Synthesis and spectral characterization of some novel thiazolyl-pyrazoline derivatives containing 1,2,3-triazole moiety

Article abstract of DOI:10.1080/10426507.2010.494647

Chemical Equation Presented A series of novel 3-aryl-5-(2-aryl-1,2,3- triazol-4-yl)-1-(4-aryl-2-thiazoyl)-pyrazolines 6a-6r were synthesized using 2-aryl-4-formyl-1,2,3-triazoles 1a,b as the starting materials. Thus, reacting 1a,b with 1-arylethanones 2a-

Full text of DOI:10.1080/10426507.2010.494647

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Spectral Characterization
of Some Novel Thiazolyl-Pyrazoline
Derivatives Containing 1,2,3-Triazole
Moiety
Hai Shi a , Fang-Ming Liu b & Song-Wei Shen b
a College of Chemistry and Chemical Engineering , Xinjiang
University , Urumqi, P.R. China
b College of Materials and Chemical Engineering , Hangzhou Normal
University , Hangzhou, P.R. China
Published online: 19 Feb 2011.
To cite this article: Hai Shi , Fang-Ming Liu & Song-Wei Shen (2011) Synthesis and Spectral
Characterization of Some Novel Thiazolyl-Pyrazoline Derivatives Containing 1,2,3-Triazole
Moiety, Phosphorus, Sulfur, and Silicon and the Related Elements, 186:2, 263-270, DOI:
10.1080/10426507.2010.494647
To link to this article: http://dx.doi.org/10.1080/10426507.2010.494647
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Phosphorus, Sulfur, and Silicon, 186:263–270, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.494647
SYNTHESIS AND SPECTRAL CHARACTERIZATION OF
SOME NOVEL THIAZOLYL-PYRAZOLINE DERIVATIVES
CONTAINING 1,2,3-TRIAZOLE MOIETY
Hai Shi,1 Fang-Ming Liu,2 and Song-Wei Shen2
1College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi,
P.R. China
2College of Materials and Chemical Engineering, Hangzhou Normal University,
Hangzhou, P.R. China
GRAPHICAL ABSTRACT
Abstract A series of novel 3-aryl-5-(2-aryl-1,2,3-triazol-4-yl)-1-(4-aryl-2-thiazoyl)-
pyrazolines 6a–6r were synthesized using 2-aryl-4-formyl-1,2,3-triazoles 1a,b as the starting
materials. Thus, reacting 1a,b with 1-arylethanones 2a–2c gave 1-aryl-3-(2-aryl-1,2,3-triazol-
4-yl)-2-propen-1-ones 3a–3f. The reaction of the latter with thiosemicarbazide afforded
3-aryl-5-(2-aryl-1,2,3-triazol-4-yl)-1-thiocarbamoyl-pyrazolines 4a–4f, which condensed
with 2-bromo-1-arylethanones 5a–5c to afford the target compounds 6a–6r. The chemical
structures of the compounds were verified by means of their IR, 1H NMR, ESI-MS spectroscopic
data, and elemental analysis.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Carbothioamide; pyrazoline; thiazole; 1,2,3-triazole
Received 20 April 2010; accepted 16 May 2010.
Address correspondence to Fang-Ming Liu, College of Materials and Chemical Engineering, Hangzhou
Normal University, Hangzhou 310036, P.R. China. E-mail: fmliu859@sohu.com
263

