Synthesis, crystal structures and spectroscopic properties of triazine-based hydrazone derivatives; a comparative experimental-theoretical study

Article abstract of DOI:10.3390/molecules20045851

We report here a comparative theoretical and experimental study of four triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process from commercially available benzil and thiosemicarbazide. The structures of all compounds were determined by using the UV-Vis., FT-IR, NMR (¹H and ¹³C) spectroscopic techniques and finally confirmed unequivocally by single crystal X-ray diffraction analysis. Experimental geometric parameters and spectroscopic properties of the triazine based hydrazones are compared with those obtained from density functional theory (DFT) studies. The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level of DFT. Optimized geometric parameters of all four compounds showed excellent correlations with the results obtained from X-ray diffraction studies. The vibrational spectra show nice correlations with the experimental IR spectra. Moreover, the simulated absorption spectra also agree well with experimental results (within 10-20 nm). The molecular electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic properties) and first hyperpolarizability (nonlinear optical response) were also computed at the B3LYP/6-31G (d, p) level of theory.

Full text of DOI:10.3390/molecules20045851

Molecules 2015, 20, 5851-5874; doi:10.3390/molecules20045851
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis, Crystal Structures and Spectroscopic Properties of
Triazine-Based Hydrazone Derivatives; A Comparative
Experimental-Theoretical Study
Muhammad Nadeem Arshad 1,*, Aisha Bibi 2, Tariq Mahmood 2,*, Abdullah M. Asiri 1,3 and
Khurshid Ayub 2,4
1
Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203,
Jeddah 21589, Saudi Arabia; E-Mail: aasiri2@gmail.com
2
Department of Chemistry, COMSATS Institute of Information Technology, University Road,
Tobe Camp, 22060 Abbottabad, Pakistan; E-Mails: aishabibi657@gmail.com (A.B.);
khurshid@ciit.net.pk (K.A.)
3
Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University,
P.O. Box 80203, Jeddah 21589, Saudi Arabia
4
Department of Chemistry, College of Science, King Faisal University, Al-Hafouf 31982,
Saudi Arabia
* Authors to whom correspondence should be addressed;
E-Mails: mnchemist@hotmail.com (M.N.A.); mahmood@ciit.net.pk (T.M.);
Tel.: +966-580-330-428 (M.N.A.); +92-992-383-591-6 (ext. 309) (T.M.).
Academic Editor: Wim Dehaen
Received: 14 February 2015 / Accepted: 23 March 2015 / Published: 3 April 2015
Abstract: We report here a comparative theoretical and experimental study of four
triazine-based hydrazone derivatives. The hydrazones are synthesized by a three step process
from commercially available benzil and thiosemicarbazide. The structures of all compounds
were determined by using the UV-Vis., FT-IR, NMR (1H and 13C) spectroscopic techniques
and finally confirmed unequivocally by single crystal X-ray diffraction analysis.
Experimental geometric parameters and spectroscopic properties of the triazine based
hydrazones are compared with those obtained from density functional theory (DFT) studies.
The model developed here comprises of geometry optimization at B3LYP/6-31G (d, p) level
of DFT. Optimized geometric parameters of all four compounds showed excellent
correlations with the results obtained from X-ray diffraction studies. The vibrational spectra
show nice correlations with the experimental IR spectra. Moreover, the simulated absorption

Molecules 2015, 20
spectra also agree well with experimental results (within 10–20 nm). The molecular
5852
electrostatic potential (MEP) mapped over the entire stabilized geometries of the compounds
indicated their chemical reactivates. Furthermore, frontier molecular orbital (electronic
properties) and first hyperpolarizability (nonlinear optical response) were also computed at
the B3LYP/6-31G (d, p) level of theory.
Keywords: triazine; hydrazone; X-ray; DFT; MEP; first hyperpolarizability
1. Introduction
Heterocyclic chemistry is essential to biology and medicine. It is not questionable to say that we are
living in the age of heterocyclic chemistry. Triazines are heterocyclic analogue of benzene containing
three nitrogen atoms with moelcular formula C3H3N3. Three isomeric triazines are shown in Figure 1.
N
N
N
N
N
N
N
N
N
1,2,3-triazine
1,2,4-triazine
1,3,5-triazine
Figure 1. Basic skeleton of different types of triazines.
In 1776, Scheele synthesized triazine through pyrolysis of uric acid, and later Serullas repeated the
work of Scheele however, the structure was first confirmed by Leibig and Wohler [1]. Molecules
containing triazine skeletons show considerable biological and pharmaceutical activities [2,3].
2-Ethoxymethyl-6-ethyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dione was synthesized and evaluated for
its antimicrobial activity [4] and later its molecular and vibrational spectra were investigated by applying
density functional theory methods [5]. Hydrazides of 1,2,4-triazine have been used as precursors for the
synthesis of various biologically active compounds [3]. Moreover, these molecules are also efficient in
dye sensitized solar cells (DSSC) [6].
Hydrazones are another class of compounds well known to possess various kinds of biological
activities [7]. They have been used as an intermediate for the preparation of heterocycles displaying
useful activities [8,9]. Recently Jani et al. has reported the synthesis and antimicrobial activities of
complexes prepared using ligands containing triazine and hydrazone functionalities [10]. The vast range
of pharmacological applications of these classes of compounds encouraged us to synthesize compounds
containing both triazine and hydrazone moieties. We report here the synthesis, crystal structures and
spectroscopic properties of some 1,2,4-triazine-based hydrazone derivatives. In continuation to our
on-going studies of various class of heterocyclic molecules [11–13], density functional theory (DFT)
studies were also performed not only to validate the experimental results, but also to explore further
structural properties as well.

Molecules 2015, 20
5853
2. Results and Discussion
2.1. Synthesis
The synthesis of all four triazine based hydrazone derivatives 1–4 was performed in three steps
starting from commercially available benzil. The first step was condensation of benzil with
thiosemicarbazide followed by another condensation of the intermediate with hydrazine hydrate to
construct the triazine ring. The hydrazine intermediate was then reacted with the respective aldehydes
to deliver hydrazones 1–4 as the final products (Scheme 1).
Scheme 1. Synthetic scheme of target compounds 1–4.
2.2. Crystallographic Studies
All four compounds were crystalized from dimethyl sulfoxide (DMSO) solution while standing in the
lab at room temperature for about three months. In order to establish the X-ray structures suitable crystals
were picked under a microscope. The structures of the compounds were established in order to
understand their three dimensional interactions in a unit cell. Complete crystallographic parameters of
all compounds 1–4 are provided in Table 1. The ORTEP diagrams of all compounds are shown
in Figure 2.

