Synthesis and crystal structure of new thiazolyl-pyrazoline derivatives bearing 1,2,4-triazole moiety

Article abstract of DOI:10.1007/s10870-011-0198-0

The title compounds 1-(4-aryl-5-triazolyl-2-thiazolyl)-3,5-diaryl-2- pyrazoline derivatives (3a-c) were synthesized by reacting 3,5-diaryl1- thiocarbamoyl -2-pyrazoline 1 with 2-bromo-1-aryl-2-(1H-1,2,4-triazol-1-yl) ethanones 2 in boiling ethanol. Their

Full text of DOI:10.1007/s10870-011-0198-0

J Chem Crystallogr (2012) 42:24–28
DOI 10.1007/s10870-011-0198-0
ORIGINAL PAPER
Synthesis and Crystal Structure of New Thiazolyl-Pyrazoline
Derivatives Bearing 1,2,4-Triazole Moiety
•
Yong-Ming Zeng Sheng-Qin Chen
•
Fang-Ming Liu
Received: 7 March 2011 / Accepted: 26 September 2011 / Published online: 10 November 2011
Ó Springer Science+Business Media, LLC 2011
Abstract The title compounds 1-(4-aryl-5-triazolyl-2-
thiazolyl)-3,5-diaryl-2-pyrazoline derivatives (3a–c) were
synthesized by reacting 3,5-diaryl1-thiocarbamoyl -2-pyr-
azoline 1 with 2-bromo-1-aryl-2-(1H-1,2,4-triazol-1-yl)
ethanones 2 in boiling ethanol. Their structures were char-
Introduction
Electron-rich nitrogen heterocyclics play an important role
in diverse biological activities. 1,2,4-Triazole derivatives
represent one of the most interesting and important classes
of compounds, possessing a wide spectrum of biological
activity such as anti-HIV, antifungal, antibacterial, COX-2
inhibitor and anticonvulsant [1–4], and some of them, for
example, Fluconazole and Itraconazole, have been used
clinically as antifungal agents [5, 6]. More recently,
thiazolyl-pyrazoline derivatives were also reported to
exhibit significant antimicrobial, antiviral and antihyper-
tensive activities [7–9].
1
acterized by IR, H-NMR, MS spectroscopic data and ele-
mentary analyses. The structure of compound (3a),
C26H18Cl2N6S, was conclusively established with X-ray
crystal structure analysis. It crystallizes in the Orthorhom-
bic space group Pna2(1), with a = 17.8160(5), b =
18.9125(7), c = 14.7926(4), a = 90°, b = 90°, c =
3
˚
90°and Dc = 1.379 mg/m for Z = 8, V = 4984.3(3) A,
˚
l(Mo–Ka) = 0.372 mm, k = 0.71070 A, the final R =
0.0527 and wR = 0.1307 for 43309 observed reflections
with I [ 2r(I). The structure is stabilized by weak C–HÁÁÁN
intramolecular hydrogen bonds and C–HÁÁÁCg p-ring inter-
molecular interactions and gives support to molecular
packing stability in the unit cell.
A literature survey shows that thiazolyl-pyrazoline
derivatives containing 1,2,4-triazole moiety have never
been reported so far. Encouraged by these facts and in
continuation of our interest in the synthesis of chemically
and biologically important heterocycles containing 1,2,4-
triazole moiety[10, 11], herein, we report the synthesis
and X-ray crystallographic study of some novel hetero-
cyclic compounds including 1,2,4-triazole, pyrazoline and
thiazole ring in the same molecule, which might exhibit
enhanced activities owing to the incorporation of differ-
ent pharmacophores into their structures R1 = H, Cl,
OCH3
Keywords 1,2,4-Triazole Á Pyrazoline Á Thiazole Á
Crystal structure
Experimental Section
Y.-M. Zeng Á F.-M. Liu
College of Chemistry and Chemical Engineering, Xinjiang
University, Urumqi 830046, People’s Republic of China
Materials and Synthesis
S.-Q. Chen Á F.-M. Liu (&)
All reagents for synthesis and analyses were purchased
from commercial sources and were used as received without
further purification. Melting points were recorded on a
mettler FP-5 capillary melting point apparatus and are
College of Materials and Chemical Engineering,
Hangzhou Normal University, Hangzhou 310036,
People’s Republic of China
e-mail: fmliu859@sohu.com
123

J Chem Crystallogr (2012) 42:24–28
25
uncorrected. Elemental analyses were performed on a Per-
kin-Elmer 2400 elemental analyzer. The IR spectra were
measured on a Bruker Equinox 55 FT-IR spectrophotometer
Calcd. (%) for C26H17 Cl3 N6 S: C, 15.23; H, 3.10; N,
60.35; Found (%): C, 15.26; H, 3.12, N, 60.35.
