PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents

Article abstract of DOI:10.1016/j.bmcl.2013.02.105

A new series of fluoro substituted pyrazoline derivatives 5a-g and 6a-g were synthesized in good to excellent yield from the corresponding pyrazole chalcones, 4a-g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction medium. The newly synthesized compounds were characterized and screened for their in vivo antiinflammatory and analgesic activity. Compounds 5g and 6g were found to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to standard drug. Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.

Full text of DOI:10.1016/j.bmcl.2013.02.105

Bioorganic & Medicinal Chemistry Letters 23 (2013) 2575–2578
Contents lists available at SciVerse ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
PEG mediated synthesis and pharmacological evaluation of some
fluoro substituted pyrazoline derivatives as antiinflammatory
and analgesic agents
Shravan Y. Jadhav a, Sachin P. Shirame a, Suresh D. Kulkarni b, Sandeep B. Patil c, Sharad K. Pasale d,
Raghunath B. Bhosale a,
⇑
a Organic Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413255, Maharashtra, India
b Pharmacology Department, Luqman College of Pharmacy, Gulberga 584102, Karnataka, India
c Pharmacology Department, Appasaheb Birnale College of Pharmacy, Sangli 416416, Maharashtra, India
d Department of Chemical Science, University of ‘Tor Vergata’, Rome, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A new series of fluoro substituted pyrazoline derivatives 5a–g and 6a–g were synthesized in good to
excellent yield from the corresponding pyrazole chalcones, 4a–g, by using polyethylene glycol-400
(PEG-400) as an alternative reaction medium. The newly synthesized compounds were characterized
and screened for their in vivo antiinflammatory and analgesic activity. Compounds 5g and 6g were found
to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f
showed significant antiinflammatory activity as compared to standard drug. Compounds 5c, 5d, 5e, 5f,
6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 18 December 2012
Revised 8 February 2013
Accepted 26 February 2013
Available online 7 March 2013
Keywords:
Pyrazolines
PEG-400
Antiinflammatory activity
Analgesic activity
Presently, the researchers have focused their interest in devel-
oping the alternative synthesis as well as insertion of a fluorine
atom into the heterocyclic compounds in order to enhance the sig-
nificant effect on the biological and physical parameters.1 As the
fluorinated compounds possess various biological activities which
is due to their lipophilicity and stability,2 the chemistry and phar-
macology of these compounds is of great interest in the medicinal
chemistry.
ever their use is restricted due to their GI side effects. The
development of alternatives to NSAIDs is being attempted all over
the world.
O
N
N
Pyrazoles are the most important class of heterocyclic com-
pounds having their broad spectrum of application in pharmaceu-
tical and agrochemical field.3 Pyrazole derivatives are found to
exhibit good antibacterial,4 antiinflammatory,5 analgesic,6 antican-
cer, radio protective,7 anti-convulsant8 and anti-depressant activ-
ity.9 Pyrazolines are well known nitrogen containing five-
membered compounds which are found to possess considerable
biological activities in the medicinal chemistry.10–13
The survey of literature reveals that many pyrazoline
derivatives have been used for clinical application as NSAIDS. Phe-
nylbutazone, Celecoxib and Deracoxib are the pyrazoline NSAIDS,
are potent antiinflammatory and analgesic agents. Antipyrine is
the first pyrazoline derivative used as an antipyrine agent. How-
(a) Antipyrine
N-substituted pyrazoline derivatives also exhibit biological
activities like COX-2 inhibitors,14 antiinflammatory, analgesic,
antimicrobial,15,16 antitumor,17 antileukemia,18 anti-depressant,19
angiotension converting enzyme inhibitory activity and hyperten-
sion.20 The N-phenyl-3-(4-fluorophenyl)-4-substituted pyrazole
derivatives are recently reported as antitubercular agents.21,22 On
the other hand, PEG solvents are known to be inexpensive, easily
available, thermally stable, recyclable, biological compatible, non-
toxic and water soluble compounds that does not hydrolyze on
long storage.23–25 Due to these advantages, PEGs of different
molecular weights are extensively used as solvents or vehicles in
various pharmaceutical industries. However, PEG polymer of low
molecular weight differ significantly from polymers of high molec-
ular weight in their physico-chemical properties, higher toxicity
and possibly genotoxicity.26 The toxicity data of different
⇑
Corresponding author. Tel./fax: +91 217 2744770.