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5854
Table 1. Crystal data and structure refinement parameters.
Identification Code
1
2
3
4
Empirical formula
C26H19N5O
417.46
C23H19N5O
381.43
296.15
monoclinic
P21/c
C24H22N6
394.48
C22H17N5O
367.41
Formula weight
Temperature/K
296.15
296.15
296.15
Crystal system
monoclinic
P21/n
triclinic
P-1
monoclinic
P21/c
Space group
a/Å
6.5745(2)
19.9133(6)
15.9805(5)
90.00
5.9756(18)
21.573(6)
14.980(4)
90.00
8.8933(10)
11.1477(11)
11.7484(13)
91.212(9)
106.044(10)
108.519(9)
1053.8(2)
2
14.9753(17)
6.1220(6)
21.038(2)
90.00
b/Å
c/Å
α/°
β/°
96.369(3)
90.00
93.45(2)
90.00
103.992(11)
90.00
γ/°
Volume/Å3
Z
2079.25(11)
4
1927.7(9)
4
1871.6(3)
4
ρ
calcmg/mm3
m/mm−1
F(000)
1.334
1.314
1.243
1.304
0.677
0.084
0.077
0.084
872.0
800.0
416.0
768.0
Crystal size/mm3
0.48 × 0.16 × 0.15 0.48 × 0.08 × 0.05 0.32 × 0.26 × 0.17
0.43 × 0.15 × 0.05
5.6 to 59.14°
−19 ≤ h ≤ 19,
−8 ≤ k ≤ 7,
−29 ≤ l ≤ 26
11939
2θ range for data collection
7.12 to 152°
−6 ≤ h ≤ 8,
−25 ≤ k ≤ 21,
−20 ≤ l ≤ 19
12339
5.76 to 58.66°
−7 ≤ h ≤ 8,
−27 ≤ k ≤ 24,
−20 ≤ l ≤ 18
11554
5.62 to 58.9°
−11 ≤ h ≤ 9,
−12 ≤ k ≤ 14,
−16 ≤ l ≤ 15
9379
Index ranges
Reflections collected
4304[R(int) =
0.0185]
4608[R(int) =
0.0727]
5004[R(int) =
0.0252]
4597[R(int) =
0.0620]
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
4304/0/290
1.036
4608/1/266
1.012
5004/0/274
1.038
4597/1/257
0.961
R1 = 0.0428,
wR2 = 0.1156
R1 = 0.0546,
wR2 = 0.1273
0.19/−0.20
R1 = 0.0626,
wR2 = 0.0925
R1 = 0.1988,
wR2 = 0.1358
0.16/−0.19
R1 = 0.0541,
wR2 = 0.1221
R1 = 0.0840,
wR2 = 0.1423
0.25/−0.16
R1 = 0.0601,
wR2 = 0.1236
R1 = 0.1880,
wR2 = 0.1670
0.13/−0.16
Final R indexes [I ≥ 2σ (I)]
Final R indexes [all data]
Largest diff. peak/hole/e Å−3
Compounds 1–4 are structurally similar regarding the triazine moiety and the two phenyl rings
attached to it. However, these hydrazones differ in the hydrazomethyl moieties attached the central
triazine ring. The triazine ring is planar mainly because all atoms are sp2 hybridized. Root mean square
deviation values of the fitted atoms of ring are 0.0285(2) Å, 0.0215(1) Å, 0.0187(1) Å and 0.0264 Å for
molecules 1–4, respectively. The dihedral angles between the triazine ring and substituted phenyl rings
are 37.99(5)° and 43.08(6)° in 1, 60.39(7)° and 31.77(1)° in 2, 61.08(8)° and 44.91(6)° in 3 and 50.02(7)°
and 34.70(1)° in compound 4. The two aromatic rings attached to the triazine moiety are twisted at
dihedral angles of 55.01(5)°, 61.85(7)°, 56.46(9)° and 57.22(7)° in all compounds 1–4 respectively. The
different dihedral angles reflect that all molecules have different spatial environment as well as Vander
Walls’ interactions in their unit cells (Figure 3). Hydrogen bond parameters of all compounds have been
listed in Table 2.

Molecules 2015, 20
5855
(1)
(2)
(3)
(4)
Figure 2. ORTEP diagrams of compounds 1–4. Thermal ellipsoids were drawn at 50%
probability level.
Compound 1 and 4 formed inverted dimers through only one carboxylic type N-H…N interaction.
The compound 2 formed inverted dimers via N-H…N classical type interactions (two). Compound 3
involved the formation of dimers through classical N-H…N interaction. These dimers are further
connected through non-classical C-H…N interaction in zig-zag manner (Figure 3). Triazine moiety is
not planer with the substituted phenyl rings (C17-C22) and dihedral angles of compounds 1–4 are
14.99(7)°, 5.13(2)°, 3.27(1)° and 14.04(2)°, respectively. Intramolecular hydrogen bonding has been
observed in compound 1 and 4 bearing hydroxyl groups at the ortho positions to produce an S(6) six
membered ring motif.
(1)
(2)
Figure 3. Cont.

Molecules 2015, 20
5856
(3)
(4)
Figure 3. Unit cell diagrams of compounds 1–4 showing the inter- and intramolecular
hydrogen bonding.
Table 2. Hydrogen bond parameters of compounds 1–4.
D
H
A
d(D-H)/Å
(1)
d(H-A)/Å
d(D-A)/Å
D-H-A/°
N4
H2
N21
0.97
1.91
2.8750(18)
171.9
(2)
C16
N4
H16
H1
N32
N22
0.93
2.58
3.496(4)
2.939(3)
168.5
0.893(10)
(3)
2.047(11)
176(3)
N4
H1
N23
N14
0.97
2.03
2.59
2.995(2)
3.449(3)
168.8
148.7
C24
H24C
0.96
(4)
O1
N4
H1O
H2
N5
0.82
1.93
2.646(3)
2.907(4)
146.1
N25
0.889(10)
2.033(12)
167(3)
12 − X, −Y, −Z, 21 − X, 1 − Y, 1 − Z, 3−X, −Y, −Z, 41 + X, +Y, +Z, 5−X, 2 − Y, −Z
2.3. Geometries Optimization
Theoretical studies have been performed to compare the geometric parameters with those obtained
from X-ray diffraction studies. The geometric parameters of title compounds 1–4 were optimized using
Gaussian 09 program at B3LYP/6-31G (d, p) level of DFT. Optimized geometries are shown in
Figure 4 and comparison of simulated bond lengths and bond angles of compounds 1–4 along with
X-ray values are listed in Tables 3–6, respectively.

Molecules 2015, 20
5857
(1)
(2)
(3)
(4)
Figure 4. Optimized geometries of compounds (1–4) at B3LYP/6-31G (d, p) level of DFT.
Table 3. Selected molecular structure parameters of compound 1.
Bond Lengths (A°) Experimental B3LYP/6-31G (d, p)
O1-C18
N1-C1
N1-C2
N2-N3
N2-C1
N3-C3
N4-N5
N4-C1
N5-C16
1.353(2)
1.341(18)
1.327(18)
1.328(17)
1.338(19)
1.336(17)
1.364(18)
1.356(19)
1.286(19)
1.430
1.335
1.335
1.315
1.354
1.347
1.354
1.368
1.294
Bond Angles (°)
116.2(12)
118.1(12)
120.2(12)
119.4(12)
117.9(13)
119.3(13)
125.4(13)
115.2(13)
120.0(12)
114.6(12)
119.4(13)
115.0(12)
116.1(16)
C2-N1-C1
N3-N2-C1
N2-N3-C3
C1-N4-N5
C16-N5-N4
N1-C1-N4
N2-C1-N1
N2-C1-N4
N1-C2-C3
N1-C2-C4
N3-C3-C2
N3-C3-C10
O1-C18-C19
116.3
116.9
121.2
123.1
116.6
120.6
125.7
113.5
119.4
115.1
118.9
114.7
118.9

Molecules 2015, 20
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Table 4. Selected molecular structure parameters of compound 2.
Bond Lengths (A°) Experimental B3LYP/6-31G (d, p)
O1-C20
O1-C23
N1-C1
N1-C2
N2-N3
N2-C1
N3-C3
N4-N5
N4-C1
1.377(3)
1.426(3)
1.332(3)
1.330(3)
1.343(3)
1.353(3)
1.334(3)
1.387(3)
1.372(3)
Bond Angles (°)
115.6(2)
117.3(2)
120.2(2)
121.9(2)
112.5(2)
122.1(2)
126.3(2)
111.6(3)
120.9(3)
115.5(2)
119.4(2)
113.9(2)
117.6(3)
1.362
1.419
1.334
1.335
1.316
1.353
1.346
1.351
1.370
C2-N1-C1
N3-N2-C1
N2-N3-C3
C1-N4-N5
C16-N5-N4
N1-C1-N4
N2-C1-N1
N2-C1-N4
N1-C2-C3
N1-C2-C4
N3-C3-C2
N3-C3-C10
C20-O1-C23
116.3
116.7
121.2
121.9
119.1
119.7
126.1
114.0
119.1
115.3
119.1
114.7
118.5
Table 5. Selected molecular structure parameters of compound 3.
Bond Lengths (A°) Experimental B3LYP/6-31G (d, p)
O1-C1
N1-C2
N2-N3
N2-C1
N3-C3
N4-N5
N4-C1
N5-C16
N6-C20
1.347(2)
1.325(2)
1.333(2)
1.351(2)
1.336(2)
1.381(2)
1.349(2)
1.282(2)
1.372(2)
1.521
1.402
1.540
1.395
1.402
1.540
1.540
1.540
1.383
Bond Angles (°)
115.3(14)
118.3(13)
119.6(14)
122.4(14)
113.8(14)
120.7(15)
125.4(15)
113.7(14)
121.2(15)
116.5(15)
119.7(14)
116.5(14)
C2-N1-C1
N3-N2-C1
N2-N3-C3
C1-N4-N5
C16-N5-N4
N1-C1-N4
N2-C1-N1
N2-C1-N4
N1-C2-C3
N1-C2-C4
N3-C3-C2
N3-C3-C10
116.3
119.9
119.6
109.4
109.4
120.9
118.1
120.9
120.4
119.1
120.4
119.1

