Synthesis and structure characterization of thiazolyl-pyrazoline derivatives bearing quinoline moiety

Article abstract of DOI:10.1080/10426507.2011.621002

A series of thiazolyl-pyrazoline derivatives containing the quinoline moiety were obtained by condensation of 2-bromo-1-phenyl-ethanone and 3-aryl-5-(2-substituted-quinolin-3-yl)-1-thiocarbamoyl-pyrazolines (4a-f). The structures of the newly synthesized compounds were characterized and their structures confirmed by IR, ¹H NMR, mass spectrometry and elemental analysis. The solid-state structure of 3-(4-chlorophenyl)-5-(2-phenylthio- quinolin-3-yl)-1-(4-phenyl-2-thiazoyl)-pyrazoline (5n) was further studied by a single-crystal X-ray diffraction analysis. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Figure S1 and Table S1.

Full text of DOI:10.1080/10426507.2011.621002

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Synthesis and Structure Characterization
of Thiazolyl-Pyrazoline Derivatives
Bearing Quinoline Moiety
Yong-Ming Zen a , Fei Chen a & Fang-Ming Liu a b
a College of Materials and Chemical Engineering, Hangzhou Normal
University, Hang Zhou, P. R China
b College of Chemistry and Chemical Engineering, Xinjiang
University, Urumqi, P. R. China
Version of record first published: 31 Jan 2012.
To cite this article: Yong-Ming Zen , Fei Chen & Fang-Ming Liu (2012): Synthesis and Structure
Characterization of Thiazolyl-Pyrazoline Derivatives Bearing Quinoline Moiety, Phosphorus, Sulfur, and
Silicon and the Related Elements, 187:3, 421-431
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Phosphorus, Sulfur, and Silicon, 187:421–431, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.621002
SYNTHESIS AND STRUCTURE CHARACTERIZATION
OF THIAZOLYL-PYRAZOLINE DERIVATIVES BEARING
QUINOLINE MOIETY
Yong-Ming Zen,1 Fei Chen,1 and Fang-Ming Liu1,2
1College of Materials and Chemical Engineering, Hangzhou Normal University,
Hang Zhou, P. R China
2College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi,
P. R. China
GRAPHICAL ABSTRACT
Abstract A series of thiazolyl-pyrazoline derivatives containing the quinoline moiety were
obtained by condensation of 2-bromo-1-phenyl-ethanone and 3-aryl-5-(2-substituted-quinolin-
3-yl)-1-thiocarbamoyl-pyrazolines (4a-f). The structures of the newly synthesized compounds
were characterized and their structures confirmed by IR, 1H NMR, mass spectrometry and
elemental analysis. The solid-state structure of 3-(4-chlorophenyl)-5-(2-phenylthio-quinolin-
3-yl)-1-(4-phenyl-2-thiazoyl)-pyrazoline (5n) was further studied by a single-crystal X-ray
diffraction analysis.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: Figure S1 and Table S1.
Keywords Thiazolyl-pyrazoline; quinoline; crystal structure; NMR spectroscopy
Received 30 June 2011; accepted 29 August 2011.
Address correspondence to Fang-Ming Liu, College of Chemistry and Chemical Engineering, Xinjiang
University, Urumqi 830046, P. R. China. E-mail: fmliu859@sohu.com
421

422
YONG-MING ZEN ET AL.
INTRODUCTION
Quinoline ring systems represent a major class of heterocycles in which the ben-
zene ring is fused with a pyridine ring and its derivatives have wide occurrence in natural
products, as well as applications as drugs and pharmaceuticals.1–4 Moreover, the quinoline
skeleton is often used as a key intermediate for the design of pharmacologically impor-
tant compounds.5–7 Therefore, the design and synthesis of new quinoline derivatives have
recently received great attention due to their broad biological and therapeutic properties
such as antimalarial,8–10 antimicrobial,11 antibacterial,12 and antiproliferative activities.13
In addition, thiazole and pyrazoline derivatives are two major five-membered heterocycles,
whose compounds, with these nuclei, are known to possess anticonvulsant, antidepressant,
antibacterial, analgesic, antimicrobial, and anticancer activities.14–20 The pyrazole deriva-
tive celebrex and thiazole derivative fentiazac are used as anti-inflammatory drugs.21,22
Taking into consideration of the above properties as well as the combination principles for
drug design, we herein report the synthesis of some new thiazolyl-pyrazoline derivatives
with the quinoline moiety, which might exhibit enhanced activities.
