Newly Synthesized Aminothiazole Based Disazo Dyes and Their Theoretical Calculations

Abstract In this study, ten novel disazo dyes based on aminothiazoles (4a-e, 5a-e) were synthesized in the first section. By using their 1H-NMR, FT-IR, and UV-Vis spectra, these synthesized dyes’ structures were verified. In the second section, the density functional theory (DFT) was used to calculate the molecular geometry, vibrational frequency and molecular electrostatic potential (MEP) diagram in the ground state using the B3LYP level and the 6-311 G(d,p) basis set. UV-vis data were obtained using the Gaussian 09 TD-DFT Cam-B3LYP 6-311 G ++ (d,p) basis set. To explore the chemical shift values, the gauge independent atomic orbital (GIAO) approach was used. Time-dependent DFT (TD-DFT) approach was used to determine the HOMO–LUMO calculations. As a consequence of our research, it was found that the experimental values and the computational spectroscopic values of the synthesized disazo compounds were consistent.


Introduction
Due to their presence in the structures of chemicals that demonstrate biological activity, heterocyclic compounds have traditionally attracted a lot of attention. 1Thiazole, a member of the family of azole heterocycles, is a five-membered heterocyclic ring that contains sulfur and nitrogen.In the area of medicinal chemistry, thiazole and its derivatives have received extensive study attention from numerous research teams across the world for the treatment of a variety of disorders.][4][5][6] Azo dyes are chemical substances with an aromatic ring attached to an azo function (-N ¼ N-), which is used to give them color.Recently, both scientific and technological perspectives have given these chemical compounds considerable attention.][9][10][11][12][13] Although there are many studies in the literature on biological agents, studies on the discovery of new agents are still ongoing.The goal is to discover more potent, less toxic, and highly beneficial therapeutic agents.
5][16][17][18][19][20] With reasonable precision, theoretical calculations can be used to support experimental results.When theoretical methods are confirmed by outcomes, experimental research or discoveries are becoming more reliable.][23] In light of this information, our study aimed to obtain new disazo dyes derivatives with heteroaromatic compounds and ten new aminothiazole-based disazo dyes (4a-e, 5a-e) were synthesized.Structures of these synthesized dyes were confirmed by 1 H-NMR, FT-IR and UV-Vis spectra.In the second part, employing the B3LYP level with the 6-311 G(d,p) basis set, in the ground state, the molecular geometry, vibrational frequency calculations and molecular electrostatic potential (MEP) diagram were performed by the density functional theory (DFT).UV-vis data were obtained using the Gaussian 09 TD-DFT Cam-B3LYP 6-311 G þþ (d,p) basis set.The gauge independent atomic orbital (GIAO) method was carried out to investigate the chemical shift values.Time-dependent DFT (TD-DFT) approach was used to determine the HOMO-LUMO calculations.As a result of our study, it was observed that the computational spectroscopic values of the synthesized disazo compounds were compatible with the experimental values.

Experimental equipment
Chemicals used for the synthesis of the compounds are available from Aldrich and Merck.The FT-IR spectra were prepared using Shimadzu IR Prestige-21 Fourier Transform Infrared device.UV-Vis spectra were determined by Shimadzu UV-1601. 1 H-NMR spectra were obtained using tetramethylsilane (TMS) as a reference in dimethylsulfoxide (DMSO-d 6) with Bruker-SpectrospinAvance DPX 400 Ultra-Shield.

Computational methods
Theoretical calculations of the synthesized compounds were performed with the Gaussian 09 program, and the visualizations were made with the GaussView 5.0.9 program. 24,25Molecular structures of the disazo dyes were optimized with the DFT method using B3LYP functional with 6-311 G(d,p) basis set. 26,27Default settings were used in geometry optimizations.Molecular geometry, vibrational frequency calculations and molecular electrostatic potential (MEP) diagram were performed with the DFT using the B3LYP level and the 6-311 G(d,p) basis set.With DFT/Cam-B3LYP 6-311 G þþ (d,p) basis set, UV-vis spectra analysis was accomplished in five different solvents. 28,29UV-vis studies were carried out by specifying 6 excited states.Calculated NMR shielding constants were obtained with Gauge Including Atomic Orbitals (GIAO) method. 30,31