264
H. SHI ET AL.
INTRODUCTION
In recent years, interests of researchers have been focused on the nitrogen- and
sulfur-containing heterocyclic compounds owing to their wide range of applications and
biological activities. Compounds with a thiazole ring have been reported to exhibit a wide
range of biological activities such as antituberculosis, anti-inflammatory, antiviral, anticon-
vulsant, and anti-HIV activities.1–5 In addition, pyrazoline derivatives have been proven
to show a broad spectrum of biological activities including anticonvulsant, antidepressant,
antibacterial, analgesic, antimicrobial, and anticancer activities.6–13 So, the synthesis of
novel pyrazoline derivatives and investigations of their chemical and biological behavior
have gained more importance in recent decades due to their various promising biological
properties. Furthermore, the 1,2,3-triazole moiety is present in a number of drugs,14,15
and there are numerous examples of biological activities in the literature including β-
lactamase inhibitory, antimicrobial, antibacterial, anti-HIV, and antiviral, and they can act
as potassium channel activators.16–20 Encouraged by these facts and in continuation of our
interest in the synthesis of chemically and biologically important heterocycles containing
the 1,2,3-triazole moiety,21,22 a series of novel pyrazoline derivatives with both thiazole and
1,2,3-triazole in the molecule were synthesized with a view to obtain higher bioactivity
leading compounds. To the best of our knowledge, this is the first report of pyrazoline
derivatives bearing a 1,2,3-triazole moiety.
RESULTS AND DISCUSSION
The synthesis of the new compounds has been carried out following the steps shown
in Scheme 1. In the initial step, the starting compounds (1-aryl-3-(2-aryl-1,2,3-triazol-4-yl)-
2-propen-1-ones) 3a–3f were obtained by the reaction of 2-aryl-4-formyl-1,2,3-triazoles
1a,b with 1-arylethanones 2a–2c in a Claisen–Schmidt condensation reaction by methods
as described in the literature.23 Then, the reaction of the compounds 3a–3f with thiosemi-
carbazide in the presence of potassium hydroxide in ethanol afforded the key intermediates
3-aryl-5-(2-aryl-1,2,3-triazol-4-yl)-1-thiocarbamoyl-pyrazolines 4a–4f (Table 1). The IR
spectra of 4a–4f exhibit C N stretching (1633 cm−1), thiocarbamoyl group N H stretch-
1
ing (3509–3364 cm−1), and C S stretching (1354–1358 cm−1) bands. In the H NMR
spectra of the compounds Ha, Hb, and Hx protons of the pyrazoline ring were observed as
doublets of doublets at δ 3.90–3.75 ppm, 3.88–3.73 ppm, and 6.38–6.28 ppm, respectively
(Jab = 17.3–17.8Hz, Jax = 4.52–4.62Hz, Jbx = 8.16–8.28Hz). The protons belonging to the
Table 1 Physical data of 3-aryl-5-(2-aryl-1,2,3-triazol-4-yl)-1-thiocarbamoyl-pyrazolines (4a–4f)
% Analyses: calcd. (found).
Compound no.
Color
Mp (◦C) Yield %
Mol. formula
C18H16N6S
C
H
N
4a
4b
4c
4d
4e
4f
White solid 214–215
White solid 230–231
White solid 242–244
White solid 240–206
White solid 207–209
White solid 271–272
84
82
78
85
83
87
62.05(62.02) 4.63(4.74) 24.12(24.23)
60.30(60.19) 4.79(4.81) 22.21(22.23)
56.47(56.35) 3.95(4.08) 21.95(21.87)
50.59(50.56) 3.54(3.57) 19.67(19.75)
C
C
C
C
19H18N6OS
18H15ClN6S
18H15BrN6S
19H17BrN6OS 49.90(49.78) 3.75(3.84) 18.38(18.36)
C18H15BrClN6S 46.82(46.80) 3.06(3.12) 18.20(18.16)