REULTS AND DISCUSSION
1
The structures of 2a–b, 3a–f, 4a–4f, and 5a–s were characterized by IR, H NMR
spectroscopy, and mass spectrometry. The structure of the compound 5n was further elu-
cidated by a single crystal X-ray diffraction analysis. Its crystal data, data collection, and
refinement parameters are given in Table 1 and selected geometric parameters are given in
Table 2. The target compounds 5a–s were prepared as depicted in Scheme 1. In the initial
step, using Claisen–Schmidt condensation, the α,β-unsaturated carbonyl compounds 3a–3f
were obtained by reacting substituted acetophenones and 2-substituted-3-formylquinoline
2a,b (Tables 3 and 4). The IR spectra of 3a–f exhibited C = O stretching modes at
1659–1663 cm−1, C–O–C stretching 1241–1244 cm−1 and C–S–C stretching 760–763 cm−1
1
bands. In addition, in the H NMR spectra of the compounds 3a–f, the protons of
α,β-unsaturated carbonyl compounds showed two doublets at 8.16 ppm for Hα and
7.96 ppm for Hβ with 15.6 Hz as the coupling constant. So, it was inferred that they
are in the trans conformations. The quinoline-H4 was observed as a doublet of doublets
Table 1 Crystal data and structure refinement for compound 5n
Empirical formula
C33H23N4S2Cl
Compound
5n
Formula weight
Temp (K)
Wavelength
Crystal system/space group
Color/shape
a (Å)
b (Å)
575.15
γ /◦
Z
Dc (mg/m3)
112.879 (2)
16
1.787
0.45 × 0.22 × 0.16
1.76–27.53
1.41
296 (2) K
0.71073 A
Triclinic/P-1
White
10.8712 (13)
12.1353 (14)
12.2884 (3)
92.061 (3)
107.176 (3)
6411
Crystal size (mm)
Theta range for collection
µ (mm−1)
Reflections collected
Data/restraints/parameters
Largest difference peak/hole
V, Å3
Goodness of fit on F2
Final R indices [I > 2σ(I)]
23504
c (Å)
6411/0/361
0.704/−0.710
1405.9(3)
1.042
α/◦
β/◦
Independent reflections
R indices (all data)
R1 = 0.0852
R1 = 0.0521
wR2 = 0.1626
wR2 = 0.1355

SYNTHESIS AND STRUCTURE CHARACTERIZATION
423
Table 2 Selected bond lengths (Å) and angles (◦) of compound 5n
S(2)–C(8)
1.716 (3)
N(4)–N(3)
1.380 (3)
S(2)–C(7)
S(1)–C(6)
S(1)–C(5)
N(1)–C(26)
C(2)–C(7)
1.734 (2)
1.751 (3)
1.772 (2)
1.311 (3)
1.513 (3)
1.293 (3)
1.388 (3)
1.288 (3)
1.367 (3)
117.87 (19)
109.7 (2)
120.4 (2)
C(21)–C(20)
C(6)–C(16)
C(21)–C(22)
C(24)–N(3)
C(23)–C(24)
C(22)–C(23)
C(9)–C(8)
1.384 (4)
1.398 (3)
1.465 (3)
1.485 (3)
1.535 (3)
1.506 (3)
1.348 (4)
1.474 (3)
120.9 (2)
106.26 (11)
107.96 (19)
100.53 (18)
N(2)–C(7)
N(2)–C(9)
N(4)–C(22)
N(3)–C(7)
C(26)–N(1)–C(27)
C(7)–N(2)–C(9)
C(20)–C(21)–C(2)
C(9)–C(10)
C(28)–C(25)–C(2)
C(21)–S(1)–C(5)
C(22)–N(4)–N(3)
N(3)–C(24)–C(23)
XH
CHO
CHO
X
O
R
1
KOH
N
N
NaOH
Cl
2a-b
1
R
1
O
S
H NHN
2
NH
R
R
2
1
N
Ph
N
X
KOH
N
NH
2
Ph
3a-f
S
N
X
1
4a-f
O
R2
Br
R
2
N
N
N
Ph S
N
X
5a-s
(2a)X=O
(2b)X=S
(3a,4a)X=O, R1=H
(3b,4b)X=O, R1=Cl
(3c,4c)X=O, R1=OCH3
(3d,4d)X=S, R1=H
(5g)X=O, R1=OCH3, R2=H
(5h)X=O, R1=OCH3, R2=Cl
(5j)X=O, R1=OCH3, R2=OCH3
(5k)X=S, R1=H, R2=H
(3e,4e)X=S, R1=Cl
(3f,4f)X=S, R1=OCH3
(5n)X=S, R =Cl, R2=H
(5a)X=O, R1=H, R2=H
(5b)X=O, R1=H, R2=Cl
(5c)X=O, R1=H, R2=OCH3
(5d)X=O, R1=Cl, R2=H
(5e)X=O, R1=Cl, R2=Cl
(5f)X=O, R1=Cl, R2=OCH3
1
(5o)X=S, R1=Cl, R2=Cl
(5p)X=S, R =Cl, R2=OCH3
1
(5q)X=S, R =OCH3, R2=H
1
(5l)X=S, R1=H, R2=Cl
(5r)X=S, R1=OCH3, R2=Cl
(5s)X=S, R1=OCH3, R2=OCH3
(5m)X=S, R =H, R2=OCH3
1
Scheme 1

424
YONG-MING ZEN ET AL.
Table 3 Physical and analytical data of compounds 2–4
% Anal calcd./Found
Compd.
no.
N
H
C
Formula/mol. wt.
