Crystal Structure, Photophysical Study, Hirshfeld Surface Analysis, and Nonlinear Optical Properties of a New Hydroxyphenylamino Meldrum’s Acid Derivative

The structural, photophysical, and vibrational properties of a new hydroxyphenylamino Meldrum’s acid derivative, 3-((2-hydroxyphenylamino)methylene)-1,5-dioxaspiro[5.5]undecane-2,4-dione (HMD), were studied. The comparison of experimental and theoretical vibrational spectra can help understand basic vibration patterns and provides a better interpretation of IR spectra. The UV–Vis spectrum of HMD was computed using density functional theory (DFT)/B3LYP/6-311 G(d,p) basis set in the gas state, and the maximum wavelength was in accord with the experimental data. The molecular electrostatic potential (MEP) and Hirshfeld surface analysis confirmed O(1)–H(1A)···O(2) intermolecular hydrogen bonds in the HMD molecule. The natural bond orbital (NBO) analysis provided delocalizing interactions between π→π* orbitals and n→σ*/π* charge transfer transitions. Finally, the thermal gravimetric (TG)/differential scanning calorimeter (DSC) and the non-linear optical (NLO) properties of HMD were also reported.


Introduction
It is known that Meldrum's acid is an important organic reagent for the Knoevenagel condensation owing to its activated methylene structure. It has become a versatile building block and valuable intermediate for the synthesis of organic six-membered heterocycles [1][2][3][4][5]. In addition, Meldrum's acid and its derivatives have also attracted much attention due to their pharmacological and biological properties, such as antioxidant [6,7], anticancer [8], antimicrobial [9], antibiotic [10], and inhibitory [11] properties and herbicidal activity [12]. With this background in mind, we have previously reported several approaches to design and synthesize the diverse heterocyclic compounds using the Meldrum's acid as the intermediate. For example, Meldrum's acid or its derivatives reacted with aldehydes in conditions of ethanol or TEAF (V triethylamine :V methanoic acid = 4:1)/DMF (N, N-dimethylformamide) [13][14][15], benzenamine (under conditions of N,N-dimethylformamide dimethyl acetal) [16,17], and 5,6-dimethyl-1H-benzoimidazole or imidazole (under conditions of trimethyl orthoformate) [18][19][20]. Our previous studies have mainly focused on the design of the synthetic methods and the analysis of crystal structures. Furthermore, to the best of our knowledge, theoretical calculations or Hirschfeld surface analyses of Meldrum's derivatives containing 1,5-dioxaspiro [5.5] undecane-2,4-dione and hydroxyphenyl groups are rare.
As a continuation of our previous work, in this study, a new hydroxyphenylamino Meldrum's acid derivative combining two different groups was synthesized. In addition, the structural, photophysical, vibrational, thermal, and nonlinear optical properties of the title compound were investigated. The calculated electronic absorption parameters of     7) 1.220 (3) 1.217 O(2)-C (9) 1.221 (3) 1.206 Bond angle (°) C(10)-N(1)-C (11) 125.90 (2) 126.85 N(1)-C(10)-C (8) 125.70 (2) 125.38 C(10)-C(8)-C (7) 122.40 (2) 121.22 C(10)-C(8)-C (9) 117.00 (2) 117.39 C(12)-C(11)-N (1) 124.00 ( As illustrated in Table 3, there were N(1)-H(1)···O(3) intramolecular interactions and O(1)-H(1A)···O(2) intermolecular interactions. As seen in Figure 2, the one-dimensional (1D) chained structure of HMD was connected by the O(1)-H(1A)···O(2) interhydrogen bonding, which played a vital role in helping to stabilize the packing in the crystal. The 3D supramolecular structure was linked by the above 1D chain (Figure 3).    (3) 1.206 Bond angle ( • ) C(10)-N(1)-C (11) 125.90 (2) 126.85 N(1)-C(10)-C (8) 125.70 (2) 125.38 C(10)-C(8)-C (7) 122.40 (2) 121.22 C(10)-C(8)-C (9) 117.00 (2) 117.39 C(12)-C(11)-N (1) 124.00 (2) 124.12 C ( As illustrated in Table 3, there were N(1)-H(1)···O(3) intramolecular interactions and O(1)-H(1A)···O(2) intermolecular interactions. As seen in Figure 2, the one-dimensional (1D) chained structure of HMD was connected by the O(1)-H(1A)···O(2) interhydrogen bonding, which played a vital role in helping to stabilize the packing in the crystal. The 3D supramolecular structure was linked by the above 1D chain ( Figure 3).    (3) 1.206 Bond angle (°) C(10)-N(1)-C (11) 125.90 (2) 126.85 N(1)-C(10)-C (8) 125.70 (2) 125.38 C(10)-C(8)-C (7) 122.40 (2) 121.22 C(10)-C(8)-C (9) 117.00 (2) 117.39 C(12)-C(11)-N (1) 124.00 ( As illustrated in Table 3, there were N(1)-H(1)···O(3) intramolecular interactio O(1)-H(1A)···O(2) intermolecular interactions. As seen in Figure 2, the one-dime (1D) chained structure of HMD was connected by the O(1)-H(1A)···O(2) interhy bonding, which played a vital role in helping to stabilize the packing in the crys 3D supramolecular structure was linked by the above 1D chain (Figure 3).      Figure 4 depicts the calculated IR spectra using the DFT method and the basis set of the B3LYP/6-311G (d, p). To reduce the difference between the computational frequencies and the experimental values, 0.967 was used as the scaling factor. The DFT computation showed the O-H stretching modes at 3718 cm −1 , which was consistent with the experimental and published values [15]. The N-H stretching peak seen at 3230 cm −1 was computed at 3297 cm −1 . Peaks in the region 3100-3000 cm −1 were owing to the νC-H of the aromatic ring. In our study, the C-H stretching vibrations were calculated at 3056 cm −1 and 3098 cm −1 . The CH2 stretching peaks of the 1,3-dioxane group were shown at 2943 cm −1 and 2862 cm −1 . These peaks were computed from 2993 cm −1 to 2904 cm −1 . For the carbonyl group, two strong bands appeared at 1718 cm −1 and 1670 cm −1 in the IR spectra and were calculated at 1744 cm −1 and 1691 cm −1 . The peaks at 1625 cm −1 , 1585 cm −1 , and 1443 cm −1 were attributed to the C=C stretching modes. The corresponding peaks were calculated at 1618 cm −1 , 1580 cm −1 , and 1427 cm −1 . The experimental spectrum of HMD showed C-O stretching vibrations at 1257 cm −1 and 1175 cm −1 , while the calculated values were 1228 cm −1 and 1171 cm −1 , which agreed with similar structural reports [16,17,21].   Figure 4 depicts the calculated IR spectra using the DFT method and the basis set of the B3LYP/6-311G (d, p). To reduce the difference between the computational frequencies and the experimental values, 0.967 was used as the scaling factor. The DFT computation showed the O-H stretching modes at 3718 cm −1 , which was consistent with the experimental and published values [15]. The N-H stretching peak seen at 3230 cm −1 was computed at 3297 cm −1 . Peaks in the region 3100-3000 cm −1 were owing to the ν C-H of the aromatic ring. In our study, the C-H stretching vibrations were calculated at 3056 cm −1 and 3098 cm −1 . The CH 2 stretching peaks of the 1,3-dioxane group were shown at 2943 cm    Figure 4 depicts the calculated IR spectra using the DFT method and the bas the B3LYP/6-311G (d, p). To reduce the difference between the computational freq and the experimental values, 0.967 was used as the scaling factor. The DFT comp showed the O-H stretching modes at 3718 cm −1 , which was consistent with the mental and published values [15]. The N-H stretching peak seen at 3230 cm −1 w puted at 3297 cm −1 . Peaks in the region 3100-3000 cm −1 were owing to the νC-H of matic ring. In our study, the C-H stretching vibrations were calculated at 3056 c 3098 cm −1 . The