Synthesis, X-ray crystallographic, spectroscopic and computational studies of aminothiazole derivatives

Article abstract of DOI:10.1016/j.molstruc.2016.11.046

Aminothiazole organic compounds have diverse biological applications. Herein we report the synthesis of two aminothiazole derivatives: 4-(biphenyl-4-yl)thiazol-2-amine (1) and 4-(2′,4′-difluorobiphenyl-4-yl)thiazol-2-amine (2) via Suzuki-Miyaura cross cou

Full text of DOI:10.1016/j.molstruc.2016.11.046

Journal of Molecular Structure 1131 (2017) 136e148
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis, X-ray crystallographic, spectroscopic and computational
studies of aminothiazole derivatives
Muhammad Adeel a, Ataualpa A.C. Braga b, Muhammad Nawaz Tahir c, Fazal Haq a,
,
, f
Muhammad Khalid d *, Mohammad A. Halim e
a Department of Chemistry, Gomal University, Dera Ismail Khan, Khyber Pakhtun Khwa, Pakistan
b
~
~
Departamento de Química Fundamental, Instituto de Química, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 748, Sao Paulo, 05508-000, Brazil
c University of Sargodha, Department of Physics, Sargodha, 40100, Punjab, Pakistan
d Department of Chemistry, University of Education Lahore, Faisalabad Campus, Pakistan
e Division of Quantum Chemistry, BICCB, Green Research Centre, 38 Green Road West, Dhaka, 1205, Bangladesh
f
ꢀ
ꢀ
ꢁ
ꢁ
Institut Lumiere Matiere, Universite Lyon 1eCNRS, Universite de Lyon, 69622, Villeurbanne Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Aminothiazole organic compounds have diverse biological applications. Herein we report the synthesis
of two aminothiazole derivatives: 4-(biphenyl-4-yl)thiazol-2-amine (1) and 4-(20,40-difluorobiphenyl-4-
yl)thiazol-2-amine (2) via Suzuki-Miyaura cross coupling reaction. The chemical structures of 1 and 2 are
confirmed using 1HNMR, 13CNMR, FT-IR, UVeVis and single crystal x-ray studies. The XRD study reveals
that the both solid state structures (1) and (2) are diffused to form poly chain structures due to presence
of intra molecular hydrogen bonding (H.B). Furthermore, these compounds were analysed by density
functional theory (DFT) at M06-2X/6-311G(d,p), B3LYP/6-31G(d) B3LYP/6-31G(d,p) and B3LYP/6-
311G(2d,p) level of theories to obtain optimized geometry, electronic and spectroscopic properties.
DFT optimized geometry supports the experimental XRD parameters. Natural bond orbital (NBO)
calculation predicted the hyper conjugative interaction and hydrogen bonding in all derivatives. The FT-
IR and thermodynamic studies also confirm the presence of hydrogen bonding network in the dimers
which agrees well with the XRD results. Moreover, UVeVis analysis reveals that maximum excitations
take place in 1 and 2 due to HOMO / LUMO(98%) and HOMO / LUMO(97%) respectively which show
good agreement to experimental data. The first order hyperpolarizability of both molecules is remarkably
greater than the value of urea. The global reactivity parameters which are obtained by frontier molecular
orbitals disclose that the molecules might be bioactive.
Received 15 July 2016
Received in revised form
14 November 2016
Accepted 14 November 2016
Available online 15 November 2016
Keywords:
Aminothiazole
Single crystal
Density functional theory
IR and Raman spectroscopy
Hydrogen bonding
Non-linear optical material
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
allergic [8], anti-hypertensive [9], schizophrenia [10], anti-
bacterial, HIV infections [5,11] and human lymphatic filarial para-
The thiazole ring consists of both sulphur and nitrogen are
available in different and diverse molecules and they have exten-
sive applications in agriculture and medicinal chemistry [1,2].
Thiazole heterocycles containing amine moiety have found appli-
cations in material science and these are used as building blocks in
organic synthesis [3]. Varieties of biologically active molecules
accommodate this interesting scaffold, aminothiazoles [4]. Ami-
nothiazoles are used as important fragments in different drugs
related to anti-tuberculosis,5 anti-inflammatory [5,6,7] anti-
sites [12].Aminothiazoles are known ligands of estrogen and
adenosine receptors antagonists [13]. Various aminothiazole de-
rivatives are used as fungicides and herbicides and have numerous
applications in agricultural field [14].
Alkyllated and arylated aminoacetyl derivatives of 2-amino-4-
phenylthiazolyl [15], 2-aminobenzothiazolyl [16], substituted 2-
amino-benzothiazolyl [17], 2-phenylamino-4-phenylthiazolyl [18],
2-amino-4-methylthiazolyl [19], as well as 3-aminobenzo[d]iso-
thiazole derivatives [20] are found to have a potent local anaes-
thetic, anti-inflammatory, analgesic, and antipyretic activities [21].
Similarly, sulfonamides of aminothiazolesare used to treat bacterial
infections, inflammations, tumours [22] and play a vital role in
insulin release [23].
* Corresponding author.
E-mail address: khalid@iq.usp.br (M. Khalid).
http://dx.doi.org/10.1016/j.molstruc.2016.11.046
0022-2860/© 2016 Elsevier B.V. All rights reserved.

