Synthesis, Optical Characterization in Solution and Solid-State, and DFT Calculations of 3-Acetyl and 3-(1′-(2′-Phenylhydrazono)ethyl)-coumarin-(7)-substituted Derivatives

Intramolecular charge transfer (ICT) effects are responsible for the photoluminescent properties of coumarins. Hence, optical properties with different applications can be obtained by ICT modulation. Herein, four 3-acetyl-2H-chromen-2-ones (1a–d) and their corresponding fluorescent hybrids 3- (phenylhydrazone)-chromen-2-ones (2a–d) were synthesized in 74–65% yields. The UV-Vis data were in the 295–428 nm range. The emission depends on the substituent in position C-7 bearing electron-donating groups. Compounds 1b–d showed good optical properties due to the D-π-A structural arrangement. In compounds 2a–d, there is a quenching effect of fluorescence in solution. However, in the solid, an increase is shown due to an aggregation-induced emission (AIE) effect given by the rotational restraints and stacking in the crystal. Computational calculations of the HOMO-LUMO orbitals indicate high absorbance and emission values of the molecules, and gap values represent the bathochromic effect and the electronic efficiency of the compounds. Compounds 1a–d and 2a–d are good candidates for optical applications, such as OLEDs, organic solar cells, or fluorescence markers.

Photoluminescent compounds and materials with fluorescent and phosphorescent properties play a fundamental role in many areas, such as biology, pharmacology, chemistry, biomedicine, and optoelectronics [7][8][9][10][11][12]. For example, coumarin compounds coupled to phenylhydrazine have been reported as fluorescent probes for visualizing living tissues [13]. Photoluminescent organic compounds derived from coumarins have been applied in twophoton absorption phenomena, optical data storage, energy limitation, and the manufacture of lasers [5]. Coumarins can be obtained in good yields [9] through synthetic techniques, such as Knoevenagel, Pechmann, and Wittig reactions. Therefore, the photophysical properties of coumarins can be easily modified by substituting in positions 3, 6, 7, and 8 to obtain hybrid materials [9,14,15], which exhibit high quantum yields, important changes in Stokes shifts, and good absorption and emission profiles [16]. On the other hand, fluorescent hybrid compounds derived from hydrazines and coumarins have shown synergic effects in their fluorescent properties [17,18]. These compounds have been applied as on-off sensors [19,20], photoluminescent dyes [21], anticonvulsants [22], hydrogels [23], and antimicrobials [24].
In this work, we describe the synthesis, structural characterization, and photoluminescence proprieties of small compounds derived from 3-acetyl-2H-chromene-2-one (1a-d) coupled with phenylhydrazine, forming the hybrid fluorescent compounds 3-(1 -(2phenylhydrazono) ethyl)-2H-2-chromen-2-one (2a-d). The optical characterization of 2a-d was performed in solution and in the solid-state, and the results contrasted with ab initio theoretical calculations. The UV-vis spectra of coumarins 1a,c and 2b have been reported in solution but not in the solid-state [25,26].

Materials and Methods
Salicilaldehyde, 4-methoxy-salicylaldehyde, 4-hydroxy-salicylaldehyde, 4-diethylaminosalicylaldehyde, ethyl acetoacetate, piperidine, glacial acetic acid, ethanol, and phenylhydrazine were purchased from Aldrich (Toluca, Mexico) and used as received. The ACS grade solvents were purchased from CTR (Jalisco, Mexico) and used without further purification. Melting points were measured on an Electrothermal Mel-Temp 1201D apparatus. IR spectra were collected using Varian 3100 FT-IR EXCALIBUR series spectrophotometer. 1 H and 13 C NMR spectra were recorded in a BRUKER Ultrashield plus 400 MHz in DMSO-d 6 solutions using (CH 3 ) 4 Si as an internal reference compound; chemical shifts (δ) are in ppm and coupling constants ( n J H-H ) in Hz. Mass analysis was performed by electro spray ionization in a high-resolution mass spectrometer Bruker micOTQF-QTOF instrument (Bruker Daltonik GmbH, Bremen, Germany). Absorbances were obtained with a Perkin Elmer Lambda 900 UV/Vis/IR spectrophotometer; emissions were obtained in an Edinburan F55 fluorometer, employing the stock solutions of 1 × 10 −3 M of compounds 1a-d and 2a-d. The fluorescence spectra were recorded under 400 nm excitation (except in the compound 2d was in 372 nm). The quantum efficiencies were obtained using an integration sphere of direct photon counting, relating the absorbed and emitted photons. The optical data in the solid state were obtained similarly.