CH2 stretching peaks of the 1,3-dioxane group were shown at 29 and 2862 cm −1 . These peaks were computed from 2993 cm −1 to 2904 cm −1 . For the c group, two strong bands appeared at 1718 cm −1 and 1670 cm −1 in the IR spectra a calculated at 1744 cm −1 and 1691 cm −1 . The peaks at 1625 cm −1 , 1585 cm −1 , and 14 were attributed to the C=C stretching modes. The corresponding peaks were calcu 1618 cm −1 , 1580 cm −1 , and 1427 cm −1 . The experimental spectrum of HMD show stretching vibrations at 1257 cm −1 and 1175 cm −1 , while the calculated values w cm −1 and 1171 cm −1 , which agreed with similar structural reports [16,17,21].   Figure 5 depicts the UV-Vis absorption spectrum from 180 nm to 400 nm, along with the calculated value. The theoretical UV-Vis spectrum was obtained using the TD-DFT methods with the same basis set, and their excitation energies included the ten excited states. The oscillator strengths, wavelengths, and electronic transition orbits are listed in Table 4. As seen in Figure 5, three prominent bands appeared at the experimental/theoretical absorption spectra. The first band at 206/191 nm was dominated by 79HOMO−1→83LUMO+2 (40.64%) with oscillator strengths of 0.1113. The second band at 234/226 nm was contributed by the electronic transition 80HOMO→83LUMO+2 (48.30%). The third band at 346/321 nm was contributed by the electronic transition 80HOMO→81LUMO (97.0%) with the oscillator strengths of 0.6683, indicating π→π* and n→π* transitions of the molecule. These results were in accordance with previous research [16,17]. Figure 5 depicts the UV-Vis absorption spectrum from 180 nm to 400 nm, along with the calculated value. The theoretical UV-Vis spectrum was obtained using the TD-DFT methods with the same basis set, and their excitation energies included the ten excited states. The oscillator strengths, wavelengths, and electronic transition orbits are listed in Table 4. As seen in Figure 5, three prominent bands appeared at the experimental/theo retical absorption spectra. The first band at 206/191 nm was dominated by 79HOMO−1→83LUMO+2 (40.64%) with oscillator strengths of 0.1113. The second band a 234/226 nm was contributed by the electronic transition 80HOMO→83LUMO+2 (48.30%) The third band at 346/321 nm was contributed by the electronic transition 80HOMO→81LUMO (97.0%) with the oscillator strengths of 0.6683, indicating π→π* and n→π* transitions of the molecule. These results were in accordance with previous research [16,17].  Furthermore, the HOMO and LUMO orbitals could be used to analyze molecula physical chemistry properties such as hardness, excitability, electron conductivity, and chemical stability ( Table 5). As seen in Table 5, the calculated energies of HOMO and LUMO were −6.10 eV and −1.87 eV, respectively. A large HOMO-LUMO energy gap o 4.23 eV denoted that this molecule had weak conductivity, low reactivity, and strong sta bility. The HMD had a large hardness value, indicating that it was not a polarizable hard molecule. Finally, Figure 6 shows the four frontier molecular orbitals of HOMO−1, HOMO LUMO, and LUMO+2.  Furthermore, the HOMO and LUMO orbitals could be used to analyze molecular physical chemistry properties such as hardness, excitability, electron conductivity, and chemical stability ( Table 5). As seen in Table 5, the calculated energies of HOMO and LUMO were −6.10 eV and −1.87 eV, respectively. A large HOMO-LUMO energy gap of 4.23 eV denoted that this molecule had weak conductivity, low reactivity, and strong stability. The HMD had a large hardness value, indicating that it was not a polarizable hard molecule. Finally, Figure 6 shows the four frontier molecular orbitals of HOMO−1, HOMO, LUMO, and LUMO+2.