3c White crystals, Yield 83.6%; m.p. 214–215 °C. IR
(KBr) m/cm-1: 1634 (C=N); 1H NMR(CDCl3 ? DMSO-
d6, 300 MHz, ppm):d8.06,8.16(2H, 2s, Triazole-H),
6.73–7.69(12H,m,phenyl-H), 5.70(dd, 1H, C5-Hx, Jax =
12.00 Hz, Jbx = 6.39 Hz), 3.92(dd, 1H, C4-Ha, Jax =
12.00 Hz, Jab = 17.60 Hz), 3.76(3H,s,CH3O), 3.30(dd,
1H, C4-Hb, Jbx = 6.39 Hz, Jab = 17.60 Hz). MS(EI)m/
z(%): 552 (M?), 91, 77; Anal. Calcd. (%) for
C27H20Cl2N6OS: C, 15.35; H,3.68; N.59.24; Found (%):
C, 15.33; H, 3.64; N, 59.25.
1
with KBr disk in the range 4000–400 cm-1.The H NMR
spectra were recorded on a Varian Inova-400 spectropho-
tometer using tetramethylsilane (TMS) as internal standard
and CDCl3 as solvent.
1-thiocarbamoyl-3,5-bis-(4-chloro-phenyl)4,5-dihydro-1H-
pyrazoline (1), Triazolylethanones and bromine substituted
triazolylethanones (2) were prepared according to the
reported methods [12–14].
The Synthesis of 1-Thiocarbamoyl-3,5-bis-
(4-chloro-phenyl)-4,5-Dihydro-1H-pyrazoline (1)
Crystal Structure Determination
The selected crystal with approximate dimensions of
0.41 9 0.29 9 0.14 mm3 was mounted thin glass fiber
with the aid of an epoxy resin. The XRD data were col-
lected with multi-scan mode at 293(2) K on a Bruker Smart
AXSCCD with a graphite monochromatic Mo–Ka radia-
A mixture of the appropriate chalcone (5 mmol) and thi-
osemicarbazide (6 mmol) was refluxed in ethanol (50 mL).
After dissolution of the reactants, a solution of KOH
(12.5 mmol) in water (5 mL) was added dropwise. The
solution was refluxed for a further 4 h. The reaction mix-
ture was allowed to cool, poured into crushed ice, and the
solid mass separated out was filtered, washed with cold
ethanol, dried, and crystallized from ethanol/water.
˚
tion (k = 0.71073 A). APEX2 software was used for data
reduction and multi-scan absorption correction. [15] A total
of 21,794 reflections (2hmax = 52.38) were collected, of
which 5,871 unique reflections (Rint = 0.0525) were used
to structural elucidation. The structures were solved by
direct methods using SHELXS97 [16] and refinement was
The Synthesis of 1-(4-aryl-5-triazolyl-2-thiazolyl)-3,5-
diaryl-2-Pyrazoline derivatives (3a–c)
carried out by the full-matrix least-squares technique on F2
using SHELXL97 [16]. The function Rw = | w(|F0|2-
P
P
|F|c2|/
w(f0)2|1/2was minimized, where w = [1/r2(F0)2?
