Synthesis, spectral analysis, X-ray crystal structures and evaluation of chemical reactivity of five new benzoindazole derivatives through experimental and theoretical studies

Article abstract of DOI:10.1016/j.molstruc.2014.07.033

The main purpose of this study was synthesis, X-ray, DFT and spectroscopic investigations of the title compounds (I-V). Five new compounds were synthesized and the detailed experimental results are reported. The crystal and molecular structures of the tit

Full text of DOI:10.1016/j.molstruc.2014.07.033

Journal of Molecular Structure 1076 (2014) 272–279
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis, spectral analysis, X-ray crystal structures and evaluation
of chemical reactivity of five new benzoindazole derivatives through
experimental and theoretical studies
Layla A. Taib a, Hassan M. Faidallah a, Zarife Sibel Sßahin b, , Abdullah M. Asiri a,c, Onur Sßahin d,
⇑
Muhammad Nadeem Arshad a,c,
⇑
a Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
b Department of Energy Systems Engineering, Faculty of Engineering and Architectures, Sinop University, 57000 Sinop, Turkey
c Centre of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
d Scientific and Technological Research Application and Research Center, Sinop University, 57010 Sinop, Turkey
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
ꢀ
ꢀ
Herein we report the synthesis, of five
new benzoindazole derivatives.
These compounds were structurally
characterized by spectroscopic and
X-ray measurements.
ꢀ
ꢀ
Electrostatic potential is calculated.
HOMO–LUMO analysis is performed
to study the band gap related
properties.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 May 2014
Received in revised form 11 July 2014
Accepted 11 July 2014
Available online 22 July 2014
The main purpose of this study was synthesis, X-ray, DFT and spectroscopic investigations of the title
compounds (I–V). Five new compounds were synthesized and the detailed experimental results are
reported. The crystal and molecular structures of the title compounds have been determined by IR, 1H
NMR, 13C NMR and single-crystal X-ray diffraction. Molecular geometries from X-ray experiment of I–
V in the ground state have been compared using the Density Functional Theory (DFT) with B3LYP/6-
31G(d,p) basis set. In addition, the molecular electrostatic potential maps and frontier molecular orbitals
were performed at B3LYP/6-31G(d,p) level of theory. DFT global chemical reactivity descriptors (chemical
hardness, total energy, electronic chemical potential and electrophilicity) are calculated for the title mol-
ecules and used to predict their relative stability and reactivity.
Keywords:
X-ray, Benzoindazole
DFT
Molecular electrostatic potential
Chemical reactivity
Ó 2014 Elsevier B.V. All rights reserved.
⇑
Introduction
Corresponding authors. Addresses: Department of Energy Systems Engineering,
Faculty of Engineering and Architectures, Sinop University, 57000 Sinop, Turkey
(Z.S. Sßahin), Chemistry Department, Faculty of Science, King Abdulaziz University,
P.O. Box 80203, Jeddah 21589, Saudi Arabia. Tel.: +90 3682715757; fax: +90
3682715770 (M.N. Arshad).
Over the past two decades, much evidence has been accumu-
lated on the importance of pyrazole derivatives and their related
fused heterocycles as chemotherapeutic agents. The pyrazole
moiety is an important pharmacophore showing a multitude of
E-mail addresses: zarifesibel@sinop.edu.tr (Z.S. Sßahin), mnachemist@hotmail.
com (M.N. Arshad).
http://dx.doi.org/10.1016/j.molstruc.2014.07.033
0022-2860/Ó 2014 Elsevier B.V. All rights reserved.

L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
273
biological and pharmacological properties. However, benzo-fused
Experimental and computational method
derivatives of pyrazole (indazole) are probably one of the least
studied nuclei owing to its scarcity in nature. The indazole ring
system is regarded as a bioisostere of indole. However, a large
number of synthetically prepared indazoles are known to show
a variety of biological activities, such as high binding affinity
for estrogen receptor [1,2], inhibition of protein kinase C-b [3],
5-HT2 receptor agonism [4], human immunodeficiency virus
(HIV) protease inhibition [5], anti-leukemic activity [6], and
non-steroidal anti-inflammatory activity [7]. Other compounds
of interest are YC-1, a benzylindazole which has been shown
to activate soluble guanylate cyclase [8], nitric oxide synthase
inhibition activity [9,10] to induce cellular apoptosis [11] and a
MCHr1 antagonism for the treatment of obesity [12]. The most
notable one is lonidamine which was found to induce apoptosis
via a direct effect on the mitochondrial permeability transition
pore [11].
