Synthesis, spectroscopic, SC-XRD characterizations and DFT based studies of ethyl2-(substituted-(2-benzylidenehydrazinyl))thiazole-4-carboxylate derivatives

Article abstract of DOI:10.1016/j.molstruc.2019.03.075

In the present study, ethyl-2-(2-(2-methylbenzylidene)hydrazinyl)thiazole-4-carboxylate (1) and ethyl-2-(2-(4-bromobenzylidene)hydrazinyl)thiazole-4-carboxylate (2) were synthesized. The characterization of synthesized compounds was accomplished by employ

Full text of DOI:10.1016/j.molstruc.2019.03.075

Accepted Manuscript
Synthesis, spectroscopic, SC-XRD characterizations and DFT based studies of
ethyl2-(substituted-(2-benzylidenehydrazinyl))thiazole-4-carboxylate derivatives
Muhammad Haroon, Muhammad Khalid, Tashfeen Akhtar, Muhammad Nawaz Tahir,
Muhammad Usman Khan, Muhammad Saleem, Rifat Jawaria
PII:
S0022-2860(19)30354-0
DOI:
https://doi.org/10.1016/j.molstruc.2019.03.075
MOLSTR 26344
Reference:
To appear in: Journal of Molecular Structure
Received Date: 2 January 2019
Revised Date: 10 March 2019
Accepted Date: 22 March 2019
Please cite this article as: M. Haroon, M. Khalid, T. Akhtar, M.N. Tahir, M.U. Khan, M. Saleem, R.
Jawaria, Synthesis, spectroscopic, SC-XRD characterizations and DFT based studies of ethyl2-
(substituted-(2-benzylidenehydrazinyl))thiazole-4-carboxylate derivatives, Journal of Molecular Structure
(2019), doi: https://doi.org/10.1016/j.molstruc.2019.03.075.
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ACCEPTED MANUSCRIPT
Synthesis, spectroscopic, SC-XRD characterizations and DFT based studies of
ethyl2-(substituted-(2-benzylidenehydrazinyl))thiazole-4-carboxylate derivatives
Muhammad Haroon,1 Muhammad Khalid,*2 Tashfeen Akhtar,*1 Muhammad Nawaz Tahir,3
Muhammad Usman Khan,4 Muhammad Saleem,5 Rifat Jawaria,2
1Department of Chemistry, Mirpur university of Science and Technology (MUST), Mirpur-1250
(AJK), Pakistan
2Department of Chemistry, Khwaja Fareed University of Engineering & Information
Technology, Rahim Yar Khan-64200, Pakistan
3Department of Physics, University of Sargodha, Sargodha-40100, Pakistan
4Department of Applied Chemistry, Government College University, Faisalabad-38000, Pakistan
5Department of Physics, Khwaja Fareed University of Engineering & Information Technology,
Rahim Yar Khan-64200, Pakistan
Corresponding authors E-mail addresses:
(Muhammad Khalid) khalid@iq.usp.br ; muhammad.khalid@kfueit.edu.pk
(Tashfeen Akhtar) Tashfeenchem@must.edu.pk
Abstract
In the present study, ethyl-2-(2-(2-methylbenzylidene)hydrazinyl)thiazole-4-carboxylate (1) and
ethyl-2-(2-(4-bromobenzylidene)hydrazinyl)thiazole-4-carboxylate (2) were synthesized. The
characterization of synthesized compounds was accomplished by employing analytical
1
13
techniques of spectroscopy as H-NMR, C-NMR, FT-IR, UV-Vis and final confirmation was
furnished using single crystal X-ray diffraction (SC-XRD) technique. The informations
regarding optimized geometry, nonlinear optical (NLO) properties and frontier molecular
orbitals (FMOs) were obtained by applying B3LYP level of DFT and 6-311+G(d,p) basis set. As
a whole, the computed results from DFT were found in close agreement to that of experimental
results. The combination of B3LYP level of time dependent DFT (TDDFT) and 6-311+G (d,p)
basis set were employed for computational calculations of vertical electronic transition states.
The stability on account of hyperconjugation and charge delocalization factors was evaluated
through the study of natural bond orbitals (NBO). The capabilities of the title compounds with