M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
137
Although various aminothiazoles derivatives related to the
substitution pattern and 4-(biphenyl-4-yl)thiazol-2-amine were
synthesized and reported elsewhere [15e21]. However, according
to the best of our knowledge, no studies regarding the title ami-
nothiazole derivatives have been reported via Suzuki-Miyaura
cross-coupling reaction. Herein, we report the synthesis of 4-
(biphenyl-4-yl)thiazol-2-amine and 4-(2',4'-difluorobiphenyl-4-yl)
thiazol-2-amine employing Suzuki-Miyaura cross-coupling reac-
tion (Scheme 1). The structures of synthesized compounds (1) and
(2) were determined experimentally using 1HNMR, 13C NMR, and
single crystal x-ray studies. Moreover, both compounds were
studied by density functional theory (DFT) [24,25]. DFT is broadly
used to determine the molecular geometry, electronic properties
including frontier molecular orbitals (FMOs), natural bond orbital
(NBO), non-linear optics (NLO), and molecular electrostatic po-
tential (MEP) and spectroscopic analysis such as FT-IR, FT-Raman,
UVeVis, and non-linear optics of organic molecules [26e29].
The main focus of the current study is to provide a detail
structural and spectroscopic insight of the 4-(biphenyl-4-yl)thia-
zol-2-amine and 4-(2',4'-difluorobiphenyl-4-yl) thiazol-2-amine
with the aid of experimental and theoretical techniques.
isotropic thermal parameters, and allowed to ride on their
respective parent carbon atoms before the final cycle of full-matrix
least-squares refinement including 169 and 175 variable parame-
ters for 1 and 2 respectively. Supplementary crystallographic data
are deposited as CIF files at Cambridge Crystallographic Data Centre
(CCDC ¼ 1483070 for 1 and 1483071 for 2).
2.3. Computational procedures
Theoretical studies were executed with Gaussian 09program
package [30] employing density functional theory (DFT)
[31e35].The initial geometry for the both derivatives (1) and (2)
was retrieved from the single crystal structures. Full optimization of
1 and 2 was carried out by B3LYP/6-31G(d), B3LYP/6-311 þ G(2d, p)
and M06-2X/311G (d, p) level of theories. All frequencies of the two
compounds are found real (positive) ensuring the optimized ge-
ometries corresponding to the true minimum in the potential en-
ergy surface. NBO, FMOs and MEP analysis of the thiazol derivatives
were calculated at M06-2X/6-311G(d,p) level of theory. The FT-IR,
FT-Raman, NLO properties and thermodynamic parameters were
examined at B3LYP/6-311G(d,p) level of theory. An empirical
scaling factor of 0.9627 [36] was used to counterpoise the sys-
tematic defects due to basis set deficiency, inconsideration of
electron correlation and vibrational anharmonicity. Photophysical
properties of these compounds were calculated by time dependent
density functional theory (TD-DFT) at B3LYP/6-311G(d,p) level. The
input files were organized utilizing Gauss View 5.0. [37] The Avo-
gadro [38], Chemcraft [39] and Gauss View 5.0 programs were used
to analyze the output files.
2. Experimental and calculation section
2.1. Reagents and instruments
All reagents were obtained from Acros Organics and in analyt-
ically pure grade. NMR spectra were recorded using a Bruker-
Advance spectrometer operating at 400 MHz for 1HNMR and
100 MHz for 13C NMR with tetramethylsilane as the internal stan-
dard. Chemical shifts are given in ppm (
d
-scale). The experimental
3. Results and discussion
FT-IR spectra of both compounds were performed by Perkin Elmer
spectrum version 10.4.3. Melting points were measured on a digital
melting point apparatus, Stuart, SMP10, U.K. and uncorrected.
3.1. Synthesis of 4-(biphenyl-4-yl)-1,3-thiazol-2-amine (1)
In a screw capped reaction tube, 4-phenyl-1,3-thiazol-2-amine
(100 mg, 0.48 mmol), Pd(PPh3)4 (8 mg, 1.5 mol%), phenyl boronic
acid (136 mg, 0.531 mmol) and K3PO4 (153 mg, 0.724 mmol) were
added to 3 mL of dioxane solvent. The resulting reaction mixture
was flushed with dry nitrogen gas for few minutes. The reaction
mixture was heated at 90e100 ꢀC for 8 h. After the completion of
the reaction, 20 mL of water was added. After cooling at room
temperature, organic and the aqueous layers were separated and
the latter was extracted with ethyl acetate three times (3 ꢁ 15 mL).
The obtained residue was then purified through column chroma-
tography and compound (1) was isolated as dark yellow crystalline
solid (95 mg, 85%).
2.2. XRD studies
X-ray diffraction data was collected at room temperature by
using Bruker Kappa APEX II CCD diffractometer with a graphite
monochromator MoK
a
radiation (
l
¼ 0.71073 Å). This X-ray
diffraction data was used to determine structures of compounds (1)
and (2). All crystallographic parameters, structure refinement and
conditions for data collections are given in Table 1. Several different
programs like APEX 2 used for data collection, SAINT for cell
refinement and SAINT was used for data reduction. SHELXS97 pro-
gram was used to solve structures. SHELXL97 program was used to
refine structures. For molecular graphics ORTEP-3 for Windows,
PLATON and Mercury 3.6 software were used. All the H atoms were
positioned geometrically (CeH ¼ 0.93 A) and refined as riding with
iso(H) ¼ xUeq(C), where x ¼ 1.2 for aryl H atoms. All non-hydrogen
atoms were refined anisotropically. The positions of all hydrogen
atoms were generated geometrically (Csp2-H ¼ 0.93 Å), assigned
3.2. Synthesis of 4-(2,4-difluorobiphenyl-4-yl)-1,3-thiazol-2-amine
(2)
In a screw capped reaction tube 4-phenyl-1,3-thiazol-2-amine
(100 mg, 0.48 mmol), 4-phenyl-1,3-thiazol-2-amine, Pd(PPh3)4
Scheme 1. (i)Pd(PPh3)4, dioxane, K3PO4, 90e100 ꢀC, H2O.

138
M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
Table 1
Single crystal XRD data of 1 and 2.