Chemistry
The starting compounds in this study are 6-arylidene-2-methyl-
cyclohexanones, synthesized via Claisen–Schmidt condensation of
aromatic aldehyde with 1-tetralone. These chalcones were reacted
with the appropriate hydrazine to afford the desired hexahydroin-
dazole derivatives I–V. The structures of these compounds were
confirmed by the 1H NMR which exhibited a characteristic doublet
of one proton intensity at d 4.64–3.62 ppm (J = 13 Hz) attributed to
the H-3 proton and a multiplet of two proton intensity at d 3.08–
3.29 ppm due to the H-3a proton which substantiate the closure
of the benzoindazoline ring (Table S4). The structures of the above
benzoindazolines I–V were further supported by 13C NMR data
which showed the expected number of aliphatic and aromatic
carbons signals (see experimental section).
Sr. No.
R
R’
I
C4H3S
C6H5
CH3
CH3
II
III
IV
V
4-Cl-C6H4 CH3
4-Cl-C6H4 C6H5
C6H5
C6H5
With the development of computational chemistry, the quan-
tum chemistry presents insights into electronic structures of mol-
ecules and strongly propels the development of the traditionally
experimental chemistry [12]. Density Functional Theory (DFT)
has been very popular for calculations in theoretical modeling
since the 1970s. A search of the Science Citation Index for articles
published in 1986 with the words ‘‘Density Functional Theory’’ in
the title or abstract yields less than 50 entries. Repeating this
search for 1996 and 2006 gives more than 1100 and 5600 entries,
respectively [13]. Today, these numbers beyond 10,000s. In many
cases the results of DFT calculations for solid-state systems
agreed quite satisfactorily with experimental data. DFT predicts
a great variety of molecular properties: molecular structures,
vibrational frequencies, atomization energies, ionization energies,
electric and magnetic properties, reaction paths, etc.
In view of these observations, herein we report the synthesis of
five new structures. Chemical structures of compounds were con-
firmed by IR, 13C NMR, 1H NMR and X-ray single-crystal determi-
nation. Molecular geometries from X-ray experiment of the title
compounds in the ground state have been compared using the
DFT method (B3LYP) with 6-31G(d,p) basis set. Besides, molecular
electrostatic potential (MEP), frontier molecular orbitals (FMO)
and global chemical reactivity descriptors were performed at
B3LYP/6-31G(d,p) level of theory.
Synthesis
Melting points were determined in open glass capillaries, on a
Gallenkamp melting point apparatus, and were uncorrected. The
infrared (IR) spectra were recorded on Perkin–Elmer 297 infrared
spectrophotometer, using the NaCl plate technique. The 1H NMR
spectra were recorded on a Varian EM 360 spectrometer; using
tetramethylsilane as the internal standard (Chemical shifts in d,
ppm). Splitting patterns were designated as follows: s: singlet;
d: doublet; m: multiplet. Follow up of the reactions and checking
the homogeneity of the compounds were made by TLC on silica
gel-protected aluminium sheets (Type 60 F254, Merck) and the
spots were detected by exposure to UV-lamp at k 254. The
starting chalcone 1 was prepared according to a literature proce-
dure [14].
2,3 Disubstituted-3,3a,4,5 tetrahydro-2H-benzo[g]indazole
A solution of the appropriate chalcone (20 mmol) in ethanol
(25 mL) was refluxed with the corresponding substituted hydra-
zine (21 mmol) for 4 h. On concentration, the separated product

274
L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
was filtered, washed with cold ethanol and recrystallized from
ethanol.
127.51, 128.05, 128.80, 128.94, 129.26, 129.46, 133.44, 140.71,
146.67, 150.53, (Ar C). (m.p. = 193–195 °C). kmax = 349 nm.
3-(4-Chloro-phenyl)-2-methyl-3,3a,4,5-tetrahydro-2H-
benzo[g]indazole (IV)
2-Methyl-3-thiophen-2-yl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole (I)
1H NMR (d/ppm, CDCl3): 1.83, 2.20 (2 m, 2H, H-4) 2.89; (s, 3H,
CH3); 2.93 (dd, J = 13.5 Hz, 2H, H-5); 3.23 (td, J = 13.5 Hz, 1H,
H-3a); 3.95 (d, J = 13 Hz, 1H, H-3); 7.01–7.30 (m, 7H, ArH); 7.94
(d, 1H). 13C NMR (d/ppm, CDCl3): 26.74 (C-4), 29.30 (C-5), 42.13
(N-CH3), 55.04 (C-3a). 79.76 (C-3), 124.29, 125.29, 125.10,
125.69, 126.72, 126.92, 128.02, 128.94, 129.36, 138.33, 142.85,
153.20 (Ar C). (m.p. = 132–134 °C). kmax = 311 nm.