Molecules 2015, 20
5859
Table 6. Selected molecular structure parameters of compound 4.
Bond Lengths (A°) Experimental B3LYP/6-31G (d)
O1-C18
N1-C1
N1-C2
N2-N3
N2-C1
N3-C3
N4-N5
N4-C1
N5-C16
1.357(4)
1.336(3)
1.337(3)
1.338(3)
1.338(3)
1.339(3)
1.383(3)
1.360(3)
1.271(3)
Bond Angles (°)
115.9(2)
117.9(2)
120.4(2)
122.5(3)
115.1(2)
120.9(3)
126.0(3)
113.1(3)
120.4(2)
116.0(2)
119.1(2)
114.3(2)
118.3(3)
1.341
1.334
1.336
1.317
1.350
1.346
1.351
1.371
1.291
C2-N1-C1
N3-N2-C1
N2-N3-C3
C1-N4-N5
C16-N5-N4
N1-C1-N4
N2-C1-N1
N2-C1-N4
N1-C2-C3
N1-C2-C4
N3-C3-C2
N3-C3-C10
O1-C18-C19
116.3
116.7
121.2
121.8
119.2
119.6
126.1
114.0
119.0
115.3
119.1
114.6
115.8
The results listed in Tables 3–6 show that X-ray and simulated bond lengths/angles of all atoms in
compounds 1–4 correlated nicely. Deviation in the selected bond lengths/angles of compound 1 was
observed in the range of 0.006–0.077 Å/0.1–3.7°. Maximum deviation in bond length was 0.077 Å for
O1-C18. Similarly maximum deviation in bond angle was 3.7° for C1-N4-N5. For 2 deviation in
selected bond lengths/angles was found in the range 0–0.036 Å/0–6.6°. Similarly the maximum deviation
in bond lengths/angles of compound 3 and 4 was observed in the range 0.011–0.258 Å/0–7.3° and
0.001–0.032 Å/0–4.1°.
Comparative analyses of the geometric data of compounds 1–4 also indicate that the intramolecular
hydrogen bonding affect the geometric parameters, particularly the C1-N2, of compound 1 and 4. The
C1-N2 bond length decreases with the increase in the strength of intramolecular hydrogen bonding. The
intramolecular hydrogen bonding is stronger in compound 1 compared to compound 4, and it is reflected
in shortened O1-C18 bond length (1.353) of compound 1. Moreover, N4-N5 bond length is also
shortened for compound 1 (strong intramolecular hydrogen bonding). The bond lengths in the triazine
central ring depend not only on the strength of the intramolecular hydrogen bonding but also on the
strength of mesomeric electron donation. In general, relatively shorter bond lengths are observed for
compound 1 whereas compound 2 shows relatively larger bond lengths. Relatively shorter bond lengths
for compounds 3 compared to 2 can be attributed to relatively strong conjugation of NMe2 group (strong
donor than methoxy through resonance) with the triazine skeleton.

Molecules 2015, 20
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2.4. Vibrational Analysis
Vibrational spectroscopy is a spectroscopic technique used in chemistry for the identification of
functional groups in order to elucidate the structure of a target molecule, kinetics of chemical reactions,
etc. Both experimental and simulated spectra are shown in the Figure 5. Comparison of prominent
frequencies of compounds 1–4 has given in Table 7.
(1)
(2)
(3)
(4)
Figure 5. Simulated (balck) and experimental (blue) vibrational spectra of compounds 1–4.
For the correction of theoretical errors in this work, the theoretical harmonic frequencies above
1700 cm−1 were scaled by a scaling factor of 0.958, and frequencies less than 1700 cm−1 were scaled by
0.9627 [14]. Compounds 1–4 mainly have NH, N=CH and aromatic ring functional groups. These
compounds have very comparable structures regarding functional groups except compound 3 which
bears a dimethyl amino group. Therefore, the vibrations in compounds 1–4 are very comparable. For
example, C=C aromatic vibrations are observed at 1611 (1), 1611 (2), 1593 (3) and 1621 cm−1 (4). The
lower stretching vibration for compound 3 compared to 1, 2 and 4 may be attributed to the better
conjugation of the dimethylamino group with the triazine skeleton. Despite similar vibrations,
characteristic distinguishing vibrations could be seen for each compound. For example, methyl groups
in 3 appear at 2950 (asymmetric stretching), 2947 (asymmetric stretching), 2891 (symmetric stretching),
2884 cm−1 (symmetric stretching). Moreover, the C-N stretching vibration is observed at 1341 cm−1.
Compound 2 was characterized by an O-Ph stretching vibration at 1244 cm−1.

Molecules 2015, 20
Table 7. Prominent experimental and simulated vibrational (cm−1) values of 1–4.
5861
1
2
3
4
Exp. B3LYP Assignment Exp. B3LYP Assignment Exp. B3LYP Assignment Exp. B3LYP Assignment
1595 ѴC=Carom
1542 ѴC=Narom
1512 ѴC=Narom
1506 ѴN=Carom
1319 ѴC-Carom
1301 ѴC-Carom
1605
ѴC=C
1605
1550
ѴC=C
ѴC=N
1613 ѴC=Carom
1565 ѴC=Carom
1536 ѴC=Narom
1510 ѴC=Narom
1611
1517
1611
1513
1593
1507
1621
1515
1542 ѴC=Narom
1511 ѴC=Narom
1499 ѴC=Carom
1318 ѴC-Carom
1538 ѴC=Narom
1511 ѴN=Carom
1508 ѴC=Narom
1367
1280
1350
1247
1428
1363
1375
1279
1353
βCHarom
1250
1127
ѴO-Ph
1341
ѴNPh
1251 ѴC-Carom
1239 1252 ѴC-Carom
1179 1127 ѴC=Narom
βCHarom
1257 ѴC-Carom 1133 1127 ѴC=Narom
1167
1060
764
1277
1126 ѴC=Narom
1171
βCHarom
1078 1081
βCHarom
βCHarom
γCHarom
1062 1061
756 775
βCHarom
βCHarom
1080
1060
βCHarom
βCHarom
1160 1126 ѴC=Narom 1062 1061
1052 1079
βCHarom
γCHarom
γCHarom
750
724
807
516
803
540
759
γCHarom
688
686
γCHarom
From Table 7 it is clear that an excellent agreement exists among simulated and experimental
vibrations. In compound 1, a strong simulated C=Carom. stretching vibration appeared at 1595 cm−1 and
showed nice agreement with the experimental 1611 cm−1. Aromatic C=C stretching vibrations in 2
depicted at 1605 cm−1 theoretically, and correlates with the experimental 1611 cm−1. Similarly the
computed aromatic C=C vibrations in compound 3 and 4 showed very nice agreement between theory
and experiment. Prominent C=N stretching vibrations of 1 found at 1542 cm−1, 1506 cm−1 and
1127 cm−1 in simulated spectrum also shows strong agreement with the experimental counterparts
appearing at 1517 cm−1, 1179 cm−1. The C=N stretching vibrations of 2, 3 and 4 also correlated
excellently between theory and experiment (for individual values see Table 7).
2.5. Nuclear Magnetic Resonance Studies (1H-NMR)
The versatility in nuclear magnetic resonance spectroscopy makes it an unavoidable tool for the
structural identification of compounds. Experimentally, NMR (both 1H and 13C) of all compounds 1–4
were recorded in DMSO and spectra are shown in the (Figures S1–S8, Supplementary Information).
1H-NMR chemical shift calculations were performed by using the fully optimized geometries at
B3LYP/6-311+G (2d, p) level by adopting the GIAO method using the internal reference standard i.e.,
tetramethylsilane. The detailed simulated 1H-NMR chemical shift values are listed in Table 8.
All compounds have NH protons that appeared at 8.43 ppm (1), 8.49 ppm (2), 8.42 ppm (3) and 8.34
ppm (4) theoretically, whereas the experimental peaks appeared at 12.31 ppm (1), 11.80 ppm (2), 11.62
ppm (3), and 12.26 ppm (4). NH protons are solvent and environment dependent; therefore, it is very
hard to compare the theoretical values with the experimental ones [15]. Compounds 1 and 4 contain OH
functional groups and are involved in intramolecular hydrogen bonding as depicted from X-ray studies,
therefore, these protons appeared theoretically at 12.87 ppm (1), 11.34 ppm (4), and show excellent
correlation with the experimental values at 12.77 ppm (1), 11.47 ppm (4). Computed chemical shift
values of azomethine protons appeared at 9.39 ppm (1), 8.00 ppm (2), 7.93 ppm (3) and 8.28 ppm (4),
whereas experimental values appeared at 9.33 ppm (1), 8.22 ppm (2), 9.65 ppm (3) and 8.45 ppm (4)
respectively. Aromatic protons of all compounds showed very excellent correlation between