|
(aP0)2?bP], (P = [F02?2Fc2]/3. The final R1 and wR2 val-
ues 0.0115 and 0.0211 are for 1,138 independent reflec-
tions [I [ 2r(I)]. All non-hydrogen atoms were assigned
anisotropic displacement parameters in the refinement. All
hydrogen atoms were added atcalculated positions and
refined usin a riding model, with C–H distances in the
General Procedure a mixture of 3,5-Bis-(4-chloro-phenyl)-
4,5-dihydro-1H -pyrazole-1-carbothioamide 1 (0.5 mmol)
and 2-bromo-1-(4-substituted phenyl)-2-(1H-1,2,4-triazol-
1-yl) ethanone 2 (0.5 mmol) in ethanol (30 mL) was heated
under reflux for 0.5 h. The progress of reaction was moni-
tored on TLC. Then the crystalline solid product separated
by filtered, washed by cold ethanol and dried. The crude
compound was recrystallized from ethanol to obtained 3a–c.
3a White crystals, Yield 80.3%; m.p. 204–205 °C. IR
(KBr)m/cm-1:1631 (C=N); 1HNMR(CDCl3 ? DMSO-d6,
400 MHz ppm):d 8.06,8.16 (2H, 2 s, Triazole-H), 6.82–
7.70 (13H, m, phenyl-H), 5.69(dd, 1H, C5-Hx,
Jax = 11.93 Hz, Jbx = 5.97 Hz), 3.94(dd, 1H, C4-Ha,
Jax = 11.93 Hz, Jab = 17.60 Hz), 3.32(dd, 1H, C4-Hb,
Jbx = 5.97 Hz, Jab = 17.60 Hz).MS(EI)m/z(%): 516 (M?),
91, 77; Anal.Calcd. (%) for C26H18Cl2N6S : C, 16.24; H,
3.51; N, 60.35; Found (%): C, 16.27; H, 3.62; N, 60.42.
3b White crystals, Yield 76.3%;.m.p. 256–258 °C. IR
(KBr)m/cm-1:1632 (C=N); 1HNMR (CDCl3 ? DMSO-d6,
400 MHz ppm): d8.06, 8.16(2H,2 s,Triazole-H), 6.75–7.70
(12H, m, phenyl-H), 5.71(dd, 1H, C5-Hx, Jax = 11.95 Hz,
Jbx = 5.99 Hz), 3.90(dd, 1H, C4-Ha, Jax = 11.95 Hz,
Jab = 17.60 Hz), 3.29(dd, 1H, C4-Hb, Jbx = 5.99 Hz,
Jab = 17.60 Hz).MS(EI)m/z(%): 552(M?), 91, 77; Anal.
˚
range 0.93 A and with their Uiso’s set at 1.2 (1.4 for methyl
groups) times the Ueq values of the appropriate carrier
atoms. Molecular structure was checked using PLATON
[17]. Data collection details and structure determination
results are summarized in Table 1. Some selected bond
distances and angles quoted in Table 2. CCDC-800971
contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge at
http://www.ccdc.cam.ac.uk/conts/ retrieving.html.
Result and Discussion
The synthetic routes leading to the desired compounds are
shown in Schemes 1.
The IR spectral, mass spectra and 1H NMR spectral data
gave strong evidence for the structure of 3a–c. The IR
spectra of 3a–c exhibit bands at 1631–1632 cm-1(C=N).
