Structural and Computational Studies of N-[(2,6-Diethylphenyl) carbamothioyl]-2,2-diphenylacetamide, N-[(3 Ethylphenyl) carbamothioyl]-2,2-diphenylacetamide and 2,2- Diphenyl-N-{[2-(trifluoromethyl) phenyl]carbamothioyl}acetamide

— Theoretical investigations are performed by DFT method of B3LYP/6-31G+(2d,p) and B3LYP/6-311G+(2d,p) basis sets for three carbonyl thiourea compounds, namely N -[(2,6-Diethylphenyl)carbamothioyl]-2,2-diphenylacetamide (Compound I), N -[(3-Ethylphenyl)carbamothioyl]-2,2-diphenylacetamide (Compound II) and 2,2-Diphenyl-N -{[2-(trifluoromethyl)phenyl]carbamothioyl}acetamide (Compound III). Theoretical calculations for bond parameters, harmonic vibration frequencies and isotropic chemical shifts are in good agreement with the experimental results. The calculated molecular vibrations show good correlation values, which are 0.998 and 0.999 with the experimental data. The energy gap for compounds I, II and III calculated at B3LYP/6-31G+(2d,p) basis set are 4.455866117, 4.297495791 and 4.313550514 eV respectively, while for B3LYP/6-311G+(2d,p) basis set the energy gap obtained are 4.453689205 (Compound I), 4.311373603 (Compound II) and 4.315727426 (Compound III) eV.


I. INTRODUCTION
HE molecular structure of carbonyl thiourea contains both hydrogen donors through the NH groups and acceptor centre through both carbonyl and thiocarbonyl groups that can coordinate with metal using oxygen and sulphur atoms [1], [2].This capability of hydrogen bond formation has lead thiourea into numerous applications especially in medicinal and pharmacology field such as for antibreast cancer [3], [4], antifungal [5], [6], antimicrobial agents [7] and potential anti-I.A. Razak is with the School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia (e-mail: arazaki@usm.my).
influenza virus [8].In recent years, the use of computational and theoretical studies by using Density Functional Theory (DFT) method has increased as this method helps to determine the molecular dipole moment, spectroscopic properties and molecular orbital analysis.The use of advanced calculation by applying the Beck's three parameters, Lee, Yang and Parr (B3LYP) approximation into the DFT method has improved the data accuracy [9].

A. Synthesis
For compound I, an acetone (30ml) solution of 2,6diethylaniline (2.01g, 13.5mmol) was added to a round-bottom flask containing 2,2-diphenylacetyl chloride (3.10g, 13.5mmol) and ammonium thiocyanate (1.03g, 13.5mmol).The mixture was put at reflux for 2.5h then filtered off and left to evaporate at room temperature.The colourless precipitate obtained was washed with water and cold ethanol.Colourless plates were obtained by recrystallization of the precipitate from MeOH solution.Compounds II and III were synthesized with a similar procedure as described in compound I.The solutions of 3-ethylaniline (1.63g, 13.5mmol) and 2-(triflouromethyl)aniline (1.25g, 8.4mmol) were used in compound II and III, respectively, as a replacement of 2,6diethylaniline used in compound I. Colorless crystals suitable for X-ray analysis were obtained by recrystallization.

B. Instrumentation Details
The crystal structures were determined by a single crystal X-ray diffraction from data collected at low temperature (100K) using the Oxford Cryosystem Cobra low-temperature attachment [15].The data were collected using a Bruker APEX2 CCD diffractometer with the graphite monochromated MoKα (λ= 0.71073 Å) radiation and with APEX2 software [16].The collected data were reduced using SAINT programme [16].The empirical absorption corrections were performed by the SADABS programme [16].The structure was solved by direct methods and refined by full matrix leastsquares using the SHELXTL software package [17].The structure analysis and presentation of the results were made using PLATON [18].Infrared spectra of the compounds were recorded from KBr discs in the spectral range of 400-4000cm -1 by using FTIR Pelkin-Elmer System 100 Spectrometer.The 1 H NMR (400.11MHz) and 13 C NMR (100.61MHz) spectra were recorded on Bruker Avance III 400 Spectrometer in solution of deuterated dimethyl sulfoxide (DMSO) as solvents at room temperature in the range of 0-15ppm and 0-200ppm.The chemical shifts were also referenced to the trimethylsilyl (TMS) as internal standard.