Crystal data
Compound (1)
Compound (2)
CCDC
1483070
1483071
Chemical formula
C15H12N2S
C15H10F2N2S
Mr
252.33
288.31
Crystal system, space group
Orthorhombic, Pccn
17.370 (2), 17.3704 (11), 8.2084 (12)
Monoclinic, P21/c
5.901 (1), 33.391 (6), 6.9745 (15)
a, b, c (Å)
Angle (ꢀ)
V (Å3)
Z
a
¼
b
¼
g
¼ 90
b
¼ 114.524 (10),
a
¼
g
¼ 90
2476.7 (5)
1250.3 (4)
8
0.24
4
0.27
m
(mmꢂ1
)
Data collection
Diffractometer
Absorption correction
Tmin, Tmax
Bruker Kappa APEXII CCD
Multi-scan (SADABS; Bruker, 2005)
0.935, 0.951
Bruker Kappa APEXII CCD
Multi-scan (SADABS; Bruker, 2005)
0.932, 0.955
No. of measured, independent and observed [I > 2
s(I)] reflections
8781, 2279, 1520
0.041
0.606
9392, 2327, 1227
0.093
0.606
Rint
(sin
Refinement
R[F2 > 2 (F2)], wR(F2), S
q/l)
(Åꢂ1
)
max
s
0.047, 0.123, 1.01
0.071, 0.196, 1.02
No. of reflections
No. of parameters
H-atom treatment
2279
169
2327
175
H-atom parameters constrained
0.19, ꢂ0.22
H-atom parameters constrained
0.48, ꢂ0.48
Dr
>
,
Dr
>
(e Åꢂ3
min
)
max
Temperature (K) ¼ 296; Radiation type ¼ Mo K
a
.
(8 mg, 1.5 mol%), 2,4-diflurophenyl boronic acid (153 mg,
0.724 mmol) and K3PO4 (153 mg, 0.724 mmol) were added to 3 mL
of dioxane solvent. The resulting reaction mixture was flushed with
dry nitrogen gas for few minutes. The reaction mixture was heated
at 90e100 ꢀC for 8 h. After the completion of the reaction, 20 mL of
water was added. After cooling at room temperature, organic and
the aqueous layers were separated and the latter was extracted
with ethyl acetate three times (3 ꢁ 15 mL). The obtained residue
was then purified through column chromatography and compound
(2) was isolated as light yellow crystalline solid (146 mg, 90%).
3.5. Aminothiazole derivative(2)
The derivative (2) crystallizes as light yellow crystal having
Monoclinic space group P21/c with Molecular formula C15 H10 F2 N2
S and molar mass 288.31 amu. The crystal stoichiometry is a
discrete 1:1 adduct with no incorporated the solvent molecule
[Fig. 2a (ORTEP diagram)] The derivative depicts distinct hydrogen
bonding between hydrogen of the amino group and nitrogen of the
thiazole ring as shown in polymeric chain structure (Fig. 2b). In this
hydrogen bonding, the hydrogen of the amino group and nitrogen
of the thiazole ring are involved. Data related to hydrogen bond,
distances and angle are shown in Table 2.
The dimeric structures of both derivatives have inter-molecular
hydrogen bonds detected between N2eH2A$$$N1 and
N2eH2B/N1 in 1 and 2 respectively. These distances are identified
as 2.18 and 2.10 Å shown in Table 2. The inter-molecular hydrogen-
bonding arrangement provide insights of the dimeric structures
which in turn transforms the compounds into supramolecular
structures.
3.3. Single-crystal X-ray
The aminothiazole derivatives were subjected to single-crystal
X-ray diffraction. The information related to crystals is shown in
Table 1 and hydrogen bond parameters are shown in Table 2.
3.4. Aminothiazole derivative (1)
Aminothiazole derivative (1) crystallizes as dark yellow crystal
in the orthorhombic space group Pccn having molecular formula
C15 H12 N2 S and molar mass 252.33 amu. It is 1:1 adduct with no
incorporation of the solvent molecule. Stoichiometry shows a
discrete adduct formation [Fig. 1a (ORTEP diagram)]and polymeric
chain structure (Fig. 1b) having hydrogen bond. The nitrogen atom
of the thiazole group of one molecule serves as hydrogen bond
acceptor and amino group on other molecule act as donor in the
formation of dimeric structure of derivative (1). Several hydrogen
bonds are present between the nitrogen and hydrogen of amino
group of the thaizole ring which leads to a supramolecular struc-
ture (Fig. 1b). The observed hydrogen bonds information is sum-
marized in Table 2.
3.6. Geometric structures
The geometrical parameters obtained by M06-2X/6-311G(d,p)
[40,41] are compared with the experimental parameters summa-
rized in Tables S1 and S2 (Supplementary information). The
comparative study indicates that the experimentally determined
bond lengths are slightly smaller than calculated bond lengths
(Tables S1 and S2 in Supplementary information). This difference is
expected because the experimental data correspond to the struc-
tures in solid phase. While, the DFT calculations associated to the
gaseous phase.
The DFT calculated bond lengths of the CeC bond of the both
benzene rings in compound (1) are found between 1.386 and
1.398 Å. Whereas, experimentally, it ranges 1.362e1.389 Å which
are much smaller as compared to the ordinary CeC single bond
length (1.540 Å) and larger as compared to the C]C double bond
(1.340 Å) [42,43]. The bond lengths of the CeC bond as shown
C4eC10 and C15eC18 between the both benzene rings are found to
be 1.482 and 1.474 Å for compound (1) and compound (2) respec-
tively. These bond lengths are also smaller as compared to the
Table 2
Selected hydrogen-bond parameters for 1 and 2.
Compounds Atoms
DeH (Å) H/A (Å) D/A (Å) <DeH/A (deg)
1
2
N2eH2A /N1 0.88(4)
N2eH2B/N1 0.94(5)
2.18(4)
2.10(6)
3.047(3) 174(4)
2.975(6) 156(5)

M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
139
Fig. 1. (a) View of the title compound with the atom numbering scheme. The thermal ellipsoids are drawn at 50% probability level, the H-atoms are shown as small circles of
arbitrary radii, (b) polymeric chains displaying hydrogen bond network.
ordinary CeC single bond length (1.540 Å). It is the evidence of
conjugation between the both benzene rings. The bond lengths of
the CeC bond in benzene rings of compound (1) are found to be
slightly different than compound (2). This difference might be
because of the fluoride group in compound (2) see Tables S1 and S2
(Supplementary information).