Molecular geometry
The geometric structures of the synthesized disazo dyes 4a-4e and 5a-5e were calculated using B3LYP functional with 6-311 G(d,p) basis set in the gas phase and represented in Figure 2. The structural parameters, bond lengths (Å), bond angles ( ) and dihedral angles ( ), were presented in Table 1.
The bond lengths between C-S in the thiazole structure were calculated in the range of 1.724-1.783.The conjugated bond lengths between C-N in the pyrazole structure were calculated in the range of 1.368-1.430.Since the C-N bond between the azo group and the thiazole ring does not participate in the conjugation and has a single bond character, it is generally calculated at around 1.400 Å in the structures.The N ¼ N double bond lengths of the azo groups in the molecules are in double bond character as expected from the structures and have been calculated around 1250 Å.The N ¼ N double bond is calculated at 1.252 Å in compound 4b and is the shortest, while it is the longest bond calculated at 1.273 Å in compound 5e.At the end of the calculations, when the table is evaluated in general, a single bond was observed between approximately 1.724 Å, a double bond between approximately 1.211 À 1.359 Å, a conjugate bond between approximately 1.391 À 1.405 Å.
When the calculated bond angles of the compounds were evaluated, it was determined that it was generally 120 .Based on the obtained bond angle values, it has been determined that the molecular geometry around the atoms is generally in the form of a trigonal planer.The smallest bond angle obtained from the synthesized compounds was calculated 113.0˚and between C23-C26-O29 and N19-N18-C9 atoms of the 4a molecule.The largest bond in the optimized geometries of the molecules was 130.5 between N5-C4-N6 in the 5c molecule.In general, bond angles at S5-C1-N4 and S4-C3-N6 atoms in the thiazole structure were calculated between 114.6 and 123.0.Table 1.Some selected calculated bond lengths (Å), bond and dihedral angles ( ) for the 4a-4e and 5a-5e molecules at the B3LYP/6-311G(d,p) level.Dihedral angles in molecules are very important in terms of determining whether the molecule is linear or not and orientations in a three-dimensional environment.Dihedral angles equal to or close to 0˚or 180˚indicate that those atoms are in the same plane.Within this framework, it is possible to examine the molecules we have synthesized in five groups.The first of these is thiazole, the second and fourth are N ¼ N groups, the third is pyrazole, and the fifth is the aromatic substituent.By determining whether these parts are in the same plane as each other, it has been tried to have information about the linearity of the molecules.Looking at the structure, it can be said that the dihedral angles of the compounds S4-C3-N6-N7 (4c-4e) which are located between the thiazole and azo groups and 5a-5e, are close to 180˚, and these groups lie in the same plane.On the other hand, the dihedral angles of S5-C1-N6-N7 and S4-C3-N6-N7, which are among the thiazole and azo groups in compounds 4a and 4b, were calculated as 32.0˚and 46.8˚, respectively.Based on these values, it was observed that these groups do not lie in the same plane in molecules 4a and 4b.

Vibrational spectra
The FTIR spectra of disazo dyes 4a-4e showed aliphatic band at 2400-2200 cm À1 , aromatic band at 3350-3000 cm À1 , azo band at 1620-1400 cm À1 .As corresponding B3LYP/6-311G (d,p) calculations, aliphatic band at 2946-2938 cm À1 , aromatic band at 3702-3535 cm À1 , azo band at 1789-1322 cm À1 were recorded.The FTIR spectra of disazo dyes 5a-5e showed aliphatic band at 23700-2200 cm À1 , aromatic band at 3300-3000 cm À1 , azo band at 1700-1400 cm À1 .As corresponding B3LYP/6-311G (d,p) calculations, aliphatic band at 2946-2943 cm À1 , aromatic band at 3701-3037 cm À1 , azo band at 1921-1710 cm À1 were recorded.When the values were compared, because of the complexity of the vibration bands, some deviations were observed.Experimentally and theoretically vibrational frequency values of all synthesized azo dyes were given in Table 2.Although there are some deviations due to tautomerization, the experimental and theoretical data of frequency values were at a level that can be considered compatible with each other.