NOVEL THIAZOLYL-PYRAZOLINE DERIVATIVES
265
S
R1
O
N
N
O
NH2NHCNH2
KOH
N
+
N
R1
N
OHC
R2
N
R2
2a-2c
1a-1b
1:(a) R =H; (b) R =Br
3a-3f
3:(a) R =H, R =H; (b) R =H, R =OCH ;
2:(a) R =H; (b) R =OCH ;
1
2
1
2
3
2
2
3
1
1
(c) R =H,R =Cl; (d) R =Br, R =H;
(c) R =Cl
2
1
2
1
2
(e) R =Br, R =OCH ; (f) R =Br, R =Cl.
1
2
3
1
2
R2
R2
O
Ha
N
Br
Ha
Hb
Hb
R1
R1
N
N
S
N
N
N
R3
N
Hx
N
N
C
N
Hx
NH2
N
S
5a-5c
5:(a) R =H; (b) R =OCH ;
4a-4f
4:(a) R =H, R =H; (b) R =H, R =OCH ;
1
2
1
2
3
3
3
3
R3
(c) R =H,R =Cl; (d) R =Br, R =H;
(c) R =Cl
3
1
2
1
2
(e) R =Br, R =OCH ; (f) R =Br, R =Cl.
1
2
3
1
2
6a-6r
6:(a) R1= H, R2=H, R3=H; (b) R1= H, R2=H, R3=OCH3; (c) R1= H, R2=H, R3=Cl; (d) R1= H, R2=OCH3, R3=H; (e) R1= H,
R2=OCH3, R3=OCH3; (f) R1= H, R2=OCH3, R3=Cl; (g) R1= H, R2=Cl, R3=H; (h) R1= H, R2=Cl, R3=OCH3; (i) R1= H,
R2=Cl, R3=Cl; (j) R1= Br, R2=H, R3=H; (k) R1= Br, R2=H, R3=OCH3; (l) R1=Br, R2=H, R3=Cl; (m) R1= Br, R2=OCH3,
R3=H; (n) R1= Br, R2=OCH3, R3=OCH3; (o) R1= Br, R2=OCH3, R3=Cl; (p) R1= Br, R2=Cl, R3=H; (q) R1= Br, R2=Cl,
R3=OCH3; (r) R1=Br, R2=Cl, R3=Cl.
Scheme 1
aromatic ring, N-H protons of the thiocarbamoyl group were seen at δ 8.02–7.24 as multi-
plet signals, and the other aliphatic groups were observed with the expected chemical shift
and integral values. In the mass spectra, the ions produced under ESI showed characteristic
[M+H]+ ion peaks and contained [M–SH]+ fragments that confirm the 3-aryl-5-(2-aryl-
1,2,3-triazol-4-yl)-1-thiocarbamoyl- pyrazolines (Table 2).
The condensation of compounds 4a–4f with various substituted 2-bromo-1-
arylethanones 5a–5c in refluxing ethanol resulted in the formation of 3-aryl-5-(2-aryl-
4–1,2,3-triazolyl)-1-(4-aryl-2-thiazoyl)- pyrazolines 6a–6r through parallel solution-phase
synthesis in good yield (Table 3).
The structures of compounds 6a–6r were confirmed by elemental analysis and IR,
1H NMR, and MS spectral data (Table 4). The IR spectra of compound 6b showed C N
and C C stretching bands at 1633 and 1577, 1479 cm−1 regions, respectively. Examples
of the spectra of 6a (IR, NMR, MS) are shown in the Supplemental Materials.
In its 1H NMR spectrum, the CH2 (Ha, Hb) and CH (Hx) protons of the pyrazoline ring
resonated as a pair of doublets of doublets at δ 3.98 ppm(Ha), δ 3.92 ppm (Hb), and δ 6.00
ppm (Hx), respectively (Jab = 17.6Hz, Jax = 7.16 Hz, Jbx = 12.04Hz). These splittings are
due to vicinal coupling with the two magnetically non-equivalent protons of the methylene
group at position 4 of the pyrazoline ring. The protons belonging to the aromatic rings and