Mulliken Population
The Mulliken population method was used to calculate the total tributions. Mulliken was also extremely effective at detecting nucleoph attacks, as well as regions sensitive to other molecular interactions. The

Mulliken Population
The Mulliken population method was used to calculate the total atomic charge distributions. Mulliken was also extremely effective at detecting nucleophilic or electrophilic attacks, as well as regions sensitive to other molecular interactions. The computed charges are listed in Table 6

Molecular Electrostatic Potential (MEP)
The MEP is related to electron density and is helpful to understand the electrophilic and nucleophilic attacks as well as the hydrogen bonding interactions. The red color represents the electron-rich zones, which were suitable for the electrophilic reactions. The blue color implies the electron-poor zones, which were related to the nucleophilic reactions [22,23]. Additionally, the electrophilic and nucleophilic regions were connected by hydrogen bonds. As shown in Figure 7, the two red regions were O2 and O3 atoms bound to the carbonyl group's C atom, which indicated that the O atom would act as an acceptor in hydrogen bonding. The blue region was located on the hydroxyl group's H1 atom. It was demonstrated that the O(1)-H(1)···O(2) intermolecular hydrogen bonds existed in the HMD molecule (Table 3).

Molecular Electrostatic Potential (MEP)
The MEP is related to electron density and is helpful to understand the elec and nucleophilic attacks as well as the hydrogen bonding interactions. The red c resents the electron-rich zones, which were suitable for the electrophilic reacti blue color implies the electron-poor zones, which were related to the nucleoph tions [22,23]. Additionally, the electrophilic and nucleophilic regions were conn hydrogen bonds. As shown in Figure 7, the two red regions were O2 and O3 atom to the carbonyl group's C atom, which indicated that the O atom would act as an in hydrogen bonding. The blue region was located on the hydroxyl group's H1 was demonstrated that the O(1)-H(1)···O(2) intermolecular hydrogen bonds exist HMD molecule (Table 3).

Hirshfeld Surface Analysis
The Hirshfeld surface (HS) mapped with dnorm is depicted in Figure 8. T mapped HS of HMD was generated to ascertain different interactions with red, w blue colors. An apparent red spot in the dnorm surface suggested strong and short while the blue region suggested that there existed farther and weaker contacts The large red spot was detected over the O(1)-H(1A)···O(2) hydrogen bond in t cule. The bond length (O(1)···O(2)) was 2.714 Å, and the results matched the valu crystal. As seen in Figure 9, the H···H interactions with a single peak composed 46.4 HS, which denoted the largest contribution of the total HS. The O···H/H···O inte observed as a wing covered 34% of the total HS, whereas the C···H/H···C interac counted for 11.5%. Other intercontacts, including C···C, H···N/N···C, C···O/O N···H/H···N, accounted for 4.2%, 2.3%, 1.4%, and 0.1%, respectively.

Hirshfeld Surface Analysis
The Hirshfeld surface (HS) mapped with d norm is depicted in Figure 8. The d norm -mapped HS of HMD was generated to ascertain different interactions with red, white, and blue colors. An apparent red spot in the d norm surface suggested strong and short contacts, while the blue region suggested that there existed farther and weaker contacts [24][25][26] The MEP is related to electron density and is helpful to understand t and nucleophilic attacks as well as the hydrogen bonding interactions. Th resents the electron-rich zones, which were suitable for the electrophilic blue color implies the electron-poor zones, which were related to the nu tions [22,23]. Additionally, the electrophilic and nucleophilic regions wer hydrogen bonds. As shown in Figure 7, the two red regions were O2 and O to the carbonyl group's C atom, which indicated that the O atom would ac in hydrogen bonding. The blue region was located on the hydroxyl grou was demonstrated that the O(1)-H(1)···O(2) intermolecular hydrogen bond HMD molecule (Table 3).

