Spectral studies of 2-pyrazoline derivatives: Structural elucidation through single crystal XRD and DFT calculations

Article abstract of DOI:10.1016/j.saa.2013.12.032

A series of biologically active N-thiocarbamoyl pyrazoline derivatives have been synthesized using anhydrous potassium carbonate as the catalyst. All the synthesized compounds were characterized by FT-IR, ¹H NMR, ¹³C NMR spectral stu

Full text of DOI:10.1016/j.saa.2013.12.032

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 124 (2014) 30–33
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Spectral studies of 2-pyrazoline derivatives: Structural elucidation
through single crystal XRD and DFT calculations
b
b
a
D. Chinnaraja a, R. Rajalakshmi a, , T. Srinivasan , D. Velmurugan , J. Jayabharathi
⇑
a Department of Chemistry, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India
b CAS in Crystallography and Biophysics, University of Madras, Chennai 600 025, Tamil Nadu, India
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
Biologically active pyrazolines, synthesized and characterized by various spectroscopic techniques NMR,
LCMS, CHN analysis, X-ray crystallographic and DFT calculations.
ꢀ
ꢀ
ꢀ
N-thiocarbamoyl pyrazoline
derivatives have been synthesized.
Spectral studies and single crystal
XRD have been carried out.
The XRD parameters and molecular
modeling was carried out.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 August 2013
Received in revised form 21 November 2013
Accepted 5 December 2013
Available online 7 January 2014
A series of biologically active N-thiocarbamoyl pyrazoline derivatives have been synthesized using anhy-
drous potassium carbonate as the catalyst. All the synthesized compounds were characterized by FT-IR,
1H NMR, 13C NMR spectral studies, LCMS, CHN Analysis and X-ray diffraction analysis (compound 7). In
order to supplement the XRD parameters, molecular modelling was carried out by Gaussian 03W. From
the optimized structure, the energy, dipolemoment and HOMO–LUMO energies of all the systems were
calculated.
Keywords:
2-Pyrazoline
Thiocarbamoyl
DFT
Ó 2013 Elsevier B.V. All rights reserved.
XRD
2-Acetyl pyridine
Introduction
reported to show a wide spectrum of biological activity, including
antibacterial, antifungal, anti infalmmatery, antiamoebic, antide-
N-thiocarbamoyl pyrazolines are considered as important com-
pounds in the organic chemistry because of their application in
heterocyclic synthesis and medicinal applications [1–4]. Pyrazo-
lines are compounds with noteworthy applications and have been
pressant and anticonvulsant activities [5–11]. They are used as
fluorescent probes [12], in some elaborate chemosensors and as
photosensitizers [13]. Moreover the 2-pyridinyl pyrazolines can
themselves serve as N,N-bidentate ligands for metal ions [14]. Thus
the characterization of 1-phenyl-3-(2-pyridyl) prop-2-en-1-one
(1–6) are reported [15]. The pyrazoline function is a quite stable
fragment in bioactive moieties to synthesize new compounds
⇑
Corresponding author. Tel./fax: +91 4144 238282, mobile: +91 98943 85181.
E-mail address: chemrajalaksmi@gmail.com (R. Rajalakshmi).
1386-1425/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2013.12.032

D. Chinnaraja et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 124 (2014) 30–33
31
possessing biological activities. This prompted us to synthesize
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-(4-chlorophenyl)-2-pyraz
oline (8)
Yield: 70%; mp: 159 °C; white solid; molecular formula C15H13
N4SCl; IR
max(cmÀ1): 1604 (C@N); 1366 (CAN); 3043(ArAH);
various substituted N-thiocarbamoyl pyrazoline derivatives. In this
article we focus the characterization of biologically active pyrazo-
line derivatives and to supplement the XRD parameters, theoretical
calculations were made using Gaussian-03 package.