E-mail address: bhosale62@yahoo.com (R.B. Bhosale).
0960-894X/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2013.02.105

2576
S. Y. Jadhav et al. / Bioorg. Med. Chem. Lett. 23 (2013) 2575–2578
R
O
H
O
H
N
i
N
ii
R
R
N
N
1 (a-g)
2 (a-g)
3 (a-g)
iii
F
R
R
O
iv
N
N
F
N
N
N
N
O
4 (a-g)
5 (a-g)
v
F
R
5a, 6a, R = 4-F
5b, 6b, R = 4-Cl
5c, 6c, R = 4-Br
5d, 6d, R = 4-Me
N
N
N
N
5e, 6e, R = 4-OMe
5f, 6f, R = 3-NO2
5g, 6g, R = 4-H
6 (a-g)
Scheme 1. Reagents and conditions: (i) Phenyl hydrazine, methanol, concd H2SO4 (2 drops), 70 °C, 4 h. (ii) DMF, POCl3, 80 °C, 5 h. (iii) 4-Fluoro acetophenone, NaOH, PEG-400,
40–50 °C, 1 h. (iv) N2H4ÁH2O, acetic acid, PEG-400, 70–75 °C, 4–5 h. (v) Phenyl hydrazine, NaOH, PEG-400, 70–75 °C, 4–5 h.
Table 1
Antiinflammatory activity of pyrazoline derivatives (5a–g and 6a–g) by carrageenan induced rat paw edema method in rats and analgesic activity by tail flick method
Entry
Antiinflammatory activity
Analgesic activity % inhibition
Mean paw volume (mL) SEM
0 h
1 h
2 h
3 h
60 min
Control
Diclofenac
Aspirin
1.25 0.01
0.85 0.02
—
1.29 0.01
0.66 0.02
—
1.32 0.001
064 0.001
—
1.38 0.001
0.58 0.01
—
—
—
119
43
44
71
110
66
109
35
41
43
71
110
66
108
35
5a
5b
5c
5d
5e
5f
5g
6a
6b
6c
6d
6e
6f
1.25 0.03⁄⁄⁄
0.88 0.01
0.76 0.04⁄⁄
1.16 0.05
1.36 0.04⁄⁄⁄
0.87 0.05
0.57 0.05⁄⁄⁄
1.15 0.03
0.78 0.01⁄⁄⁄
0.76 0.02⁄⁄
1.15 0.02
1.35 0.01⁄⁄⁄
0.86 0.02
0.58 0.01⁄⁄⁄
1.20 0.04⁄⁄
0.84 0.04
0.88 0.04⁄⁄
1.39 0.06
1.36 0.01⁄⁄
0.89 0.04
0.58 0.05⁄⁄⁄
1.19 0.04
0.77 0.04⁄⁄
0.87 0.04⁄⁄
1.29 0.06
1.30 0.01⁄⁄
0.79 0.05
0.59 0.04⁄⁄⁄
1.37 0.003⁄⁄⁄
0.68 0.001
0.66 0.005⁄⁄
1.32 0.004
1.48 0.006⁄⁄
0.86 0.006
0.38 0.003⁄⁄⁄
1.36 0.003
0.64 0.001⁄⁄⁄
0.69 0.005⁄⁄
1.32 0.005
1.42 0.006⁄⁄
0.84 0.006
0.38 0.003⁄⁄⁄
1.09 0.004⁄⁄
0.98 0.002
0.68 0.001⁄⁄
1.26 0.006
1.47 0.003⁄⁄
0.69 0.005
0.59 0.003⁄⁄⁄
1.08 0.004
0.96 0.002⁄⁄
0.68 0.001⁄⁄
1.26 0.006
1.48 0.003⁄⁄
0.69 0.005
0.59 0.003⁄⁄⁄
6g
SEM—standard error mean; n = 6, ⁄P < 0.05, ⁄⁄P <0.01, ⁄⁄⁄P <0.001; —, not determined.
molecular weight PEG’s are also available and some of them are al-
ready approved for internal consumption by the USA FDA.27 The
use of PEG as a green and alternative reaction medium in organic
reactions is relatively recent.28
Appreciation of these findings motivated us to synthesize some
new fluoro substituted pyrazoline derivatives by using polyethyl-
ene glycol (PEG-400) as an alternative reaction medium which
have been found to possess an interesting profile for antiinflamma-
tory and analgesic activity.