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experimental and theoretically calculated chemical shifts. Simulated aromatic protons of 1 appeared in
the range 8.98–7.28 ppm, which agrees very well with the experimental chemical shifts at 8.23–7.25 ppm.
For compound 2, theoretical chemical shifts of aromatic protons (8.79–6.83 ppm) also correlate very
nicely with the experimental chemical shifts (7.61–7.00 ppm). Similarly theoretical aromatic protons of
3 and 4 appeared in the range 8.87–6.74 ppm and 8.87–6.99 ppm, respectively which correlate nicely
with the experimental chemical shifts at 7.68–6.74 ppm and 7.67–7.00 ppm. Theoretical data of all
compounds showed close agreement with the experimental data.
Table 8. Simulated 1H-NMR chemical shifts of 1–4 (ppm) at B3LYP/6-311+G (2d, p) level
(atomic labels are with reference to Figure 4).
(1) B3LYP (ppm) (2) B3LYP (ppm) (3) B3LYP (ppm) (4) B3LYP (ppm)
51H
31H
10H
19H
29H
41H
48H
47H
13H
23H
46H
14H
8H
12.87
9.39
8.98
8.67
8.43
8.39
8.06
8.05
7.97
7.89
7.83
7.64
7.64
7.63
7.62
7.55
7.40
7.36
7.28
10H
19H
48H
29H
31H
13H
23H
14H
25H
8H
8.88
8.79
8.67
8.49
8.00
7.84
7.83
7.63
7.62
7.57
7.44
7.35
7.31
7.29
7.21
6.83
4.11
3.71
3.71
10H
19H
40H
29H
31H
13H
23H
14H
8H
8.87
8.82
8.64
8.42
7.93
7.82
7.80
7.62
7.60
7.59
7.37
7.33
7.31
7.20
6.87
6.74
3.41
3.40
3.08
3.06
2.75
2.71
43H
10H
19H
29H
31H
13H
23H
14H
25H
41H
8H
11.34
8.87
8.76
8.34
8.28
7.90
7.85
7.68
7.66
7.58
7.57
7.46
7.37
7.37
7.33
7.25
6.99
25H
38H
24H
12H
21H
43H
42H
49H
46H
47H
51H
45H
50H
41H
24H
12H
40H
21H
42H
46H
47H
45H
44H
24H
40H
12H
21H
45H
25H
49H
44H
24H
21H
12H
Since these hydrazones are structurally similar regarding the triazine skeleton therefore most of the
chemical shifts appear similar in the NMR spectra. However, distinct differences have been observed in
the chemical shifts arising from differences in the hydrazomethyl fragment. For example, the
naphthalene moiety in 1 can easily be identified by a downfield chemical shift at 9.39 ppm (31H) which
arises due to peri-hydrogens. Moreover, increased number of downfield chemical shifts between
8–9 ppm also supported the naphthalene part of compound 1. The ortho hydroxyl groups in compound 1
and 4 were supported by downfield chemical shifts at 12.77 ppm (1) and 11.47 ppm (4) (vide supra).
The characteristic methoxy group of compound 2 appeared at 3.79 ppm in the experimental NMR
spectrum which correlates nicely with the theoretical chemical shift at 4.11–3.71 ppm. Similarly, the

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characteristic dimethyl amino group in 3 was confirmed by chemical shift at 3.1 ppm, corresponding to
six protons.
2.6. Frontier Molecular Orbital Analysis (FMO) and UV-Vis. Absorption Studies
FMO analysis is a physical property used to determine, ability to absorb light, electronic as well as
optical properties of organic compounds [16]. In molecular interaction, the highest occupied molecular
orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) play the key role. HOMO is the
orbital which has ability to donate electrons and its energy corresponds to ionization potential (I. P.),
while LUMO has electrons accepting ability, and its energy corresponds to electron affinity (E. A.).
FMO analysis was computed at the same level as used for optimization along with additional keyword
pop = full, and HOMO-LUMO surfaces of all four molecules 1–4 shown in Figure 6 and energies are
listed in the Table 9. The FMO analysis showed that the HOMO is mainly concentrated on the triazine
moiety, azomethine and aromatic ring attached to the azomethine moiety. The LUMO is mainly
concentrated on the triazine and a phenyl ring attached to it. The HOMO-LUMO energy gap for 4 was
the highest and equal to 0.133 eV and for 3 it was the lowest and equal to 0.119 a. u. (3.24 eV). The
isodensities of HOMO and LUMO not only help explain the HOMO-LUMO gap but also deliver useful
information regarding the stability of a compound. The isodensity in the HOMO gives a maximum
spread in compound 4 (it also encompasses a benzene ring) which reflects the higher conjugation in 4.
These observations indicate the HOMO in 4 should have the lowest energy among all four compounds
studied, and indeed this is the case. The extended conjugation in 4 would render it more stability towards
ionization (vide infra). On the other hand, HOMO is 3 has the minimum density on the hydrazone
scaffold which renders it the compound with the highest energy (0.18 eV). The higher energy of HOMO
in 3 is expected due to the presence of a dimethylamino group. The situation is slightly different for the
LUMOs; the extent of conjugation in LUMO in all four compounds is similar (Figure 6). However, the
intensities are slightly different. Relatively higher intensities are observed for compounds 1 and 4 which
render them of lower energy compared to the LUMO in compounds 2 and 3. It is interesting to note that
the compounds 1 and 4 have intramolecular hydrogen bonding. It can be argued that intramolecular
hydrogen bonding provides low energy to the LUMO. The HOMO-LUMO gap is the sum of the effect
on HOMO and LUMO. For example, in compound 4, both HOMO and LUMO are stabilized but the
effect on the HOMO is larger than on the LUMO, and it ultimately results in an increased band gap. On
the other hand, both HOMO and LUMO are destabilized in 3 but, the effect on the former is more
pronounced than the latter, and it ultimately leads to a decrease in the band gap.
The experimental UV–Vis. absorption spectra of all compounds 1–4 were recorded within 200–600 nm
range in dimethyl sulphoxide (DMSO), and the combined spectra are shown in Figure 7.
The theoretical absorption studies were also carried out by using TD-DFT method at B3LYP/6-31G
(d, p) level of theory in gas phase, and polarizable continuum model (PCM) was applied to account for
solvent effect (For simulated UV-Vis. spectra see Figures S9–S10). A comparison of characteristic
experimental and simulated UV–vis. absorption wavelengths (λmax) of 1–4 is given in Table 10.