1H NMR (d/ppm, CDCl3): 1.83, 2.12 (2 m, 2H, H-4); 2.89 (dd,
J = 13.5 Hz, 2H, H-5); 3.11 (td, J = 13.5 Hz, 1H, H-3a); 3.66 (d,
J = 13 Hz, 1H, H-3); 7.14–7.44 (m, 14H, ArH); 7.96 (t, 1H). 13C
NMR (d/ppm, CDCl3): 26.80 (C-4), 29.27 (C-5), 42.06 (C-3a),
79.82 (C-3), 124.22, 126.71, 128.81, 128.95, 129.23, 133.63,
138.15, 152.39 (Ar C). (m.p. = 112–114 °C). kmax = 317 nm.
2,3-Diphenyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole (V)
2-Methyl-3-phenyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole (II)
1H NMR (d/ppm, CDCl3): 1.97, 2.31 (2 m, 2H, H-4); 2.92 (dd,
J = 13.5 Hz, 2H, H-5); 3.27 (td, J = 13.5 Hz, 1H, H-3a); 4.63 (d,
J = 13 Hz, 1H, H-3); 6.82–7.48 (m, 14H, ArH); 8.07 (dd, 1H). 13C
NMR (d/ppm, CDCl3): 27.81 (C-4), 27.42 (C-5), 29.34, 56.35 (C-
3a), 73.29 (C-3), 114.83, 119.95, 124.45, 126.14, 126.67, 127.68,
128.25, 128.73, 128.92, 129.09, 129.25, 129.25, 138.06, 142.23,
146.91, 150.45 (Ar C). (m.p. = 152–154 °C). kmax = 349.5 nm.
1H NMR (d/ppm, CDCl3): 1.85, 2.15 (2 m, 2H, H-4) 2.83; (s, 3H,
CH3); 2.88 (dd, J = 13.5 Hz, 2H, H-5); 3.16 (td, J = 13.5 Hz, 1H, H-
3a); 3.70 (d, J = 13 Hz, 1H, H-3); 7.14–7.96 (m, 9H, ArH). 13C NMR
(d/ppm, CDCl3): 26.85 (C-4), 29.31 (C-5), 42.08 (N-CH3),
54.69 (C-3a). 80.54 (C-3), 124.20, 126.66, 127.50, 127.94, 128.27,
128.75, 128.93, 129.12, 138.23, 139.50, 152.61 (Ar C).
(m.p. = 136–138 °C). kmax = 318 nm.
3-(4-Chloro-phenyl)-2-phenyl-3,3a,4,5-tetrahydro-2H-
X-ray crystallography
benzo[g]indazole (III)
Suitable crystals of I–V were selected for data collection which
was performed on an Agilent SuperNova CCD diffractometer with
1H NMR (d/ppm, CDCl3): 1.96, 2.28 (2 m, 2H, H-4) 2.78; (s, 3H,
CH3); 2.93 (dd, J = 13.5 Hz, 2H, H-5); 3.23 (td, J = 13.5 Hz, 1H,
H-3a); 4.59 (d, J = 13 Hz, 1H, H-3); 6.83–7.42 (m, 8H, ArH); 8.06
(m, 1H). 13C NMR (d/ppm, CDCl3): 26.37 (C-4), 29.30 (C-5), 56.33
(N-CH3), 72.65, 79.83 (C-3), 114.90, 120.25, 124.29, 126.74,
mirror monochromated Cu K
a radiation at 296 K. The structures
were solved by direct methods using SHELXS-97 [15] and refined
by full-matrix least-squares methods on F2 using SHELXL-97 [15]
from within the WINGX [16] suite of software. All non-hydrogen
Table 1
Parameters for data collection and structure refinement of I-V.