t
3442–3369 (NH2); 1H NMR (CDCl3) d(ppm): 3.3 (dd, 1H, HA, J1:
7.5, J2: 16.18), 3.9 (dd, 1H, HB, J1: 12.5, J2: 18), 6.3 (dd, 1H, HC, J1:
7.6 J2: 12.57), 6.5 and 6.4 (2H, NH2), 6.8–8.7(ArAH), 213C NMR
(CDCl3) d(ppm): 152.37 C@N, 177.67 (C@S), 43.08 CH2, 63.94 CH,
113.63–149.93(ArAC). Anal. Calcd. (%) for: C, 56.87; H, 4.17; N,
17.82. Found (%): C, 56.81; H, 4.11; N, 17.72; LC–MS (m/z): 316.
Experimental section
Instruments
The IR spectrum was recorded in AVATAR-330 FT-IR spectro-
photometer and only noteworthy absorption levels (reciprocal
centimeters) were listed. 1H NMR spectra were recorded at 300
and 400 MHz on Bruker AMX 300 and 400 MHz spectrophotometer
using CDCl3 as solvent and TMS as internal standard. 13C NMR
spectra were recorded at 75 and 100 MHz on Bruker AMX 300
and 400 MHz spectrophotometer using CDCl3. The tubes used for
recording NMR spectra were 5 mm diameter. The reactions and
the purity of the products were assessed by performing TLC. All
the reported melting points were taken in open capillaries and
were uncorrected. Geometry optimization was carried out by
Gaussion-03 (AM1) package for all the compounds (7–12).
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-(4-methoxyphenyl)-
2-pyrazoline (9)
Yield: 70%; mp: 177 °C; pale yellow powder; molecular formula
C
16H16N4SO; IR t
max(cmÀ1): 1621 (C@N); 1378 (CAN); 3043
(ArAH); 3442–3369 (NH2); 1H NMR (CDCl3) d(ppm): 3.3 (dd, 1H,
HA, J1: 7.5, J2: 16.74), 4.0 (dd, 1H, HB, J1: 12, J2: 18), 6.1 (dd, 1H,
HC, J1: 7.6 J2: 12.45), 6.5 and 6.4 (2H, NH2), 3.9 (S,3H, OCH3),
6.8–8.5(ArAH), 13C NMR (CDCl3) d(ppm): 161.88 C@N, 177.92
(C@S), 50.00 CH2, 94.98 CH, 55.43 (OCH3), 114.22–149.21(ArAC).
Anal. Calcd. (%) for: C, 61.49; H, 5.03; N, 17.63. Found (%): C,
61.51; H, 5.12; N, 17.42; LC–MS (m/z): 312.
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-(3,4-dimethoxyphenyl)-
2-pyrazoline (10)
Synthesis
Yield: 60%; mp: 147 °C; yellow solid; molecular formula C17H18
N4O2S; IR
t
max(cmÀ1): 1594 (C@N); 1387 (CAN); 3052(ArAH);
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-phenyl-2-pyrazolines
(7–12)
3442–3369 (NH2); 1H NMR (CDCl3) d(ppm): 3.4 (dd, 1H, HA, J1:
7.6, J2: 16.82), 4.1 (dd, 1H, HB, J1: 12, J2: 18), 6.3 (dd, 1H, HC, J1:
7.6 J2: 12.33), 6.5 and 6.4 (2H, NH2), 3.8 (S,6H, (OCH3)2),
6.7–8.4(ArAH), 13C NMR (CDCl3) d(ppm): 161.61 C@N, 177.38
(C@S), 50.13 CH2, 95.22 CH, 56.16 (OCH3), 109.02–149.37(ArAC).).
Anal. Calcd. (%) for: C, 59.67; H, 5.47; N, 16.33. Found (%): C, 59.71;
H, 5.41; N, 16.37; LC–MS (m/z): 342.
Synthesis of pyrazoline derivative was performed in a manner
as outlined in Scheme S1. The cyclization of chalcones with thio-
semicarbazide under basic condition (anhydrous potassium car-
bonate) in 50 mL of ethanol led to the formation of pyrazoline
compound and it is stable in solid state. The structures of pyrazo-
line derivatives (7–12), are given in Scheme S1.
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-(2,4-dichlorophenyl)-
2-pyrazoline (7)
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-(3,4,5-trimethoxyphenyl)-
2-pyrazoline (11)
Yield 70%; mp 115 °C; white crystal; molecular formula C15H12
N4SCl2; tmax cmÀ1 1595 (C@N), 3061 (HC@Ar), 3442–3369 (NH2);
1H NMR (300 MHZ CDCl3) d(ppm): 3.3 (dd, 1H, J1 = 4.2HZ,
J2 = 18.9HZ, HA), 4.0 (dd, 1H, J1 = 11.7 3HZ, J2 = 18.9HZ HB), 6.2 (dd,
1H, J1 = 4.2HZ, J2 = 11.7HZ Hc), 6.5 and 6.4 (2H, NH2), 6.9–8.6 (m,
7H, ArAH); 13C NMR (75 MHZ CDCl3) d(ppm): 157.38 (C@N),
177.25 (C@S), 41.74(C-4), 61.23(C-5), 121.48–149.69 (aromatic
carbons). Anal. Calcd. (%) for: C, 51.29; H, 3.42; N, 15.93. Found
(%): C, 51.31; H, 3.40; N, 15.82; LC–MS (m/z): 350.