The theoretically bond angles of compounds have also been
investigated in the current study. The reasonable agreement is
found between theoretically and experimentally determined bond
angles as demonstrated in Tables S1 and S2 (Supplementary in-
formation). Both compounds were optimized at B3LYP/6-31G(d)
B3LYP/6-311 þ G(2d, p) and M06-2X/6-311G(d, p) level of the-
ories. Root mean square errors (RMSE) are calculated using geo-
metric parameters which indicate slightly difference among these
parameters as shown in Table S3.
which are associated to intra-molecular donoreacceptor in-
teractions. The stabilization energy E(2) [48e50] is obtained by
analysing the relationship between the donoreacceptor in-
teractions using the second-order perturbation theory using
Equation (1).
ꢀ
ꢁ
2
Fi;j
Eð2Þ ¼ q
(1)
iεj ꢂ εi
Where: qi,
,
and Fi,j define orbital occupancy, diagonal, off-
j
i
diagonal NBO Fock matrix elements [51] respectively.
NBO results suggest that the donoreacceptor interactions are
stabilized by the delocalization of the lone pair orbital (nN) of N32
LP (1) and N34 LP (1) towards the anti bonding orbitals (s*) of
N3/H20 and N5/H23 in these compounds. As a result the second
order perturbation stabilization energies are found to be
10.12 kJ molꢂ1 and 9.69 kJ molꢂ1 in compound (1) and compound
(2), respectively as can be seen in Tables 3 and 4. This provides a
reasonable explanation to the presence of hydrogen bonding (HB)
net work in the dimeric structures in gas phase and solid state. The
pictorial presentation of these NBOs is shown in Fig. 4.
3.7. Natural bond orbitals
In X-ray, the polymeric structures (1b & 2b) have the N/HeN
hydrogen-bonds (H-bond) as showed in Figs. 1 and 2. Therefore,
NBO calculation [44,45] has been performed using dimeric struc-
tures to receive more orbital level insights on the nature and for-
mation of the H-bonds in the two compounds. NBO study [46,47]
also indicates the hyper conjugative interactions in the crystals
The stabilization energies have been determined as 7.51 and
6.98 kJ molꢂ1 for the following transitions such as
s
(N35eH52)/
s*(S31eC50) and
s(N3eH21)/s*(S1eC18) respectively in

140
M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
Fig. 2. (a) View of the title compound with the atom numbering scheme. The thermal ellipsoids are drawn at 50% probability level, the H-atoms are shown as small circles of
arbitrary radii, (b) polymeric chains displaying hydrogen bond network.
compounds (1) and (2) which show interactions for the hydrogen
bonds between the sulfur and hydrogen of amino group (NeH/S),
which also stabilized the supramolecular structure.
having
ICT
transitions
*(C10eC15),
i.e.
p
(N2eC18)/
p
*(C16eC17),
p(C11eC12)/
p
p
*(C13eC14),
p(C13eC14)/
p
*(C10eC15) and
p
*(C11eC 12) consist of E(2) i.e. 27.07, 27.63,
26.80, 29.63 and 28.40 kJ molꢂ1 respectively (Table 3). Compound
(2) containing ICT transitions i.e.
p
(N4eC20)/
p
*(C18eC19),
3.8. Hyperconjugative interactions
p
(C6eC7)/
p
*(C8eC9),
p*(C10eC11),
p
(C10eC11)/p
*(C6eC7)
and
p
*(C8eC9) involving E(2) i.e. 25.39, 25.21, 34.49, 23.50 and
The strong intra-molecular hyperconjugative interactions are
found causing intra-molecular charge transfer (ICT) which in turn
stabilize these compounds.
32.87 kJ mol-1 respectively (Table 4).
3.9. Intra-molecular interactions (s/s*)
The stabilization energies have been determined as 5.39, 7.51,
4.14, 3.02 and 3.10 kJ molꢂ1 from the following transitions such as
3.11. Intra-molecular interactions (LP/p*)
s
s
(N3eH20)/
s
*(N2eC18),
s
(N3eH21)/
s*(S1eC18), s(C4eC5)/
The most important interaction energy in the two molecules is
occurred due to the electron donation from N32 LP(1) and F35 LP(1)
*(C4eC9), *(C4eC10) and
s
s
*(C5eC6), respectively shown in
Table 3. Compound (2) also shows such type of interactions as
presented in Table S4 (Supplementary information). Hence, these
interactions may contribute towards the stability of the electronic
structure.
to the antibonding acceptor [N32eC48(p*)] and [N34eC50(p*)]
resulting high stabilization energy of 51.98 and 51.30 kJ molꢂ1
produced respectively (Tables 3 and 4). We report some represen-
tative interactions herein, other interactions are collected in
Tables S4 and S5 (Supplementary information). From NBO analysis,
we can infer that the strong intra-molecular hyper conjugation
interactions and inter-molecular hydrogen bonding are responsible
to yield more stability in these electronic structures in gas phase as
well as in the solid-state structures.
3.10. Intra-molecular interactions (p/p*)
Interestingly, the
p/p* interactions play prominent role to
offer stronger stabilization in both compounds. Compound (1)

M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
141
Fig. 3. Optimized dimer (1) and (2) geometries calculated at M06-2X/6-311G(d,p) level of theory and showing hydrogen bond distances (angstrom) and atom labels.