266

NOVEL THIAZOLYL-PYRAZOLINE DERIVATIVES
267
Table 3 Physical data of 3-aryl-5-(2-aryl-4–1,2,3-triazolyl)-1-(4-aryl-2-thiazoyl)-pyrazolines (6a–6r)
% Analyses: calcd. (found).
Compound no.
Color
Mp (◦C) Yield %
Mol. formula
C26H20N6S
C
H
N
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
Yellow solid 202–204
Yellow solid 201–202
Yellow solid 195–197
Yellow solid 198–199
Yellow solid 193–195
Yellow solid 186–188
Yellow solid 208–209
Yellow solid 209–210
Yellow solid 248–249
Yellow solid 169–170
Yellow solid 218–219
Yellow solid 223–224
Yellow solid 191–193
Yellow solid 254–256
Yellow solid 277–279
Yellow solid 259–261
Yellow solid 216–218
Yellow solid 267–269
80
83
78
86
75
83
81
78
79
78
85
77
78
82
86
85
75
87
69.62 (69.56) 4.49 (4.54) 18.74 (18.70)
67.76 (67.70) 4.63 (4.70) 17.56 (17.65)
64.66 (64.62) 3.97 (4.01) 17.40 (17.38)
67.76 (67.66) 4.63 (4.71) 17.56 (17.47)
66.12 (65.66) 4.76 (4.85) 16.52 (16.47)
63.21 (62.94) 4.13 (4.55) 16.38 (16.34)
64.66 (64.56) 3.97 (4.04) 17.40 (17.46)
63.21 (62.99) 4.13 (4.25) 16.38 (16.43)
60.35 (60.24) 3.51 (3.89) 16.24 (16.37)
59.21 (59.15) 3.63 (4.66) 15.93 (16.01)
58.17 (58.15) 3.80 (3.89) 15.08 (15.10)
C27H22N6OS
C26H19ClN6S
C27H22N6OS
C28H24N6O2S
C
C
C
C
C
C
C
C
C
C
C
C
C
27H21ClN6OS
26H19ClN6S
27H21ClN6OS
26H18Cl2N6S
26H19BrN6S
27H21BrN6OS
26H18BrClN6S 55.58 (55.54) 3.23 (3.27) 14.96 (14.88)
27H21BrN6OS 58.17 (58.15) 3.80 (3.83) 15.08 (15.17)
28H23BrN6O2S 57.24 (57.13) 3.95 (4.01) 14.30 (14.34)
27H20BrClN6OS 54.79 (54.75) 3.41 (3.42) 14.20 (14.22)
26H18BrClN6S 55.58 (55.51) 3.23 (3.25) 14.96 (14.89)
27H20BrClN6OS 54.79 (54.75) 3.41 (3.44) 14.20 (14.27)
26H17BrCl2N6S 52.37 (52.32) 2.87 (2.90) 14.09 (14.14)
thiazole ring appeared at δ 8.06–6.76 ppm as multiplet signals. The signal for 1,2,3-trizole
and methoxyl was recorded at δ 8.14 ppm and δ 3.84 ppm, respectively.
The mass spectrum of compound 6c showed a molecular ion peak M+ at m/z 482
(base peak), 484 [M+2]+. The pattern of molecular ion peaks confirmed the presence of a
chlorine atom in the 6c, and the other significant peaks appeared at m/z 449, 378, 338, 273,
209, 173, 91, which is strong evidence for the structure.
In summary, a series of novel pyrazoline derivatives 6a–6r that contain both thiazole
and 1,2,3-triazole have been designed and synthesized. The structures of 4a–4f and 6a–6r
were confirmed by IR, 1H NMR, MS, and elemental analysis.
EXPERIMENTAL
All purchased solvents and chemicals were of analytical grade and used without
further purification. Melting points were uncorrected and were recorded on an X-5 micro
melting point apparatus. The solid-state IR spectra on KBr were recorded on a Bruker
1
Tensor 27 IR spectrophotometer. H NMR spectra were recorded with a Varian Mercury
400MHz using CDCl3 as the deuterated solvent and TMS as the internal standard at room
temperature. MS were recorded on an Agilent 5975 mass selective detector. Elemental
analyses were performed on a Perkin-Elmer 240 CHN analyzer. The starting compounds
2-aryl-4-formyl-1,2,3-triazoles 1a,b were prepared according to the literature.24
General Procedure for the Preparation of 3-Aryl-5-(2-aryl-1,2,3-triazol-
4-yl)-1-thio-carbamoyl-pyrazolines (4a–4f)
A mixture of the appropriate 3a–3f (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