Crystal data
I
II
III
IV
V
Chemical formula
Crystal shape/colour
Formula weight
Crystal system
C
16H16N2S
C18H18N2
Plate, colourless
262.34
C18H17ClN2
Block, colourless
296.79
C23H19ClN2
Plate, colourless
358.85
Monoclinic
P21/n
C23H20N2
Block, colourless
324.41
Monoclinic
P21
Prism, colourless
268.37
Triclinic
Triclinic
Triclinic
ꢀ
ꢀ
ꢀ
Space group
P1
P1
P1
0
9.1949 (3)
10.4874 (3)
16.4212 (5)
9.5479 (10)
10.1750 (9)
16.6959 (11)
7.7683 (4)
8.3158 (4)
13.2502 (6)
12.7229 (5)
8.9584 (2)
a (AÅ)
0
9.2733 (3)
6.3403 (1)
b (AÅ)
0
15.9338 (5)
15.6090 (5)
c (AÅ)
a
(°)
b (°)
(°)
100.773 (3)
100.041
110.851 (3)
296
97.093 (7)
99.710 (7)
112.078 (9)
296
72.268 (4)
81.874 (4)
68.481 (5)
296
90.00
90.031 (4)
90.00
296
1879.92 (11)
90.00
96.153 (2)
90.00
296
881.47 (3)
c
Temperature (K)
Volume (AÅ3)
0
1402.78 (7)
1450.2 (2)
758.04 (6)
Z
4
4
2
4
2
Dx (Mg mꢁ3
)
1.271
1.93
568
1.202
0.55
560
1.300
2.17
312
1.268
1.84
752
1.222
0.55
344
l
(mmꢁ1
F000
)
Crystal size (mm)
Absorption correction
Tmin
0.42 ꢂ 0.19 ꢂ 0.07
Multi-scan
0.334
0.35 ꢂ 0.21 ꢂ 0.06
Multi-scan
0.924
0.43 ꢂ 0.25 ꢂ 0.14
0.37 ꢂ 0.25 ꢂ 0.05
Multi-scan
0.779
0.39 ꢂ 0.25 ꢂ 0.14
Multi-scan
0.831
Multi-scan
0.912
Tmax
1.000
1.000
1.000
1.000
1.000
Measured reflections
Independent reflections
Observed reflections
Rint
29,178
5841
5028
18,045
6011
4989
6887
3147
2824
0.015
10,149
3910
2976
8180
3243
3120
0.014
0.028
0.016
0.029
hmax (°)
76.5
76.5
76.4
76.2
26.0
Refinement on
F2
F2
F2
F2
F2
R[F2 > 2
r
(F2)], wR(F2), S
0.083, 0.324, 1.48
5841
0.039, 0.108, 1.03
6011
0.039, 0.114, 1.06
3147
0.050, 0.151, 1.04
3910
0.031, 0.084, 1.10
3243
No. of reflections
No. of parameters
345
1.51, ꢁ0.76
363
0.13, ꢁ0.16
197
0.22, ꢁ0.24
235
0.30, ꢁ0.44
226
0.09, ꢁ0.10
0
D
qmax
,
D
qmin (eAÅꢁ3
)

L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
275
atoms were refined with anisotropic parameters. The H atoms of C
atoms were located from different maps and then treated as riding
atoms with CAH distances of 0.93–0.98 Å. The crystal of I used for
data collection was rather thin and not good in quality. This is the
reason of the low quality of some crystallographic parameters. The
largest diff. peak is a significantly larger than for other ones. Molec-
ular diagrams were created using MERCURY [17]. Supramolecular
analyses were made and the diagrams were prepared with the
aid of PLATON [18]. The parameters for data collection and struc-
ture refinement of complexes I–V are listed in Table 1.
for calculating nuclear magnetic shielding tensor. To investigate
the reactive sites of the compounds I–V, the molecular electrostatic
potentials were calculated using the same method. Additionally,
the frontier orbitals and DFT global chemical reactivity descriptors
were evaluated using the B3LYP/6-31G(d,p).
Results and discussion
Description of the crystal structures
The crystallographic analyses reveal that the compounds I–V
appear very similar. The bond lengths and angles are reported in
Tables S1 and S2 (Supporting material) together with other
relevant geometrical data.
Theoretical methods
All theoretical computations were done by using Gaussian 03
software package [19], and Gauss-view visualization program
[20]. For calculation of molecular geometries were used the
obtained atomic coordinates from X-ray geometry. The compounds
I–V were optimized by using DFT method proposed by Hohenberg
and Kohn, starting from the experimental structures [21,22]. DFT
calculations with a hybrid functional B3LYP (Becke’s three param-
eter hybrid functional using the Lee–Young–Parr (LYP) correlation
functional) [23,24] at 6-31G(d,p) double-zeta basis set with polar-
ization functions on both heavy and hydrogen atoms [25] using the
Berny method [26,27] were performed. The harmonic vibrational
frequencies were analytically calculated by taking the second-
order derivative of energy using the same level of theory. 1H
NMR and 13C NMR chemical shifts are calculated within GIAO
approach [28,29] which is one of the most common approaches
Compounds I–V
The molecular structures of I–V with the atom numbering
schemes are shown in Fig. 1. The asymmetric units of I and II con-
tain two crystallographically independent molecules, while the
asymmetric unit of III–V contain one molecule. In I–V, the NAN
bond distance range from 1.402(1) to 1.416(1) Å, respectively.