3.12. FT-IR analysis
3.14. CeH vibration
The selective vibrational modes were assigned using the ani-
mation option of Avogadro software. These bands are systematized
from small to high frequency along with specific assignments. The
computed vibrational frequencies are scaled using the SQM
approach are tabularized in Tables 5 and 6. A scale factor of 0.9627
is utilized to omit the anharmonicity effects [36].
The CeH stretching vibrational modes of hetero aromatic
compounds are ranged between 3100 and 3000 cmꢂ1 [54]. In
accordance with the current study, the CeH frequencies appeared
in the range from 3160 cmꢂ1 to 3076 cmꢂ1 for 1 and ranged be-
tween 3160 cmꢂ1 and 3071 cmꢂ1 for 2 in FT-IR and their experi-
mental FT-IR spectrum values are found to be 3111e2851 and
3111e2852 for 1 and 2 respectively (Tables 5 and 6).
3.13. CeC]C vibrations
The vibrational bands of CeC in benzene derivatives appear at
1650-1400 cmꢂ1 [52,53]. In the current study, the bands are
appeared in the range from 1605 to 1551 cmꢂ1 which shows good
agreement with experimental 1634e1532 for 1 and from 1611 to
2 which also shows good agreement with
experimental1634-1531. Theirassignments are shown in Tables 5
and 6
3.15. NH2 vibration
In the recent study, asymmetric and symmetric vibrational
bands for NH2 of both molecules are appeared at 3552 and
3440 cmꢂ1. In the same way, experimental asymmetric and sym-
metric vibrational bands for NH2 of both molecules are found to be
3427 and 3279 cmꢂ1 see Tables 5 and 6
1596 cmꢂ1 for

142
M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
Table 3
(IIR ¼ 29.5506)] in monomeric structure (2) respectively as can be
seen in Fig. 5 (see also Tables S6 and S7 in the Supplementary in-
formation). Whereas, the both dimeric structures (1), and (2) dis-
played the NH2 band at 3290.04 cmꢂ1 with high intensity
Second order perturbation theory analysis of selected Fock matrix of dimer (1) using
NBO method with M06-2X/6-311G(d,p) level theory.
Donor NBO (i) Type Acceptor NBO (j) Type E(2)a
E(j)ꢂE(i)b F(i,j)c
(IIR
¼
827.4536)and 3231.061 cmꢂ1 with high intensity
N3eH 20
N3eH21
C4eC5
C4eC5
C4eC5
N2eC18
C11eC12
C11eC12
C13eC14
C13eC14
N32
s
s
s
s
s
p
p
p
p
p
N2eC18
S1eC18
C4eC9
C4eC10
C5eC6
C16eC17
C10eC15
C13eC14
C10eC15
C11eC12
s
s
s
s
s
p
p
p
p
p
*
*
*
*
*
*
*
*
*
*
5.39
1.37
0.077
0.076
0.068
0.056
0.059
0.102
0.091
0.090
0.091
0.090
0.093
0.132
7.519 0.94
(IIR ¼ 703.8786) respectively. The lessening in vibrational fre-
quencies and amplification in intensities are obtained in both
dimeric structures. This is a clear proof of the existence of H-bonds
in the investigated derivatives [55], as seen in Fig. 5 (see also
Tables S6 and S7 in the Supplementary information).
4.14
3.02
3.10
1.40
1.31
1.42
27.07 0.44
27.63 0.36
26.80 0.37
29.63 0.35
28.40 0.35
10.12 0.83
51.98 0.38
3.17. UVeVisible analysis
LP(1) N3eH20
LP(1) N32eC48
s*
p*
N32
UVeVisible analysis was carried out to understand the nature of
electronic excitations within 1 and 2 using TD-DFT-B3LYP/6-
311G(d,p) level of theory in a gas phase. The calculated wave-
lengths, electronic excitation energies, oscillator strengths and
percentage of molecular orbitals are summarized in Tables S8 and
S9 (Supplementary information). Table S8 shows that the magni-
tudes of maximum wavelengths [lmax (nm)] are obtained to be
304.86, 258.36 and 249.19 nm with oscillator strengths of 0.5702,
0.2302 and 0.1307 respectively for 1. Table S9 reveals that the ex-
tents of [lmax (nm)] are observed to be 306.46, 259.93 and 247.00
with oscillator strengths of 0.468, 0.3597 and 0.0887 respectively.
Remaining electronic transitions as shown in Tables S8 and S9 are
consisting of very low or zero extent of oscillator strengths (a
dimensionless quantity that defines the capability of an electronic
transition) which indicates forbidden electronic transitions.
a
Energy of hyper conjugative interaction (stabilization energy), unit in kJ molꢂ1
(a.u.).
b
c
Energy difference between donor and acceptor i and j NBO orbital.
Fock matrix element between i and j NBO orbital.
Table 4
Second order perturbation theory analysis of selected Fock matrix of dimer (2) using
NBO method with M06-2X/6-311G(d,p) level theory.
Donor NBO (i) Type
Acceptor NBO (j) Type E(2)a
E(j)ꢂE(i)b F(i,j)c
N4eC20
C6eC7
C6eC7
C10eC11
C10eC11
N34
p
p
p
p
p
C18eC19
C18eC19
C10eC11
C 6-C7
p
p
p
p
p
*
*
*
*
*
25.39 0.45
0.100
0.084
0.098
0.085
0.100
0.089
0.131
25.21 0.35
34.49 0.34
23.50 0.38
32.87 0.37
C8eC9
The oscillator strength for the transition at 304.86 nm is larger
in extent as compared to other excitations is attributed to the
excitation HOMO/ LUMO (98%). The compound 2 shows the
transition at 306.46 nm can be assigned to the HOMO/ LUMO
LP (1) N5eH23
LP (1) N34eC50
s*
9.69
0.98
F35
p*
51.30 0.37
a
Energy of hyper conjugative interaction (stabilization energy), unit in kJ molꢂ1
(a.u.).