Hirshfeld Surface Analysis
The Hirshfeld surface (HS) mapped with dnorm is depicted in Figur mapped HS of HMD was generated to ascertain different interactions with blue colors. An apparent red spot in the dnorm surface suggested strong and while the blue region suggested that there existed farther and weaker co The large red spot was detected over the O(1)-H(1A)···O(2) hydrogen bon cule. The bond length (O(1)···O(2)) was 2.714 Å, and the results matched th crystal. As seen in Figure 9, the H···H interactions with a single peak compos HS, which denoted the largest contribution of the total HS. The O···H/H· observed as a wing covered 34% of the total HS, whereas the C···H/H···C counted for 11.5%. Other intercontacts, including C···C, H···N/N···C, C N···H/H···N, accounted for 4.2%, 2.3%, 1.4%, and 0.1%, respectively. As seen in Figure 9, the H···H interactions with a single peak composed 46.4% of the HS, which denoted the largest contribution of the total HS. The O···H/H···O interactions observed as a wing covered 34% of the total HS, whereas the C···H/H···C interactions accounted for 11.5%. Other intercontacts, including C···C, H···N/N···C, C···O/O···C, and N···H/H···N, accounted for 4.2%, 2.3%, 1.4%, and 0.1%, respectively.

Natural Bond Analysis (NBO)
The properties of bond orbitals and their occupation, as well as the charge transfer from the donor to the acceptor, can be analyzed by the NBO method. Delocalizing interactions between occupied and empty orbitals were decided by the stabilization energy E (2) . The value of E(2) was greater, indicating a more intense interaction between the donor and acceptor ( Table 7).

Non-Linear Properties (NLO)
The mean polarizability (α), the anisotropy of polarizability (Δα), and the first hyperpolarizability parameters (β) are the basic parameters of NLO material. These values

Natural Bond Analysis (NBO)
The properties of bond orbitals and their occupation, as well as the charge transfer from the donor to the acceptor, can be analyzed by the NBO method. Delocalizing interactions between occupied and empty orbitals were decided by the stabilization energy E (2) . The value of E(2) was greater, indicating a more intense interaction between the donor and acceptor (Table 7). Table 7. The stabilization energy E (2) for HMD.

Non-Linear Properties (NLO)
The mean polarizability (α), the anisotropy of polarizability (∆α), and the first hyperpolarizability parameters (β) are the basic parameters of NLO material. These values Molecules 2023, 28, 2181 9 of 12 of HMD calculated using the same basis set are helpful to understand the relationships between the structure and properties.
Their equations are as follows: As a critical NLO material, the above three parameters of the Urea molecule had been reported as 5.07643717 × 10 −24 , 2.13568262 × 10 −24 , and 7.2228469891 × 10 −31 esu [27]. However, the NLO parameters of HMD were computed as 320.397 × 10 −24 esu, 276.361 × 10 −24 , and 1.94064 × 10 −30 , which were 63.11, 129.40, and 2.69 times than that of urea, respectively, as illustrated in Table 8. The high ∆α and β values of HMD implied that the molecule could be used as an organic NLO material.

TG and DSC Analysis
The thermal behavior of HMD was determined by the thermal gravimetric (TG) and differential scanning calorimeter (DSC) (Figure 10). A three-step decomposition occurred between 152 • C and 678 • C. The first weight loss of 7.2% was observed from 152 • C to 219 • C. The second weight loss of 68.9% occurred in the range of 239-262 • C. The third weight loss of 23.9% was from 262 • C to 678 • C.
One endothermic and one exothermic peak could be seen on the DSC curve. The TG curve showed no weight loss between 219 • C and 239 • C, whereas the DSC curve showed one endothermic peak at 226 • C with a starting temperature of 213 • C corresponding to its melting point. The weight (68.9%) gradually decreased after 226 • C, implying that the major groups, such as the 2-hydroxyphenylamino ring and the 1,3-dioxane ring, had decomposed. The combustion and oxidation of HMD resulted in one exothermic peak at 615 • C.