C. Theoretical Calculation
The molecular geometries were optimized by using Density Functional Theory hybrid method with Becke's nonlocal three parameter exchange and the Lee, Young and Parr correction (B3LYP) using the 6-31G+(2d,p) and 6-311G+(2d,p) basis sets as implemented in the GAUSSIAN 09 program package [19].The optimized structural parameters were used to calculate the vibrational wavenumbers and isotropic chemical shifts.The gauge-invariant atomic orbital (GIAO) method was used to calculate the 1 H and 13 C NMR chemical shifts in ppm relative to TMS as internal standard.The GIAO approach allows the computation of the absolute chemical shielding due to the electronic environment of the individual nuclei and this method is often more accurate than those calculated with other approaches for the same basis set [20].Gauss View molecular visualization program has been used for the animation of vibrational band assignments, HOMO and LUMO diagrams and preparation of the spectrum [21].1.The X-ray crystallography analysis and crystal packing for all compounds have been published [12]- [14].In order to study their properties at the minimum energy, the molecular geometries obtained from the X-ray single crystal analysis were optimized to standard convergence criteria in two different basis sets of B3LYP/6-31G+(2d,p) and B3LYP/6-311G+(2d,p).All selected bond lengths and angles are concluded in Table I and the optimized structures of the compounds are shown in Fig. 1.The value of bond lengths and bond angles were in a good agreement with the experimental data except for the hydrogen-attached atoms, which showed higher values than the experimental results.The disagreement between the experimental and theoretical values was due to the environmental factor where the theoretical calculations were performed in gaseous state, whereas the experimental data belonged to the solid phase.
The simulation data for all compounds revealed that the bond lengths of C-N (Table I) are shorter than the normal C-N single bond character (1.48 Å), which also indicates a partial double bond character.The reason for these C-N bonds is because of the resonance effect in this part of the molecules.The same resonance effect was also observed from the C-S bonds [normal C-S single bond = 1.82 Å and normal C=S double bond = 1.56 Å].All other bond lengths were within the expected range.The partial double bond character of C-N and C-S bonds is shown in the optimized structure [Figs.1(a)-(f)] by the dashed line.Atiş [21] stated that the bond characters of the structure are presumed as a result of the intramolecular Hbond locking the molecules into a planar six-numbered ring structure.The molecular structures obtained from X-ray Single Crystal Analysis (Fig. 1) have confirmed the existence of intramolecular N-H…O hydrogen bond in all compounds.In addition, for compound II an extra intramolecular C-H…S is observed.The dashed lines (Fig. 1) represent the intramolecular hydrogen bonds and the same bond length character is also observed from the previously reported structure of the same molecular species [10], [11].
The calculated bond angles of all compounds were in a good agreement with the experimental data where the angle differences were between 0 to 2°.The bond angles of C-N-C within the thiourea moiety gave the value range of 120 to 133 where the same range of angles were also reported from the previous studies [21]- [23].These results show sp 2 hybridization on the N1 and N2 atoms across the C-N-C-N group [24].In addition, the calculated S-C-N-C-N-O group were essentially planar for all compounds and comparable with the experimental results.IV.VIBRATIONAL ANALYSIS The harmonic vibrational frequencies for compounds I, II and III are calculated at B3LYP/6-31+(2d,p) and B3LYP/6 311G+(2d,p) basis.However, the calculated and the experimental frequencies revealed the overestimation of the calculated wavenumbers corresponding to the observed results neglecting the anharmonicity in the real system.In order to improve the agreement with the experiment data, scaling factor of 0.9613 is used to scale down the calculated harmonic wavenumbers.Table II shows the selected experimental frequencies, relative intensities and probable assignments.The presented results discuss only selected important band in carbonyl thiourea group which are:

A. νN-H band
The stretching N−H group was clearly observed in the range of 3220cm -1 to 3475 cm -1 for B3LYP/6 3216.58 cm -1 to 3467.77cm -1 for B3LYP/6 while the experimental vibrational frequencies ranged from 3244.77 cm -1 to 3451.44 cm -1 .The peaks were clearly found at the most highest values of wavenumbers where these

NALYSIS
The harmonic vibrational frequencies for compounds I, II 1+(2d,p) and B3LYP/6-311G+(2d,p) basis.However, the calculated and the experimental frequencies revealed the overestimation of the calculated wavenumbers corresponding to the observed results neglecting the anharmonicity in the real system.In order to prove the agreement with the experiment data, scaling factor of 0.9613 is used to scale down the calculated harmonic wavenumbers.Table II shows the selected experimental frequencies, relative intensities and probable assignments.The cuss only selected important band in y observed in the range for B3LYP/6-31G+(2d,p) and of for B3LYP/6-311G+(2d,p), the experimental vibrational frequencies ranged from .The peaks were clearly found at the most highest values of wavenumbers where these stretching assignments were due to the formation of intra intermolecular hydrogen bonds formed by the N

B. νC-O band
The FTIR experimental data show the carbonyl stretching bands were found at the range of 1618.68 to 1684.01 cm the strong calculated carbonyl bands were clearly observed at 1654.40-1672.35cm -1 for both basis sets.The decreasing compared to the vibration of carbonyl group (1710 cm -1 ).The effect of conjugated resonance and the formation of intramolecular N-H…O hydrogen bond within the molecules may have caused the strong C=O stretching bands.