The synthesis of pyrazoline derivatives were prepared as out-
lined in Scheme 1. The substituted 1,3-diphenyl-1H-pyrazole-4-
carbaldehydes 3a–g were prepared by Vilsmeier–Haack reaction
on acetophenone hydrazones 2 obtained from various substituted
acetophenones 1 according to literature method.29 The pyrazole
chalcones 4a–g were prepared by the reaction of various substi-
tuted pyrazole aldehydes 3a–g with 4-fluoroacetophenone and
NaOH in PEG-400. These pyrazole chalcones 4a–g were treated
with hydrazine hydrate/acetic acid and phenyl hydrazine/NaOH

S. Y. Jadhav et al. / Bioorg. Med. Chem. Lett. 23 (2013) 2575–2578
2577
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in PEG-400 and heated for about 4–5 h to afford pyrazoline deriv-
atives 5a–g and 6a–g respectively. The completion of the reaction
was monitored by TLC. All the synthesized compounds were char-
acterized by IR, 1H NMR and Mass spectroscopy.33,34
IR spectra of compounds 5f and 5g reveals that, the (C@O)
absorption bands were observed in the region 1654–1660 cmÀ1
and the (C@N) stretching was observed at 1595 cmÀ1 whereas in
the IR spectra of compounds 6f and 6g, the (C@O) absorption bands
were not observed in the region 1654–1660 cmÀ1 and the (C@N)
stretching was found in the same region. These stretching vibration
values confirm the formation of desired pyrazoline derivatives. In
the 1H NMR spectra of compounds 5f, 5g and 6f, 6g, the chiral
CH proton appeared at d 5.8–5.9 and 5.53–5.57, respectively as
doublet of doublet, while the pro-chiral methylene protons ap-
peared at d 3.07–3.77 and d 3.23–3.98 respectively as two distinct
doublet of a doublet there by indicating the magnetic non-
equivalency of the two protons. These newly synthesized
compounds are also confirmed by mass spectral analysis.
12. Dawane, B. S.; Konda, S. G.; Mandwad, G. G.; Shaikh, B. M. Eur. J. Med. Chem.
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All these newly synthesized pyrazoline derivatives were evalu-
ated for their antiinflammatory activity30 at 50 mg/kg p.o. against
carrageenan induced paw edema method in wistar rats,31 and
compared with the standard drug Diclofenac sodium. The effects
of synthesized compounds and standard drug on paw edema in-
duced by carrageenan are shown in Table 1. The antiinflammatory
result reveals that compounds 5g and 6g showed excellent activity
whereas the compounds 5b, 5c, 5f, 6b, 6c and 6f showed
significant activity after comparing with Diclofenac. The remaining
pyrazoline derivatives showed weak antiinflammatory activity.
All these compounds were also evaluated for their analgesic
activity at 25 mg/kg p.o. by radiant heat tail flick method in rats.32
The results are summarized in Table 1 and are expressed as per-
centage analgesia. All compounds showed analgesic activity in
the range of 35–110% and were compared with the standard drug
Aspirin. The analgesic result revealed that the compounds 5c, 5d,
5e, 5f, 6c, 6d, 6e, and 6f showed significant activity as compared
with standard drug Aspirin, while as remaining compounds
showed moderate analgesic activity after 1 h treatment.
21. Coutinho, E. C.; Khunt, R. C.; Khedkar, V. M.; Chawda, R. S.; Chauhan, N. A.;
Parikh, A. R. Bioorg. Med. Chem. Lett. 2012, 22, 666.
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26. Olga, Biondi; Salvatore, Motta; Pasquale, Mosesso Mutagenesis 2002, 17, 261.
27. Chen, J.; Spear, S. K.; Huddleston, J. G.; Rogers, R. D. Green Chem. 2005, 7, 64.
28. (a) Li, J. H.; Liu, W. J.; Xie, Y. X. J. Org. Chem. 2005, 70, 5409; (b) Jain, S. L.;
Singhal, S.; Sain, B. Green Chem. 2007, 9, 740; (c) Han, W.; Liu, C.; Jin, Z.-L. Org.
Lett. 2007, 9, 4005.
