules A and B, with the s atom-atom contact being 3.330( 6) Å (between N10 and C13).At the same time, m A forms a strong π-π stacking interaction with the neighboring molecule A in the structure.The distance between the least-squares planes of the heterocyclic systems 3.159(6) Å.In turn, the B molecule in the crystal of the compound also binds to the boring B molecule through the π-π stacking interaction; in this case, the distance b the least-squares planes of the heterocyclic systems equals 3.278(6) Å. Figure 3 illu molecular packing in the unit cell.There is only a slight π-π interaction between molecules A and B, with the shortest atom-atom contact being 3.330( 6) Å (between N10 and C13).At the same time, molecule A forms a strong π-π stacking interaction with the neighboring molecule A in the crystal structure.The distance between the least-squares planes of the heterocyclic systems equals 3.159(6) Å.In turn, the B molecule in the crystal of the compound also binds to the neighboring B molecule through the π-π stacking interaction; in this case, the distance between the least-squares planes of the heterocyclic systems equals 3.278(6) Å. Figure 3 illustrates molecular packing in the unit cell.

Optical Investigations
The UV-vis absorption spectra of compounds 4a-k were first recorded in THF (Fig- ure 4a, Table 1, entries 1-11).The compounds possess the main absorption band in the visible region, at 397-404 nm, and two less intense bands are present in the ultraviolet range, at 309-315 and 258-262 nm.The substituents attached at various positions of the organoboron compounds 4a-k have a negligible effect on the position of the absorption bands.

Optical Investigations
The UV-vis absorption spectra of compounds 4a-k were first recorded in THF (Figure 4a, Table 1, entries 1-11).The compounds possess the main absorption band in the visible region, at 397-404 nm, and two less intense bands are present in the ultraviolet range, at 309-315 and 258-262 nm.The substituents attached at various positions of the organoboron compounds 4a-k have a negligible effect on the position of the absorption bands.

Optical Investigations
The UV-vis absorption spectra of compounds 4a-k were first recorded in THF (Figure 4a, Table 1, entries 1-11).The compounds possess the main absorption band in the visible region, at 397-404 nm, and two less intense bands are present in the ultraviolet range, at 309-315 and 258-262 nm.The substituents attached at various positions of the organoboron compounds 4a-k have a negligible effect on the position of the absorption bands.The fluorescence emissions of compounds 4a-k were first recorded in THF (Figure 4b, Table 1, entries 1-11).The emission maxima are observed at 531-543 nm, and the Stokes shifts are in a range of 128-142 nm.Again, different substituents in the molecular structure of compounds 4a-k do not influence the positions of emission maxima.4 ′′ ,5 ′′′ -Dimethylsubstituted compound 4g, and 5 ′′′ -chloro-substituted analogues 4i-k, however, show slightly batochromic shifts compared to the other compounds.The dyes display a low quantum yield, ranging from 0.1 to 4.3%, which is in accordance with previously reported observations of similar boron complexes [44].As iminoboronates are known to possess an AIEE effect [45], we further recorded the emission spectra of compounds 4a-k in mixed THF-water solutions with different water contents (0-90%).As shown in Figure 5a-c, the emission intensity and quantum yield (2.7%) of compound 4a are lower in the pure THF solution.As the water fraction increases to 80%, the emission intensity increases, and the quantum yield reaches the maximum value of 26.2%, which is about 10-fold that in the pure THF solution.Further increases in the water fraction has a negative effect on the quantum yield.This observation is in agreement with the AIEE phenomenon: when water is added, the compound precipitates, forming regular particles, which leads to enhanced fluorescence intensity and amorphous particles, thus leading to decreased fluorescence intensity [59].Compounds 4b-k displayed similar behavior (Figures S1-S10).
in mixed THF-water solutions with different water contents (0-90%).As shown in Figure 5a-c, the emission intensity and quantum yield (2.7%) of compound 4a are lower in the pure THF solution.As the water fraction increases to 80%, the emission intensity increases, and the quantum yield reaches the maximum value of 26.2%, which is about 10-fold that in the pure THF solution.Further increases in the water fraction has a negative effect on the quantum yield.This observation is in agreement with the AIEE phenomenon: when water is added, the compound precipitates, forming regular particles, which leads to enhanced fluorescence intensity and amorphous particles, thus leading to decreased fluorescence intensity [59].Compounds 4b-k displayed similar behavior (Figures S1-S10).The optical properties of compound 4a were further investigated in additional solvents, such as polar protic (MeOH) and polar aprotic (ACN and DMF).As can be observed from UV-vis spectroscopy data, the absorption bands of compound 4a are slightly blueshifted in more polar solvents (MeOH, ACN, DMF) in comparison to THF (Table 1, entries 12-14, Figure 4a).Fluorescence emissions of compound 4a in MeOH, ACN and DMF possess maxima at 531 nm, and the Stokes shifts are 140, 141, and 138 nm, respectively, which are slightly larger comparing to one in THF solution (133 nm) (Table 1, entry 1, Figure 4b).Compound 4a displays low quantum yields of 3.1, 1.6, and 1.5 in MeOH, ACN, and DMF, respectively (Table 1, entries 12-14).The optical properties of compound 4a were further investigated in additional solvents, such as polar protic (MeOH) and polar aprotic (ACN and DMF).As can be observed from UV-vis spectroscopy data, the absorption bands of compound 4a are slightly blue-shifted in more polar solvents (MeOH, ACN, DMF) in comparison to THF (Table 1, entries 12-14, Figure 4a).Fluorescence emissions of compound 4a in MeOH, ACN and DMF possess maxima at 531 nm, and the Stokes shifts are 140, 141, and 138 nm, respectively, which are slightly larger comparing to one in THF solution (133 nm) (Table 1, entry 1, Figure 4b).Compound 4a displays low quantum yields of 3.1, 1.6, and 1.5 in MeOH, ACN, and DMF, respectively (Table 1, entries 12-14).