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respect to charge transfer and involvement of various sites in chemical activities were evaluated
quantitatively by employing the analysis involving frontier molecular orbitals (FMOs). The studies
revealed that the compounds possess sizable NLO character as the NLO properties of urea
molecule were found smaller as compared to the compounds under investigation which means that
such compounds are significant in perspective of technology applications.
Keywords: Thiazoles; SC-XRD; NBO; FMO; NLO properties
Introduction
The synthesis of functional molecules with applications in various fields by employing cheaper
raw materials and better synthetic strategies is frequently attempted by researchers. Usually, low
cost, simple and environmentally benign methods are employed for 1,3-thiazoles [1]. As far as,
the significance in the field of natural product and medicinal chemistry is concerned, 1,3-
thiazoles are very important nitrogen and sulphur containing five membered analogues. The
features responsible for many applications in these scaffolds, are C-N and C-S bonds [2-4].The
fascinating structural scaffolds of thiazoles can be achieved by either from natural sources or
synthesis. A variety of methods have been reported in literature for synthesizing 1,3-thiazoles [5,
6]. Primary thioamides or ureas and carbonyl compounds in one step pathway lead to the
formation of 1,3-thiazoles via famous Hantzsch’s synthesis.
In general, thiazoles with formula C3H3NS show a pale yellow color and are easily recognized by
their pyridine type odour. The chemical shift value of thiazole nucleus around 7.27 to 8.77 in 1H-
NMR clearly reflect the aromatic nature, pi electron delocalization and as well as strong
diamagnetic ring current associated with thiazole nucleus [7]. The alkylation at nitrogen atom of
thiazole nucleus leads to the formation of thiazolium salts and thiazolium cations thus obtained
serve as effective catalysts in setter reaction and benzoin condensation. The free carbene and
transition metal based complexes can be easily prepared by employing thiazoles [8]. Dyes are
also prepared by employing thiazoles, especially isthiazole orange, containing thiazole moiety in
the form of benzothiazole which have the binding capability with nucleic acids and other uses in
biosensors and imaging [9-11]. Thiazoles have also gained attention of material science due to its
applications in liquid crystals, sensors and molecular switches. As far as the pharmacological

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applications of 1,3-thiazoles are concerned, these scaffolds are antiviral [12], antifungal,
antibacterial [13], anticancer [14], antitubercular [15] and anti-inflammatory [16].
The low dielectric constant, very fast broad band electronic responses are very important
parameters for optoelectronic technologies and thiazole nucleus has the potential to be used in
optoelectronic technologies which is clearly evident by the extensive work of experimental and
theoretical communities on thiazoles for exploring its NLO potential [17-19]. The
pharmacological and NLO applications along with other applications attracted us [20-26] and,
we hereby report the synthesis of two novel thiazole compounds : ethyl-2-(2-(2-methylbenzyl-
idene)hydra-zinyl)thiazole-4-carboxylate (1) andethyl-2-(2-(4-bromobenzylidene)hydrazinyl)-
thiazole-4-carboxylate (2). The characterization of compounds (1) and (2) was accomplished
1
through H-NMR, 13C-NMR, FT-IR, UV-Vis spectroscopy, which was also authenticated by
employing single crystal X-ray diffraction (SC-XRD) technique. Nowadays, comparative studies
based on theoretical and experimental work is carried out through computational modeling which
gives a clear insight about the properties of materials. So, the synthesized compounds were
further studied through DFT and a clear perception regarding electronic properties such as
natural bond orbitals (NBOs), frontier molecular orbitals (FMOs), spectroscopic analysis as FT-
IR, UV-Vis, nonlinear optical (NLO) and molecular geometry properties was achieved. The
combination of theoretical studies along with experimental studies for 1 and 2 was used for clear
understanding of structural and spectroscopic data which is the major theme of current whole
work.
Experimental section
Chemicals and instrumentations
The solvents and substrates employed during this work were highly pure with analytical grade
and used as it is without prior purification. The pre-coated aluminum sheets (Merck) with silica
gel 60 HF254 were employed for monitoring and purification purpose through thin layer
chromatographic technique (TLC). Gallenkamp apparatus was employed for recording melting
points of synthesized compounds. FTIR spectrophotometer equipped with ATR, IR Affinity-1
MIRacle 10, SHIMADZU (Japan) was used to record infrared spectra. Bruker Avance 300 MHz
1
spectrometer was employed to record H and 13C NMR spectra. Bruker Kappa APEX II CCD

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diffractometer containing monochromator (graphite) with MoKα radiation (λ = 0.71073 Å) was
used to collect the X-ray diffraction data.
XRD studies
The data of diffraction collection was employed for the identification of crystals of title
compounds. in the conditions employed during data collection for the purpose of structural
refinement along with the parameters used are presented in Table S1. The data reduction and cell
refinements were carried out by SAINT programs and data collection was accomplished by
APEX 2. Moreover, SHELXS97 program was used for solving the structure of compound 1 and
SHELXL97 program was employed for structural refinements. The softwares like ORTEP-3,
PLATON, Mercury 3.6 were used for windows and molecular graphics respectively. CIF file is
submitted at Cambridge Crystallographic Data Centre (CCDC=1881529 and 1881530) for
supplementary crystallographic data.
Computational analysis
The entire work with respect to quantum chemical calculations was conducted by making use of
DFT [27-29] with the aid of Gaussian 09 program package [30]. XRD driven crystal structure
was used to approach the initial geometries of 1 and 2. B3LYP level of DFT and 6-311+G(d,p)
basis set were used for entire optimization of 1 and 2 in gas phase with no restriction in
symmetry. The frequency analysis was conducted at same DFT/B3LYP/6-311+G(d,p) functions
to confirm the stability associated with optimized geometries of molecules. The optimized
geometries were pointed out at real positive by the negative eigen values obtained during
frequency calculations associated with true minimum with respect to potential energy surface.
Gaussian 09 embedded NBO 3.1 program package was used for natural bond orbital (NBO)
analysis by applying the aforesaid level of DFT and basis set. Similarly, B3LYP/6-311+G(d,p)
level of DFT was also employed for FMO and NLO analysis. The time dependent density
function theory (TDDFT) at B3LYP level of DFT and 6-311+G(d,p) basis set were employed for
UV-Vis spectral analysis used in determining photophysical properties. Gauss View 5.0 was
used for organizing input files [31]. Furthermore, Gauss View programs, Avogadro [32] and
Chemcraft [33] were used for the interpretation of output results.