123

26
J Chem Crystallogr (2012) 42:24–28
Table 1 Crystal data and structure refinement
3
V (A )
˚
Formula
C26H18Cl2N6S
4984.3(3)
Crystal color
Formula weight
Temperature
Colorless
Crystal size (mm)
Crystal system
Space group
c (°)
0.36 9 0.26 9 0.19
517.43
Orthorhombic
293(2) K
Pna2(1)
˚
a (A)
17.8160(5)
90
˚
b (A)
18.9125(7)
Z
8
˚
c (A)
14.7926(4)
Dc (mg/m3)
h range (°)
l/mm
1.379
a (°)
90
3.14–27.48
b (°)
Data/restraints/parameters
90
0.372
11066/1/632
Reflections collected
R indices (all data)
43309
Final R indices [I [ 2r(I)]
R1 = 0.0527, wR2 = 0.1307
R1 = 0.1094, wR2 = 0.1639
˚
Table 2 Selected bond lengths (A), bond angels (°) and torsion angles (°) of compounds
N(7)–C(35)
1.283(5)
1.379(4)
1.553(5)
1.510(5)
1.738(4)
1.412(5)
119.4(3)
116.9(5)
119.0(5)
118.9(5)
N(8)–C(42)
1.369(5)
1.479(5)
1.506(6)
1.447(5)
1.360(5)
1.473(5)
119.6(4)
119.7(3)
117.9(3)
101.0(4)
C(43)–C(46)–C(47)–C(52)
119.0(5)
-73.1(5)
-179.1(3)
105.9(6)
178.2(4)
-0.1(3)
-178.9(4)
178.7(4)
2.8(6)
N(7)–N(8)
N(8)–C(33)
N(11)–N(10)–C(43)–C(46)
C(27)–C(28)–C(29)–Cl(3)
C(44)–N(10)–C(43)–C(46)
C(31)–C(30)–C(29)–Cl(3)
C(43)–S(20–C(42)–N(9)
C(41)–C(40)–C(39)–Cl(4)
N(7)–N(8)–C(42)–N(9)
N(7)–C(35)–C(36)–C(41)
C(46)–N(9)–C(42)–S(2)
C(33)–C(34)
C(32)–C(33)
C(34)–C(35)
C(35)–C(36)
S(2)–C(42)
C(43)–C(46)
N(10)–C(43)
C(46)–C(47)
C(38)–C(39)–Cl(4)
N(12)–C(45)–N(11)
C(30)–C(29)–Cl(3)
C(28)–C(29)–Cl(3)
C(40)–C(39)–Cl(4)
N(8)–C(42)–S(2)
N(9)–C(42)–S(2)
C(45)–N(11)–N(10)
0.1(2)
S
Scheme 1 The synthesis of
title compounds
O
S
H2N
N
NH2
R1
N
H
Cl
NH2
Cl
N
N
N
Cl
N
KOH/EtOH
Cl
S
N
1
EtOH
N
Cl
N
N
O
N
O
R1
NaAc / HAC
Br2
N
N
R1
Cl
N
Br
N
3a-c
2
1
Also, their H NMR spectra revealed multiplet between d
7.79 and 6.73 ppm due to the protons of aromatic rings, the
signal for 1,2,4-trizole and methoxyl appeared at d
8.19–8.06 ppm and d 3.82–3.74 ppm, respectively. Three
distinct double doublets of the ABX system (a CH proton
and two anisochronous protons of a CH2) appeared at d
5.71–3.29 ppm, as has been observed in pyrazoline ring.
The EI mass spectra of compounds 3a–c revealed the
existence of the molecular ion peaks and anticipant frag-
mentation peaks, which were in good accordance with the
given structures of products. For example, the mass spec-
trum of 3a had the molecular ion peaks at m/z 448 (100%).
The structure of the crystal 3a is displayed in Fig. 1. The
C(33), C(34), C(35), N(7) and N(8) atoms form a five-
membered ring, X-ray analysis reveals that the five-
membered ring of pyrazoline adopts an envelope confor-
mation with the atom C(33) deviating from the plane
defined by the atoms C(34), C(35), N(7) and N(8) of
˚
0.2753 A. The N7–N8 and N8–C33 bond distances of
˚
1.379(4) and 1.479(5) A are showing they belong to single
˚
bond. However, the C35=N7 bond distance of 1.283(5) A
is falling into the C=N double bond distance region.