Uv-vis spectrum
The variation of maximum absorption wavelengths of the synthesized disazo dyes in acetic acid, DMSO, DMF, chloroform and methanol was investigated experimentally and theoretically.The concentrations in each solvent were different due to the resolution (at 10 À8 -10 À6 M).As seen Table 4, for disazo dyes 4a-4e, while only one maximum absorption peak was observed in dye 4d, dyes 4a, 4b, 4c and 4e had two maximum absorption peaks for all used solvents.For dye 4a, the first kmax values did not change much, but second kmax value of acetic acid showed a bathochromic shift according to the chloroform.For dye 4b, first and second kmax values of DMF, DMSO, acetic acid and methanol were more bathochromic shift according to the chloroform.For dye 4c, when the first kmax values were examined, it was observed that absorption maxima in DMSO and methanol did not change so much, hypsochromic shift in acetic acid and bathochromic shift in DMF was observed according to the chloroform.When the second kmax values were examined, methanol, acetic acid, DMF and DMSO showed hypsochromic shift according to chloroform.For dye 4d, absorption maxima in acetic acid did not change much, while DMSO, DMF and methanol showed a batochromic shift according to chloroform.For dye 4e, when the first kmax values were examined, kmax value of DMF, DMSO, acetic acid and methanol showed a bathochromic shift according to the chloroform.When the second kmax values were examined, hipsochromic shift in acetic acid and bathochromic shift in DMSO, DMF, methanol was observed according to the chloroform.As seen Table 4, for disazo dyes 5a-5e, while only one maximum absorption peak was observed in dye 5a and 5b, dyes 5c, 5d and 5e had two maximum absorption peaks.For dye 5a, absorption maxima in DMF showed a batochromic shift, while DMSO, acetic acid and methanol showed a hypsochromic shift according to chloroform.For dye 5b, absorption maxima in acetic acid showed a hypsochromic shift, while DMSO, DMF and methanol showed a bathochromic shift according to chloroform.For dye 5c, when the first kmax values were examined, it was observed that absorption maxima with DMF, acetic acid and methanol did not change much, kmax value of DMSO showed a bathochromic shift according to the chloroform.When the second kmax values were examined, acetic acid did not change much, hipsochromic shift in methanol and bathochromic shift in DMSO, DMF, acetic acid was observed according to the chloroform.For dye 5d, in the spectra in chloroform, acetic acid, DMSO two maximum, in DMF, methanol one maximum were observed.When kmax values were examined, absorption maxima in acetic acid did not change much, while DMSO, DMF and methanol showed a batochromic shift according to chloroform.For dye 5e, when the first and second kmax values were examined, it was observed that absorption maxima with DMF, DMSO, acetic acid and methanol showed a batochromic shift according to chloroform.When the calculated kmax values of dyes 4a-4e and 5a-5e were examined, three maximums were observed in all dyes except dyes 4c and 4d at all used solvents.But, when all maximums are compared among themselves, the effect of solvents were not observed.The HOMO and LUMO of the compounds were calculated at the DFT/B3LYP 6-311 G/(d,p) level using the HOMO S -LUMO S Gaussian W09 package program.Obtained surface images are given in Figure 3.
When the LUMOs of the synthesized compounds were examined, an even distribution was observed on the molecules.It can be stated that HOMOs are dense at N ¼ N double bonds and between C-N in the quintuple ring.The gap between the HOMO and LUMO of the compounds is very important in terms of evaluating their effectiveness in chemical reactions.While HOMO-LUMO has high vacancy energy is hard, HOMO-LUMO molecules with low vacancy energies are soft; they are expected to be more reactive in chemical reactions.The calculated HOMO energies of the synthesized compounds were between À6.061 and À5.373 eV, while the LUMO energies were between À3.227 and À2.644 eV.On the other hand, HOMO-LUMO gap energies of all compounds were determined between 2.670 and 3.180 eV.Based on the values obtained, the molecule with the highest HOMO-LUMO gap energy is 4b with À3.180 eV.It was determined that the compound with the smallest HOMO-LUMO gap energy was 4d with À2,670 eV.In light of these values, it was concluded that the hardest molecule among the synthesized compounds was 4b, and the softest compound expected to be reactive in chemical reactions was 4d.
When these values were compared among themselves, the highest HOMO value was calculated as À5.914 eV in the 5a compound, and the highest LUMO value was calculated as À3.227 eV in the 4d compound.Energy gaps between these two boundaries were found one by one.The highest value was calculated as 3.180 eV in compound 4b.Compound 4b may react with more difficulty than the other nine compounds obtained.Compound 4d was calculated as 2.670 eV.It can be stimulated more easily and react more easily than other compounds.