General Methods of Synthesis and Characterization
3-Acetyl-2H-chromene-2-one (1a-d) were prepared following reported procedures [15,27] with modifications. 4-Substituted-salicylaldehydes, ethyl acetoacetate, and piperidine were dissolved in 15 mL of ethanol and placed under reflux at 78 • C for 24 h. After cooling, the solvent was removed by vacuum filtration, and the resulting solid was recrystallized from cold ethanol.

Determination of Quantum Yield
Fluorescence quantum yield (Φ) for coumarins (1a-d) and hydrazones (2a-d) were measured through the integration sphere direct excitation method, with "Direct Excitation" measurements, which record the scatter and the emission of the sample being directly excited by the radiation from the excitation monochromator only. The absolute fluorescence quantum yield (Φ) is the ratio of the number of photons emitted to the number of photons absorbed, according to Equation (1).
The absolute fluorescence quantum yield (Φ Dexc ) was calculated with the direct excitation method according to Equation (2).
where E denotes the emission region of sample and solvent, S the excitation scatter region of sample and solvent, and A, B the experimental setup and integral of the scans of samples and solvent.
For calculating the integrals, the selection of the integral regions, and the final calculation of Φ Dexc , we used the quantum yield wizard supplied with the equipment software [33].

Computational Details
Geometry optimizations were carried out using the framework of density functional theory implemented in ORCA software [34]. For the exchange and correlation, the PBE0 hybrid functional [35,36] was combined with a complete electronic basis set aug-cc-pVDZ [37]. A vibrational frequency analysis was effectuated to verify minima energy states; only positive values were found in all cases. The HOMO-LUMO gap energies were calculated, and frontier orbitals were plotted using Chemcraft [38]. Excited states were determined using TD-DFT [39][40][41] under the same level of theory PBE0/aug-cc-pVDZ [42], and solvent effects were included using a conductor-like polarizable model (CPCM) [43,44] considering THF, acetonitrile, and toluene.

Synthesis and Structural Characterization
Coumarins 1a-d were synthesized by the Knoevenagel [28] condensation of ethyl acetoacetate with the corresponding 4-substituted salicylaldehyde (Scheme 1), with yields higher than 80%. Afterward, the functionalization of 3-acetyl-coumarin derivatives 1a-d with phenylhydrazine was performed through acid catalysis with glacial acetic acid to obtain compounds 2a-d (Scheme 1). The experimental yields are in the 65-74% range, according to precise reports about the synthesis of the same compounds [2,29,32,45]. The H-4 signal in the 1 H NMR spectra indicated the formation of compounds 1a-d (Figures S1-S8), appearing in the 8.40-8.67 ppm range [31]. The functionalization with phenylhydrazine in compounds 2a-d, generated an anisotropic effect perpendicularly extended from the phenyl group of the hydrazone fragment to the pyran ring, causing the protection of H-4 and shifting the signal to lower frequencies in the 8.00-8.15 ppm range. The NH proton in the phenylhydrazone was shifted to high frequencies appearing in the 9.31-9.46 ppm range; whereas the 13 C-NMR signal was shielded from 194.6-195.5 ppm, for compounds 1a-d, to the range of 146.0-146.4 ppm in compounds 2a-d (Figures S9-S16). The IR spectra of compounds 1a-d showed the C=O band in the 1658-1681 cm −1 range. Meanwhile, compounds 2a-d showed the characteristic hydrazone C=N and N-H bands in the 1589-1608 cm −1 and 3294-3325 cm −1 ranges, respectively. Selected 1 H and 13 C NMR values and IR wavenumbers are listed in Table 1.