(97%) excitation. These transitions are contributed from
p* excitation. Moreover, the experimental maximum wavelengths
lmax (nm)] of both compounds were obtained in the ethyl acetate
p-
b
c
Energy difference between donor and acceptor i and j NBO orbital.
Fock matrix element between i and j NBO orbital.
[
(ETOAc) which show good agreement to the calculated values as
shown in Tables S8 and S9.
3.16. Hydrogen bond vibrations
The findings of XRD and NBO analysis suggest that both de-
rivatives having hydrogen bonding pattern (N/HeN) see in
Figs. 1e3 which drives them to construct the supramolecular
structures. Hence, we performed IR absorption spectroscopy based
on DFT analysis regarding monomers and dimers of both molecules
with a particular objective to justify the H-bonding pattern. The
scaled symmetric and asymmetric stretching vibrations for NH2 are
3.18. NMR analysis
The 1H and 13C NMR chemical shifts values for 1 and 2 have been
determined experimentally in CDCl3. While, 1H and 13C NMR
chemical shift values were calculated for both compounds in the
gas phase with b3lyp 6-311 þ G(2d, p).
In the 1H NMR spectrum of 4-(biphenyl-4-yl)-1,3-thiazol-2-
amine (1), a broad singlet peak at 5.49 is due to NH2 protons, a
singlet peak at 6.72 is assigned to CH proton of thiazole ring, a
multiplet at 7.33 due to CH proton of phenyl ring, a multiplet at 7.40
found
at
[3439.819
cmꢂ1
(IIR
¼
45.6388)]
and
[3552.292 cmꢂ1(IIR ¼ 29.1265)] in monomeric structure (1) and
[3439.964 cmꢂ1 (IIR
¼
46.5985)] and [3552.381 cmꢂ1
Fig. 4. HB dimeric structures are constructed by the nitrogen and the anti-bonding orbital of the NH group interaction.

M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
143
Table 5
eight methine (CH) carbons while peaks at
d
¼ 130.13, 134.40,
Computed frequencies and assignments for vibrations of monomer (1) at B3LYP/6-
311G(d,p) level of theory.
136.34, 149.96, 159.68, 162.10, 168.72 are assigned to quartenary
carbons and peak observed at 168.72 is assigned to (CeNH2). On the
other hand, theoretical chemical shift values (1H and 13C NMR)
were calculated of both compounds in the gas phase with b3lyp 6-
311 þ G(2d, p) which show deviation to experimental values might
be because of medium affects as shown in Table 7.
Frequency
unscaled
Frequency
scaled
Experimental
frequency
Vibrational
assignments
1372
1449
1321
1395
1259
1288
r
r
CeHAromat
CeHAromat
þ
y
d
CeN
þ
CeHAromat
1489
1527
1544
1575
1611
1434
1470
1486
1516
1551
1337
1394
1456
1472
1532
r
r
r
r
CeHAromat
CeHAromat
CeHAromat
CeHAromat
3.19. Frontier molecular orbitals (FMOs) study
DFT at M06-2X method with 6-311G(d, p) basis set is applied to
compute the energy of HOMO and LUMO levels and the energies
are shown in Table S10.
The frontier molecular orbitals (FMOs) play a significant func-
tion in the electric and optical features, UVeVis spectra and
quantum chemistry [56,57]. The pictorial demonstration of these
different FMOs is shown in Figs. 6 and 7.
The HOMO demonstrates the donor orbitals and the LUMO
demonstrates acceptor orbitals [58]. The surface of FMOs is dis-
played to interpreting the bonding frame work of these com-
pounds. Hence, six significant molecular orbitals have been
investigated i.e. LUMO, LUMOþ1, LUMOþ2, HOMO, HOMO-1 and
HOMO-2 demonstrate the respective acceptor and donor levels,
two energy state above and two levels below respectively. The
computed energy data of these six molecular orbitals and the cor-
responding energy gaps in gas phase are shown in Table S10. The
energies of FMOs (LUMO & HOMO) have been used to investigate
the global reactivity descriptors [59] using the equations given in
y
(as)CeC]Cþ
b
CeC]
C
1668
1605
1634
y
(s)CeC]Cþ (
b)
CeC]C
3195
3200
3202
3208
3226
3283
3573
3690
3076
3081
3083
3088
3106
3160
3440
3552
2851
2922
2959
3038
3093
3111
3279
3427
y
y
y
y
y
y
y
y
(as)CeHAromat
(s þ as)CeHAromatic
(s)CeHAromatic
(s)CeHAromatic
(s)CeHAromatic
CeHC]CHeS
(s)HNH2
(as)HNH2
Frequencies are given in cmꢂ1
¼ rocking, s ¼ symmetric, as ¼ asymmetric.
,
y
¼ stretching,
b
¼ in-plane bending,
d
¼ scissoring,
r
Table 6
Computed frequencies and assignments for vibrations of monomer (2) at B3LYP/6-
311G(d,p) level of theory.
Frequency
unscaled
Frequency
scaled
Experimental
frequency
Vibrational assignments
the supplementary information. The chemical potential (
hardness ( ), global softness (S) and global electrophilicity index
) are known as global reactivity parameters [60e64]. These pa-
m), global
h
1176
1447
1475
1528
1549
1658
1132
1393
1420
1472
1492
1596
1261
1288
1304
1394
1471
1531
y
CeF
(u
r
r
r
r
d
CeHAromat
CeHAromat
CeHAromat
CeHAromat
CeHNH2
CeC]C
þd CeHAromat
rameters are considered as highly successful descriptors for bio-
logical activity [65]. Moreover, electro negativity (X) [66] electron
affinity (EA) and ionization potential (IP) [67] are also determined
using the energies of frontier molecular orbitals.