268

269

270
H. SHI ET AL.
reaction mixture 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.
General Procedure for the Preparation of 3-Aryl-5-(2-aryl-4–1,2,3-triazol-
4-yl)-1-(4-aryl-2-thiazoyl)-pyrazolines (6a–6r)
A mixture of 4a–4f (1 mmol) and 5a–5c (1 mmol) was refuxed in anhydrous ethanol
(20 mL). After completion of the reaction (monitored by TLC), the mixture was al-
lowed to cool. Then the solid product was collected. The product was recrystallized from
DMF/ethanol to give 6a–6r.
REFERENCES
1. Ashtekar, D. R.; Fernandes, F.; Khadse, B. G.; Shirodkar, M. V. N. Chemotherapy 1987, 33,
22–27.
2. Holla, B. S.; Malini, K. V.; Rao, B. S.; Sarojini, B. K.; Kumari, N. S. Eur. J. Med. Chem. 2003,
38, 313–318.
3. Kritsanida, M.; Mouroutsou, A.; Marakos, P.; Pouli, N.; Papakonstantinou-Garoufalias, S.; Pan-
necouque, C.; Witvrouw, M.; Clercq, E. D. Il Farmaco 2002, 57, 253–257.
4. Sharpe, C. J.; Shadbolt, R. S.; Ashford, A.; Ross, J. W. J. Med. Chem. 1971, 14, 977–982.
5. Maass, G.; Immendoerfer, U.; Koenig, B.; Leser, U.; Mueller, B.; Goody, R.; Pfaff, E. Antimicrob.
Agents Chemother. 1993, 37, 2612–2617.
6. Siddiqui, N.; Alam, P.; Ahsan, W. Arch. Pharm. Chem. Life Sci. 2009, 342, 173–181.
¨
¨
7. Ozdemir, Z.; Kandilci, H. B.; Gu¨mu¨s¸el, B.; C¸ alıs¸, U.; Bilgin, A. A. Eur. J. Med. Chem. 2007, 42,
373–379.
8. Nauduri, D.; Reddy, G. B. Chem. Pharm. Bull. Tokyo 1998, 46, 1254–1260.
9. Holla, B. S.; Akberali, P. M.; Shivananda, M. K. Farmaco 2000, 55, 256–263.
10. Gu¨rsoy, A.; Demirayak, S¸.; C¸ apan, G.; Erol, K.; Vural, K. Eur. J. Med. Chem. 2000, 35, 359–364.
¨
11. Ozdemir, A.; Turan-Zitouni, G.; Kaplancikli, Z. A.; Revial, G.; Gu¨ven, K. Eur. J. Med. Chem.
2007, 42, 403–409.
12. Ali, M. A.; Shaharyar, M. Bioorg. Med. Chem. 2007, 15, 1896–1902.
13. Manna, F.; Chimenti, F.; Fioravanti, R.; Bolasco, A.; Secci, D.; Chimenti, P.; Ferlini, C.; Scambia,
G. Bioorg. Med.Chem. Lett. 2005, 15, 4632–4635.
14. Micetich, R. G.; Maiti, S. N.; Spevak, P.; Hall, T. W.; Yamabe, S.; Ishida, N.; Tanaka, M.;
Yamazaki, T.; Nakai, A.; Ogawa, K. J. Med. Chem. 1987, 30, 1469–1474.
15. Jacobs, M. R.; Aronoff, S. C.; Johenning, S.; Shlaes, D. M.; Yamabe, S. Antimicrob. Agents
Chemother. 1986, 29(6), 980–985.
16. Bo¨hm, R.; Karow, C. Pharmazie 1981, 36, 243–247.
17. Genin, M. J.; Allwine, D. A.; Anderson, D. J.; Barbachyn, M. R.; Emmert, D. E.; Garmon, S. A.;
Graber, D. R.; Grega, K. C.; Hester, J. B.; Hutchinson, D. K.; Morris, J.; Reischer, R. J.; Ford, C.
W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H. J. Med. Chem. 2000,
43, 953–970.
18. Alvarez, R.; Velazquez, S.; San-Felix, A.; Aquaro, S.; Clercq, E. D.; Perno, C. F.; Karlsson, A.;
Balzarini, J.; Camarasa, M. J. J. Med. Chem. 1994, 37, 4185–4195.
19. Makabe, O.; Suzuki, H.; Umezawa, S. Bull. Chem. Soc. Jpn. 1977, 50, 2689–2693.
20. Calderone, V.; Giorgi, I.; Livi, O.; Martinotti, E.; Mantuano, E.; Martelli, A.; Nardi, A. Eur. J.
Med. Chem. 2005, 40, 521–528.
21. Liu, F. M.; Wang, B. L.; Li, Y. P. Chem. J. Chin. Univ. 2002, 23, 2097–2100.
22. Yang, D. B.; Liu, F. M.; Xu, F.; Yang, C.; Ye, J. W.; Shen, S. W.; Zhou, Y. L.; Li, W. Mol. Divers.
2008, 12, 103–109.
23. Li, F.; Xie, Z. F.; Liu, F. M. Chem. J. Chin. Univ. 2006, 27, 1058–1061.
24. Hassan, M. M. Carbohydr. Res. 1982, 108, 307–314.