Molecular Modeling and Spectroscopic Studies of Benzothiazole

The Fourier Transform (FT) infrared and FT-Raman spectra of benzothiazole (BT) have been recorded and analyzed. The equilibriumgeometry, bonding features, and harmonic vibrational frequencies have been investigated by ab initio and density functional theory (DFT)methods.The assignments of the vibrational spectra have been carried out.The computed optimized geometric bond lengths and bond angles show good agreement with experimental data of the title compound. The calculated HOMO and LUMO energies indicate that charge transfer occurs within the molecule. Stability of the molecule due to conjugative interactions arising from charge delocalization has been analyzed using natural bond orbital (NBO) analysis.The results show that the electron density (ED) in the σ∗ and π∗ antibonding orbital and second-order delocalization energies E(2) confirm the occurrence of intramolecular charge transfer (ICT).The calculated results were applied to simulate infrared and Raman spectra BT which show good agreement with recorded spectra.


Introduction
Benzothiazole (BT) molecule contains a thiazole ring fused with benzene ring.Thiazole ring is a five-member ring consists of one nitrogen and one sulfur atom in the ring.Benzothiazole is thus a bicyclic aromatic ring system.A number of BT derivatives have been studied as central muscle relaxants and found to interfere with glutamate neurotransmission in biochemical, electrophysiological, and behavioral experiments [1].Substituted benzothiazoles have been studied and found to have various chemical reactivity and biological activity.Benzothiazole ring is found to possess pharmacological activities such as antiviral [2], antibacterial [3], antimicrobial [4], and fungicidal activities [5].They are also useful as antiallergic [6], antidiabeticantitumor [7], antitumor [8], anti-inflammatory [9], anthelmintic [10], and anti-HIV agents.Phenyl substituted benzothiazoles show antitumor activity [11][12][13] while condensed pyrimido benzothiazoles and benzothiazoloquinazolines show antiviral activity.Substituted 6-nitro-and 6-amino-benzothiazoles show antimicrobial activity.
Molecular spectroscopic methods, in particular, experimental IR and Raman spectroscopy, have been successfully employed for structural investigation of complex molecular compounds.These techniques are especially effective when used in combination with direct methods of structural analysis in hydrogen bond investigations.The aim of the present work is theoretical and experimental spectroscopic investigation of BT molecular structure to gain insight into the structure and physical properties of the molecular structure.The FT-IR and FT-Raman spectra were simulated and compared with experimental results.Ab initio and DFT calculations have been performed to support the wave number assignments.

Methodology
2.1.Experimental Details.The compound under investigation, namely, BT, is spectral grade purchased from M/S Aldrich Chemicals, USA, and it is used as such without further purification.The FT-IR spectrum of the compound was recorded in Perkin-Elmer Spectrometer in the range of 4000-100 cm −1 using KBr pellet technique.The spectral resolution is 0.1 cm −1 .The FT-Raman spectrum of the compound was recorded in the BRUKER RFS 27 and Standalone FT-Raman 2.2.Computational Details.The molecular geometry optimization and vibrational frequency calculations were carried out on benzothiazole, with GAUSSIAN 09W software package [14] HF functional [15,16] combined with standard 6-311G and 6-311++G (d, p) basis set (referred to as "large" basis) and the density functional method used is B3LYP, that is, Becke's three-parameter hybrid functional with the Lee-Yang-Parr correlation functional method with 6-311++G (d, p).The harmonic vibrational frequencies calculated for BT at HF and B3LYP levels using the triple split valence basis set along with the diffuse and polarization functions.It may be pointed out that computed wave number corresponds to the isolated molecular state in the gaseous phase whereas the experimental wave numbers correspond to the solid state spectra.In order to evaluate the energetic behavior of the title compound, we carried out calculations in vacuo and in organic solvent (ethanol).The energies of important molecular orbitals of BT, the highest occupied MOs (HOMO), and the lowest unoccupied MOs (LUMO) were calculated using HF/6-311++G (d, p) method.NBO analysis has been performed on the BT molecule at the HF/6-311++G (d, p) and B3LYP/6-311++G (d, p) level in order to elucidate the intramolecular, rehybridization, and delocalization of electron density within the molecule.The result of interaction is a loss of occupancy from the density of electron in NBO of the idealized Lewis structure into an empty non-Lewis orbital.For each donor () and acceptor (), the stabilization energy (2) associated with the delocalization  →  is estimated as where ⟨||⟩ 2 or   2 is the Fock matrix element  and  NBO orbital's,  *  and −  are the energies of  and  * NBOs, and   is the population of the donor  orbital.Zero point vibrational energy, internal energy and its translational, rotational, and vibrational contributions, entropy, and heat capacity of BT are computed through the calculation of partition functions [17][18][19].