þy(s)CeC]Cþ
b
These reactivity parameters are also recently used in under-
standing the site selectivity and the reactivity [68e70].The com-
pounds that possess positive electron affinity are known as electron
acceptors and might participate in charge transfer reactions. The
electron donation strength for any donor compound can be
measured using its ionization potential is the energy which needed
to take off an electron from the HOMO. Electro negativity is known
as one of the most important chemical properties which define the
power of specie to attract electrons towards itself. The large EHO-
MOeELUMO difference defines a hard specie, which means specie is
more stable and less reactive. While, small EHOMOeELUMO gap de-
fines a soft specie, which means specie is less stable and more
reactive. The obtained findings indicate that the both molecules are
less stable and more reactive see Table S11.
1665
1674
3189
3192
3206
3224
3227
3228
3282
3573
3690
1603
1611
3071
3073
3087
3104
3106
3107
3160
3440
3552
1614
1634
y
y
y
y
y
y
y
y
y
y
y
(s)CeC]C þ
b
b
CeC]C
CeC]C
(s)CeC]C þ
(as) CeHAromat
(as)CeHAromat
2752
2852
2924
2959
3088
3111
3279
3427
(s þ as)CeHAromatic
(s)CeHAromatic
(s)CeHAromatic
(s)CeHAromatic
CeHC]CHeS
(s)HNH2
(as)HNH2
Frequencies are given in cmꢂ1
¼ rocking, s ¼ symmetric, as ¼ asymmetric.
,
y
¼ stretching,
b
¼ in-plane bending,
d
¼ scissoring,
r
show 2 CH protons, 4 CH protons of aromatic ring are resonating as
doublet at 7.59, a doublet at 7.80 is assigned to 2CH protons of
phenyl ring. Similarly for 13C NMR spectrum of 4-(biphenyl-4-yl)-
3.20. Molecular electrostatic potential (MEP)
1,3-thiazol-2-amine, the peaks at
128.79 representing nine methine (CH) carbons while peaks at
¼ 131.83, 137.67, 139.55, 149.81, 168.72 are assigned to quartenary
d
¼ 102.55, 126.63, 127.34, 127.04,
MEP plays a vital role in order to analyze the physical-chemical
properties in chemical structures [71e74]. Electrostatic potential is
enhanced in the order of red < orange < yellow < green < blue [75].
As seen from Fig. S6, the red colour in our dimers indicates the
electron rich places as fluoride and nitrogen atoms. The blue colour
indicates the electron deficient region as hydrogen atoms and some
carbon atoms. MEP shows hydrogen bonding interactions which is
in agreement with our experimental results as well as NBO analysis.
d
carbons and peak observed at 168.72 is assigned to (CeNH2).
In the 1H NMR spectrum of 4-(2,4-difluorobiphenyl-4-yl)-1,3-
thiazol-2-amine (2), a broad singlet peak at 5.02 is due to NH2
protons, a multiplet at 6.77 is assigned to CH proton of thiazole ring,
a multiplet at 6.90e6.99 is due to 2 CH protons of phenyl ring, a
doublet at 7.50 is showing two CH proton, 2 CH protons of aromatic
ring are resonating as doublet at 7.82. Similarly for 13C NMR spec-
trum of 4-(2,4-difluorobiphenyl-4-yl)-1,3-thiazol-2-amine, the
3.2.1. Non-linear optical (NLO) properties
peaks at
d
¼ 102.19, 115.68, 126.04, 126.54, 127.05, representing
The organic compounds have become the centre of attraction
due to their unique characters and potent potential applications in

144
M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
Fig. 5. FT-IR absorption spectra calculated at B3LYP/6-311G(d,p) level of theory.
Table 7
Experimental and calculated 1H and 13C NMR chemical shifts values for 1 and 2.
Number of atoms in 1
Experimental
DFT
Number of atoms in 2
Experimental
DFT
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
H
H
H
H
H
139.55
128.79
126.63
126.63
126.63
128.79
137.67
128.03
127.34
131.83
127.34
128.03
149.81
102.55
168.72
7.59
5.49
5.49
7.59
7.33
7.59
7.59
7.40
7.80
194.91
170.07
183.28
182.36
183.21
170.46
191.23
165.48
167.88
181.29
177.74
166.09
93.44
77.90
101.45
8.99
10.18
11.14
5.55
4.87
5.60
9.08
8.77
9.48
9.64
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
H
H
H
134.40
126.04
115.68
162.10
102.19
159.68
136.34
126.54
127.05
130.13
127.05
126.54
149.96
102.19
168.72
7.39e7.45
5.02
5.02
6.90e6.99
6.77
7.50
7.82
7.82
7.50
6.90e6.99
156.49
170.24
143.51
102.59
119.32
97.47
178.26
175.43
167.50
182.28
178.034
166.67
100.00
74.46
105.56
8.49
11.04
10.01
4.8
5.27
10.14
9.00
9.26
9.08
5.22
7.80
7.40
6.72
8.87
5.46
nonlinear optics (NLO), photonics and electronics [76e79]. The
sketch of dynamic organic compounds for utilization in NLO
response is established on the basis of asymmetric polarization. It is
directed through electron contributor and withdrawing groups on
suitable location of the compound. The NLO response is enhanced
with increasing the electron contributor and withdrawing groups

M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
145
Fig. 6. Frontier molecular orbitals of 1. Energy in Hartree (a.u).
Fig. 7. Frontier molecular orbitals of 2. Energy in Hartree (a.u).
efficiency attached to the
also studied NLO parameters of the
using B3LYP level of theory with 6-311G (d, p) basis set.