C. νC-N band
The C−N vibrational bands were observed at 1551, 1265 and 1171 cm -1 respectively to reported in the related structure of thiourea [22].In compounds I, II and III, the same values of wavenumbers were found from the experimental vibration of CN-H bands revealed the existence of intra molecular N-H…O hydrogen bond.Determinations of the C−N vibrational bands were difficult but by the help of DFT method calculations, the stretching C and assigned within the same range with the experimental values (Table II).

D. νC-S band
The IR absorptions of C=S band were observed at the range of 692.58 to 699.19 cm -1 .The calculated C=S bands were in a good agreement with the experimental results.The C=S bands showed higher values of frequencies observed in compound II.These higher frequency values in compound II may have been due to the formation of an extra intra molecular C-H…S hydrogen bond observed in the molecular structure generated by the X-Ray single crystal analysis.
Fig. 2 presents the linearity calculated vibrational frequency.The computed frequency values usually contain known systematic error and therefore by plotting the correlation graph, the determined.As can be seen from the correlation graphs, obtained correlations were 0.998 for compound I and 0.999 for compounds II and III, and both basis sets gave the same correlation values.In compounds I, II and III, the use of higher basis set did not affect the results of the vibrational studies where the experimental and theoretical results for both basis sets fitted each other well.stretching assignments were due to the formation of intra-and ds formed by the N−H.
The FTIR experimental data show the carbonyl stretching bands were found at the range of 1618.68 to 1684.01 cm -1 and the strong calculated carbonyl bands were clearly observed at for both basis sets.These values were decreasing compared to the vibration of carbonyl group ( 1710).The effect of conjugated resonance and the formation of H…O hydrogen bond within the molecules may have caused the strong C=O stretching bands.N vibrational bands were observed at 1551, 1265 respectively to δ CN-H , ν C(O)-N and ν C(S)-N as reported in the related structure of thiourea [22].In compounds I, II and III, the same values of wavenumbers were found from the experimental data (Table II).The H bands revealed the existence of intra-H…O hydrogen bond.Determinations of the N vibrational bands were difficult but by the help of DFT method calculations, the stretching C−N vibrations were found assigned within the same range with the experimental The IR absorptions of C=S band were observed at the range .The calculated C=S bands were in a good agreement with the experimental results.The calculated C=S bands showed higher values of frequencies observed in compound II.These higher frequency values in compound II may have been due to the formation of an extra intra-H…S hydrogen bond observed in the molecular Ray single crystal analysis.presents the linearity between the experimental and calculated vibrational frequency.The computed frequency values usually contain known systematic error and therefore by plotting the correlation graph, the best basis set can be determined.As can be seen from the correlation graphs, obtained correlations were 0.998 for compound I and 0.999 for compounds II and III, and both basis sets gave the same correlation values.In compounds I, II and III, the use of igher basis set did not affect the results of the vibrational studies where the experimental and theoretical results for both basis sets fitted each other well.Fig. 2 The linear corrected between the calculation and FT

V. NMR ANALYSIS
The compounds were calculated by using DFT method with basis sets of B3LYP/6-31G+(2d,p) and B3LYP/6-311G+(2d,p).All the experimental and calculated results are tabulated in Table III.As can be seen from the table, the experimental and theoretical values were in a good agreement where the values had the same range of chemical shift.The results of the calculated values were corrected via the TMS isotropic chemical shift values.
In 1 H NMR, the NH resonance can be clearly seen where two single peaks were observed at the most downfield area (11.697 and 11.871ppm in compound I, 11.852 and 12.364 ppm in compound II, and 12.308 and 12.144ppm in compound III).Meanwhile, the calculated chemical shifts showed higher values for about 0.5 to 3.5ppm differences with the experimental results.The high shifted values were due to the presence of strong intramolecular N-H…O hydrogen bonds in the molecules.The calculated chemical shifts for hydrogen attached to isobutene moiety were in the range of 4.2 to 4.5 ppm where the differences were 1ppm with the experimental data.The hydrogen atoms of the aromatic ring, methylene group and methyl group were generally in the normal range and comparable with the experimental data (Table III).
In 13 CNMR, δ values of thione group and carbonyl group were 180.73 (δ C=S ) and 173.42 (δ C=O ) ppm (compound I), 178.57(δ C=S ) and 173.49(δ C=O ) ppm (compound II), and 181.32 (δ C=S ) and 173.88 (δ C=O ) ppm (compound III).These groups were at the most deshielded area compared to other carbon atoms because of the environmental factor and the increase of electronegativity from sulphur and oxygen atoms.Theoretical values gave variety values of C=S and C=O chemical shift from both basis sets where the difference was almost 1 to 5ppm.Other carbon atoms were located in the same range as the previously reported structures [22], [23] and calculated δ values were in a good agreement with the experimental results.
The results of the 1 H and 13 C NMR calculated from two different basis sets were not systematic in relation with the experimental results.Even though in the same basis set, there were some values in a very good agreement and there were some that are not.Overall, the calculated chemical shifts were in the normal range and in a good agreement with the experimental results especially of the 13 C NMR.