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Results and discussion
Synthesis
Ethyl bromopyruvate was treated with substituted-(1-benzylidenehydrazinyl)-2-carbothioamide
under refluxing conditions in absolute ethanol for 3 hours. TLC was employed to determine
completion of reaction. The solid compounds obtained on adding reaction mixture to ice cold
water, were separated by filtration after washing with excess water and dried [34].
Scheme 1. Synthesis of 1 and 2.
Ethyl-2-(2-(2-methylbenzylidene)hydrazinyl)thiazole-4-carboxylate (1)
Off white solid; IR (ATR, cm-1): 1087 (C-O stretching, ester), 1443 (C-H bending, aliphatic),
1577 (C=C ring stretching), 1724 (C=O stretching), 2939 (C-H stretching, aliphatic); 1H-NMR
(300 MHz, CDCl3): δ 1.29 (3H, t, -CH3 ester), 2.33 (3H, s, -CH3, Ar), 4.24 (2H, q, -CH2 – CH3),
7.39 (2H, m, Ar), 7.47 (1H, m, Ar), 7.79 (1H, s, thiazole C– 5), 7.90 (1H, m, Ar), 7.96 (1H, s, -N
– NH – C), 12.22 (1H, s, - CH=N). 13C-NMR (75 MHz, CDCl3): δ 14.61 (-CH3), 21.39 (2-CH3,
Ar), 60.92 (-O – CH2 -), 119.84 (thiazole C – 5), 126.71, 128.08, 130.40, 131.25, 133.77, 139.74
(Ar), 138.00 (-CH=N), 143.29 (thiazole C – 4), 161.41 (C=O), 168.29 (thiazole C – 2). Melting
point: 154-155oC; Yield: 87%.
Ethyl-2-(2-(4-bromobenzylidene)hydrazinyl)thiazole-4-carboxylate (2)
Light yellow solid. IR (ATR, cm-1): 1087 (C-O stretching, ester), 1442 (C-H bending, aliphatic),
1
1573 (C=C ring stretching), 1715 (C=O stretching), 2983 (C-H stretching, aliphatic); H-NMR
(300 MHz, CDCl3): δ 1.28 (3H, t, -CH3), 4.24 (2H, q, -CH2 – CH3), 7.61 (4H, m, Ar), 7.78 (1H,
s, thiazole C – 5), 7.97 (1H, s, - CH=N), 12.34 (1H, s, -N – NH – C). 13C-NMR (75 MHz,
CDCl3): δ 14.63 (-CH3), 60.88 (-OCH2-), 119.59 (thiazole C – 5), 123.01, 128.65, 132.29, 133.91
(Ar), 141.13 (-CH=N), 143.30 (thiazole C – 4), 161.43 (C=O), 168.45 (thiazole C – 2). Melting
point: 270-271oC; Yield: 90%.

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Structral Insight by XRD stduy
The parameters of data collection along with data refinements for crystals of 1 and 2 are very
precisely presented in Table S1.
In ethyl-2-[(2E)-2-(2-methylbenzylidene)hydrazinyl]-1,3-thiazole-4-carboxylate, the (1E)-(2-
methylbenzylidene)hydrazine moiety A (C1-C8/N1/N2), 1,3-thiazole ring B (C9-C11/N3/S1)
seem to be planar on account of r. m. s. deviation of 0.0213 and 0.0004 Å, respectively and a
little bit twisted i.e. around dihedral angle of 7.53 (23)°. The carboxylic group C (C12/O1/O2) is
definitely planar in the molecule. The dihedral angle is found 6.7 (8)° and 0.9 (9)° for A/C and
B/C respectively. As far as ethyl groups is concerned, C13 and C14 are found out of plane with
respect to C by 0.034 (16) and 1.440 (21) Å. The N-atom (N3) of thiazole ring and carbonyl O-
atom (O1) act as acceptor for NH group and CH of benzene ring (Table S2, Figure S2). The
cyclic rings also exhibit π−π interactions between one another at a distance of 3.3850(18) to
4.1369 (18) Å. The molecules get stability through these interactions.
In ethyl-2-[(2E)-2-(4-bromobenzylidene)hydrazinyl]-1,3-thiazole-4-carboxylate, the (1E)-(4-
bromobenzylidene)hydrazine moiety A (C1-C7/N1/N2/Br1), 1,3-thiazole ring B (C8-
C10/N3/S1) and ethyl carboxylate group C (C11/C12A/C13A/O1/O2) are planar with r. m. s.
deviation of 0.0303, 0.0072 and 0.0126 Å, respectively. It is found that 7.9 (5)°, 8.19 (1.09)° and
3.86 (1.20)°, is the dihedral angle for A/B, A/C and B/C respectively. The ethyl group attached
to carboxylate at two set of sites, is disordered, with occupancy ratio of 0.742(19):0.258(19). The
N-atom (N3) of thiazole ring and carbonyl O-atom (O1) act as acceptor for NH group and CH of
benzene ring (Table S2, Figure S4). There exists π…π interactions between the cyclic rings at a
distance of 3.316(4) to 3.765(4) Å. These interactions stabilize the molecules.
Molecular geometric parameters
The optimization of structural parameters with respect to compounds (1) and (2) was achieved by
performing full computational optimization. The structural parameters (bond angles and bond
lengths) were optimized by calculations through B3LYP level of DFT and 6-311+G(d, p) basis
set. For the comparison of optimized molecular structure with experimental molecular structure
of the title compounds, bond angles and bond lengths measured experimentally and those
theoretically calculated are shown in Tables S3 and S4 (supplementary information) respectively.