Color/yield%
Mp (◦C)
2a
2b
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
5.28/5.34
4.98/4.86
3.99/3.96
3.63/3.65
3.67/3.74
3.81/3.95
3.35/3.73
3.52/3.43
5.57/5.61 76.96/77.09 C17H15NO2/265.11
5.37/5.42 72.57/72.73 C17 H15NOS/281.09
Yellow/90
Yellow/88
Yellow/89
150–151
123–124
183.6–184.7
152.6–153.4
187–188
135–136
121–122
168–169
214.1–215.8
230.4–231.2
242.1–244.4
198.8–199.6
203.1–205.5
273.2–274.5
4.88/4.90 82.03/82.22
4.08/4.13 74.71/74.04
5.02/5.21 78.72/78.63
4.66/4.54 78.45/78.71
4.82/4.62 71.84/71.75
4.82/4.84 75.54/75.62
C
C
C
C
C
C
24H17NO2/351.12
24H161.12ClNO2/410.12 Yellow/94
25H19NO3/381.14
24H17NOS/367.10
25H20NOSCl/417.10
25H19NO2S/397.11
White/89
Yellow/85
White/91
White/95
White/89
Yellow/87.7
White/93
White/94
Yellow/84
Yellow/79
13.20/13.16 4.75/4.74 70.73/70.67 C25H2oN4SO/424.52
12.21/12.14 4.17/4.13 65.42/65.38
12.72/12.35 4.58/4.74 68.15/68.01
10.02/9.94
11.79/11.43 4.03/4.261 63.21/63.80
11.91/11.54 4.71/4.86 66.36/67.08
C
C
C
C
C
25H19ClN4SO/458.16
25H20N4S2/440.11
33H23N4SOCl/559.08
25H19ClN4S2/474.07
26H22N4OS2/470.12
4.15/4.10 70.68/70.79
at 8.42–8.43 ppm, the protons belonging to the aromatic ring were seen at δ 8.13–6.66 as
multiplet signals.
The chalcones were subsequently treated with thiosemicarbazide in the presence of
potassium hydroxide in ethanol, to afford 4a–f. The IR spectra of compounds 4a–f showed
the stretching band of N–H and C = S at 3410–3415 cm−1 and 1359–1365 cm−1. Its
1H NMR spectrum revealed three distinct doubles of doublets of the ABX system in the
pyrazoline ring at δ 3.27–3.30 ppm, 4.01–4.04 ppm, and 6.17–6.20 ppm, respectively.
The condensation reaction between 4a–f and 2-bromo-1-arylethanones in boiling
ethanol led to the formation of 5a–s in good yields (Tables 5 and 6). The progress of each
reaction was monitored by thin layer chromatography. The IR spectra of 5a–s showed strong
stretching vibration at 1608–1589 cm−1. Due to the presence of C = N and sharp absorption
at 1257–1263 cm−1 for C–O–C single bond and strong absorption at 757–763 cm−1 for
1
C–S–C bond. In addition, the H NMR spectrum of compound 5I shows a characteristic
singlet of the quinoline-H4 at δ 7.98 ppm. Three distinct doublets of doublets at δ 3.29 ppm
(Ha), δ 4.02 ppm (Hb), and δ 6.194 ppm (Hx) are attributed to the CH2 (Ha, Hb) and CH
(Hx) protons of the ABX system in the pyrazoline ring. The mass spectrum of the titled
compounds revealed the existence of the molecular ion peaks and significant fragment ion
peaks, which is strong evidence for the structures (Table 6).
The molecular structure of the title compound is shown in Figure 1. The higher occu-
pancy in the three-dimensional packing arrangement is shown in Figure S 1 (Supplemental
Materials).
The X-ray diffraction study of the compound 5n has shown that 3-(4-Chlorophenyl)-
5-(2-phenylthio-quinolin-3-yl)-1-(4-phenyl-2-thiazoyl)-pyrazoline(C33H23N4S2Cl) crysta-
llizes in the triclinic system with space grouping P-1. The compound 5n contains four ring
systems: the quinoline ring, the phenyl ring, the thiazole ring, and the pyrazoline ring. The
thiazole ring as the center adopts an envelope conformation with N(2), C(7), C(8), and C(9)
lying in a plane, and S(2) locates 0.23 Å out of the plane, which is nearly coplanar with
the pyrazoline ring and phenyl ring C10–C15 (dihedral angle is 13.33◦ and 10.49◦). The
pyrazoline ring is almost planar with maximum deviations of 0.0339 Å for the C22 atoms,

SYNTHESIS AND STRUCTURE CHARACTERIZATION
425
Table 4 IR, 1H NMR, and mass of compounds (2a–b, 3a–f, 4a–f)
Compd.
no.