UV-vis Absorption and Photoluminescence Spectra
The UV-vis and fluorescence spectroscopic data of compounds 1a-d and 2a-d, measured in tetrahydrofuran and acetonitrile solvents at room temperature, are listed in Table 2. Their scarce solubility in solvents, such as ethanol, DMF, and water, limited the tests in these solvents. The absorption and emission spectra in solution are shown in Figures 1 and 2, respectively. The maximum absorbance bands are attributed to π → π* and n → π* electronic transitions. The absorption band in 1b-d showed a red-shift due to the insertion of electron-donor substituents in the C-7 position. The largest red-shift in 1b is attributed to the strong electron-donor character of the diethylamino group [4,9]. Similar behavior is conserved in phenylhydrazone derivatives, wherein 2b shows the largest bathochromic effect in the absorption band. The molar absorptivity depends on the solvent used, obtaining higher values with acetonitrile than with THF. In contrast to the full palette observed in the absorption, compounds 1a,d and 2a showed no emission band. The maximum wavelength of the coumarin emission band is around 453-494 nm. The increase of emission is related to the nature of the substituent in C-7 following the order: N (CH 2 CH 3 ) 2 > OH > OCH 3 > H, in agreement with the strength of the substituent electron-donor properties [4,9]. Compound 1b showed the largest quantum yield (Φ F ) with values above 80%.   Compounds 1b,d, and 2c showed the best photophysical properties in the solid-state. Their fluorescence spectra are shown in Figure 3, and their photophysical properties are listed in Table 3. The emission λ max of coumarin 1b was red-shifted to 595 nm in comparison with the solution (477 nm), and unexpectedly, compound 1d turned emissive, showing a band at 540 nm, although with low Φ F values (<6.6%) in both cases. In contrast, hydrazone 2c has emissive properties compared to the solution: emission at 582 nm and Φ F value of 52.6. These results revealed that the intermolecular interactions in the solid-state favor the emissive relaxation mechanism from an excited state. The X-ray molecular structures of compounds 1a,b,d are known [46][47][48][49]. Hence, a brief analysis of their photoluminescent properties in relation with their molecular structure in the solid state seems appropriate.
The powder X-ray diffractogram of 1a,b,d was obtained and compared to the single crystal reported ones, shown in Figure S17. In the solid, the free rotation of the pendant -OMe and 3-Ac groups is restricted due to intermolecular hydrogen bonds, leading to a coplanar system and increasing the emissive properties of 1d. Therefore, the solid-state exerts an aggregation-induced emission (AIE) effect [46] on 1d. In the solid, the molecules of 1d are π-stacked along the (100) direction, at a distance of 3.509 Å between the benzo fused (Bz) and lactone (L) rings centroids (Cg (Bz)-Cg (L)) [47], in agreement with medium strength π-D-π-A interactions arranged in the head-to-tail fashion [50]. It is worth mentioning that the Bz ring acts as the donor and the L ring as the acceptor. In contrast, coumarin 1a crystallizes in two forms, triclinic (form A) and monoclinic (form B). Form A (herein obtained) is a head-to-head stacked, while form B generates head-to-tail π-stacked dimers with long Cg (Bz)-Cg (L) distances of 4.77 Å and 3.98 Å, respectively [48]. On the contrary, an aggregation-caused quenching (ACQ) effect is observed on 1b. In the crystal lattice, the molecules of 1b are arranged in dimers through antiparallel type carbonyl-carbonyl interactions [51] at Cg (Bz)-Cg (L) distance of 6.38 Å and the amino-ethyl groups pointing to opposite directions [49]. The free rotation of the pendant -NEt 2 and 3-Ac groups in 1b is restricted as in 1d, but with the contrary effect. This brief analysis supports that the Φ F in the solid-state depends on the crystal lattice arrangement. Coumarin molecules that show head-to-tail π-staking arrangement with a Cg(Bz)-Cg(L) distance shorter than 3.5 Å seem to favor large Φ F values. The large value of Φ F of hydrazone 2c in the solid-state is also explained as an AIE effect. Intermolecular hydrogen bonding, probably between the -OH and the C=N functionality, should favor an entire head-to-tail π-staking arrangement in the crystal lattice with the appropriate Cg (Bz)-Cg (L) distance, as mentioned earlier.  Compounds 1-5 have been used as fluorescent dyes for cellular imaging (1), indicators of bathochromic effects with red emissions (2), chemosensors for anions (3), for the study of nonlinear optical properties (4), and observation of highly fluorescent compounds depending on the substituents (5). Their photophysical properties are listed in Table 4. 7-Diethylamino substituted coumarin 1b showed better photophysical properties (Φ F ) in solution than compounds 1-5, previously reported and shown in Figure 4 [6,7,10,16,52]. Then, compound 1b in solution and 2c in the solid-state could be evaluated in similar applications, since they have even better optical properties, and their synthesis is simpler and with higher chemical yields than the reported compounds 1-7.