29. Kira, M. A.; Abdel-Raeman, M. O.; Gadall, K. Z. Tetrahedron Lett. 1969, 2, 109.
30. Pharmacology: Wistar rat of either sex weighing 150–220 g were obtained from
Animal house, Luqman College of Pharmacy, Gulberga, Karnataka, India. All the
animals were housed under standard ambient conditions of temperature
(25 2 °C) and relative humidity of 50 5%. A 12/12 h light/dark cycle was
maintained. All the animals were allowed to have free access to water and
standard palletized laboratory animal diet 24 h before pharmacological
studies. All experiments were carried out using six animals per group. The
experimental procedures and protocols used in this study were reviewed and
approved by the Institutional Animal Ethical Committee (IAEC) of Luqman
College of Pharmacy, Gulberga, constituted in accordance with the guidelines
of the Committee for the Purpose of Control and Supervision of Experiments on
Animals (CPCSEA/346), Government of India.
The new series of fluoro substituted pyrazoline derivatives were
synthesized using PEG-400 as an alternative reaction medium and
identified as anti inflammatory and analgesic agents. The reaction
was clean and the products were obtained in excellent yields
without formation of any detectable side products. Among the 14
compounds screened, the four compounds 5c, 5f, 6c and 6f showed
significant activities in both screens when compared to standard
drugs Diclofenac and Aspirin. Hence, it can be concluded that,
the tested pyrazolines derivatives can considered as potential anti-
inflammatory and analgesic agents. Further studies in relation to
cytotoxicity and ADME are warranted for the better understanding.
31. Muniappan, M.; Sundararaj, T. J. Ethnopharmacol. 2003, 88, 161.
32. Meena Kumari, K.; Amberkar, M. V.; Shanbhag, T.; Bairy, K. L.; Shenoy, S. Indian
J. Physiol. Pharmacol. 2011, 55, 13.
33. Synthesis of pyrazoline derivatives (5a–g): A mixture of pyrazole chalcones 4a–g
(1.0 mM) were placed in a 100 mL round bottom flask with 10 mL of PEG-400.
To this solution hydrazine hydrate (99%) (2.0 mM) and 1 mL glacial acetic acid
were added drop wise and heated at 70–75 °C for about 4–5 h. Reaction
progress was monitored by TLC. After completion of the reaction, reaction
mixture was cooled, poured into crushed ice, precipitate formed was filtered
off and recrystallized from ethanol, affording compounds 5a–g. Compound 5a:
yield: 80%; mp: 232–233 °C; IR (KBr) cmÀ1: 3059, 1656, 1600, 1505, 1414,
1229; 1H NMR (300 MHz, CDCl3):
d 2.43 (s, 3H, N-acetyl), 3.06 (dd, 1H,
pyrazoline H), 3.57–3.69 (dd, 1H, pyrazoline H), 5.81–5.86 (dd, 1H, pyrazoline
H), 7.07–7.76 (m, 13H, ArH), 7.78 (s, 1H, pyrazole-H). Compound 5b: yield:
84%; mp: 228–230 °C; IR (KBr) cmÀ1: 3059, 1656, 1600, 1505, 1414, 1229; 1H
NMR (500 MHz, CDCl3): d 2.46 (s, 3H, N-acetyl), 3.05–3.10 (dd, 1H, pyrazoline
H), 3.61–3.65 (dd, 1H, pyrazoline H), 5.85–5.88 (dd, 1H, pyrazoline H), 7.10–
7.73 (m, 13H, ArH), 7.80 (s, 1H, pyrazole-H); MS: m/z = 459 (M+1). Compound
5c: yield: 78%; mp: 213–214 °C; IR (KBr) cmÀ1: 3062, 1657, 1599, 1505, 1415,
1229; 1H NMR (300 MHz, CDCl3): d 2.44 (s, 3H, N-acetyl), 3.01–3.08 (dd, 1H,
pyrazoline H), 3.61–3.65 (dd, 1H, pyrazoline H), 5.82–5.87(dd, 1H, pyrazoline
H), 7.07–7.68 (m, 13H, ArH), 7.78 (s, 1H, pyrazole-H); MS: m/z = 505 (M+2).