These values are comparable to those observed in other indazole
derivatives [30–33]. Each pyrazole ring is twisted about the CAC
bond (r.m.s. deviation for the fitted atoms = 0.1333 and 0.1398 Å
for I, 0.1461 and 0.1410 Å for II, 0.1452 Å for III, 0.0625 Å for IV
and 0.1040 Å for V). Each cyclohexene ring adopts a half-chair con-
formation. The puckering parameters (q2, q3, QT, h and
u) are
Fig. 1. The molecules of I–V showing the atom-labelling scheme.

276
L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
Table 2
CAHꢃ ꢃ ꢃ
p interactions distances (Å) and angles (°).
DAHꢃ ꢃ ꢃA
DAH
Hꢃ ꢃ ꢃA
Dꢃ ꢃ ꢃA
DAHꢃ ꢃ ꢃA
Symmetry codes
I
C2AH2ꢃ ꢃ ꢃCg(1)i
C4AH4ꢃ ꢃ ꢃCg(2)ii
C18AH18ꢃ ꢃ ꢃCg(2)i
C30AH30ꢃ ꢃ ꢃCg(1)
0.93
0.93
0.93
0.93
3.190
2.918
3.282
2.866
4.107 (7)
3.692 (6)
4.197 (9)
3.747 (8)
169
142
168
159
(i) x, y + 1, z
(ii) ꢁx, 2 ꢁ y, 1 ꢁ z
Cg(1)@S1AC12/C15
Cg(2)@S2AC28/C31
II
C2AH2ꢃ ꢃ ꢃCg(2)i
0.93
0.97
0.93
3.335
2.739
3.057
4.237 (7)
3.651 (7)
3.962 (8)
164
157
165
(i) x, y ꢁ 1, z
Cg(1)@C1/C6
Cg(2)@C12/C17
C10AH10Aꢃ ꢃ ꢃCg(1)ii
C17AH17ꢃ ꢃ ꢃCg(1)iii
(ii) 2 ꢁ x, ꢁy, ꢁz
(iii) 1 ꢁ x, ꢁy, ꢁz
III
C8AH8ꢃ ꢃ ꢃCg(1)i
0.98
0.98
2.782
2.986
3.711 (3)
3.964 (5)
158
175
(i) 1 ꢁ x, ꢁy, ꢁz
Cg(1)@C1/C6
Cg(1)@C1/C6
C11AH11ꢃ ꢃ ꢃCg(1)ii
(ii) 1 ꢁ x, 1 ꢁ y, ꢁz
IV
V
C14AH14ꢃ ꢃ ꢃCg(1)i
0.93
2.663
3.560 (7)
162
(i) x ꢁ 1/2, 3/2 ꢁ , 1/2 + z
C3AH3ꢃ ꢃ ꢃCg(2)i
0.93
0.93
0.97
3.085
3.320
3.266
3.754 (9)
4.088 (7)
4.069
130
142
141
(i) 1 ꢁ x, 1/2 + y, 1 ꢁ z
Cg(1)@C1/C6
Cg(2)@C12/C17
Cg(3)@C18/C23
C14AH14ꢃ ꢃ ꢃCg(3)ii
C10AH10Bꢃ ꢃ ꢃCg(1)iii
(ii) x + 1, y, z
(iii) 1 ꢁ x, y ꢁ 1/2; 1 ꢁ z
0.3643 Å, 0.3030 Å, 0.4738°, 50.25° and 229.60° for C1AC6/C10
ring and 0.3680 Å, 0.2959 Å, 0.4722°, 51.20° and 228.31° for
C17AC22/C26 ring in I, 0.3484 Å, 0.2935 Å, 0.4556°, 49.89° and
231.77° for C1AC6/C10 ring and 0.3585 Å, ꢁ0.2946 Å, 0.4641°,
129.41° and 48.03° for C19AC24/C28 ring in II, 0.3610 Å, ꢁ0.2995 Å,
0.4691°, 129.69° and 54.75° in III, 0.3941 Å, ꢁ0.3162 Å, 0.5053°,
128.74° and 37.40° in IV and 0.4054 Å, ꢁ0.2910 Å, 0.4990°,
125.68° and 45.89° in V. The largest deviations from the best
planes are 0.3337 (20) Å for C9 and 0.3325 (20) Å for C25 in I,
0.3221 (9) Å for C9 and 0.3263 (9) Å for C27 in II, 0.3340 (10) Å
for C9 in III, 0.3423 (22) Å for C9 in IV and 0.3496 (11) Å for C9
in V. The thiophene rings in I form dihedral angles of 79.27 (9)°
and 84.72 (9)°, with the least-squares plane through the pyrazole
ring. The dihedral angles between phenyl and pyrazole ring planes
are 80.19 (4)° and 88.22 (4)° in II and 76.12 (4)° and 14.96 (8)° in V.