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The tabulated results illustrate that XRD based bond angles and bond lengths are in good
agreement with the corresponding DFT calculated structural parameters. The deviation in the
structural aspects like bond angles and bond lengths of compound 1 were noticed in the range of
5.2° ± 3.2° and 0.035 ± 0.014Å respectively. Similarly, in case of compound (2), divergence in
bond length was detected as 0.038 ± 0.034Å, while the deviation in bond angles was found as
5.1° ± 2.9° (Tables S3 and S4). C–C bond distance calculated on the basis of DFT in the benzene
ring was found in the range of 1.388-1.419Å in 1 and 1.387-1.405Å in 2 which matches quite
finely with the ranges calculated on the basis of XRD 1.353-1.400Å and 1.366-1.396Å
respectively. The values associated with bond length of carbonyl group C=O in 1 and 2 are
calculated as 1.206Å and 1.206Å for C(18)-O(2) and C(18)-O(3) by employing DFT and are in
well agreement to that of values based on XRD i.e. 1.202 Å and 1.216 Å respectively. C-S bond
lengths in 1 are calculated through DFT as 1.765Å and 1.739Å for C(15)-S(1) and C(16)-S(1)
that are coinciding with values measured by XRD i.e.1.752Å and 1.709Å. In case of compound2,
C-S bond lengths calculated on the basis of DFT is 1.764Å, 1.739Å whereas 1.746Å, 1.730Å by
means of XRD for C(15)-S(2) and C(16)-S(2) respectively. The highest value of deviation in
case of bond angle is observed for N(4)-N(5)-C(15) and N(5)-C(15)-N(6) in 1 as 120.8°, 123.0°
(DFT) and 116.6°, 126.2° (XRD) respectively. The bond angles were found to display deviation
in 2 for N(5)-N(6)-C(15) and C(8)-C(9)-C(10) with value of 120.9°, 120.8° through DFT and
115.8°, 123.7° through XRD respectively.
In summary, comparative analysis of the parameters associated with structure (bond length and
bond angles) was attained using DFT and XRD indicate that both structural parameters are in
good agreement with each other and can provide a starting point to calculate other properties.
Natural bond orbital (NBO) analysis
The important description of orbital hybridization, atomic charge and orbital interaction was
made by using NBO analysis [35]. The technique in itself is decent on account of inter and
intramolecular interactions due to the data obtained from interactions of virtual orbitals to that of
filled orbitals [36]. The enormous interactions among donor and acceptors lead to large
stabilization energy. NBO investigation is advantageous to transfer of electron density form
occupied electronic orbital to unoccupied orbitals [21]. The stabilization energy formula in
accordance with second order perturbation approach is represented by equation 1.

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(F )2
i, j
E(2) = q
(1)
i ε j
−εi
Where qi represents occupancy of donor orbital, ꢀ and ꢀꢂ are the off-diagonal NBO Fock matrix
ꢁ
elements, E(2) is stabilization energy and F(i.j) is the diagonal. The better level of interactions
between bonding and antibonding orbitals is quite clear from the extent of perturbation
stabilization energy [E(2)]. The studies based on NBO for 1 and 2 was conducted by employing
B3LYP/6-311+G(d,p) level of DFT and the outcomes with respect to some characteristic
interactions are presented in Table S5 and S6.
In general, four types of trasitions are found for the title compounds which are, σ→ σ*, π→π*,
LP→σ* and LP→π*. The most prominent transitions noticed for the investigated compounds are
from π→π*, while the transitions from LP→σ* and LP→π* are slightly dominant. On the other
hand, transitions from σ→ σ* are least dominant. The charge transfer among 1 and 2 can be
examined involving π→π* interactions which is a clear evidence for conjugation in 1 and 2. The
most credible electronic transitions seen for the compounds under study are: π(O2–C28)→
π*(C25–C27) in 1 with stabilization energy 44.26 kcal/mol, π(O3–C25)→π*(C22–C24) in 2 with
57.73 kcal/mol stabilization energy. Thus the observed stabilization energy values for the studied
compounds are highest ones among all stabilization energy values. The charge transfer due to
presence of electron withdrawing bromine atom and intramolecular interactions based on
hyperconjugation formed the basis for greater value of stabilization energy for 2 in comparison
to 1. Keen examination of charge transfer on account of π→π* interactions among investigated
compounds lead to the fact that title compounds exhibit conjugation. A few other transitions seen
in 1 reflecting the presence of conjugation are π(N4–C22)→π*(C12–C21), π(C12–C21)→ π*(N4–
C22), π(C12–C21)→π*(C17–C19), π(C13–C15)→π*(C12–C21) and π(C13–C15)→π*(C17–C19) with
values of stabilization energy found to be 13.39, 31.41, 21.84, 22.87 and 20.57 kcal/mol
respectively. In the same scenario, transitions such as π(N8–C21)→π*(C22–C24), π(C22–
C24)→π*(O3–C25), π(N8–C21)→π*(C22–C24), π(N40–C53)→π*(C54–C56) and π(C54–C56)→π*(O35–
C57) observed in 2 reflects conjugation involved in the stabilization energy values calculated to
be 17.16, 13.90, 21.33, 15.89 and 13.49 kcal/mol respectively.
The σ→σ* interactions originate from feeble donor (σ)-acceptor (σ*) interaction results in small
values of stabilization energy as compared to originated with π→π* transitions. The relatively
smaller stabilization energy 0.62 kcal/mol was observed for 1 due to σ(O3–C28)→σ*(O2–C28)