Yield: 65%; mp: 183 °C; pale yellow powder; molecular formula
C
18H20N4SO3S; IR t
max(cmÀ1): 1600 (C@N); 1385 (CAN); 3051
(ArAH); 3442–3369 (NH2); 1H NMR (CDCl3) d(ppm): 3.3 (dd, 1H,
HA, J1: 7.6, J2: 16.65), 4.1 (dd, 1H, HB, J1: 12, J2: 18), 6.2 (dd, 1H,
HC, J1: 7.6 J2: 18.41), 6.5 and 6.4 (2H, NH2), 3.9 (S, 9H, (OCH3)3),
6.8–8.5(ArAH), 13C NMR (CDCl3) d(ppm): 161.61 C@N, 177.74
(C@S), 50.63 CH2, 95.25 CH, 56.77 (OCH3), 110.05–149.65(ArAC).
Anal. Calcd. (%) for: C, 58.07; H, 5.31; N, 15.27. Found (%): C,
58.11; H, 5.22; N, 15.25; LC–MS (m/z): 372.
Table 1
The selected bond distance, bond angles and dihedral angle for compound 7.
Connectivity
Bond distance*
Connectivity
Bond angle*
Connectivity
Dihedral angle*
S1AC7
C1AN1
C5AN1
C5AC4
C7AN4
C6AN2
N2AN3
N3AC9
C6AC8
C8AC9
N3AC7
1.6838(1.6205)
1.3467(1.3612)
1.331(1.3421)
1.369(1.4088)
1.329(1.3685)
1.2817(1.5042)
1.3976(1.3608)
1.4839(1.3228)
1.492(1.5592)
1.542(1.5221)
1.354(1.425)
C7AN3AN2
N2AN3AC9
C6AN2AN3
C5AN1AC1
N2AC6AC8
N1AC1AC2
N4AC7AN3
N4AC7AS1
N3AC7AS1
C15AC10AC11
C6AC8AC9
N1AC5AC4
C13AC12AC11
C4AC3AC2
C3AC2AC1
N3AC9AC8
C12AC11AC10
118.37(121.71)
112.50(110.34)
107.91(111.91)
117.29(117.48)
114.92(102.98)
122.72(122.34)
116.11(118.72)
122.43(120.76)
121.46(120.44)
116.62(118.45)
102.63(101.58)
123.81(123.99)
118.76(119.42)
119.41(119.12)
118.32(118.93)
101.30(113.11)
122.35(120.93)
N3AN2AC6AC1
N2AC6AC1AC2
N2AC6AC1AN1
N2AN3AC7AS1
N2AN3AC7AN4
C9AN3AC7AS1
C7AN3AN2AC6
C9AN3AN2AC6
C7AN3AC9AC8
N2AN3AC9AC10
C9AC10AC15AC14
C9AC10AC11AC12
C6AC1AC2AC3
N1AC1AC2AC3
C1AN1AC5AC4
C6AC8AC9AN3
C6AC8AC9AC10
175.03(À176.40)
16.4(À169.02)
À160.89(10.97)
172.20(157.89)
À7.4(À24.80)
9.7(11.36)
À159.05(À149.93)
5.93(À1.43)
154.80(149.57)
112.45(119.86)
179.32(À179.77)
0.8(179.88)
À176.26(179.84)
0.8(À0.15)
1.9(0.06)
7.59(1.26)
À113.36(À120.97)
*
The values in the parenthesis are theoretically calculated.

32
D. Chinnaraja et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 124 (2014) 30–33
Table 2
Dipole moment, optimized energy level, HOMO LUMO energies of 7–12.
Compounds
Dipole moment
Optimized energy
level kcal/mol
HOMO
LUMO
7. (DACl)2
8. AOCH3
9. (AOCH3)2
10. PACl
11. NA(CH3)2
12. (AOCH3)3
5.92
4.18
3.78
5.67
5.19
4.85
143.85
113.07
72.99
148.85
166.74
67.11
À0.28
À0.31
À0.31
À0.31
0.30
À0.19
À0.02
0.03
0.03
À0.02
À0.31
0.03
COMPOUNDS
HOMO
LUMO
7
8
9
10
11
12
Fig. 1. The 3D plot of –HOMO–LUMO orbital picture of 7–12.