IR (cm−1
)
1H NMR (CDCl3)
MS, m/z (M+)
2a
1706 (C O), 1617
(C N), 1238
9.56 (s, 1H, –CHO), 8.26 (s, 1H,
quinolin-H4), 8.13–7.23 (m, 9H, Ar H)
265 (M+), 221, 192,
165, 143, 128, 101,
91, 78
(C
O C)
2b
3a
1705 (C O), 1626,
9.58 (s, 1H, –CHO), 8.24 (s, 1H,
281 (M+), 236, 204,
165, 128, 101, 77, 56
351 (M+), 279, 258,
246,149, 135, 105,
77
(C N, 762 (C
1661 (C O), 1603
(C N), 1242
S
C)
quinolin-H4), 8.10–7.19 (m, 9H, Ar H)
8.43 (s, 1H, quinolin-H4), 8.17 (d, 1H, J =
15.6 Hz, Hβ ), 7.98 (d, 1H, J = 15.6 Hz,
Hα), 8.11–6.71 (m, 14H, Ar H)
8.42 (s, 1H, quinolin-H4), 8.19 (d, 1H, J =
15.6 Hz, Hβ ), 7.99 (d, 1H, J = 15.6 Hz,
Hα), 8.13–6.72 (m, 13H, Ar H)
(C
O C)
3b
3c
1663 (C O), 1612
(C N), 1244
410(M+), 292, 246,
217, 139, 111, 77
(C
O C), 689
(C Cl)
1660 (C O), 1605
(C N), 1241
8.44 (s, 1H, quinolin-H4), 8.16 (d, 1H, J =
15.7 Hz, Hβ ), 7.96 (d, 1H, J = 15.7 Hz,
Hα), 8.09–6.98 (m, 13H, Ar H), 3.89 (s,
3H, –OCH3)
381(M+), 288, 246,
217, 135, 107, 92, 77
(C
O C)
3d
3e
3f
1659 (C O), 1609,
(C N), 760 (C
8.42 (s, 1H, quinolin-H4), 8.15 (d, 1H, J =
15.5 Hz, Hβ ), 7.96(d, 1H, J = 15.5 Hz,
Hα), 8.02–6.67 (m, 14H, Ar H)
8.43 (s, 1H, quinolin-H4), 8.10 (d, 1H, J =
15.6 Hz, Hβ ), 7.92 (d, 1H, J = 15.6 Hz,
Hα), 8.03–6.69 (m, 14H, Ar H)
8.44 (s, 1H, quinolin-H4), 8.18 (d, 1H, J =
15.7 Hz, Hβ ), 7.97 (d, 1H, J = 15.7 Hz,
Hα), 8.02–6.66 (m, 13H, Ar H), 3.89 (s,
3H, –OCH3)
366(M+), 336, 262,
227,171, 151, 125
S
S
S
C)
1661 (C O), 1615
(C N), 763 (C
683 (C Cl)
1662 (C O), 1613
(C N), 762 (C
402 (M+), 383, 292,
262, 185, 139, 111
C)
C)
396 (M+), 288, 262,
230, 185, 135, 107
4a
4b
4c
4d
4e
3410, 3264 (N H), 3094
(Ar H), 1594, 1512,
1473 (C N, C C),
1361 (C S)
6.15–7.85 (17H, m, Ar H), 6.19 (dd, 1H,
Hx, Jax = 12.0 Hz,Jbx = 6.4 Hz), 4.03
(dd, 1H, Ha, Jax = 12.0 Hz, Jab = 17.6
Hz), 3.29(dd, 1H, Hb, Jbx = 6.4 Hz, Jab
= 17.6 Hz)
424 (M+), 391, 364,
331, 246, 228, 201,
145, 128, 77
3410, 3264 (N H), 3043
(Ar H), 1612, 1513,
1472 (C N, C C),
1364 (C S), 763
(C Cl)
3415, 3268(N H), 3154
(Ar H), 1592, 1516,
1472 (C N,C C),
1359 (C S)
6.83–7.69 (16H,m,Ar H), 6.18 (dd, 1H,
Hx, Jax = 12.1 Hz, Jbx = 6.3 Hz), 4.01
(dd, 1H, Ha, Jax = 12.1 Hz,Jab = 17.5
Hz), 3.27(dd, 1H, Hb, Jbx = 6.3Hz, Jab
= 17.5Hz)
458 (M+), 425, 398,
365, 320, 246, 228,
201, 128, 77
6.82–7.72 (16H, m, Ar H), 6.17 (dd, 1H,
Hx, Jax = 11.9 Hz, Jbx = 6.5 Hz), 4.04
(dd, 1H, Ha, Jax = 11.9 Hz, Jab = 17.6
Hz), 3.30 (dd, 1H, Hb, Jbx = 6.5 Hz, Jab
= 17.6 Hz), 3.80 (3H, s, CH3O)
454 (M+), 421, 394,
361, 320, 246, 228,
201, 175, 133, 77
3412, 3264 (N H),
3031(Ar H), 1613,
1513, 1473 (C N,
6.70–7.59 (17H, m,Ar H), 6.20 (dd, 1H,
Hx, Jax = 12.0 Hz, Jbx = 6.4 Hz), 4.02
(dd, 1H, Ha, Jax = 12.0 Hz, Jab = 17.9
Hz), 3.28 (dd, 1H, Hb, Jbx = 6.4 Hz, Jab
= 17.9 Hz)
336 (M+), 262, 227,
200, 171, 108, 77
C
C), 1361 (C S)
3414, 3261 (N H), 3085
(Ar H), 1599, 1515,
1474 (C N, C C),
1365 (C S),
6.82–7.79 (16H, m, Ar H), 6.18 (dd, 1H,
Hx, Jax = 12.0 Hz, Jbx = 6.3 Hz), 4.01
(dd, 1H, Ha, Jax = 12.0 Hz,
365 (M+), 330, 277,
262, 236, 228, 214,
201, 187, 153, 128
Jab = 17.4 Hz), 3.30 (dd, 1H, Hb, Jbx =
6.3 Hz, Jab = 17.4 Hz)
(Continued on next page)

426
YONG-MING ZEN ET AL.