General Method
The IR spectrum of HMD using KBr pellet (400-4000 cm −1 ) was measu Thermo Nicolet iS5 spectrophotometer. ( 1 H and 13 C) NMR was acquired usin Avance III-600 in the DMSO-d6 solution. The TG-DSC curves were recorded u METTLER TOLEDC tgdsc 3 in air, which heated up at a rate of 10 °C/min betwee 800 °C. The UV-Vis spectra were determined using a TU-1901 spectrophotomet

Synthesis
The ethanol solution of 1,5-dioxaspiro [5.5]undecane-2,4-dione (0.02 mol, 3.6 magnetically stirred for 3 h at 60 °C with 1.2 equivalent amount of trimethyl orth (0.024 mol, 2.544 g). After that, an equal amount of o-aminophenol (0.02 mol, 2.1 added, and the solution was allowed to react for another 3 h at the same tempera mixture was then cooled and washed with distilled water two to three times befo recrystallized with ethanol, filtered, and dried to yield the yellow powder.

Single Crystal Studies
A transparent yellow block crystal was measured on an Xcalibur Eos Gemin tometer with the Mo-Kα radiation (0.71073 Å). Its structure was achieved using S 2016 [28,29]. The H atoms of HMD were positioned at suitable positions and using a riding mode. The non-hydrogen atoms were accomplished by anisotrop ment.

General Method
The IR spectrum of HMD using KBr pellet (400-4000 cm −1 ) was measured on a Thermo Nicolet iS5 spectrophotometer. ( 1 H and 13 C) NMR was acquired using Bruker Avance III-600 in the DMSO-d 6 solution. The TG-DSC curves were recorded using the METTLER TOLEDC tgdsc 3 in air, which heated up at a rate of 10 • C/min between 25 and 800 • C. The UV-Vis spectra were determined using a TU-1901 spectrophotometer.

Synthesis
The ethanol solution of 1,5-dioxaspiro [5.5]undecane-2,4-dione (0.02 mol, 3.68 g) was magnetically stirred for 3 h at 60 • C with 1.2 equivalent amount of trimethyl orthoformate (0.024 mol, 2.544 g). After that, an equal amount of o-aminophenol (0.02 mol, 2.18 g) was added, and the solution was allowed to react for another 3 h at the same temperature. The mixture was then cooled and washed with distilled water two to three times before being recrystallized with ethanol, filtered, and dried to yield the yellow powder. The yield was 21.45%. The m.p. was 213.1-213.7 • C. The 1 H NMR (600 MHz, DMSO-d 6 ) δ values (ppm) were 11.46 (s, 1H, -NH), 10

Single Crystal Studies
A transparent yellow block crystal was measured on an Xcalibur Eos Gemini diffractometer with the Mo-Kα radiation (0.71073 Å). Its structure was achieved using SHELXT-2016 [28,29]. The H atoms of HMD were positioned at suitable positions and adjusted using a riding mode. The non-hydrogen atoms were accomplished by anisotropic refinement.

Theoretical Details
The optimized structure and vibrational analyses were performed with the DFT method using B3LYP/6−311G(d,p) in the Gaussian 09 package [30][31][32][33]. The electronic transition of HDM was carried out using the TD-DFT approach, which was based on the B3LYP/6−311G(d, p). The Hirshfeld surfaces and two-dimensional fingerprints were analyzed by the CrystalExplorer 17.5 [34] (Supplementary Materials).

Conclusions
Some chemical and photophysical properties of the new hydroxyphenylamin Meldrum's acid derivative (HMD) can be understood by combining the experimental and theoretical techniques. The structural insights and vibrational spectra of the title molecule were explored using DFT calculations. The UV-Vis spectrum of HMD was compared with the experimental results. They corresponded to the π→π* and n→π* transitions of the molecule. The strong intramolecular charge transfers of π→π* and n→σ*/π* were discussed using the NBO analysis. The O(1)-H(1A)···O(2) intermolecular hydrogen bonds of the molecule could be verified by the MEP and Hirshfeld surface analysis. The large HOMO-LUMO energy gap explained the strength of the stabilization of the molecule. Finally, the NLO properties of HMD were calculated. The results showed that the molecule had a strong NLO response and might be used to design new organic NLO materials.
Author Contributions: W.Z., conceptualization, supervision, data curation, investigation, writing-original draft, and writing-review and editing. X.W., funding acquisition. Y.Z., DFT computation. T.Z., synthesis and investigation. All authors have read and agreed to the published version of the manuscript.