Synthesis of 1-thiocarbamoyl-3-pyridyl-5-(4-N,N-dimethylamin-
ophenyl)-2-pyrazoline (12)
3442–3369 (NH2); 1H NMR (CDCl3) d(ppm): 3.3 (dd, 1H, HA, J1: 7.0,
J2: 18.15), 4.0 (dd, 1H, HB, J1: 12.5, J2: 18), 6.3 (dd, 1H, HC, J1: 7.0 J2:
12.59), 6.5 and 6.4 (2H, NH2), 2.9 (S, 6H, (CH3)2), 6.7–8.6 (ArAH),
13C NMR (CDCl3) d(ppm): 152.37 C@N, 177.45 (C@S), 64.33 CH2,
Yield: 75%; mp: 133 °C; Orange powder; molecular formula
C
17H19N5S; IR t
max(cmÀ1): 1599 (C@N); 1355 (CAN); 3065(ArAH);

D. Chinnaraja et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 124 (2014) 30–33
33
113.63 CH, 43.13 (CH3), 119.33–149.93(ArAC). Anal. Calcd. (%) for:
C, 62.70; H, 5.66; N, 21.63. Found (%): C, 62.71; H, 5.71; N, 21.42;
LC–MS (m/z): 325.
geometry of the molecule was confirmed by XRD data which is fur-
ther evidenced from the molecular modelling studies. Only se-
lected bond distances, bond angles and dihedral angles are given
in Table 1.
Results and discussion
HOMO–LUMO analysis
The optimized energy, dipole moment and HOMO–LUMO ener-
gies of the compound (7–12) were calculated theoretically and are
given in Table 2. From the HOMO and LUMO analysis it is clear that
the intra molecular charge transfer must occur within the mole-
cule. The 3D plot of HOMO and LUMO orbital picture is displayed
in Fig. 1 (7–12). From the dipole moment values given in Table 2,
it is evident that all the pyrazoline derivatives are highly polar
and expected to possess Non–Linear Optical properties. Analyses
of NLO behavior of the synthesized compounds are currently in
progress.
Spectral analysis
Several N-thiocarbamoyl pyrazoline derivatives were synthe-
sized according to Scheme 1. Allthe synthesized compounds were
characterized by IR, 1H and 13C NMR, Mass spectral techniques
(LC–MS) and CHN analysis. In the IR spectrum of compound 7,
the stretching frequency at 1595 cmÀ1 is due to (C@N), the doublet
at 3442 and 3369 cmÀ1 is due to (NH2) and the aromatic (CAH)
stretching frequencies are observed at 3061 cmÀ1. High resolution
1H NMR, 13C NMR have been recorded in CDCl3 and analyzed. In the
1H NMR spectrum of compound 7, the double doublet centered at
3.3 ppm with coupling constants J1 = 4.2 HZ and J2 = 18.9 HZ are
due to Ha proton at (C-4) and another double doublet centered at
4.0 ppm with coupling constants J1 = 11.7 HZ and J2 = 18.9 Hz are
due to Hb proton at C-4. The double doublet observed at 6.2 ppm
with J1 = 4.2 HZ and J2 = 11.7 HZ is due to Hc proton at C-5. The
two amino protons are appearing at 2.03 ppm. The signals appear-
ing at 6.9 and 8.6 ppm are obviously due to aromatic protons.
Conclusion
Biologically active pyrazoline derivatives have been synthesized
and characterized by various spectroscopic techniques. ORTEP dia-
gram of 1-thiocarbamoyl-3-pyridyl-5-(2,4-dichlorophenyl)-2-pyr-
azoline shows that pyrazoline derivatives exist as non-coplanar
rings. DFT calculations also support the same and are expected to
be highly polar. From the HOMO–LUMO electron density analysis
it is evident that the intermolecular charge transfer takes place
within the molecule.
In the 13C NMR spectrum of compound
7 the signal at
41.74 ppm is assigned to methylene carbon (C-4). The signal ob-
served at 157.38 ppm, is due to (C@N) C-3 carbon. The signal at
61.23 ppm is assigned to C-5 carbon. The down field signal at
177.25 ppm is obviously due to the thiocarbamoyl (H2NAC@S)
carbon. The aromatic carbons could be readily distinguished by
their characteristic absorption between 121.48 and 149.69 ppm.
Similar results were obtained for all other synthesized compounds
(8–12). The LC–MS compound 7 shows molecular ion peak at (m/
z): 350.