Compound 5d: yield: 85%; mp: 198 °C; IR (KBr) cmÀ1: 3192, 2915, 2839,
1648,1595,1501, 1407, 1222; 1H NMR (300 MHz, CDCl3): d 2.36 (s, 3H, –CH3)
2.44 (s, 3H, N-acetyl), 3.02–3.09 (dd, 1H, pyrazoline H), 3.54–3.64 (dd, 1H,
pyrazoline H), 5.87–5.92 (dd, 1H, pyrazoline H), 7.04–7.69 (m, 13H, ArH), 7.76
(s, 1H, H-5 of pyrazole); MS: m/z = 439 (M+1). Compound 5e: yield: 83%; mp:
162–164 °C; IR (KBr) cmÀ1: 2995, 2892,1660, 1601, 1507,1359, 1239, 1154,
1052; 1H NMR (500 MHz, CDCl3): d 2.46 (s, 3H, N-acetyl), 3.83 (s, 3H, –OCH3),
3.06–3.1(dd, 1H, pyrazoline H), 3.58–3.63 (dd, 1H, pyrazoline H), 5.87–5.91
(dd, 1H, pyrazoline H), 6.95–7.71 (m, 13H, ArH), 7.79 (s, 1H, pyrazole-H); MS:
Acknowledgment
The author S.Y.J. is thankful to the University Grants Commis-
sion (WRO), Pune for the award Teacher Fellowship under XI plan.
References and notes
1. Kuznetsova, L.; Ungureanu, M. I.; Pepe, A. J. Fluorine Chem. 2004, 125, 415.
2. Haga, T.; Fujikawa, K.; Koyanag, T.; Nakajima, T.; Hayashi, K. Heterocycles 1984,
22, 117.
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4. Damlijanovic, I.; Vukicevic, M.; Radulovic, N.; Palic, R.; Ellmerer, E.; Ratkovic, Z.;
Joksovic, M. D.; Vukicevic, R. D. Bioorg. Med. Chem. Lett. 2009, 1093, 19.
5. Sharma, P. K.; Kumar, S.; Kumar, P.; Kaushik, P.; Kaushik, D.; Dhingra, Y.; Aneja,
K. R. Eur. J. Med. Chem. 2010, 45, 2650.
6. Sherif, A. F.; Rostom, M. A.; Shalaby, M. A.; El-Demellawy Eur. J. Med. Chem.
2003, 38, 959.
7. Mosafa, M. G.; Fatma, A. R.; Saleh, I. A.; Ahmed, M. A.; Sarah, A. A. Eur. J. Med.
Chem. 2010, 45, 171.
m/z = 455 (M+1). Compound 5f: yield: 74%; mp: 247–248 °C; IR (KBr) cmÀ1
:
2995, 2892, 1660, 1595, 1507, 1359, 1239, 1154, 1052; 1H NMR (300 MHz,
CDCl3): d 2.44 (s, 3H, N-acetyl), 3.07–3.14 (dd, 1H, pyrazoline H), 3.68–3.77 (dd,
1H, pyrazoline H), 5.83–5.88 (dd, 1H, pyrazoline H), 7.07–8.60 (m, 13H, ArH),
7.79 (s, 1H, pyrazole-H). Compound 5g: yield: 85%; mp:174–175 °C; IR (KBr)
cmÀ1: 3010, 1654, 1595, 1503, 1240; 1H NMR (300 MHz, CDCl3): d 2.44 (s, 3H,
8. Nikhila, D.; Amnekar, K. P.; Bhusari Eur. J. Med. Chem. 2010, 45, 149.

2578
S. Y. Jadhav et al. / Bioorg. Med. Chem. Lett. 23 (2013) 2575–2578
N-acetyl), 3.03–3.10 (dd, 1H, pyrazoline H), 3.56–3.66 (dd, 1H, pyrazoline H),
5.87–5.92 (dd, 1H, pyrazoline H), 7.05–7.76 (m, 14H, ArH), 7.78 (s, 1H,
pyrazole-H); MS: m/z = 425 (M+1).