Results and Discussion
3.1.Molecular Geometry.The optimized geometry of the molecule under investigation with IUPAC numbering scheme for the atoms is presented in Figure 1.The data of structural parameters obtained by ab initio method as compared to density functional theory for benzothiazole are reported in Table 1.The comparative graphs of bond lengths and bond angles of the title molecule are presented in Figure 2. From the computed values, it is found that most of the optimized bond lengths are slightly larger than the experimental values, this may be due to the fact that theoretical calculations belong to isolated molecules in gaseous phase and the experimental results belong to molecules in solid state.Comparing bond angles and lengths obtained by B3LYP method with those obtained by HF, as a whole the values got by the former are higher than those obtained be the later method.It may be pointed out that the values calculated by B3LYP method correlate satisfactorily with the experimental data.From the data shown in Table 1, it is seen that both HF and DFT (B3LYP/6-311++G (d, p)) levels of theory in general estimate the same values of some bond lengths and bond angles.It is well known that HF methods underestimate and DFT method overestimates bond lengths, particularly the C-H bond lengths [20,21].This theoretical pattern is also found for benzothiazole molecule.
The carbon-carbon bonds in benzene are not of equal length which is justified by the presence of fused thiazole ring.However, the differences between the six C-C distances are small.The longest bond distance in C4-C5 bond is due to the fusion of thiazole moiety at these carbons.Comparing the bond distances of the hetero aromatic ring, it is found that the bond distances in hetero aromatic ring differ significantly from each other due to the difference in electronegativities of the bonded atoms.The S1-C2 bond distance is the longest (1.7651 Å) while the C2-N3 is the shortest (1.2874 Å).The longest S1-C2 distance attributes the pure single bond character.The C5-S1 and C2-S1 bond distances of BT determined by B3LYP/6-311++G (d, p) method are 1.75 Å and 1.7651 Å, respectively, in between the 1.81 Å average distance for a carbon-sulfur bond and the 1.61 Å which indicate that the actual bond order is between one and two which is due to conjugative effect in benzothiazole.Due to ring strain the C2-N3 double bond distance is 1.268 Å, 1.268 Å, 1.263 Å in HF, and 1.2874 Å for B3LYP/6-311++G (d, p) bigger than single bond C2-H10.With the electron donating substituents on the benzene ring, the symmetry of the ring is distorted, yielding ring angles smaller than 120 ∘ at the point of substitution and slightly larger than 120 ∘ at the ortho-and metapositions [22].It is observed that in BT molecule the bond angle at the point of substitution C4-C5-C9 is 118.7 ∘ in HF and 118.9    in DFT while the bond angles in at ortho to the substituted carbon, C6-C7-C8 position is found to be 120.8677,120.908 degree at HF and DFT respectively.This may be due to mesomeric effect of the thiazole ring.The meta position angle C7-C8-C9 is greater than 120 ∘ and is found to be 120.91 ∘ , 121.078 ∘ .More distortion in bond parameters is observed in the heteroring than in the benzene ring.The variation in bond angle depends on the electronegativity of the central atom, the presence of lone pair of electrons, and the conjugation of the double bonds.If the electro negativity of the central atom is less, the bond angle decreases.Thus, the bond angle C5-S1-C2 is very less (88.2122 ∘ , 88.2011 ∘ ) than the bond angle C8-N3-C2 (110.755∘ , 110.742 ∘ ) which is due to the fact that electronegativity of nitrogen is greater than sulfur.

Vibrational Assignments.
The BT molecule consists of 14 atoms and so it has 36 normal vibrational modes.The observed vibrational assignments and analysis of BT are discussed in terms of fundamental bands.The harmonic vibrational frequencies calculated for BT at HF and B3LYP levels along with the observed FT-IR and FT-Raman frequencies for various modes of vibrations have been presented in Table 2.The comparative values of IR and Raman intensities are given in Table 3.The recorded FT-IR and FT-Raman spectra of BT are given in in Figures 3(a) and 3(b) respectively.Theoretical FT-IR and FT-Raman spectra are reported in Figures 4 and 5, respectively.It may be pointed out here that computed wave numbers correspond to the isolated molecular state in the gas phase whereas the experimental wave numbers correspond to the solid state spectra.The calculated vibrational frequencies using different methods are compared with experimentally observed values.The calculated vibrational wave numbers are consistent with the experimental results.Few bands predicted theoretically in FT-IR spectra were not observed in the experimental spectrum of BT molecule may be due to their very weak intensity.