Theoretical Calculations
The theoretical data of the molecular orbitals allowed us to explain the spectroscopic behavior and the electronic effects in the molecules. The HOMO (H), LUMO (L), H-L gap, and Eg op energy values are listed in Table 5. The H-L gap energies are similar among them. Nevertheless, the smallest value corresponds to compound 1b, whose λ max is displaced towards the red. Likewise, the H-L gap represents the excited state electronic transition [6,38] from S 0 to S 1 . Compounds 2a-d show low H-L gap values similar to coumarins 1a-d. The theoretical values, listed in Table 5, agree with the experimental optical values.  Table 2).
The optical gap values (Eg op ) for coumarins rank from 2.90 to 4.18 eV, and they are smaller than the theoretical data  [55]. The experimental values are comparable with the data for well-known luminophores 3, 6, and 7 listed in Table 6 and whose structures are shown in Figure 5.  The data of compounds 1b-d showed HOMO-LUMO interactions (Table S1) in a higher percentage of contribution energy due to the ED groups generating n → π* transitions, in contrast to compound 1a, which causes HOMO-1-LUMO π → π* transitions, in agreement with the experimental data.
Compounds 2a-d showed π → π* and n → π*transitions represented by the HOMO-LUMO, HOMO+1-LUMO-1 orbitals (supplementary material Table S2), indicating a D-A behavior of the molecules which is consistent with the experimental data. Figure 5 shows the FMOs (frontier molecular orbitals) of compounds 1a-d. The structures show a planar geometry through the benzopyran ring. The HOMO-LUMO and HOMO-1-LUMO electronic distributions indicate the presence of π → π* and n → π* transitions, confirming the excitation of the FMOs from S 0 to S 1 .
In compounds 2a-d, the phenylhydrazine group acts as an ED group. In this case, it represents the energy of the HOMO, and often, the whole part of the coumarin where the substituent in the benzopyrone ring acts as EA group, represented by the energy of the LUMO ( Figure 6). The previous result agrees with the experimental findings, suggesting that the electronic cloud of the ED moiety moves towards the EA, which is from the phenylhydrazine to the coumarin. The hydrazo-coumarins 2a-d showed low quantum yields and unobservable emissions because the electronic cloud does not include the ED group which is interacting with the solvents. Compound 2c shows different behavior in the FMOs, and its electron density is both as HOMO and LUMO in the hydrazone group, generating only n → π* type transitions, which agrees with its behavior in the solid-state, since the solvent generates the quenching of the fluorescence in solution.

Conclusions
Molecules 1a-d and 2a-d can be good candidates for semiconductor compounds suitable to be used in several optical applications. The photophysical properties of coumarins 1a-d and their hydrazone derivatives 2a-d were compared. The bandgap indicates the efficient ICT, which confirms the D-A type structure. Compounds 1b and 2c presented the best optical properties. Compound 1b showed absorbances at λ > 420 nm and emission at λ > 460 nm in solution and quantum yields >80%. Compound 2c also showed good emission values in the solid-state due to the push-pull system, supported by the π-π interactions. Compound 1d turned emissive in the solid-state due to the π-πinteractions in the crystal network. This work also confirms that small coumarins derivatives possess photoluminescent properties which can be tuned in both solution and in the solid-state.