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HOMO (1)
LUMO (1)
HOMO (2)
HOMO (3)
LUMO (2)
LUMO (3)
HOMO (4)
LUMO (4)
Figure 6. HOMO, LUMO surfaces of compounds 1–4 simulated at B3LYP/6-31G (d, p).
Table 9. Frontier orbital energy (a. u).
Compound
E (HOMO)
−0.196
E (LUMO)
−0.0713
−0.064
ΔE (LUMO‒HOMO)
1
2
3
4
0.124
0.132
0.119
0.133
−0.196
−0.18
−0.060
−0.204
−0.072
The experimental UV-vis. spectrum of compound 1 showed an absorption maximum at 374 nm,
which is in excellent agreement with the computed values of 380 nm in the gas phase and 390.3 nm in
DMSO. The experimental absorption maxima of 2 appeared at 337 nm, and shows excellent correlation
with simulated values at 354.2 nm (gas phase) and 358.2 nm (DMSO). Similarly the theoretical and
experimental absorption maxima’s of 3 and 4 showed very excellent correlations (for individual values
see Table 10). The observed absorption maxima of compounds 1–4 can also be correlated with the
HOMO-LUMO band gap. Compounds 2 and 4 have the highest band gaps (Table 9) and this is consistent

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with the UV results that these compounds have the highest energy of absorption (shorter absorption
maximum). The band gap in compound 4 is 0.13 a. u. which corresponds to 350 nm (3.536 eV). This is
identical to theoretical absorption maximum of compound 4 at 350.2 nm. Therefore, it can be concluded
that the π‒π* transition in these compounds is a HOMO-LUMO transition. It is also interesting to note
that compounds having intra-molecular hydrogen bonding (1 and 4) have the low molar absorptivity
(Figure 7).
4.0
3.5
3.0
Compound 1
Compound 2
Compound 3
Compound 4
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
300
400
500
600
Wavelegth (nm)
Figure 7. Combined experimental UV-vis. spectra of all compounds 1–4.
Table 10. Experimental and simulated (B3LYP/6-31G (d, p)) UV-vis. λmax (nm) values of
title compounds 1–4.
Experimental
λmax (abs.) (DMSO)
Theoretical (TD-SCF/B3LYP/6-31G (d, p))
λ
max (osc. Strength),
λmax (osc. Strength)
DMSO
Compound
Assignment
Gas Phase
380.8 (0.782)
345.2 (1.189)
370.4 (1.147)
350.2 (0.739)
(1)
(2)
(3)
(4)
333 (0.419), 374 (0.454)
337 (1.903)
390.3 (0.945)
358.2 (1.401)
395.5 (1.196)
356.1 (1.007)
π‒π*
π‒π*
π‒π*
π‒π*
366 (2.834)
312 (0.567), 342 (0.697)
2.7. Molecular Electrostatic Potential (MEP)
One of the most interesting features of quantum chemistry is the ability to explain the reactivity of
compounds under investigation. In terms of reactivity the electrostatic potential plays an important role.
It determines the reactivity of a chemical system by predicting electrophilic as well as nucleophilic sites
in target molecules [17]. This is one of the basic properties, which affect the behavior of a whole target
molecule [18]. Mathematically, MEP can be defined by the following equation:
V(r) = ∑(ZA/RA-r) − (ꢁ(ꢂ′)/ꢂ′ − ꢂ)dr′
(1)
ꢀ

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Summation (∑) runs over all nuclei, ZA is charge of nucleus which is located at RA and ρ(r') is electron
density. MEP is also proved very useful in structural biology to determine ligand-substrate interactions,
change in energy upon interactions and determination of local reactivity of large target molecules under
investigation, drug receptor and in enzyme-substrate interactions. The molecular electrostatic potential
of compounds 1–4 was computed at the B3LYP/6-31G (d, p) level of DFT and the corresponding
surfaces are shown in Figure 8.
(1)
(2)
(3)
(4)
Figure 8. MEP surfaces of compounds 1–4.
During MEP mapping two basic regions appear i.e., red and blue, the preferred nucleophilic site is
represented by red color and the preferred electrophilic site is represented by blue color. According to
the MEP analysis of compound 1, a negative potential is −5.243 × 10−2 concentrated on the oxygen of
the -OH group attached to the naphthalene moiety and on nitrogens of the triazine ring (N27, N28), this is
the preferred site for electrophilic attack as well as for metal atoms. Positive potential reflecting a
nucleophilic site was 5.243 × 10−2 and was concentrated on the proton attached to N32 and on the proton
of the azomethine moiety (–C32=N33). For compound 2, the negative potential is −5.691 × 10−2
concentrated on the triazine ring, whereas the corresponding positive potential value is 5.691 × 10−2. An
almost similar trend was observed during the MEP analysis of 3, having a negative potential value
−6.094 × 10−2 and positive value of 6.094 × 10−2. Compound 4 showed a negative potential value of
−5.240 × 10−2 concentrated on the oxygen of the -OH and the nitrogens of the triazine ring (N27, N28).
The value of its positive potential is 5.240 × 10−2, concentrated on the protons attached to the azomethine
moiety (–C32=N33) and showing the nucleophilic site.
Very similar to the other properties mentioned above, compounds 1–4 can be divided into two distinct
groups based on MEP: (a) with intramolecular hydrogen bonding (b) without intramolecular hydrogen
bonding. The intramolecular hydrogen bonding confers to the oxygen of the hydroxyl group a negative

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potential and also makes it a suitable site for electrophilic attack. The more pronounced effect in
compound 1 and 4 is observed for proton attached to N4 (the proton becomes more acidic). These
analyses clearly reveal that small changes in the structure can lead to dramatic changes in
the reactivity
2.8. Hyperpolarizability and Non-Linear Optical Properties
Molecules having asymmetric polarization because of the presence of electron donor and electron
acceptor groups in a π-conjugated system are strong candidates for NLO applications. Materials with
high NLO properties are vital in optoelectronic and non-linear optics and have great effect in information
technology and other industries [19]. With the advancements in laser technology, NLO materials are
used as important materials for photonic communication and digital memory, in industry, national
defense and medicine [20]. In order to establish the relation between molecular structure and NLO
properties, first the hyperpolarizibility of compounds 1–4 was computed at the DFT- B3LYP/6-31G (d,
p) level of theory along with additional key word POLAR and mathematically calculated by following
Equation (2):
βtot = [(βxxx + βxyy + βxzz)2 + (βyyy + βyzz + βyxx)2 + (βzzz + βzxx + βzyy)2]1/2
(2)
The value of first hyperpolarazibility appears in a. u. and converted to e.s.u using Equation (2)
a. u. = 8.6393 × 10−33 e. s. u. The calculated first hyperpolarizibility parameters of compounds 1–4 are
listed in Table 11.
Table 11. First hyperpolarizability parameters of 1–4.
Compound
βxxx
1
2
3
4
2300.433
6.139
3639.217
41.559
207.2331
−402.645
17.3065
64.606
−3.485
1.523
8152.091
−559.94
−62.360
−357.94
−46.037
94.261
1281.031
223.445
−303.73
−459.49
40.0394
42.973
0.236
βxxy
βxyy
−520.79
−244.06
584.743
33.763
1.283
βyyy
βxxz
βxyz
βyyz
−15.970
−8.302
37.649
βxzz
39.428
14.681
9.201
34.723
17.0493
7.664
βyzz
4.147
βzzz
9.715
−8.129
70.233
βtot. (esu)
16.647
29.797
8.957
Organic molecules having extended π-conjugation systems and electron donating groups possess
higher NLO properties. As reflected from Table 11, the values of the first hyperpolarizibility show the
same trend with as electron donating capacity and extended π-conjugation pattern, that is 3 > 2 > 1 > 4.
Moreover, the first hyperpolarizability can also be correlated to the band gap. Compound 4 (with the
highest band gap) has the lowest hyperpolarizability. On the other hand, the easy flow of electrons from
one terminus of molecule to the other renders a lower hyperpolarizability value in compound 3. From
the Table, it is clear that 3 has the highest value compared to others and can be a potential NLO candidate
when compared to 1, 2 and 4.