Acknowledgements
We are grateful to the UGC Networking Resource Centre, Uni-
versity of Hyderabad for providing characterization facilities and
to Dr. R. Nagarajan, School of Chemistry, University of Hyderabad
for providing laboratory facilities.
ORTEP diagram
Appendix A. Supplementary material
The structure as well as the stereochemistry of compound 7 was
confirmed by X-ray crystallographic analysis. Compound 7 shows
an extended system involving pyridyl-C@N2AN3-thiocarbamoyl
system with atoms N2 and N1 present in an anticonformation.
The C1AC6 bond distance (1.46 Aꢀ) is lightly shorter than CAC sin-
gle bond length but longer than C@C bond length. But the C9AC10
bond distance (1.515 Aꢀ) is almost equal to CAC single bond dis-
tance and hence the rotation of the molecule is possible and the
molecule belongs to triclinic (p1) crystal lattice. The ORTEP dia-
gram Fig. S1 and close packing structures are given in Fig. S2.
Though the five membered rings cannot be planar due to the
presence of two SP3 carbon atoms, from the ORTEP diagram it
seems that the thiocarbamoyl group and pyrazoline ring are lying
in a plane but the aryl ring is perpendicular to the plane of the mol-
ecule. The XRD parameters for compound (7) are given below.
The crystallographic data of compound 7 (Figs. S1 and S2) have
been deposited at Cambridge Crystallographic Data Centre (CCDC
number: 893125). Copies of the data can be obtained free of charge
on application to CCDC, 12 Union road, Cambridge CB2 1EZ UK. UK
(fax: +44(01)1223 336033 or e-mail: deposit@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.saa.2013.12.032.
References
[1] D.N. Dhar, The Chemistry of Chalcones and Related Compounds, JohnWiley,
New York, 1981.
[2] K.B. Raut, Wender, J. Org. Chem. 25 (1960) 50–52.
[3] Z.S. Ariyan, H.J. Suschitzky, J. Chem. Soc. (1961). pp. 2242.
[4] A. Jurasek, V. Knoppava, M. Danderova, J. Kovar, Reinprecht, Tetrahedron 34
(1978) 1833–1836.
[5] M.A. Berghot, E.B. Moawad, Eur. J. Pharm. Sci. 20 (2003) 173–179.
[6] D. Nauduri, G.B. Reddy, Chem. Pharm. Bull. 46 (1998) 1254–1260.
[7] S.S. Korgaokar, P.H. Patil, M.T. Shah, H.H. Parekh, Indian J. Pharm. Sci. 58 (1996)
222–225.
Computational studies
[8] R.H. Udupi, A.R. Kushnoor, A.R. Bhat, Indian J. Heterocycl. Chem. 8 (1998)
63–66.
[9] M. Abid, A. Azam, Bioorg. Med. Chem. 15 (2005) 2213–2220.
[10] A. Bilgin, E. Palaska, R. Sunal, Arzneim.-Forsch. 43 (1993) 1041–1044.
[11] K.S. Guniz, S. Rollas, H. Erdeniz, M. Kiraz, E.A. Cevdet, A. Vidin, Eur. J. Med.
Chem. 35 (2000) 761–777.
[12] Y. Fushizaki, K. Sakikawa, Jpn. Patent. JP. (1971) 4600357.
[13] R.A. Bissell, A.P. de Silva, H.Q.N. Gunaratne, P.L.M. Lynch, G.E.M. Maguire, C.P.
McCoy, K.R.A.S. Sandanayake, Top. Curr. Chem. 168 (1993) 223–264.
[14] P. Wang, N. Onozawa-Komatsuzaki, Y. Himeda, H. Sugihara, H. Arakawa, K.
Kasuga, Tetrahedron. Lett. 42 (2001) 9199–9201.
Molecular modelling
Molecular modelling was carried out by Gaussian-03 package
using B3LYP/6-31G⁄(d, p) method. In order to supplement the
XRD data the theoretical parameters were compared with the
XRD data and are displayed in Table 1. The bond length, bond angle
and dihedral angle were extracted from the optimized structure of
(7). The theoretical parameters are higher than that of XRD param-
eters because the theoretical calculations were made for molecules
which are in gaseous state. The representative molecular model-
ling of compound 7 is shown in Fig. S1. The non-co-planar
[15] Y.R. Prasad, P. Praveen kumar, P. Ravikumar, A. Srinivasan rao, E-J. Chem. 5
(2008) 144–148.