VI. MOLECULAR ORBITAL ANALYSIS
The highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) and the energy gap of HOMO and LUMO for all compounds calculated at two different basis sets, B3LYP/6-31G+(2d,p) and B3LYP/6-311G+(2d,p) are shown in Fig. 3. Analysis on the frontier orbitals of a molecule helped to determine the electrical and optical properties and the steps to react with other molecule [20], [25].The charge transfer interaction from the ground state (HOMO) to the excited state (LUMO) gave the value of energy gap (∆E) where the smaller the band gap, the higher the stability of the molecule.
As observed in Fig. 3, the charge density of HOMO for all compounds mainly accumulated on the C=S group and small parts from its neighbouring atoms.In the excited state (LUMO), the charge density mostly delocalized within the carbonyl-thiourea moiety.Higher surface charges were located at sulphur and nitrogen atoms, which had the potential to act as coordination points.For basis set B3LYP/6-31G+(2d,p), the energy gap of compounds I, II and III were 4.455866117, 4.297495791 and 4.313550514 eV respectively.Meanwhile, basis set B3LYP/6-311G+(2d,p) gave the values of energy gap of 4.453689205 (Compound I), 4.311373603 (Compound II) and 4.315727426 (Compound III) eV.The same range of energy gap values were observed from both basis sets but there were differences in the dipole moment values.Compounds I and II gave the values of the dipole moments ranging from 2.9714 to 3.2557 Debye, whereas, in compound III the dipole moment values were 1.9989 and 1.9616 Debye for both basis sets.These differences were perhaps due to the different substituent groups attached to the phenyl ring that affected the molecular polarization where the triflouromethyl group in compound III is often described to have more significant electronegativity character as to be compared to the propane group.

VII. CONCLUSION
The crystal structure of compounds I, II and III were synthesized and characterized by X-Ray Crystallography analysis, FT-IR and NMR spectroscopy.The optimized molecular structure for all compound were calculated using DFT/B3LYP6-31G+(2d,p) and DFT/B3LYP6-311G+(2d,p) basis sets along with the vibrational frequencies and the isotropic chemical shift.The calculated parameters from the DFT/B3LYP6-311G+(2d,p) and DFT/B3LYP6-31G+(2d,p) basis set gave good agreement in all the experimental data.The correlation values of 0.998 and 0.999 were obtained from the vibrational frequency studies.The chemical shift obtained from the 13 C NMR was in a very good agreement with the experimental data.Compound II gave the smallest energy gap (4.29eV and 4.31eV) as compared to compounds I and III.The energy gap values for all compounds ranged at the same values where the compounds may have had the potential for optical and electronic properties.The different substituent groups attached to benzene ring did not affect the energy of the compounds but they did affect the values of the dipole moment, where compound III had the smallest values of dipole moments from both basis sets.

Fig. 1
Fig. 1 The molecular structure of Compounds I, II and III obtained from Single Crystal X-Ray Analysis; [(a),(c),(e) structure at basis set of B3LYP/6-31G +( 2d,p) and [ optimized structure at basis set of B3LYP/6

a
The atoms numbering are referred to the X-ray molecular diagram b The isotropic chemical shift with respect to Tetramethysilane (TMS) in B3LYP 6 NMR.bThe isotropic chemical shift with respect to Tetramethysilane (TMS) in B3LYP 6 NMR.

Fig. 3
Fig. 3 The atomic orbital composition of the frontier molecular orbital of Compounds I, II and III World Academy of Science, Engineering and Technology International Journal of Chemical and Molecular Engineering Vol:7, No:10, 2013 777 International Scholarly and Scientific Research & Innovation 7(10) 2013 ISNI:0000000091950263 Open Science Index, Chemical and Molecular Engineering Vol:7, No:10, 2013 publications.waset.org/17218/pdf The atoms numbering are referred to the X-ray molecular diagram in Fig.1. a World Academy of Science, Engineering and Technology International Journal of Chemical and Molecular Engineering Vol:7, No:10, 2013 779 International Scholarly and Scientific Research & Innovation 7(10) 2013 ISNI:0000000091950263 Open Science Index, Chemical and Molecular Engineering Vol:7, No:10, 2013 publications.waset.org/17218/pdf a vibrational assignment of ν, stretching; ρ, rocking.