Table 4 IR, 1H NMR, and mass of compounds (2a–b, 3a–f, 4a–f) (Continued)
Compd.
no.
IR (cm−1
)
1H NMR (CDCl3)
MS, m/z (M+)
4f
3415, 3265 (N H), 3049
(Ar H), 1606, 1518,
1472 (C N, C C),
1363 (C S), 689
(C Cl)
6.76–7.71 (16H, m, Ar H), 6.22 (dd, 1H,
Hx, Jax = 12.1 Hz, Jbx = 6.4 Hz), 4.03
(dd, 1H, Ha, Jax = 12.1 Hz, Jab = 17.6
Hz), 3.28 (dd, 1H, Hb, Jbx = 6.4 Hz,
Jab = 17.6 Hz), 3.80 (3H, s, CH3O)
361 (M+), 302, 262,
236, 187, 77, 60
whereas the quinoline ring is coplanar, which forms dihedral angles of 69.42◦ and 79.91◦
with the plane of phenyl ring C1–C6 and the pyrazoline ring, respectively. Noteworthy, the
bond N(3)–N(4) (mean value 1.380(3) Å) is essentially a single bond, N(4)–C(22) (mean
value 1.288(3) Å) approaches a double bond, and C(22)–C(21) (mean value 1.465(3) Å),
the formal signal bond to the aryl residue, exhibits some conjugation effect (the normal
C–C single bond (1.53 Å)). The C7–N3 bond distance of 1.367(3) Å is smaller than a
typical C–N single bond (1.47–1.50 Å), which clearly indicates the double bond nature
of the N(3)=C(7) bond due to the conjugation of N(3) with thiazole ring. The packing
of the molecules in the unit cell results from the formation of C–H . . . . S intermolecular
hydrogen bonding between two additional molecules. Sulfur atom (S1) forms hydrogen
bonds with H–N(7) bond of the adjacent molecule but with no classical hydrogen bonds of
the intramolecular type.
In conclusion, we have obtained a series of pyrazoline derivatives 5a–s that con-
tain both thiazole and quinoline moiety. Meanwhile, the X-ray crystallography further
Table 5 Physical and analytical data of compounds 5
% Anal calcd./Found
Compd. no.
N
H
C
Formula/mol. wt.
Color/yield%
mp (◦C)
5a
5b
5c
5d
5e
5f
5g
5h
5j
10.68/10.57 4.61/4.54 75.55/75.14 C33H24N4SO/524.63
Yellow/36.7
Yellow/37.7
Yellow/35.6
Yellow/31.3
221.1–221.8
241.1–242.4
205.1–206.4
178.2–189.4
215.1–215.8
245.7–246.4
235.1–236.2
195.7–196.3
207.3–208.8
226.7–227.7
192.5–193.3
241.5–242.6
239.3–240.2
232.3–232.9
221.3–222.4
185.2–186.5
225.8–226.1
235.2–236.3
10.02/9.94 4.15/4.10 70.68/70.79
10.10/10.02 4.72/4.74 73.62/73.87
10.02/9.94 4.15/4.10 70.68/70.79
C
C
C
C
C
33H23ClN4SO/559.08
34H26N4O2S/554.66
33H23N4SOCl/559.08
33H22Cl2N4SO/593.52 Yellow/39.5
34H25N4O2SCl/589.11 Yellow/38.7
9.44/9.43
9.51/9.54
3.74/3.61 66.78/66.80
4.28/4.26 69.32/69.48
10.10/10.17 4.72/4.61 73.62/73.83 C34H26N4O2S/554.66
Yellow/35.6
34H25N4O2SCl/589.11 Yellow/32.8
9.51/9.44
9.58/9.49
4.28/4.23 69.32/69.64
4.83/4.84 71.90/71.83
C
C
C
C
C
C
C
35H28N4O3S/584.69
33H24N4S2/540.70
33H23N4S2Cl/575.15
34H26N4OS2/570,73
33H23N4S2Cl/575.15
Yellow/33.8
Yellow/36.9
Yellow/32.3
Yellow/37.2
Yellow/35.9
5k
5l
10.36/10.25 4.47/4.36 73.30/73.22
9.74/9.69
9.82/9.87
9.74/9.67
9.19/9.14
9.26/9.28
9.82/9.75
9.26/9.28
9.33/9.38
4.03/4.14 68.91/68.88
4.59/4.47 71.55/71.78
4.03/4.15 68.91/68.97
3.64/3.25 65.02/65.18
5m
5n
5o
5p
5q
5r
5s
33H22Cl2N4S2/609.59 Yellow/35.5
4.16/4.33 67.48/67.43 C34H25N4OS2Cl/605.17 Yellow/32.4
4.59/4.46 71.55/71.43
4.16/4.21 67.48/67.36
4.70/4.59 69.97/70.11
C34H26N4OS2/570.73
C34H25ClN4OS2/605.17 White/38.9
C35H28N4O2S2/600.75 Yellow/33.2
Yellow/39.7

SYNTHESIS AND STRUCTURE CHARACTERIZATION
427
Table 6 IR, 1H NMR, and mass of the compounds (5a–s)
Comp
No.