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2.9. Chemical Reactivity
Global chemical reactivity indices such as total energy, chemical hardness (η), electrophilicity (ω),
electronic chemical potential, and dipole moment (µ) are used to describe the reactivity as well as
stability of any chemical compounds [21]. The chemical hardness can be defined in term of following
equation (3):
η = (EHOMO − ELUMO)/2
(3)
Using above equation chemical hardness of compound 1–4 were calculated and listed in Table 12
along with other parameters.
Table 12. Reactivity indices of compounds 1–4.
Properties
ETotal (eV)
EHOMO
1
2
3
4
0.124
0.132
0.119
0.133
−0.196 −0.196 −0.18 −0.204
−0.0713 −0.064 −0.060 −0.072
ELUMO
η (eV)
0.062
0.066
0.059
0.066
µ (eV)
−0.133 −0.13 −0.120 −0.138
ω (eV)
0.142
1.01
0.128
3.12
0.119
5.37
0.143
0.57
µ(Debye)
Compounds having a high HOMO-LUMO energy gap are stable and chemically harder than
compounds having a small HOMO-LUMO energy gap. From Table 12 it is clear that 4 is hard and more
stable (less reactive), while 3 is soft and least stable of all (more reactive). The electrophilicity index (ω)
is based on thermodynamic properties and measures the favorable change in energy when a chemical
system attains saturation by addition of electrons. It can be defined as the decrease in energy due to flow
of electrons from the HOMO to the LUMO in molecules. It also plays an important role in determining
the chemical reactivity of system and mathematically defined by the following equation (4) [22]:
ω = µ2/2η
(4)
where, µ is the electronic chemical potential, η is chemical hardness. Results from Table 12 show that 4
is strong electrophilic while 3 is nucleophilic in nature. Electronic chemical potential (µ) describes the
charge transfer within a system in the ground state. It is define as the negative of the electronegitivity [23]
and defined mathematically by the following equation (5):
µ = (EHOMO + ELUMO)/2
(5)
Physically it is defined as the tendency of electrons to escape from the equilibrium state. Compounds
having greater values of chemical potential are most reactive than ones with small electronic chemical
potential. From the Table 12, it is clear that 3 is most reactive while 4 is least reactive of all.

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3. Experimental
3.1. General Information
All chemicals and solvents were purchased from BDH (Poole, UK), and used without further
purification. A Stuart Scientific SMP3, version 5.0 melting point apparatus (Bibby Scientific Limited,
Staffordshire, UK) was used to record the melting points, and the reported m.p. are uncorrected. 1H-NMR
spectra were recorded on an AVANCE-III 600 MHz instrument (Bruker, Fallanden, Switzerland) at
300 K, and chemical shifts are reported in ppm with reference to the residual solvent signal. FT-IR
spectra were recorded neat conditions on a Thermo Scientific NICOLET iS 50 FT-IR spectrometer
(Thermo Scientific, Madison, WI, USA). UV-vis. studies were performed by using Evolution
300UV/VIS spectrophotometer (Thermo Scientific).
3.2. Synthesis of 5,6-Diphenyl-4H-[1,2,4]triazine-3-thione
Benzil (6 g, 28.5 mmol) was dissolved in glacial acetic acid (150 mL) and added to a solution of
thiosemicarbazide (2.59 g, 28.5 mmol) in hot water (100 mL). The mixture was refluxed for 4 h, and the
precipitate that appeared was filtered while the solution was hot. The orange crystals obtained were
recrystallized from ethanol to give reddish crystals (yield: 5.27 g, 87.82%, m.p. 222–224 °C).
3.3. Synthesis of 3-Hydrazinyl-5,6-diphenyl-1,2,4-triazine
A mixture of 5,6-diphenyl-4H-[1,2,4]triazine-3-thione (5 g, 18.84 mmol) and hydrazine hydrate
(10 mL) in isopropyl alcohol (20 mL) was refluxed for 4–6 h, until no more H2S was evolved. Acetic
acid was added dropwise into mixture till neutralization to remove the excess of hydrazine. The mixture
was cooled. The solid obtained was filtered off and crystalized from ethanol to give yellowish crystals
(84% yield, m.p. 175–178 °C).
3.4. Synthesis of Compounds 1–4
In an oven dried flask containing ethanol (15 mL), 3-hydrazinyl-5,6-diphenyl-1,2,4-triazine (0.1 g,
0.379 mmol) and the respective aldehyde (0.379 mmol) were mixed together. The mixture was refluxed
for 2 h with stirring and then cooled. Reaction progress was monitored by TLC. The precipitates obtained
were then filtered off to yield the final products.
(Z)-((2-(5,6-Diphenyl-1,2,4-triazin-3-yl)hydrazono)methyl)naphthalene-2-ol (1): IR (neat, cm−1): ν = 756,
1062, 1179, 1239, 1280, 1367, 1517, 1611, 2810; 1H-NMR (DMSO, ppm): 12.77, (1H, s, OH,), 12.31
(1H, b, NH), 9.33 (1H, s, =CH-), 8.22 (1H, d, Ar-H, J = 8.4 Hz), 7.90 (2H, dd, Ar-H, J = 6.0 Hz, 4.2 Hz),
7.61 (1H, t, Ar-H, J = 8.4 Hz), 7.52 (2H, d, Ar-H, J = 7.2 Hz), 7.47 (1H, d, Ar-H, J = 7.8 Hz, 7.2 Hz),
13
7.38–7.44 (8H, m, Ar-H), 7.31 (1H, d, Ar-H, J = 9 Hz); C-NMR (DMSO, ppm): 157.28, 156.47,
142.87, 136.06, 135.81, 131.94, 131.29, 130.50, 129.45, 129.08, 128.95, 128.56, 128.33, 127.82, 127.62,
123.49, 120.58, 118.95, 108.97, UV-vis. λmax (DMSO) = 333 nm, 374 nm,; m.p. 310–312 °C.
(Z)-3-(2-(4-Methoxybenzylidene)hydrazinyl)methyl)-5,6-diphenyl-1,2,4-triazine (2): IR (neat, cm−1): 764,
1060, 1167, 1247, 1350, 1513, 1612; 1H-NMR (DMSO, ppm): 11.80, (1H, b, NH,), 8.22 (1H, s, =CH-),