Molecular electrostatic potential diagram
The molecular electrostatic potential (MEP) diagrams of the molecules were calculated at the B3LYP/6-311G(d,p) level with the Gaussian 09 packet basis set.Three-dimensional MEP diagrams of the synthesized molecules are given in Figure 4, respectively.
MEP provides important information in the nucleophilic electrophilic region description of the molecule.In these regions, the red ones represent electron-rich regions and the blue ones represent electron-poor regions.In general, red charge density was observed on the nitrogen atoms in the thiazole and pyrazole rings.Electron charge density was also observed on the oxygen atom in the carbonyl group of the carboxylic acid groups in 4a and 5a molecules.Although not as much as these atoms, some charge density was also determined on the H atoms on the pyrazole ring.The electron richness in these groups appears to be related to the high electronegativity of these atoms.When the regions with a high positive charge density of the molecules were examined, it was observed that these regions were generally concentrated on the N-H proton in the pyrazole ring.It has been observed that the positive charge density is high on the proton in the carboxyl group in the 4a and 5a molecules.There is also a positive charge density on the NH 2 group in molecules 4a, 4e, 5a and 5e.It has been observed that the positive charge density is high on the phenolic proton in the 4b, 4c, 4d, 5b, 5c and 5d molecules because this proton is loosely attached to the structure.As a result, these regions give us information about possible interaction regions of synthesized molecules in nucleophilic and electrophilic reactions.

Conclusion
Synthesized ten new aminothiazole based disazo dyes (4a-e, 5a-e) in this study were identified their structural and some spectroscopic properties with the measurements of FT-IR, 1 H NMR and UV-Vis spectra.Also, their theoretical calculations were accomplished with DFT method employing the B3LYP level with the 6-311 G(d,p) basis set.With DFT/Cam-B3LYP 6-311 G þþ (d,p) basis set, UV-vis spectra analysis was accomplished in five different solvents.It was seen that the results obtained from the theoretical calculations support the experimental analysis results.When bond lengths were examined, it was observed that a single bond between approximately 1.724 Å, the double bond between approximately 1.211 Å À 1.359 Å, conjugate bond between approximately 1.391 Å À1.405 Å.When the bond angles were examined, it has been determined that the molecular geometries were generally trigonal planer and the angle was generally 120 . When the dihedral angles in the molecules were evaluated, it can be mentioned that; since the dihedral angles of the compounds S4-C3-N6-N7 (4c-4e) and 5a-5e, which were located between the thiazole and azo groups, were close to 180˚, these groups lie in the same plane, on the other hand, since the dihedral angles of S5-C1-N6-N7 and S4-C3-N6-N7, which were between the thiazole and azo groups in compounds 4a-4b, were calculated as 32.0˚and 46.8˚, respectively, and therefore, these groups did not lie in the same plane in the 4a and 4b molecule.When the HOMO and LUMO values, which were important in terms of evaluating their effectiveness in chemical reactions, were examined, it was observed that there was an equal distribution of the molecules when the LUMOs were examined, while in HOMOs, it was more intense between the N ¼ N double bonds and the C-N in the quintuple ring.As a result of the obtained MEP images, the dye with the largest scale is 4c, while the dye with the smallest scale is 5a.
Figure 1.The synthesis reactions of ten new aminothiazole-based disazo dyes.

Figure 3 .
Figure 3. Molecular orbital surfaces and energy levels for the HOMO and LUMO computed at DFT/B3LYP/6-311G(d,p) level.

4. 5 .
Frontier molecular orbital (FMOs) analysis HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies are important parameters for quantum chemistry used to understand chemical interactions.In addition, information about the reactivity of molecules and active sites can be obtained from the Frontier Molecular Orbital distribution.

Table 4 .
Experimentally and theoretically maximum absorption wavelengths of the synthesized disazo dyes.