IR (cm−1
)
1H NMR (CDCl3)
MS.m/z (M+)
5a
5b
5c
5d
5e
5f
3085 (Ar H), 1631,
1512, 1474 (C N,
6.15–7.85 (21H, m, Ar H), 6.19 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 5.1 Hz), 4.03
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.8
Hz), 3.29 (dd, 1H, Hb, Jbx = 5.1 Hz, Jab
= 16.8 Hz)
524 (M+), 491, 431, 328,
246, 174, 129, 77
C
(C
C), 1257
C)
O
3043 (Ar H), 1626,
1592, 1512 (C N,
6.46–7.77 (20H, m, phenyl–H), 6.21 (dd,
1H, Hx, Jax = 10.9 Hz, Jbx = 4.9 Hz),
5 558 (M+), 525, 465, 362,
246, 220, 127
C
(C
C), 1261
C)
4.12 (dd, 1H, Ha, Jax = 10.99 Hz, Jab =
O
16.8 Hz), 3.31 (dd, 1H, Hb, Jbx = 4.97 Hz,
Jab = 16.8 Hz)
3063 (Ar H), 1632,
1538, 1462 (C N,
6.15–7.85 (20H, m, Ar H), 6.23 (dd, 1H,
Hx, Jax = 10.9 Hz,Jbx = 5.0 Hz), 3.99
(dd, 1H, Ha, Jax = 10.9 Hz, Jab = 16.8
Hz), 3.75 (3H, s, CH3O), 3.30 (dd, 1H, Hb,
Jbx = 5.0 Hz, Jab = 16.8Hz)
554 (M+), 482, 424, 364,
246, 145, 128
C
(C
C), 1261
C)
O
3029 (Ar H), 1652,
1583, 1484 (C N,
6.15–7.85 (20H, m, Ar H), 6.20 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 4.9 Hz), 4.02
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.7
558 (M+), 525, 465, 246,
220, 174, 129
C
(C
C), 1263
C), 749
O
Hz), 3.31 (dd, 1H, Hb, Jbx = 4.9 Hz, Jab
16.7 Hz)
=
=
(C Cl)
3056 (Ar H), 1663,
1569, 1474 (C N,
6.15–7.85 (19H, m, Ar H), 6.18 (dd, 1H,
Hx, Jax = 10.9 Hz, Jbx = 5.0 Hz), 4.01
(dd, 1H, Ha, Jax = 10.9 Hz, Jab = 16.8
Hz), 3.29 (dd, 1H, Hb, Jbx = 5.0 Hz, Jab
16.8 Hz)
592 (M+), 499, 398, 362,
246, 220, 173, 139, 111, 77
C
(C
C), 1264
C), 783
O
(C Cl)
3049 (Ar H), 1656,
1524, 1462 (C N,
6.15–7.85 (18H, m, Ar H), 6.19 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 4.9 Hz), 4.02
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.7
Hz), 3.76 (3H, s, CH3O), 3.30 (dd, 1H,
Hb, Jbx = 4.9 Hz, Jab = 16.7 Hz)
6.15–7.85 (20H,m,Ar H), 6.24 (dd, 1H,
C5–Hx, Jax = 10.9 Hz, Jbx = 5.0 Hz),
4.10 (dd, 1H, C4–Ha, Jax = 10.9 Hz, Jab
588 (M+), 555, 495,374, 358,
294, 246, 189, 159, 127,
77, 60
C
(C
C), 1263
C), 689
O
(C Cl)
3032 (Ar H), 1646,
1575, 1468 (C N,
5g
5h
5j
554 (M+), 506, 445, 292,
246, 189, 133
C
(C
C), 1258
C)
=
O
16.8 Hz), 3.32 (dd, 1H, C4–Hb, Jbx = 5.0
Hz, Jab = 16.8 Hz)
3059 (Ar H), 1689,
1574, 1457 (C N,
6.15–7.85 (19H, m, Ar H), 6.16 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 5.0 Hz), 3.98
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.7
588 (M+), 555, 495, 379,
264, 294, 246, 173, 133, 77
C
(C
C), 1259
C), 738
O
Hz), 3.32 (dd, 1H, Hb, Jbx = 5.0 Hz, Jab
=
(C Cl)
3018 (Ar H), 1643,
1536, 1491 (C N,
16.7 Hz)
6.15–7.85 (19H, m, Ar H), 6.21 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 5.0 Hz), 4.07
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.8
Hz), 3.81 (3H, s, CH3O), 3.28 (dd, 1H,
Hb, Jbx = 5.0 Hz, Jab = 16.8 Hz)
6.15–7.85 (21H, m, Ar H), 6.13 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 5.0 Hz), 4.02
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.8
Hz), 3.29 (dd, 1H, Hb, Jbx = 5.0 Hz, Jab
16.8 Hz)
584 (M+), 536, 491, 246,
189, 133, 77
C
(C
C), 1258
C)
O
5k
5l
3035 (Ar H), 1674,
1576, 1474 (C N,
539 (M+), 508, 460,163, 127,
77, 57
C
(C
C), 757
C)
S
=
3024 (Ar H), 1642,
1569, 1475 (C N,
6.15–7.85 (20H, m, Ar H), 6.19 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 5.0 Hz), 4.02
575 (M+), 574, 541, 465,
438, 362, 287, 262, 236,
(Continued on next page)

428
YONG-MING ZEN ET AL.