Because of the existence of conjugate system of C35=N7
and phenyl ring (C36–C41), the distance of C(35)–C(36)
123

J Chem Crystallogr (2012) 42:24–28
27
˚
(1.447 A) is shorter than the normal C–C single bond
˚
(1.53 A). The torsion angles of N7–C35–C36–C41, N8–
Globally, the molecule has a distinctive curved confor-
mation. In the crystal structure, there is no classic hydrogen
bonds. The crystal structure is stabilized by weak C–HÁÁÁN
intramolecular hydrogen bonds and C–HÁÁÁCg intermolec-
ular interactions (Table 3). The bond lengths of C(8)–
H8ÁÁÁCg(7), C(31)–H(31A)ÁÁÁCg(8)and C(48)–H(48A)ÁÁÁ
C33–C32–C27 and N7–N8–C4–N9 are 2.8(6)°, 119.4(4)°,
and 169.9(4)°, respectively. The plane of C(34)–C(35)–
N(7)–N(8) is nearly parallel with the phenyl ring of C(36)–
C(41) and thiazole ring, forming a dihedral angle of 4.0(2)°
and 10.7(2)°, respectively, while it is nearly perpendicular
with the phenyl ring C(27)–C(32), forming a dihedral angle
of 86.7(2)°.
˚
Cg(9) correspond to 2.75, 2.65, and 2.86 A, respec-
Q Q
tively. Additionally, the
–
stacking interactions were
observed with the centroid–centroid separation of Cg(1)–
˚
˚
Cg(8) = 5.189(2) A, Cg(1)–Cg(10) = 5.312(3) A, Cg(1)–
The thiazole ring is planar with maximum deviations of
˚
0.01(4) and -0.01(3) A for the S2 and C42 atoms,
˚
Cg(12) = 4.186(3) A, which link the two independent
respectively. The smaller bond length of the N(8)–C(42)
molecule. [Cg(1) is center of gravity of ring (S1, N3, C16,
C17, C21); Cg(10) is the center of gravity of ring (C27,
C28, C29, C30, C31, C32) and Cg(12) is the center of
gravity of ring (C47, C48, C49, C50, C51, C52)]. The
perpendicular distance between Cg(1)–Cg(8), Cg(1)–
Cg(10) and Cg(1)–Cg(12) are 2.3840(16), 1.2066(14) and
˚
˚
(1.369 A) than a typical C–N single bond(1.47–1.50 A),
[18] clearly indicates the double bond nature of the
N(8)=C(42) bond due to the conjugation of N(8) with
thiazole ring. The dihedral angles of thiazole plane forms
with the triazole and the phenyl ring of C47–C52 are 101°
and 20.7°, respectively.
˚
3.3036(15) A, respectively.
Fig. 1 ORTEP view and
packing diagram of molecular
structure of compound 3a
123

28
J Chem Crystallogr (2012) 42:24–28
Table 3 intra- and inter-molecular interaction
Intramolecular interactions (A°)
D–HÁÁÁA
D–H
0.93
0.93
HÁÁÁA
2.58
2.49
DÁÁÁA
3.137(5)
D–HÁÁÁA
119
C(48)–H(48A)ÁÁÁN(10)
C(52)–H(52A)ÁÁÁN(9)
Intermolecular interactions (A°)
D–HÁÁÁA
2.819(5)
101
HÁÁÁA
2.75
2.65
2.86
DÁÁÁA
3.072(5)
2.818(5)
3.558(4)
D–HÁÁÁA
133
Symmetry code
2 - x, 1 - y, ‘ ? z
x, y, z
C(8) –H(8B)ÁÁÁCg(7)a
C(31)–H(31A)ÁÁÁCg(8)b
C(48)–H(48A)ÁÁÁCg(9)c
100
133
x, y, z
a
Cg7 = S2–C43–C46–N9–C42
b
Cg(8) = N7–N8–C33–C34–C35
c
Cg9 = N10–N11–N12–C44–C45
10. Yang DB, Liu FM, Shen SW, Chen SQ (2010) Chin J Org Chem
30(2):244
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