General
All the starting materials were purchased from commercial suppliers and used as received.Flash column chromatography was performed on silica gel (60 Å; 230-400 µm; supplied by Sigma-Aldrich; Merck KGaA, Darmstadt, Germany).The reaction progress was monitored by TLC analysis on Macherey-Nagel™ ALUGRAM ® Xtra SIL G/UV254 plates (Macherey-Nagel GmbH & Co. KG, Düren, Germany) which were visualized by UV light (254 and 365 nm wavelengths).
Melting points were determined on a Büchi M-565 melting point apparatus and were not corrected.IR spectra of neat samples were recorded on a Bruker Vertex 70v FT-IR spectrometer (Bruker Optik GmbH, Ettlingen, Germany), and the results were reported as the frequency of absorption (cm −1 ).Mass spectra were obtained using a Shimadzu LCMS-2020 (ESI + ) spectrometer (Shimadzu Corporation, Kyoto, Japan).High-resolution mass spectra were measured on a Bruker MicrOTOF-Q III (ESI + ) apparatus (Bruker Daltonik GmbH, Bremen, Germany).
Single crystals were investigated at 160 K on a Rigaku, XtaLAB Synergy, Dualflex, HyPix diffractometer (Rigaku Corporation, Tokyo, Japan) using monochromated Cu-Kα radiation (λ = 1.54184Å).The crystal structure of 4a was solved by direct methods [62] and refined by full-matrix least squares [63].All nonhydrogen atoms were refined in anisotropical approximation.Hydrogen atoms were refined by riding model with Uiso(H) = 1.2Ueq(C).Crystal data for 4a: triclinic: a = 8.0614( 2 The UV-vis spectra were recorded on a Shimadzu 2600 UV/vis (Shimadzu Corporation, Japan).The fluorescence spectra were recorded on an FL920 fluorescence spectrometer from Edinburgh Instruments (Edinburgh Analytical Instruments Limited, Edinburgh, UK).The PL quantum yields were measured from dilute solutions by an absolute method using the Edinburgh Instruments integrating sphere excited with a Xe lamp.It was ensured that the optical densities of the sample solutions were below 0.1 to avoid reabsorption effects.All the optical measurements were performed at room temperature under ambient conditions.
The following abbreviation is used in reporting the NMR data: Pz, pyrazole.The 1 H, 13 C, and 11 B NMR spectra, as well as the HRMS data of the new compounds, are provided in Figures S11-S56 of the Supplementary Materials.