Table 6 IR, 1H NMR, and mass of the compounds (5a–s) (Continued)
Comp
No.
IR (cm−1
)
1H NMR (CDCl3)
MS.m/z (M+)
163, 127, 77
C
(C
C), 768
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.8
Hz), 3.29 (dd, 1HHb, Jbx = 5.0 Hz, Jab
16.8 Hz)
S
C), 723
=
(C Cl)
3032 (Ar H), 1646,
1576, 1474 (C N,
5m
5n
5o
5p
5q
5r
6.15–7.85 (20H, m, Ar H), 6.16 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 4.9 Hz), 4.03
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.7
Hz), 3.74 (3H, s, CH3O), 3.30 (dd, 1H,
Hb, Jbx = 4.9 Hz, Jab = 16.7 Hz)
570 (M+), 465, 304, 236,
163, 127, 77, 57
C
(C
C), 763
C)
S
3062 (Ar H), 1647,
1579, 1476 (C N,
6.15–7.85 (20H, m, Ar H), 6.19 (dd, 1H,
Hx, Jax = 10.9 Hz, Jbx = 4.9 Hz), 3.99
(dd, 1H, Ha, Jax = 10.9 Hz, Jab = 16.8
Hz), 3.32 (dd, 1H, Hb, Jbx = 4.9 Hz, Jab
16.8 Hz)
575 (M+), 512, 479, 378,
170, 133, 115, 77
C
(C
C), 761
C), 692
S
=
(C Cl)
3051 (Ar H), 1678,
1590, 1463(C N,
6.15–7.85 (19H, m, Ar H), 6.21 (dd, 1H,
608 (M+), 584, 479, 364,
337, 308, 274, 241, 186,
137, 121
Hx, Jax = 11.0Hz, Jbx = 4.9 Hz), 4.05 (dd,
1H, Ha, Jax = 11.0 Hz, Jab = 16.7 Hz),
3.29 (dd, 1H, Hb, Jbx = 4.9 Hz, Jab = 16.7
Hz)
C
(C
C), 762
C), 749
S
(C Cl)
3022 (Ar H), 1653,
1589, 1475 (C N,
6.15–7.85 (19H, m, Ar H), 6.15 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 5.0 Hz), 3.98
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.8
Hz), 3.76 (3H, s, CH3O), 3.30 (dd, 1H,
Hb, Jbx = 5.0 Hz, Jab = 16.8 Hz)
605 (M+), 540, 512, 479,
375, 321, 256, 191, 170,
159, 115
C
(C
C), 763
C), 728
S
(C Cl)
3034 (Ar H), 1665,
1574, 1488 (C N,
6.15–7.85 (20H, m, Ar H), 6.17 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 4.9 Hz), 3.99
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.8
Hz), 3.80 (3H, s, CH3O), 3.29 (dd, 1H,
Hb, Jbx = 4.9 Hz, Jab = 16.8 Hz)
570 (M+), 506, 478, 317,
239, 175, 77
C
(C
C), 758
C)
S
3040 (Ar H), 1654,
1589, 1484 (C N,
6.15–7.85 (19H, m, Ar H), 6.24 (dd, 1H,
Hx, Jax = 11.0 Hz, Jbx = 4.9 Hz), 4.02
(dd, 1H, Ha, Jax = 11.0 Hz, Jab = 16.7
Hz), 3.80 (3H, s, CH3O), 3.35 (dd, 1H,
C4–Hb, Jbx = 4.9 Hz, Jab = 16.7 Hz)
6.15–7.85 (19H, m, Ar H), 6.18 (dd, 1H,
Hx, Jax = 10.9 Hz, Jbx = 5.0 Hz), 4.01
(dd, 1H, Ha, Jax = 10.9 Hz, Jab = 16.7
Hz), 3.82 (6H, s, CH3O), 3.31 (3H, s,
CH3O), 3.34 (dd, 1H, Hb, Jbx = 5.0 Hz,
Jab = 16.7 Hz).