Molecules 2015, 20
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7.66 (2H, d, Ar-H, J = 9 Hz), 7.46 (3H, dd, Ar-H, J = 7.8 Hz, 7.2 Hz), 7.36 (7H, m, Ar-H), 7.00 (2H, d,
Ar-H, J = 9 Hz), 3.77 (3H, s, CH3); 13C-NMR (DMSO, ppm): 160.35, 158.56, 156.36, 150.59, 143.96,
136.17, 135.99, 130.20, 129.41, 128.92, 128.36, 128.26, 128.24, 128.17, 127.32, 114.31, 55.25; UV-vis.
λ
max (DMSO) = 337 nm; m.p. 267–268 °C.
(Z)-4-((2-(5,6-Diphenyl-1,2,4-triazin-3-yl)hydrazono)methyl)-N,N-dimethylaniline (3): IR (neat, cm−1): 516,
807, 1052, 1160, 1277, 1363, 1428, 1507, 1593; 1H-NMR (DMSO, ppm): 11.62, (1H, b, NH), 9.65 (1H,
s, =CH-), 7.53 (2H, d, Ar-H, J = 9 Hz), 7.45 (3H, dd, Ar-H, J = 7.8, 7.2 Hz), 7.35–7.38 (7H, m, Ar-H),
13
6.75 (2H, d, Ar-H J = 9 Hz), 2.96 (6H, s, CH3); C-NMR (DMSO, ppm): 189.89, 156.28, 154.21,
151.13, 150.18, 145.07, 136.05, 130.16, 129.38, 128.96, 128.29, 128.25, 128.23, 127.95, 124.48, 122.13,
111.87, 111.05; UV-vis. λmax (DMSO) = 366 nm; m.p. 263–265 °C.
(Z)-2-((2-(5,6-Diphenyl-1,2,4-triazin-3-yl)hydrazono)methyl)-phenol (4): IR (neat, cm−1): 688, 750,
1062, 1078, 1133, 1279, 1375, 1515, 1621; 1H-NMR (DMSO, ppm): 12.26, (1H, b, NH,), 11.47, (1H, s,
OH,), 8.45 (1H, s, =CH-), 7.48 (3H, d, Ar-H, J = 7.8 Hz), 7.45 (1H, dd, Ar-H, J = 7.8 Hz, 7.2 Hz),
7.41–7.42 (2H, m, Ar-H), 7.36–7.49 (5H, m, Ar-H), 7.26 (1H, t, Ar-H J = 8.4 Hz), 6.90–6.94 (2H, m,
13
Ar-H); C-NMR (DMSO, ppm): 158.08, 157.13, 156.44, 151.14, 145.00, 136.05, 135.80, 130.64,
130.43, 129.46, 129.06, 128.52, 128.29, 119.30, 118.88, 116.39; UV-vis. λmax (DMSO) = 312 nm,
342 nm; m.p. 273–274 °C.
3.5. Crystallography
Compounds were crystalized in dimethyl sulfoxide (DMSO) while keeping their solution at room
temperature i.e., 25 °C for about three months. Suitable crystals were selected under microscope and
fixed on glass tip using glue supported by copper tube and magnetic base. These were mounted on an
Agilent SuperNova (dual source) diffractometer (Agilent Technologies, Santa Clara, CA, USA)
equipped with graphite-monochromatic Cu/Mo Kα radiation for data collection. The data collection was
accomplished using CrysAlisPro software [24] at 296 K under the Mo Kα radiation. The structure
solution was performed using SHELXS–97 and refined by full–matrix least–squares methods on F2
using SHELXL–97 [25], in-built with X-Seed [26]. All non–hydrogen atoms were refined
anisotropically by full–matrix least squares methods [25]. The C-H hydrogen atoms were positioned
geometrically and treated as riding atoms where C–H = 0.93 Å with Uiso(H) = 1.2 Ueq(C) for aromatic
carbon atoms and C–H = 0.96 Å with Uiso(H) = 1.5 Ueq(C) for methyl carbon atoms. H atoms bonded
to N in all four compounds were located in a difference maps and refined isotropically 0.89 (1) for N-H
using DFIX commands. The O-H hydrogen atoms in 1 & 4 were refined geometrically with O-H = 0.82
and Uiso(H) = 1.5 Ueq(O) for oxygen atom. The figures were drawn using ORTEP-3 [27] and
PLATON [28] programs inbuilt with WINGX [27]. The cifs for these compounds have been submitted
to CCDC to obtain CCDC numbers (1028227, 1028228, 1028229 and 1034522 for compounds 1–4
respectively). These data files can be obtained free of charges on application to CCDC 12 Union Road,
Cambridge CB21 EZ, UK. (Fax: (+44) 1223 336-033; e-mail: data_request@ccdc.cam. ac.uk).

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3.6. Computational Details
Theoretical studies were performed using the Gaussian 09 software at the density functional theory
(DFT) level as instituted in the program [29]. The visualization of the results/optimized geometries was
achieved by using Gauss View 05 [30]. The energy minima optimization of all compounds was carried
out at B3LYP/6-31G (d, p) levels of theory. The B3LYP method provides a nice balance between cost
and accuracy, and it is known to perform very well for the prediction of geometries of a number of
synthetic [31,32] and natural products [33,34]. Frequency simulations were performed at the same level,
to confirm the optimized geometries as a true minimum (no imaginary frequency was observed). In
addition, frequency simulations at B3LYP/6-311G (d, p) level were used for vibrational analysis.
Nuclear magnetic resonance studies were performed at B3LYP/6-311+G (2d, p) level, by adopting
GIAO method. Chemical shift values were referred by using the internal reference standard i.e.,
tetramethylsilane. UV-vis. absorption studies were simulated by using TD-DFT method and at
B3LYP/6-31G (d, p) level of theory. MEP, FMO and first hyperpolarizability analyses were simulated
at B3LYP/6-31G (d, p) level of DFT.
4. Conclusions
In this study, four triazine-based hydrazone derivatives have been synthesized in good yields, and
characterized using FT-IR, UV-Vis., 1H- and 13C-NMR spectroscopic techniques. The structures of these
hydrazones were also confirmed unequivocally by single crystal X-ray diffraction studies. The DFT
studies showed a strong agreement between the simulated and experimental results. Intra-molecular
hydrogen bonding in compounds 1 and 4 results in a decrease in certain bond lengths in the triazine core.
The structural variation in the hydroazamethyl part has a significant effect on the electronic properties
of compounds 1–4. The molar absorptivity of transitions in the UV-Vis spectra (compounds 1 and 4) is
considerably decreased by the intramolecular hydrogen bonding. The absorption at the longest
wavelength in the UV-Vis spectrum is a π–π* transition from the HOMO to the LUMO, and correlates
with the calculated HOMO-LUMO band gap. Frontier molecular orbital analysis showed that
compounds 1 and 3 have very low HOMO-LUMO energy gaps, and therefore are kinetically less stable.
The molecular electrostatic potential investigations revealed that the electronegative region in all
compounds was spread over the triazine moiety. Chemical reactivity indices predict the highest and
lowest activity for 3 and 4, respectively. The lowest band gap is calculated for compound 3, which gives
it interesting electronic properties. The first hyperpolarizability analysis of all compounds was
performed and compound 3 again showed the highest value compared to 1, 2 and 4. This indicates that
3 may have a very good nonlinear optical response. Triazine-based hydrazone derivatives have very
wide applications not only in the clinical field but also in other areas of chemistry and hopefully the
results of this study will increase the interest of researchers working in this field.
Supplementary Materials
Cartesian co-ordinates of optimized geometries and cif files of all compounds 1–4 are given in
1
13
supporting information. Experimental H-, C-NMR are also provided in the Supporting Information

Molecules 2015, 20
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along with simulated UV-vis. spectra. Supplementary materials can be accessed at:
http://www.mdpi.com/1420-3049/20/04/5851/s1.
Acknowledgments
This work was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University,
Jeddah, under grant no. (130-345-D1435). The authors, therefore, acknowledge with thanks DSR
technical and financial support.
Author Contributions
M.N.A. and A.M.A. planed the study, synthesize the molecules, performed crystallography, spectral
analysis and compiled the results. T.M. and A.B. performed the theoretical calculations and arranged
the results with the help of K.A. All the authors have same contribution in making the final shape of
present manuscript.
Conflicts of Interest
The authors declare no conflict of interest.
References
1. Smolin, E.M.; Rapoport, L. s-Triazine and Derivatives. In The Chemistry of Heterocyclic Compounds;
Weissberger, A., Ed.; Wiley Intercience Publisher Inc.: New York, NY, USA, 1959; Volume 13,
pp. 597–626.
2. Patel, R.V.; Kumari, P.; Rajani, D.P.; Pannecouque, C.; de Clercq, E.; Chikhalia, K.H.
Antimicrobial, anti-TB, anticancer and anti-HIV evaluation of new s-triazine-based heterocycles.
Future Med. Chem. 2012, 4, 1053–1065.
3. Khoshneviszadeh, M.; Mohammad, H.; Foroumadi, G.A.; Miri, R.; Firuzi, O.; Madadkar-Sobhani, A.;
Edraki, N.; Parsa, M.; Shafiee, A. Design, synthesis and biological evaluation of novel
anti-cytokine 1,2,4-triazine derivatives. Bioorg. Med. Chem. 2013, 21, 6708–6717.
4. El-Brollosy, N.R. Synthesis and antimicrobial evaluation of 6-azauracil non-nucleosides.
Monatsh. Chem. 2008, 139, 1483–1490.
5. Mary, Y.S.; Abdul-Malek, S.; Al-Tamimi El-Brollosy, N.R.; El-Emam, A.A.; Jojo, P.J.;
Panicker, C.Y.; Alsenoy, C.V. Molecular structure and vibrational spectra of 2-Ethoxymethyl-6-
ethyl-2,3,4,5-tetrahydro-1,2,4-triazine-3,5-dione, a potential chemotherapeutic agent, by density
functional methods. Spectrochim. Acta Part A 2014, 133, 439–448.
6. Liu, J.; Wang, K.; Zhang, X.; Li, C.; You, X. Triazine dyes as photosensitizers for dye-sensitized
solar cells. Tetrahedron 2013, 69, 190–200.
7. Rafat, M.; Fleita, D.H.; Sakka, O.K. Novel Synthesis of Hydrazide-Hydrazone Derivatives and
Their Utilization in the Synthesis of Coumarin, Pyridine, Thiazole and Thiophene Derivatives with
Antitumor Activity. Molecules 2011, 16, 16–27.
8. Vicini, P.; Zani, F.; Cozzini, P.; Doytchinova, I. Hydrazones of 1,2-benzisothiazole hydrazides:
Synthesis, antimicrobial activity and QSAR investigations. Eur. J. Med. Chem. 2002, 37, 553–564.