In finite field (FF) method, when specie is incorporated to a
static field (F), the resulting energy (E) is represented by Equation
(2).
p
-conjugated system [80]. Therefore, we
-conjugated molecules (1 & 2)
ꢀ
ꢁ
1
〈
a
〉 ¼
3
axx
þ
ayy
þ
azz
(3)
(4)
p
1
ꢂ
ꢄ
ꢃ
2
btot
¼
¼
b2x þ b2y þ b2z
ꢂ
ꢃ
ꢂ
ꢃ
2
btot
bxxx
þ
bxyy
þ
bxzz 2 þ byyy
þ
þ
byzz
þ
byxx
1
ꢅ
2
ꢂ
ꢃ
2
1
2
1
E ¼ E0
ꢂ
miFi ꢂ aijFiFjFk ꢂ gijklFiFjFkFl
24
(2)
þ
bzzz
þ
bzxx
þ
bxyz
(5)
(6)
Where E0 stands for the molecular energy in the nonattendance of
electronic field. btot and stand for polarizability, first and second
h
h
ii
1
5
a,
g
g
¼
gxxxx
þ
gyyyy
þ
gzzzz þ 2 gxxyy
gyyzz
þ
gxxzz
hyperpolarizability tensors in x, y and z directions are calculated
using Equations (3)e(6) respectively.
The components of the dipole moment, total dipole moment,

146
M. Adeel et al. / Journal of Molecular Structure 1131 (2017) 136e148
the change molar entropy ð
D
S0mÞ for 1 is found greater than 2 which
the polarizability the first order and the second order hyper-
polarizability values of both molecules are summarized in
Table S12.
indicates the presence of relatively heavy groups (fluoride groups)
in 2.
The components of the dipole moment and polarizability of
both molecules are different in all the directions as shown in
Table S12. These components indicate the non-uniform charge
distribution along the three directions. But the dipole moment and
polarizability are found greater in extent for 2 than 1, might be due
to the influence of fluoride groups on the skeleton of 2. The first
order polarizability along x direction is around ꢂ98.67 a. u. It is
larger than its y and z directions (positive directions) for 1. In the
case of 2, the first order polarizability along x direction is 200 a. u.
also larger than its y and z directions with negative directions.
The second order polarizability along x directions for both
molecules is larger than its y and z directions. They also indicate
that both molecules are non-uniform distribution of the charges.
The total dipole moment and polarizability, are found to be 1.95 a.
4. Conclusion
In this study, two compounds including 4-(biphenyl-4-yl)thia-
zol-2-amine (1) and 4-(2',4'-difluorobiphenyl-4-yl)thiazol-2-amine
(2) are synthesized and their structural information are obtained by
1HNMR, 13C NMR, and single crystal x-ray techniques. The XRD
studies suggest that the crystal structures of (1) and (2) are dark
yellow-shaped having orthorhombic with space group Pccn and
light yellow-shaped having monoclinic with space group P21/c
respectively. Both structures show the hydrogen bonding network.
This hydrogen bonding promote the supramolecular structures.
Crystal structures of both compounds are compared with opti-
mized structure calculated by DFT. NBO results predict that intra-
molecular charge transfer (ICT) and inter-molecular hydrogen
bonding lead to stable dimeric structures. The FT-IR spectroscopic
analysis and thermodynamic properties of monomers and dimers
also confirm the hydrogen bond network. These non-bonding in-
teractions are in good agreement with XRD results. UVeVis analysis
u. (1) and 3.21 a. u. (2) and ꢂ1.48
ꢁ
10ꢂ23 (esu) (1)
and ꢂ1.63 ꢁ 10ꢂ23 (esu) (2), respectively. The first order hyper
polarizability and second order hyper polarizability are found to be
1.39 ꢁ 10ꢂ30 (esu) (1) and 1.65 ꢁ 10ꢂ30 (esu) (2) and ꢂ9.27 ꢁ 10ꢂ29
(esu) (1) and ꢂ11.4 ꢁ 10ꢂ29 (esu) (2) respectively see Table S12. All
these parameters for 2 are greater in magnitude as compared to 1,
might be due to electron withdrawing influence.
reveals that maximum excitations take place from p-p
* excitations.
The global reactivity parameters which are calculated by frontier
molecular orbitals indicate that these compounds are reactive. The
first order hyperpolarizability is found to be 1.39 ꢁ 10ꢂ30 (esu) for 1
and 1.65 ꢁ 10ꢂ30 (esu) for 2. These values are 4 and 4.5 times
greater as compared to the reference urea value
(urea ¼ 0.3728 ꢁ 10ꢂ30 esu), respectively which implies that these
compounds may show non-linear optical properties.
Moreover, we compared our obtained parameters with urea
compound because it is frequently used as reference molecule for
comparative NLO analysis [78]. The total dipole moment of both
molecules remarkably greater than the dipole moment of urea (For
urea l ¼ 1.3732D). Similarly the first order hyperpolarizability of
both molecules also remarkably greater than the value of urea
(b
¼ 0.372 ꢁ 10ꢂ30 esu).
Acknowledgments
3.22. Thermodynamic properties
The authors are grateful to Sumaira Khalid for her valuable
suggestions for a care full reading. Authors like to acknowledge
Higher Education Commission (HEC), Pakistan for funding. We also
acknowledge Dr. Ana Paula L. Batista for her cooperation.
The standard thermodynamic functions such as entropy (S),
heat capacity at constant pressure (Cp) and enthalpy
D
H¼H(T)ꢂH(0)
for monomeric and dimeric structures (1 & 2) based on vibrational
analyses and statistical thermodynamics were obtained at tem-
perature ranged from 25 to 1000 K using B3LYP/6-311G(d,p) level of
theory in a gas phase as shown in Tables S13 and S14. Statistical
thermodynamics calculations have key importance to processing
properties as a function of temperature. Indeed, the molecular
energies (produced from electronic excitations, molecular vibra-
tional, translational and rotational motions) are transformed into
entropies, heat capacities and enthalpies in statistical thermody-
namics calculations. The entropies, heat capacities, and enthalpy
changes are enhancing with temperature ranging from 25 to
1000 K. Mainly because, the molecular vibrational intensities in-
crease with temperature.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.molstruc.2016.11.046.
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