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transition. In a similar fashion, it was observed for 2 due to σ(C26–C29)→σ*(O4–C25) transitions
which leads to smaller stabilization energy value 2.18 kcal/mol. The observed values are the
lowest observed stabilization energy values for 1 and 2 respectively. These least energy values
are observed due to the presence of weak interactions between the electron donor-acceptor units.
In addition, some transitions such as LP(S1)→π*(N7-C4), and LP(O36)→π*(O35-C55) are seen in
case of resonance which forms the basis for substantial values of stabilization energy i.e.37.38
and 46.78 kcal/mol in 1 and 2 respectively. The presented discussion leads to the conclusion that
compounds under study are involved in the intramolecular charge transfer, hyperconjugative
interactions and extended conjugation which is the main reason for the stability of title
compounds.
Figure 1. HB trimeric structures (1) are constructed by the oxygen lone pair and the anti-bonding
orbital of the NH group interaction.

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Figure 2. HB trimeric structures (2) are constructed by the oxygen lone pair and the anti-bonding
orbital of the NH group interaction.
FT-IR analysis
The vibrational spectroscopy is taken as a tool by both theoretical and experimental communities
for exploring molecular vibrations involved. In a similar context, the nature of vibrational modes
for investigated compounds 1 and 2 were explored by applying DFT based analysis for IR
absorption spectroscopy with the help of B3LYP/6-311+G(d,p) level of DFT in gas phase. The
animation option of Gauss View software was employed for assigning vibrational modes. The
experimental absorption spectrum of 1 and 2 is displayed in Figures S7 and S8 while calculated
and experimental absorption frequencies for 1 and 2 are presented in Tables S7 and S8
(Supplementary information) respectively.
C–H vibrational bands
The experimentally observed vibrational bands for C-H were compared with those of obtained
through computational calculations and it was observed that vibrational bands at 1455, 3021 and
3155 cm-1 calculated for compound 1 were in good settlement to that of experimental vibrational
bands at 1443, 2962 and 3151 cm-1 respectively. Similarly, the vibrational bands for C-H bond
were computed at 1081 and 1595 cm-1 was supported strongly by the experimental data for C-H
bond at 1087 and 1573 cm-1 respectively.

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Moreover, C-H vibrational bands on account of stretching in heteroaromatic and aromatic rings
are appeared at 3100-3000 cm-1 [37]. The diversified weak to moderate bands for C-H vibrations
were attributed to aromatic heterocycles and their derivatives which were found closer to that of
aromatic rings. The band remains unaffected by the nature of substituents in this particular IR
region. Pure symmetric vibrational bands with absorption frequencies 3191 cm-1 and 3206 cm-1
are observed in 1 and 2 respectively. The computation of absolute asymmetric stretching
vibrations resulted in absorption at 3155, 3161 and 3269 cm-1 for 1. The results for computations
of the same for 2 showed absorption at 3166 and 3192 cm-1. The absorption frequencies for
mixed symmetric and asymmetric vibrations were noticed at 3176 cm-1 for 1 and 3202 cm-1 for 2
respectively (see Tables S7 and S8 (Supplementary information)).
C-C stretching vibrational bands
The absorption frequencies in the range of 1650-1400 cm−1 are usually assigned to C=C
stretching [38]. The calculated results for compound 1 reflected the absorption on account of C-
C vibrational mode at 1455, 1496, 1518, 1641 cm-1 in 1 and 1426, 1470, 1527, 1617, 1661 cm-1
in 2 respectively. The computed absorption bands at 1455 cm-1 and 1595 cm-1 clearly matching
to that of experimental data for absorption bands found at 1443 cm-1 and 1573 cm-1 in 1 and 2
respectively (Tables S7 and S8).
Methyl group vibrational bands
The generally observed range for the absorption band of C-H stretching associated with C-H
bond of methyl group is found at 3000-2800 cm-1in IR spectrum [39]. In our investigations for 1
and 2, absorption bands observed at 3034 cm-1 in 1 and 3035, 3051 cm-1 in 2 were considered
due to pure symmetric stretching vibrations respectively. The asymmetric stretching vibrations of
methyl group were computed with absorption bands at 3087, 3096, 3129 cm-1 in 1 and at 3085,
3113 cm-1 in 2 respectively. Mixed symmetric and asymmetric mode of methyl group C-H
vibrations were noticed with frequencies found at 3069, 3107, 3108 cm-1 in 1 and at 3102 cm-1 in
2 respectively. Furthermore, experimentally observed vibrational bands for methyl group C-H
3116 cm-1 in 1 and 1442, 2983 cm-1 in 2 are in good agreement with DFT computed vibrational
bands at 3108 cm-1 in 1 and 1427, 3035 cm-1 in 2 respectively (Tables S7 and S8).