CDCl3): d 3.19–3.23 (dd, 1H, –CH2– pyrazoline H); 3.82–3.87 (dd, 1H, –CH2–
pyrazoline H); 5.49–5.52 (dd, 1H, –CH– pyrazoline H); 6.83–7.73 (m, 18H, Ar-
H); 7.82 (s, 1H, pyrazole-H). Compound 6d: yield: 86%; mp: 185–186 °C; IR
(KBr) cmÀ1: 3019, 2924, 1595, 1496, 1383, 1321, 1216; 1H NMR (500 MHz,
CDCl3): d 2.46 (s, 3H, Methyl H); 3.21-3.26 (dd, 1H, –CH2– pyrazoline H); 3.82–
3.88 (dd, 1H, –CH2– pyrazoline H); 5.52–5.55 (dd, 1H, –CH– pyrazoline H);
6.82–7.74 (m, 18H, Ar-H); 7.78 (s, 1H, pyrazole-H); MS: m/z = 473 (M+1).
Compound 6e: yield: 88%; mp: 168 °C; IR (KBr) cmÀ1: 3025, 2994, 1598, 1498,
1453, 1388, 1292; 1H NMR (500 MHz, CDCl3): d 3.91 (s, 3H, Methoxy H); 3.21–
3.26 (dd, 1H, –CH2– pyrazoline H); 3.81–3.87 (dd, 1H, –CH2– pyrazoline H);
5.50–5.53 (dd, 1H, –CH– pyrazoline H); 6.82–7.76 (m, 18H, Ar-H); 7.78 (s, 1H,
pyrazole-H); MS: m/z = 489 (M+1). Compound 6f: yield: 78%; mp: 242–244 °C;
IR (KBr) cmÀ1: 3058, 1595, 1528, 1497, 1344, 1220; 1H NMR (500 MHz, CDCl3):
d 3.24–3.29 (dd, 1H, –CH2– pyrazoline H); 3.92–3.98 (dd, 1H, –CH2– pyrazoline
H); 5.54–5.57 (dd, 1H, –CH– pyrazoline H); 6.83–8.69 (m, 18H, Ar-H); 7.87 (s,
34. Synthesis of pyrazoline derivatives (6a–g): A mixture of pyrazole chalcones 4a–g
(1.0 mM) were placed in a 100 mL round bottom flask with 10 mL of PEG-400.
To this solution phenyl hydrazine (1.0 mM) and 40% NaOH (2 mL) were added
drop wise and heated at 70–75 °C for about 4–5 h depending upon the
substituent’s present in the compound. Reaction progress was monitored by
TLC. After completion of the reaction, reaction mixture was cooled, poured into
crushed ice, precipitate formed was filtered off and recrystallized from ethanol,
affording compounds 6a–g. Compound 6a: yield: 82%; mp: 170–172 °C; IR
(KBr) cmÀ1: 3057, 1595, 1495, 1455, 1380, 1322, 1220; 1H NMR (500 MHz,
CDCl3): d 3.19–3.24 (dd, 1H, –CH2– pyrazoline H); 3.82–3.90 (dd, 1H, –CH2–
pyrazoline H); 5.49–5.52 (dd, 1H, –CH– pyrazoline H); 6.84–7.79 (m ,18H, Ar-
H); 7.90 (s, 1H, pyrazole-H). Compound 6b: yield: 80%; mp: 156–157 °C; IR
(KBr) cmÀ1: 3055, 1596, 1497, 1384, 1323, 1221; 1H NMR (500 MHz, CDCl3): d
3.19–3.24 (dd, 1H, –CH2– pyrazoline H); 3.82–3.85 (dd, 1H, –CH2– pyrazoline
H); 5.49–5.52 (dd, 1H, –CH– pyrazoline H); 6.83–7.78 (m, 18H, Ar-H); 7.80 (s,
1H, pyrazole-H); MS: m/z = 493 (M+1). Compound 6c: yield: 79%; mp: 138–
140 °C; IR (KBr) cmÀ1: 3049, 1594, 1493, 1385, 1325, 1218; 1H NMR (500 MHz,
1H, pyrazole-H). Compound 6g: yield: 86%; mp: 150–152 °C; IR (KBr) cmÀ1
:
3059, 1594, 1495; 1374, 1217; 1H NMR (500 MHz, CDCl3): d 3.23–3.27 (dd, 1H,
–CH2– pyrazoline H); 3.83-3.89 (dd, 1H, –CH2– pyrazoline H); 5.53–5.57 (dd,
1H, –CH– pyrazoline H); 6.82–7.84 (m, 19H, Ar-H); 7.80 (s, 1H, pyrazole-H);
MS: m/z = 459 (M+1).