Synthetic Procedures
General procedure for the compound 4a-k synthesis: To a mixture of 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde (1) (188 mg, 1 mmol) in EtOH (5 mL), appropriate anthranilic acid 2 (1 mmol) and phenylboronic acid 3 (1 mmol) were added.The reaction mixture was stirred at 70 • C for 48 h.After completing the reaction, as determined via TLC, the reaction mixture was cooled to room temperature.Then, the reaction mixture was filtered, and the obtained solid was washed with ethanol and acetone to acquire pure products 4a-k.

Figure 2 .
Figure 2. ORTEP diagram of structure 4a with bond lengths characterizing the tetrahedron (molecules A and B are connected to each other via a pseudoinversion center).

Figure 2 .
Figure 2. ORTEP diagram of structure 4a with bond lengths characterizing the tetrahedron of boron (molecules A and B are connected to each other via a pseudoinversion center).The heterocyclic system is almost planar; only one boron atom deviates from the plane of the remaining atoms of this system (the deviations are 0.573(7) Å for A and 0.588(7) Å for B).The plane of the phenyl substituent in position 10 makes a dihedral angle with the plane of the heterocycle equal to 17.3(4) • (in A) and 16.1(4) • (in B).The phenyl ring in position 7 is perpendicular to the heterocycle; the dihedral angles are 89.7(4)• in A and 88.8(4) • in B.There is only a slight π-π interaction between molecules A and B, with the shortest atom-atom contact being 3.330(6) Å (between N10 and C13).At the same time, molecule A forms a strong π-π stacking interaction with the neighboring molecule A in the crystal structure.The distance between the least-squares planes of the heterocyclic systems equals 3.159(6) Å.In turn, the B molecule in the crystal of the compound also binds to the neighboring B molecule through the π-π stacking interaction; in this case, the distance between the least-squares planes of the heterocyclic systems equals 3.278(6) Å. Figure3illustrates molecular packing in the unit cell.

Figure 3 .
Figure 3. Molecular packing in crystal structure 4a.Both molecules A (as well as molecules B) are connected by a crystallographic center of inversion; molecules B and A are connected by a pseudoinversion center.

Figure 3 .
Figure 3. Molecular packing in crystal structure 4a.Both molecules A (as well as molecules B) are connected by a crystallographic center of inversion; molecules B and A are connected by a pseudoinversion center.

Molecules 2024, 29 , 3432 6 of 15 Figure 3 .
Figure 3. Molecular packing in crystal structure 4a.Both molecules A (as well as molecules B) are connected by a crystallographic center of inversion; molecules B and A are connected by a pseudoinversion center.

Figure 4 .
Figure 4. (a) UV-vis absorption spectra of compounds 4a-k in different solvents: a THF, b MeOH, c ACN, and d DMF; (b) fluorescence emission spectra (λ ex = 400 nm) of compounds 4a-h in different solvents: a THF, b MeOH, c ACN, and d DMF.

Figure 5 .
Figure 5. (a) Fluorescence emission spectra (λex = 440 nm) of compound 4a in mixed THF-water solutions with different water fractions (0-90%); (b) the relationship between the quantum yield of 4a and the water fraction in mixed THF-water solutions; (c) fluorescence photograph of compound 4a in THF (left) and mixed THF-water (20/80) solution (right) under 365 nm wavelength UV light.

Figure 5 .
Figure 5. (a) Fluorescence emission spectra (λ ex = 440 nm) of compound 4a in mixed THF-water solutions with different water fractions (0-90%); (b) the relationship between the quantum yield of 4a and the water fraction in mixed THF-water solutions; (c) fluorescence photograph of compound 4a in THF (left) and mixed THF-water (20/80) solution (right) under 365 nm wavelength UV light.