The pyrazole ring exhibits dihedral angles of 64.90 (5)° for III and
81.12 (9)° and 22.48 (9)° for IV with the phenyl rings. By contrast,
the pyrazole-C-bound phenyl group in IV and V is almost perpen-
dicular to the pyrazole ring, so that to a first approximation, each
geometrical parameters can be caused by gas-phase modeling
which neglects the environmental (steric, electrostatic and
intermolecular interactions) influence of the neighboring mole-
cules. According to these results, it is seen that the B3LYP
calculations well reproduce the geometries of the compounds.
The calculated geometric parameters also represent good approxi-
mations and they can be used as foundation to predict and to
explore the other properties for the compounds.
Vibrational spectra
Experimental and calculated FT-IR spectrum of the title com-
pound was given in Fig. S2. Some of the characteristic frequencies
for the title compounds have given in Table S3 (in supporting
material) and the correlation graphic which described harmony
between the calculated and experimental frequencies are plotted
(Fig. S3). The harmonic frequencies by DFT calculations are usually
higher than the corresponding experimental ones due to the facts
of the electron correlation approximate treatment, anharmonicity
effects, basis set deficiencies, etc. [34]. After scaling, the theoretical
frequencies will match well with experimental ones. The theoreti-
cal harmonic frequencies were scaled by the empirical factor of
0.9627 according to Ref. [34] to correct the theoretical errors in this
work. The experimental frequencies are slightly lower than the cal-
culated values. These discrepancies are caused by environment and
the fact that the theoretical calculations neglect the anharmonicity
effect [35]. In the experimental IR results, aromatic CAH stretchiꢁn1g
molecule has a stunted T-shape. Each compound has CAHꢃ ꢃ ꢃ
interactions. Details of these interactions are given in Table 2.
interactions play a crucial role in
p
These intermolecular CAHꢃ ꢃ ꢃ
p
the architecture of the networks (Fig. S1 in Supporting material).
Theoretical studies
bands of I–V were observed range between 3036 and 3063 cm
,
.
Optimized geometries
while the theoretical values range between 3080 and 3114 cmꢁ1
The geometric parameters of I–V were calculated at the B3LYP/
6-31G(d,p) level by DFT method and listed in Tables S1 and S2,
together with corresponding experimental values. As can be seen
in Table S1, the most of the optimized bond lengths are slightly dif-
ferent from the experimental results, since the molecular states are
different during the experimental and theoretical processes. Many
packing molecules are treated in condensed phase during experi-
mental measurement, while one isolated molecule is considered
in gas phase during the theoretical calculation. The biggest devia-
tions of the selected bond lengths are 0.179 Å (C(12)AC(15)) for
I, 0.044 Å (C(30)AC(31)) for II, 0.013 Å (N(1)AN(2)) for III,
0.021 Å (C(14)AC(15)) for IV and 0.028 Å (C(14)AC(15)) for V. In
order to compare the theoretical results with the experimental val-
ues, root mean square error (RMSE) is used. The calculated (RMSE)s
for bond lengths are 0.055 Å, 0.013 Å, 0.008 Å, 0.009 Å and 0.011 Å
for I–V, respectively. As shown, the best fit between experimental
and calculated bond lengths is seen in molecule III. Besides,
the dihedral angles between the ring-planes as well as the bond
angles are listed in Table S2 and compared with the experimental
data. The small differences between the calculated and observed
While the aromatic CAC stretching vibrations were seen range
between 1581 and 1595 cmꢁ1, the same bands were calculated
range between 1589 and 1608 cmꢁ1. These stretching modes are
consistent with those reported in the literature [36].