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C–N vibrational bands
The peaks representing C-N vibrational bands were appeared at wave numbers 758, 945 and
1641cm-1 in compound (1). On the other hand in compound (2), bands observed at 693, 968,
1617 and 1661cm-1 were assigned to the C-N vibrations (Tables S7 and S8).
UV-Visible analysis
The charge transfer, vertical excitation and the absorption properties of 1 and 2 can be easily
explained by UV-Visible spectral analysis. So, TDDFT studies at B3LYP level along with 6-
311+G(d,p) basis set were conducted in gas phase to serve the purpose. Consequently, various
calculated parameters on the basis of TDDFT like wavelengths of maximum absorption (λmax),
oscillator strength (f), excitation energy (EDFT), and the orbitals mainly involved for excitations
in 1 and 2 are listed in Table 1.
Table 1: Wave length, excitation energy and oscillator strength for 1 and 2.
Compounds
ꢃ
Exp (nm)
ꢃ
DFT (nm)
413
300
712
502
318
ꢄꢅꢆꢇ (eV)
2.9961
4.1258
1.7391
2.4688
3.8933
f
MO contributions
L(95%), H-1 L(3%)
L+1(66%), H-2→L(4%)
0.4295
0.0748
0.0017
0.1763
H
H
H
H
→
→
→
→
→
→
336a
712b
L(99%), H
L (99%)
L(99%)
1
0.0264 H-3
→
→
→
L(21%), H
L(4%)
L(10%), H-3
→
L+2(68%), H-6 L(3%),
→
H-4
286
587
821
321
4.3373
2.1108
1.5099
3.8675
0.2991 H-6
0.0681
0.001
→
L(28%),H-1→L(11%)
504a
702b
H
→
L(98%)
L(98%)
L(2%), H-1
→L+3(5%)
H→
0.4007 H-5
→
→L(79%) H→L+1(5%),
H
0.1841 H-5
H-2
0.0422 H-6
0.0094 H-5
313
3.9650
→
→
→
→
L(23%), H-4
→
L(4%),H-3
→
L( 3%)
→
L(10%),
2
L(48%), H-1
→
L(4%), H
L+1(22%), H
L(5%),H-3
→
299
295
4.1452
4.1961
L(16%), H
L(34%), H-4
L+1(24%), H→L+2(5%),
→
L+2(57%)
→
→L(17%),H-
2
→
L(6%),H
→
H
→L+3(3)
ꢈ
Exp= experimental wavelengths; ꢈDFT= calculated wavelengths; E = Excitation energy (eV); ꢈ=wave length (nm);
f = oscillator strength; MO = molecular orbitals; H = HOMO, L = LUMO; ꢈ (nm); a= THF and b=DMF
Table 1 is equipped with the findings of experimental data of wavelengths (ꢈExp), calculated data
of wavelength (ꢈDFT), oscillator strength (f) and percentage of contribution associated with
molecular orbitals in transitions. The values of computed absorption maxima (ꢈDFT) are found to
be 300 and 712 nm with percentage of molecular orbital contribution [H→L(99%)] for