Molecules 2015, 20
5873
9. Rahman, V.M.; Mukhtar, S.; Ansari, W.H.; Lemiere, G. Synthesis, stereochemistry and biological
activity of some novel long alkyl chain substituted thiazolidin-4-ones and thiazan-4-one from
10-undecenoic acid hydrazide. Eur. J. Med. Chem. 2005, 40, 173–184.
10. Jani, G.R.; Vyas, K.B.; Franco, Z. Preparation and Antimicrobial Activity of s-Triazine Hydrazones
of 7-Hydroxy Coumarin and their Metal Complexes. Eur. J. Chem. 2009, 6, 1228–1232.
11. Taib, L.A.; Faidallah, H.M.; Şahin, Z.S.; Asiri, A.M.; Şahin, O.; Arshad, M.N. Synthesis, spectral
analysis, X-ray crystal structures and evaluation of chemical reactivity of five new benzoindazole
derivatives through experimental and theoretical studies. J. Mol. Struct. 2014, 1076, 272–279.
12. Javed, I.; Khurshid, A.; Arshad, M.N.; Wang, Y. Photophysical and electrochemical properties and
temperature dependent geometrical isomerism in alkyl quinacridonediimines. New J. Chem. 2014,
38, 752–761.
13. Arshad, M.N.; Şahin, O.; Zia-ur-Rehman, M.; Khan, I.U.; Asiri, A.M.; Rafique, H.M.
4-hydroxy-2H-1, 2-benzothiazine-3-carbohydrazide 1, 1-dioxide-oxalohydrazide (1:1): X-ray
structure and DFT calculations. J. Struct. Chem. 2013, 54, 437–442.
14. Sundaraganesan, N.; Ilakiamani, S.; Saleem, H.; Wojciechowski, P.M.; Michalska, D. FT-Raman
and FT-IR spectra, vibrational assignments and density functional studies of 5-bromo-2-
nitropyridine. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2005, 61, 2995–3001.
15. Arshad, M.N.; Mahmood, T.; Khan, A.F.; Zia-Ur-Rehman, M.; Asiri, A.M.; Khan, I.U.; Un-Nisa, R.;
Ayub, K.; Mukhtar, A.; Saeed, M.T. Synthesis, crystal structure and spectroscopic properties of
1,2-benzothiazine derivatives: An experimental and DFT study. Chin. J. Struct. Chem. 2015, 34,
15–25.
16. Ebenezar, J.D.; Ramalingam, S.; Raja, C.R.; Helan, V. Precise spectroscopic [IR, Raman and NMR]
investigation and gaussian hybrid computational analysis (UV-visible, NIR, MEP Maps and Kubo
Gap) on L-valine. J. Theor. Comput. Sci. 2013, 1, 1–13.
17. Szabo, L.; Chiş, V.; Pirnau, A.; Leopold, N.; Cozar, O.; Orosz, S. Spectroscopic and theoretical
study of amlodipine besylate. J. Mol. Struct. 2009, 924, 385–392.
18. Bartošková, M.; Friedl, Z. The Relationship between the heats of formation and the molecular
electrostatic potentials of polyazaarenes. Cent. Eur. J. Energy Mater. 2013, 10, 103–112.
19. Sagadevan, S. Investigation on the optical properties of nonlinear optical (NLO) single crystal:
L-Valine zinc hydrochloride. Am. J. Opt. Photonics 2014, 2, 24–27.
20. Zhang, J.; Liang, X.; Jiang, Y.; Wang, G.; Qu, C.; Zhao, B. Computational study on the
second-order nonlinear optical properties of coumarin derivatives with N-p-vinylphenyl carbazole
chromophores. Asian J. Chem. 2014, 26, 7404–7408.
21. Mebi, C.A. DFT study on structure, electronic properties, and reactivity of cis-isomers
of [(NC5H4-S)2Fe(CO)2]. J. Chem. Sci. 2011, 123, 727–773.
22. Sukumar, N. A Matter of Density; Wiley: Hoboken, NJ, USA, 2012; pp. 157–201.
23. Špirtović-Halilović, S.; Salihovic, M.; Džudžević-Čančar, H.; Trifunovic, S.; Roca, S.; Softic, D.;
Završnik, D. DFT study and microbiology of some coumarin-based compounds containing
a chalcone moiety. J. Serb. Chem. Soc. 2014, 79, 435–443.
24. CrysAlis PRO; Agilent Technologies: Yarnton, UK, 2012.
25. Sheldrick, G.M. A short History of SHELX. Acta Crystallogr. 2007, A64, 112–122.

Molecules 2015, 20
5874
26. Barbour, L.J. A software tool for Supramolecular Crystallography. J. Supramol. Chem. 2001, 1,
189–191.
27. Farrugia, L.J. WinGX and ORTEP for windows: An update. J. Appl. Crystallogr. 2012, 45,
849–854.
28. Spek, A.L. Structure validation in chemical crystallography. Acta Crystallogr. 2009, D65,
148–155.
29. Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.;
Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; et al. Gaussian 09, Revision C.01;
Gaussian, Inc.: Wallingford, CT, USA, 2010.
30. Roy, D.; Todd, K.; John, M. Gauss View, Version 5; Semichem, Inc.: Shawnee Mission, KS,
USA, 2009.
31. Hung, T.Q.; Hoang, D.H.; Thang, N.N.; Dang, T.T.; Ayub, K.; Villinger, A.; Friedrich, A.;
Lochbrunner, S.; Flechsig, G.-U.; Langer, P. Palladium catalyzed synthesis and physical properties
of indolo[2,3-b]quinoxalines. Org. Biomol. Chem. 2014, 12, 6151–6166.
32. Babar, A.; Khalid, H.; Ayub, K.; Saleem, S.; Waseem, A.; Mahmood, T.; Munawar, M.A.;
Abbas, G.; Khan, A.F. Synthesis, characterization and density functional theory study of some new
2-anilinothiazoles. J. Mol. Struct. 2014, 1072, 221–227.
33. Ullah, H.; Rauf, A.; Ullah, Z.; Fazl-i-Sattar; Anwar, M.; Shah, A.-H.A.; Uddin, G.; Ayub, K.
Density functional theory and phytochemical study of Pistagremic acid. Spectrochim. Acta A Mol.
Biomol. Spectrosc. 2014, 118, 210–214.
34. Fazl-i-Sattar; Ullah, Z.; Ata-ur-Rahman; Rauf, A.; Tariq, M.; Tahir, A.A.; Ayub, K.; Ullah, H.
Phytochemical, spectroscopic and density functional theory study of Diospyrin, and non-bonding
interactions of Diospyrin with atmospheric gases. Spectrochim. Acta Part A Mol. Biomol. Spectrosc.
2015, 141, 71–79.
Sample Availability: Samples of the compounds 1–4 are available from the authors.
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