NMR spectra
The measured 13C and 1H NMR spectra are shown in Figs. S4–
S13. GIAO 1H and 13C chemical shift values (with respect to TMS)
were calculated using the B3LYP method with 6-31G(d,p) basis
set and generally compared to the experimental 1H and 13C chem-
ical shift values. The results of these calculations are shown in
Table S4. The calculated 1H chemical shift values (with respect to
TMS) are range between 1.49 and 8.53 ppm at B3LYP/6-31G(d,p)
level, whereas the experimental results are observed to be
1.83–8.18 ppm. The aromatic CAH signals were observed to be
6.62–8.18 ppm. These were calculated 6.43–8.83 ppm at B3LYP
level. The CH3 hydrogens appear at 2.83, 2.82, 2.78 ppm for I, II
and III respectively, and are determined computationally at
between 2.61 and 3.62 ppm. 13C NMR spectras show signals at

L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
277
possible sites of electrophilic attack in both molecules. The most
negative potential sites are on the N1 atoms in the all molecules
and V(r) values are (expressed in a.u.) ꢁ0.040 for I, ꢁ0.0448 for II,
ꢁ0.039 for III, ꢁ0.022 for IV and ꢁ0.036 for V. According to this
results, the N atoms are the most suitable regions for the electro-
philic reaction and they can easily react with atoms having high
electrophilic attraction such as metal atoms. The Mulliken charges
of atoms of the title compounds are also calculated at the B3LYP
level are listed in Table S5. The nitrogen atoms in all molecules bear
the majority of negative charges.
range between 26.71 and 29.72 ppm due to the methylene C
atoms. These signals were calculated at range between 21.48 and
25.08 ppm. While the methyl C atoms are observed at 42.13,
42.51 and 42.02 ppm for I, II and III, respectively. These signals
were calculated at 33.58, 33.5 and 33.43 ppm, respectively. The
other calculated chemical shift values can be seen in Table S4. As
can be seen from Table S4, the theoretical 1H and 13C chemical shift
results are generally closer to the experimental 1H and 13C shift
data.
Mulliken atomic charges and molecular electrostatic potential
Frontier molecular orbitals
Molecular electrostatic potential (MEP) maps are often used for
the qualitative interpretation of electrophilic and nucleophilic
reactions [37], rationalize intermolecular interactions between
polar species, the calculation of atomic charges [38] and define
regions of local negative and positive potential in the molecule
[39]. This surface represents the distance from a molecule at which
a positive test charge experiences a certain amount of attraction or
repulsion and they highlight the bonding possibilities during com-
plex formation. Molecular electrostatic potential V(r) is defined by
Eq. (1):
The frontier molecular orbitals play an important role in the
electric and optical properties, as well as in UV–vis spectra and
chemical reactions [43]. The HOMO and LUMO are also important
in determining such properties as molecular reactivity and the
ability of a molecule to absorb light. LUMO (lowest unoccupied
molecular orbital) is the molecular orbital of lowest energy that
is not occupied by electrons and represents the ability to obtain
an electron, HOMO (highest occupied molecular orbital) is molec-
ular orbital of highest energy that is occupied by electrons and rep-
resent the ability to donate an electron [44]. Fig. 3 shows the
distributions and energy levels of the HOMO and LUMO orbitals
computed at the DFT/B3LYP/6-31G(d,p) level for I–V. In I and II,
while the HOMOs are mainly localized on the whole molecules
except for pyrazole (I) and phenyl (II) rings in A molecule, the
LUMOs are populated on B molecule. Similarly, in the other three
molecules (III–IV–V), the HOMOs and LUMOs are mainly localized
on the whole structure except phenyl rings. The HOMO–LUMO
energy separation can be used as a sign of kinetic stability [45].
A large HOMO–LUMO gap implies high kinetic stability and low
chemical reactivity, as it is energetically unfavorable to add elec-
tron to a high-lying LUMO, to extract electrons from low-lying
HOMO [46]. Therefore it is said that the most stable molecule is
III, while the most unstable molecule is V in them.
Z
X
ZA
RA ꢁ r
q
ðr0Þ
VðrÞ ¼
ꢁ
dr0
ð1Þ
ðr0 ꢁ rÞ
A
where ZA is the charge of nucleus A, located RA,
q
(r0) is the electronic
density function of the molecule and r0 is dummy integration vari-
able [40]. To investigate the reactive sites of I–V the molecular elec-
trostatic potentials were evaluated using the B3LYP/6-31G(d,p)
method. The negative (red) regions of MEP were related to electro-
philic reactivity and the positive (blue) regions to nucleophilic reac-
tivity. The electrostatic potential V(r) is also well suited for
analyzing processes based on the ‘‘recognition’’ of one molecule
by another, as in drug–receptor, and enzyme–substrate interac-
tions, because it is through their potentials that the two species first
‘‘see’’ each other [41,42]. As it can be seen in Fig. 2, there are several
Fig. 2. Molecular electrostatic potential maps of I–V calculated at B3LYP/6-31G(d,p) level.