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compound (1) (Table 1). The DFT based absorption maxima (ꢈDFT) values are found to be 587
and 821 nm with percentage of molecular orbital contribution [H→L(98%)] for compound (2).
The wavelength value of 2 is greater than 1 due to electron withdrawing bromo group in 2 which
leads to a red shift in the absorption band. Alternatively, we can say that 2 is red shifted in
comparison with 1. Furthermore, calculated wavelengths (ꢈDFT) 300 and 712 nm for 1 matched
nicely with the experimental (ꢈExp) value 336 (THF) and 712 nm (DMF) respectively. Similarly,
in 2, aforesaid calculated wavelengths (ꢈDFT) are adequately connected to their experimental
(ꢈExp) value 504 and 702 nm. The solvent effect is responsible for the minor difference between
ꢈ
Exp and ꢈDFT value. The calculation of λDFT values was conducted in gas phase for 1 and 2 while
ꢈExp were obtained in THF and DMF solvents. Moreover, the wavelength values in DMF are
obtained greater than THF due to high polarity effect which leads to the red shift in UV-Vis
absorption band.
Frontier Molecular Orbital (FMO) analysis
The calculations based on DFT using B3LYP level along with 6-311+G(d,p) were conducted for
computing the energy associated with HOMO and LUMO of 1 and 2. FMO theory can be
employed to study optoelectronic properties of any molecule, its reactivity and the aptitude to
absorbed light [40, 41].
Table 2: Molecular frontier orbital energies for 1 and 2
1
2
MO(s)
HOMO
LUMO
HOMO-1
LUMO+1
HOMO-2
LUMO+2
E (eV)
-5.864
-1.882
-7.061
-1.424
-7.252
-0.643
∆E (eV)
E (eV)
HOMO
LUMO
HOMO-1
LUMO+1
HOMO-2
LUMO+2
∆E (eV)
-5.989
-2.170
-7.149
-1.338
-7.688
-1.071
E (eV)
3.982
3.819
5.637
6.609
5.811
6.617
E= energy, ∆E(eV) = ELUMO-EHOMO; HOMO, highest occupied molecular orbital; LUMO, lowest unoccupied
molecular orbital, MO, molecular orbital
The coplanar structures for 1 and 2 are quite clear, which also encouraged the intramolecular
charge transfer (ICT). The diagrams of FMO are presented in Figure 3, which shows the
electronic distribution in HOMO-2, HOMO-1 and HOMO with LUMO, LUMO+1 and
LUMO+2 for 1 and 2. The FMO phenomenon suggests that the ICT character of the HOMO to
LUMO transition exist. The delocalization of HOMO on all the atoms of a molecule except

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carbonyl and OMe groups while concentration of LUMO at all the atoms except OMe and
carbonyl group for 1 can be easily observed from Figure 3. It is well known that HOMO orbitals
represent bonding character, while LUMO reflects anti-bonding character. In addition to that,
HOMO-LUMO gap (Egap) along with calculated energy levels associated to 1 and 2 are
summarized in Table 2. As Table 2 indicates that the Egap value in respect of 1 and 2 are 3.982
eV and 3.819 eV respectively. The data obtained from theoretical calculations clearly indicates
that substituents with different electron donor/acceptor capacity affects the electronic properties
and substituents can effectively tune the optical properties of compounds. The obtained values
indicate that the title molecule 1 has greater Egap than 2. Consequently, the lower Egap illustrates
that the 2 possesses strong capability for electron transfer and better NLO properties.
Compound 1
Compound 2
Figure 3. Frontier molecular orbitals of 1 and 2. H= HOMO and L=LUMO

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EHOMO, ELUMO and energy gaps (∆E) associated to them are effectively employed to predict
global reactivity descriptors [42-45] which assist in a clear description of the chemical reactivity,
internal charge transfer, and stability of 1and 2. The equations employed for calculation of global
reactivity descriptors are given in supplementary information and results are presented in Table
3.
Table 3: Global softness (
σ), global electrophilicity (ω), global hardness (η), chemical potential (ꢀ),
electron affinity (A), ionization potential (I) and electronegativity (
χ)
I
A
ꢀ
σ
η
ω
χ
1
2
5.864
5.989
1.882
2.170
3.873
4.079
1.991
1.909
-3.873
-4.079
3.7669
4.3577
0.2513
0.2618
An inverse relation is found between energy gaps, softness as well as reactivity of species.
Moreover, it has direct relation to the hardness and stability of the molecule. Consequently, the
molecules with larger energy gaps are considered bit harder molecules which resist any change
in electronic configuration and clearly links low reactivity with more kinetic stability. On the
other side, the molecules with low energy gaps are soft molecules having tunable character, high
reactivity and least kinetic stability. The 1 and 2 showed higher ionization potential values as
compared to that of electron affinity values as presented in Table 3. The values of electron
affinity and ionization potential for 2 are greater than 1. The observed values of chemical
hardness for 1 and 2 are higher than their softness. The greater chemical hardness, thus, indicates
less reactivity or more stability of compounds 1 and 2. However, the values of chemical hardness
are higher for compound 1 as compared with compound 2 which definitely reflects more stability
of 1 than 2 (see Table 3). The stability and reactivity of compounds can also be connected with
another parameter i.e. chemical potential of the compound. There is a direct relation between the
chemical potential of the compound and stability whereas it is inversely related to reactivity. The
order of chemical potential for 1 and 2 are as under:
[2 (ꢀ = -4.079 eV)] < [1 (ꢀ = -3.873 eV)].
The result with respect to stability and reactivity of compounds 1 and 2 on the basis of chemical
potential is almost similar to that of the result obtained from chemical hardness data i.e.
compound 1 is more stable and less reactive than 2.. However, both the molecules are quite
stable overall as reflected by their chemical hardness.