C-H Stretching.
Aromatic compounds commonly exhibit multiple weak bands in the region 3100-3000 cm −1 [23][24][25] due to aromatic C-H stretching vibrations.In the present case, the C-H stretching vibrations are captured at 3061, 3150 cm −1 in (mode no.32, 33) FT-IR spectrum and corresponding Raman spectrum observed at 3063 cm −1 .The aromatic C-H in-plane bending modes of benzene and its derivatives are observed in the region 1300-1000 cm −1 .The C-H out-of-plane bending modes [26][27][28][29] are usually of medium intensity and absorption in the region 950-600 cm −1 .In the case of BT, the bands observed at 1069, 1124, 1157, 1198, and 1264 cm −1 (mode no.17, 19, 20, 21, and 22) in IR and at 1292 cm −1 in Raman spectra are assigned to the C-H in-plane bending vibrations.The C-H out of plane bending mode of benzene derivatives is observed in the region 1000-600 cm −1 .The aromatic C-H out of plane bending vibrations of BT are assigned to the medium to weak bands observed at 1014 and 978 cm −1 (mode no.14, 15) in the infrared spectrum and 1016 cm −1 in Raman spectrum.The aromatic C-H inplane and out of plane bending vibrations have substantial overlapping with the ring C-C-C in-plane and out of plane bending modes, respectively.

C-S Stretching.
The C-S and S-H bonds are highly polarizable and hence exhibit stronger spectral activity.The C-S stretching vibration is expected in the region 710-685 cm −1 [30].The C-S stretching vibrations were observed in the region 609-716 cm −1 for 2-mercapto benzothiazole [31].The calculated values of the vibrations range from 572 cm −1 to 876 cm −1 .For 2-mercaptobenzoxazole [32], the calculated values of the vibrations range from 579 cm −1 to 892 cm −1 and the observed C-S stretching vibration is 954 cm −1 .In our title molecule, the C-S stretching is observed at 667 and 799 cm −1 (mode no. 9, 11) in FT-IR.The FT-Raman spectrum value at 801 cm −1 as a medium band is assigned to C-S stretching vibration.The calculated frequencies of 668, 652, 600, and 626 cm −1 exactly correlate with experimental observation as well as the literature data.The C-S vibration is a pure mode as evident from Table 2.The inplane and out-of-plane C-S stretching vibration also exactly correlates with experimental observations.

C=N Vibrations.
The C=N stretching vibrations [33][34][35][36] are observed in the range 1672-1566 cm −1 .Varsanyi [37] has suggested that an IR band at 1626 cm −1 for C=N stretching and Raman frequency is assigned to the C=N stretching vibration of benzothizaole [38].The respective

Ring Vibrations.
The carbon-carbon stretching modes of the benzene ring are expected to be in the range from 1650 to 1200 cm −1 and are usually not very sensitive to substitution by small substituents, but heavy halogens diminish the frequency [39,40].In the Raman spectrum of BT, the carboncarbon stretching bands appeared at 1596, 1575, 1478, and The infrared band at 873 cm −1 and two Raman bands at 1000 and 700 cm −1 (mode no.13) are assigned to C-C-C inplane bending vibrations of BT.The C-C in-plane bending vibrations appeared as the combination vibrations with C-H in-plane bending vibrations.The bands assigned to C-C-C out-of-plane bending vibrations are observed at 585, 531 cm −1 in (mode no.6, 7) FTIR spectrum and 505 cm −1 in Raman spectrum for BT.The ring breathing vibrations are generally very strong in Raman spectrum.This mode is found in the region 1100−1000 cm −1 for a heavy substituted compound and is strongly Raman active.This is confirmed by the very weak intense Raman band at 706 cm −    to be higher than B3LYP at 6-311+G (d, p) level whereas in the case of Raman activities the trend is reverse.

NBO Analysis.
The natural bond orbital analysis provides an efficient method for studying intra-and intermolecular bonding and interaction among bonds and also provides a convenient basis for investigating charge transfer or conjugative interaction in molecular systems.Some electron donor orbital, acceptor orbital, and the interacting stabilization energy resulting from the second-order microdisturbance theory are reported [41].NBO analysis has been performed on the title molecule in order to elucidate the intermolecular, rehybridization, and delocalization of electron density within the molecule, which are presented in Tables 4 and 5.A large diversity of energy values was found.The stronger donor character is shown by the p-type lone pair of the nitrogen atoms.The most important interaction ( −  * ) energies, related to the resonance in the molecules, are electron donation from the LP(1)S atoms of the electron donating groups to the antibonding acceptor  * (C-N) of the phenyl