605 (M+), 541, 478, 344,
256, 239, 191, 115
C
(C
C), 759
C), 763
S
(C Cl)
3052 (Ar H), 1647,
1593, 1479 (C N,
5s
600 (M+), 508, 475, 254,
205, 170
C
(C
C), 762
C)
S
confirmed the molecular conformation of 3-(4-Chlorophenyl)-5-(2-phenylthio-quinolin-3-
yl)-1-(4-phenyl-2-thiazoyl)-pyrazo-line.
EXPERIMENTAL
All purchased solvents and chemicals were of analytical grade and were used without
further purification. All reagents were of commercial availability. The starting compound
123 were prepared according to previously reported procedures. Melting points were mea-
sured on a mettler FP-5 capillary melting point apparatus and were uncorrected. Elemental

SYNTHESIS AND STRUCTURE CHARACTERIZATION
429
Figure 1 Molecular structure of 5n.
analyses were performed on a PerkinElmer 2400 elemental analyzer. The solid-state IR
spectra were recorded from potassium bromide pellet on a Bruker Tensor 27 Spectropho-
1
tometer. The H NMR spectra were recorded on a Varian Inova-400 spectrophotometer
using CDCl3 as the deuterated solvent and TMS as the internal standard at room temper-
ature. Electron-impact–mass spectrometry (EI-MS) spectra were obtained with an Agilent
5975 apparatus.
General Procedure (2a–b): 2-Substituted-3-formylquinoline
Equimolar amounts of the phenol or benzenethiol (20 mmol) and potassium hydroxide
(20 mmol) were dissolved in dimethyl sulfoxide (10 mL). After dissolution of the reactants,
a solution of 1 (20 mmol) was added dropwise to dimethyl sulfoxide. The mixture was
◦
◦
refluxed for 6 h (85 C–90 C) and monitored by TLC until the reaction was completed.
After cooling, the reaction mixture was poured into ice water and neutralized with dilute
hydrochloric acid to pH 5–6.
General Procedure (3a–f): 3-(2-Substituted- quinolin-3-yl)-1-aryl-2-
propen-1-ones
Acetophenone (20 mmol) was added to a solution of 2a–b (20 mmol) in aqueous KOH
◦
(10 mL, 35% KOH) at 0 C. The reaction mixture was stirred for 2 h at ice temperature.
After standing overnight, the solid was collected by filtration and washed with water to
give crystals 3a–f.

430
YONG-MING ZEN ET AL.
General Procedure (4a–f): Reaction of α,β-unsaturated Ketone
and Thiosemicarbazide
A mixture of the appropriate 3a–f (5 mmol) and thiosemicarbazide (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 mixture was allowed to cool and poured into crushed ice, and the solid
mass separated out was filtered, washed with cold ethanol, dried, and crystallized.
General Procedure (5a–s): Reaction with 2-bromo-1-phenyl-ethanone
and Thiocarbamoyl-pyrazoline
A mixture of 4a–f (0.5 mmol) and 2-bromo-1-phenyl-ethanone (0.5 mmol) in ethanol
(30 mL) was heated under reflux for 30 min. The reaction mixture was cooled to room
temperature. The crude product separated by filtered was recrystallized to give 5a–s.
X-Ray Structure Determination of 5n. Single crystals were obtained by slow
evaporation of an ethanol solution. The data on a crystal with dimensions 0.45 × 0.22 ×
0.16 mm were collected on a Bruker SMART APEX-IICCD diffractometer up to (2θ) max
of 55.03◦ at 296(2) K with graphite-monochromatized Mo Kα radiation (λ = 0.71073 Å)
using multiscan techniques. A total of 6411 (Rint = 0.0290) independent reflections were
collected, among which 23504 reflections were considered as observed [I > 2σ(I)] and used
for the structure refinement. The structures were solved by direct methods and refined by
full matrix least squares with the Bruker’s SHELXL-97 program. All nonhydrogen atoms
were refined anisotropically, and the hydrogen atom involved in the hydrogen bond was
found in the difference Fourier map; all other hydrogen atoms were located geometrically,
and all hydrogens were refined as “riding model” with their Uiso’s set at 1.2 (1.4 for methyl
groups) times the Ueq values of the appropriate carrier atoms. Figure 1 was drawn using
the XP program. Cell data for C33H23N4S3Cl, Triclinic, space group P-1, a = 10.8712
(13) Å, b = 12.1353(14) Å, c = 12.2884(915) Å, Z = 16, cell volume = 1405.9(3) Å3, µ
= 1.41 mm−1. The final R1 and wR2 values are 0.0521 and 0.1355, respectively, for 6411
independent reflections [I > 2σ(I)] and 361 parameters.
CCDC-819890 contains all bond lengths and angles, coordinates, and displacement
parameters for this paper. These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre (CCDC) via e-mail: deposit @ccdc.cam.ac.uk.
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