278
L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
Fig. 3. Molecular orbital surfaces and energy levels for the HOMO and LUMO of I–V computed at B3LYP/6-31G(d,p) level.
The electronic absorption spectra of the title compounds were
While hard molecules have a large HOMO–LUMO energy gap,
soft molecules have a small HOMO–LUMO energy gap. A small
HOMO–LUMO energy gap means small excitation energies.
Therefore, hard molecules, with a large gap, will have their electron
density changed more hardly than a soft molecule [47]. The results
in Table 3 indicate that while III is the hardest and least reactive
among them.
recorded within the 250–400 nm range and representative spectra
are shown in Fig. S14. As can be seen from Fig. S14, electronic
absorption spectra showed a single band at 311 nm (for I),
318 nm (for II), 349 nm (for III), 317 nm (for IV) and 349.5 nm
(for V). These electronic absorptions correspond to the transition
from the ground to the first excited state (from HOMO to LUMO).
Electronic chemical potential is defined as the negative of elec-
tronegativity of a molecule [48] and is approximated using Eq. (3)
[49]
Chemical reactivity
Chemical hardness is a useful concept for understanding the
behavior of chemical systems and is associated with the stability
and reactivity of a chemical system. Chemical hardness is defined
by Eq. (2) [47]:
l
l
¼ ðEHOMO þ ELUMOÞ=2
ð3Þ
define the escaping tendency of electrons from an equilibrium
system [50]. Table 3 contains the computed electronic chemical
potential values for I–V. The trend in electronic chemical potential
for the molecules is V < II < IV < I < III. Therefore, the molecule V
is the least stable and the most reactive of the all.
g
¼ ðEHOMO ꢁ ELUMOÞ=2
ð2Þ
Table 3
Global chemical reactivity indices for I–V.
I
II
III
IV
V
ETOTAL (Hartree)
EHOMO (eV)
ELUMO (eV)
ꢁ61,336.28
ꢁ43,880.07
ꢁ5.1095
ꢁ1.1017
2.0039
ꢁ34,446.35
ꢁ5.3479
ꢁ1.008
ꢁ39,663.90
ꢁ5.0535
ꢁ1.1679
1.9428
ꢁ27159.72
ꢁ4.9220
ꢁ1.0628
1.9296
ꢁ5.3120
ꢁ0.9938
2.1591
g
l
(eV)
(eV)
2.1610
ꢁ3.1529
ꢁ3.1056
ꢁ3.1780
ꢁ3.1107
ꢁ2.9924
w (eV)
(Debye)
2.3021
2.4065
2.3368
2.4903
2.3203
l
2.9087
4.5491
2.0538
3.0052
3.0547

L.A. Taib et al. / Journal of Molecular Structure 1076 (2014) 272–279
279
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In this study, five novel molecules [2-methyl-3-thiophen-2-yl-3,
3a,4,5-tetrahydro-2H-benzo[g]indazole (I), 2-methyl-3-phenyl-3,3a,
4,5-tetrahydro-2H-benzo[g]indazole (II), 3-(4-chloro-phenyl)-2-
phenyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole (III), 3-(4-chloro-
phenyl)-2-methyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole (IV),
2,3-diphenyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole (V)] have
been synthesized and characterized by using IR, 1H NMR, 13C
NMR and X-ray single-crystal diffraction. Molecular geometries
from X-ray experiment of I–V in the ground state have been
compared using the Density Functional Theory (DFT) with B3LYP/
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to the XRD values and are used as foundations to investigate the
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Appendix A. Supplementary material
Crystallographic data for the structure reported in this article
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication numbers 976279 for I,
976280 for II, 976281 for III, 976282 for IV and 976283 for V.
Copies of the data can be obtained free of charge on application
to CCDC 12 Union Road, Cambridge CB21 EZ, UK. (Fax: +44 1223
336-033; e-mail: data_request@ccdc.cam.ac.uk). Supplementary
data associated with this article can be found, in the online version,
at http://dx.doi.org/10.1016/j.molstruc.2014.07.033.
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