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Nonlinear optical (NLO) properties
The structural diversity of organic compounds enables them to serve as the potential candidates
in the fields of electronics, photonics and nonlinear optics (NLO) [46, 47]. The asymmetric
polarization is the basis for establishing NLO response for the sketch of dynamic organic
compounds. The response is actually depending on the electron donating or withdrawing groups
in the compounds at suitable locations. The electron withdrawing or donating groups enhance
NLO response as this type of response is connected with conjugated system of π framework [48-
53]. B3LYP level of DFT and 6-311G (d, p) basis set was employed for observing the NLO
parameters for the compounds under study.
The resulting energy (E) by applying finite field (FF) method, where species are introduced to a
static field (F), is represented by equation 2.
1
1
(2)
ꢉ = ꢉꢊ − ꢋꢂꢌ − ꢍꢂꢁꢌ ꢌ ꢌꢎ − ꢏꢂꢁꢎꢐꢌ ꢌ ꢌꢎꢌ
ꢐ
ꢂ
ꢂ ꢁ
ꢂ ꢁ
2
24
Where E0 represents molecular energy without electronic field.
〈 〉
〈 〉
ꢍ , ꢑꢒꢓꢒ and ꢏ represent polarizability, especially first and second hyperpolarizability tensors
along x, y and z directions and calculations for such tensors are conducted by using equations 3-
5 respectively.
(3)
<
α >=1/ 3(α xx +α yy +α zz )
Keeping in view x, y and z-direction tensors, calculations for first hyperpolarizability (βtot) and
〈 〉
second hyperpolarizability ꢏ are conducting with the help of equations 4 and 5.
(4)
(5)
βtot =[(βxxx
+
βxyy
+
βxzz )2 +(βyyy
+ βxxy + + βxxz +
βyzz )2 +(βzzz βyyz )2 ]1/2
1
〈ϒ〉 =
ϒ
xxxx + ϒyyyy + ϒzzzz + 2[ϒxxyy + ϒyyzz + ϒxxzz ]
(
)
5
The first order polarizability along x, y and z directions are found to be 248.508, 201.201, 318.97
a.u. respectively which results in αtotal value of 256.22 a.u. for . Similarly in 2, the calculated
vales of αxx, αyy, αzz and αtotal are found to be 316.722, 191.790, 340.979 and 283.163 (a.u)
respectively. In the case of , the total first order polarizability (α total) is found larger than .The
1
2
1
findings of the second order polarizability (βtot) values along with their major contributing
tensors such as βxxx, βxxy, βxyy, βyyy, βxxz, βyyz, βxzz, βyzz, and βzzz are found to be 2440.449, 302.767, -
80.957, 22.434, 80.334, 576.98, 15.474, 908.445, -306.713 and 1490.682 (a.u) respectively for 1.
Moreover, the results of βtot values along wither their major contributing tensor for compound
2

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such as βxxx, βxxy, βxyy, βyyy, βxxz, βyyz, βxzz, βyzz, and βzzz are found to be -1172.908, 224.481, 11.220,
-114.356, 1262.172, -69.228, -1399.872, 349.922, 1531.748 and 2771.66 (a.u) respectively. The
findings of the second order polarizability (βtot) values for 2 reflect that it is higher in magnitude
than 1, and the same may be due to electron withdrawing effect. The standard molecule
repeatedly used in literature for comparing dipole moment and first hyperpolarizability data is
urea. Compounds 1 and 2 exhibit larger values of dipole moment as compared to urea (1.3732 D)
[54]. Similarly, βtot values of 1 and 2 are found greater than the urea molecule (βtot (urea) = 43
a.u) [54].
Conclusion
In current study, two compounds with chemical formula of C14H15N3O2S and C13H12BrN3O2S
were synthesized and their crystal structures were characterized by both experimental and
computational methods. A number of experimental techniques were performed for the prepared
1
compounds including H-NMR, 13C-NMR, FT-IR, UV-Vis and SC-XRD. X-rays analysis
revealed that the both structures crystallize in the Orthorhombic space group P212121, with cell
parameters a = 4.7024 (8), b=10.519 (2), c=28.922 (7) Å, for 1 and a=5.1687 (17), b=10.829 (6),
c=26.472 (9) for 2. Spectroscopic investigation (H-NMR, FT-IR) were according to the proposed
structure. Moreover, DFT based FT-IR spectra and UV-Vis absorption was in excellent
agreement with the experimental spectroscopic data. Natural bond orbital (NBO) study showed
that both compounds are involved in the intra molecular charge transfer, hence greater molecular
stability on account of hyperconjugation. Charge transfer properties and chemical activities at
different sites of the title compounds were quantitatively determined by performing frontier
molecular orbital (FMO) analysis. The energy associated to FMOs was employed as a parameter
towards calculation of global reactivity descriptors which in turn indicated the kinetic stability
and electron donating ability of synthesized compounds. Nonlinear optical (NLO) properties were
observed larger as compared to the urea molecule indicating the considerable NLO character and
may have significant contribution for technological applications.
Acknowledgments
Authors are thankful to Departamento de Química Fundamental, Instituto de Quimica,
Universidade de São Paulo, Av. Prof. LineuPrestes, 748, São Paulo, 05508-000, Brazil for
providing theoretical lab facilities for DFT study.

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Highlights
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Two novel ethyl-2-(substituted-(2-benzylidenehydrazinyl))thiazole-4-carboxylate crystals
were synthesized.
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XRD, 1H-NMR, 13C-NMR, FT-IR and UV-Vis were performed for the characterization.
Computational study was done at B3LYP/6-311+G(d,p) level for comparative analysis.
Comparative study reveals a good agreement between experimental and DFT results.
FMOs, NBO analysis and nonlinear optical (NLO) properties were calculated.