Frontier Molecular Orbitals (FMOs).
The highest occupied molecular orbitals (HOMOs) and the lowest-lying unoccupied molecular orbitals (LUMOs) are called frontier molecular orbital's (FMOs).The FMOs play an important role in the optical and electric properties, as well as in quantum chemistry and UV-vis spectra [37].The HOMO represents the ability to donate an electron; LUMO as an electron acceptor represents the ability to obtain an electron.The energy gap between HOMO and LUMO determines the kinetic stability, chemical reactivity, and optical polarizability and chemical hardness-softness of a molecule [42,43].
In order to evaluate the energetic behavior of the title compound, we carried out calculations in vacuo and in organic solvent (ethanol).The energies of important molecular orbitals of BT, the highest occupied MOs (HOMO) the lowest unoccupied MOs (LUMO) were calculated using HF/6-311++G (d, p).The energy values of HOMO and LUMO are −0.2449,−0.05227, respectively.The 3D plots of the HOMO, LUMO orbitals computed for BT molecule are illustrated in Figure 6.The positive phase is red and the negative one is green.It is evident from the figure that while the HOMO is localized on almost the whole molecule, LUMO is localized on the thiazole ring.Both the HOMOs and the LUMOs are mostly  antibonding type orbitals.The calculated energy value of HOMO is −6.4099 eV and LUMO is −2.038 eV, respectively.The energy separation between the HOMO and the LUMO is −4.4061 eV, respectively.The energy gap of HOMO-LUMO explains the eventual charge transfer interaction within the molecule, which influences the biological activity.The wavelength of maximum absorption, excitation energies  (eV), and oscillator strengths () of benzothiazole are calculated and given in Table 6. Figure 7 contains theoretically deduced UV-vis spectrum of BT in ethanol employing the TD-HF/6-311++G (d, p) method.positive and negative charges.Dipole moments are strictly determined for neutral molecules.For charged systems, its value depends on the choice of origin and molecular orientation.As a result of HF and DFT (B3LYP) calculations, the highest dipole moment was observed for B3LYP/6-311G++(d,p) whereas the smallest one was observed for HF/6-311++G (d, p) in each molecule.
On the basis of vibrational analysis, the statically thermodynamic functions: heat capacity (C), entropy (S), and enthalpy changes (DH) for the title molecule were obtained from the theoretical harmonic frequencies and listed in Table 7. From the data in this table, it can be observed that these thermodynamic functions are increasing with temperature ranging from 100 to 600 K due to the fact that the molecular vibrational intensities increase with temperature [44].

Conclusion
In the present work, we have performed the experimental and theoretical vibrational analysis of a pharmaceutically important heterocyclic aromatic molecule, benzothiazole for the first time.The optimized molecular geometry, vibrational frequencies, infrared activities, and Raman scattering activities of the molecule in the ground state have been calculated by using ab initio HF and DFT (B3LYP) methods with 6-311++G (d, p) basis set.The vibrational frequencies were calculated and scaled values are compared with the recorded FT-IR and FT-Raman spectra of the compound.The observed and the calculated frequencies are found to be in good agreement.Furthermore, the thermodynamic and total dipole moment properties of the compound have been calculated in order to get insight into molecular structure of the compound.These computations are carried out with the main aim that the results will be of assistance in the quest of the experimental and theoretical evidence for the title molecule in biological activity and coordination chemistry.

Figure 2 :
Figure 2: Bond length and bond angle difference between theoretical (HF and DFT) approaches.

Figure 6 :
Figure 6: The molecular orbitals and energies for the HOMO and LUMO of the title compound.

Figure 7 :
Figure 7: Theoretical UV-vis spectrum in ethanol for the title molecule calculated with the TD-HF/6-311++G (d, p) method.
C in-plane and out of plane bending modes of BT are presented in Table3.Normal coordinate analysis shows that significant mixing of C-C-C in-plane bending with C-H inplane bending occurs.Similarly, the skeletal out of plane bending modes are overlapped with C-H out of plane bending modes significantly.The theoretically calculated values of C=N Stretching vibrations are in the region 1717, 1704, and 1629 cm −1 .

Table 4 :
Second-order perturbation theory analysis of Fock matrix in NBO basis for benzothiazole.

Table 4 :
Continued.Energy difference between donor and acceptor  and  NBO orbitals.c F(, ) is the Fock matrix element between  and  NBO orbitals. b
a E(2) means energy of hyper conjugative interaction (stabilization energy).b Energy difference between donor and acceptor i and j NBO orbitals.c F (i, j) is the Fock matrix element between i and j NBO orbitals.

Table 7 :
The calculated thermodynamical parameter of benzothiazole.