Synthesis and antibacterial activity of some 3,5-diphenyl and 1,3,5-triphenyl-2-pyrazolines

Article abstract of DOI:10.1002/jccs.200400117

Some new 3,5-diphenyl and 1,3,5-triphenyl-2-pyrazolines derivatives were synthesized by reacting 1,3-diphenyl-2-propen-1-ones with hydrazine hydrates and phenyl hydrazine in ethanol. The structural elucidation of the compounds was performed by IR, ¹H NMR and elemental analysis. All examined compounds showed appreciable antibacterial activity.

Full text of DOI:10.1002/jccs.200400117

Journal of the Chinese Chemical Society, 2004, 51, 775-778
775
Synthesis and Antibacterial Activity of Some 3,5-Diphenyl and
1,3,5-Triphenyl-2-pyrazolines
Sunita Shinde,a Wamanrao Jadhav,a Rajendra Pawarb and Sudhakar Bhusareb*
aOrganic Chemistry Synthesis Laboratory, Dnyanopasak College, Parbhani 431 401, MS, India
bDepartment of Medicinal Chemistry, School of Pharmacy, The Hebrew University of Jerusalem,
Jerusalem-91120, Israel
Some new 3,5-diphenyl and 1,3,5-triphenyl-2-pyrazolines derivatives were synthesized by reacting
1,3-diphenyl-2-propen-1-ones with hydrazine hydrates and phenyl hydrazine in ethanol. The structural eluci-
dation of the compounds was performed by IR, 1H NMR and elemental analysis. All examined compounds
showed appreciable antibacterial activity.
Keywords: Chalcone; Pyrazolines; Hydrazine hydrate; Phenyl hydrazine; Biological activity.
INTRODUCTION
Considerable interest has been focused on the pyrazole
1H NMR and elemental analysis. IR spectra of the com-
pounds showed C=N and C=C stretching bands at 1630 and
1590 cm-1, respectively. In the 1H NMR spectra Ha, Hb and
Hx protons of 2-pyrazoline ring were seen as doublets of dou-
blets at 3.15-3.30, 4.00-4.10 and 5.50-5.70 ppm (Jab =18.20,
Jax = 6.80, Jbx = 11.60 Hz), respectively. The protons belong-
ing to the aromatic ring and phenyl constituents were ob-
served at expected chemical shift and integral values. The el-
emental analysis data of these compounds showed good
agreements with calculated values of % C, H, and N.
structure, which is known to possess a broad spectrum of bio-
logical activities such as tranquilizing, muscle relaxant, psy-
cho analeptic, anticonvulsant, antihypotensive and antide-
pressant activity.1-4 1,3,5-Triphenyl-2-pyrazolines are well
known fluorescent compounds with high quantum yields and
are widely used as whitening or brightening reagents.5 In ad-
dition, these compounds have been utilized as fluorescence
probes in some elaborate chemosensors.6-7
Antibacterial activity
Most of the new target synthesized compounds were
tested for their antibacterial activity in vitro against bacterial
strains such as E. coli, S. typhi and S. dysentrae employing
the cup-plate method technique8 at 50-100 mg/mL concentra-
tion. The results showed all the compounds exhibited a
marked degree of activity against bacteria at the minimum in-
hibitory concentration (MIC) of 50 mg/mL in comparison to
tetracycline which was taken as a standard drug. Also, the re-
sults showed the degree of inhibition varied with the tested
compounds (Table 1).
RESULTS AND DISCUSSION
In this study some new 3,5-diphenyl and 1,3,5-triphen-
yl-2-pyrazoline derivatives were synthesized and the anti-
bacterial activities were studied by using three different path-
ogenic bacteria. 1,3-Diphenyl-2-propen-1-ones (Chalcones)
were synthesized by condensing appropriate acetophenones
with benzaldehydes in dilute ethanolic sodium hydroxide so-
lution at room temperature. The 3,5-diphenyl-2-pyrazolines
(4a-d) and 1,3,5-triphenyl-2-pyrazolines (5a-d) were synthe-
sized by the reaction of appropriate 1,3-diphenyl propen-1-
ones derivatives (3a-d) with hydrazine hydrate and phenyl
hydrazine according to the condensation reaction of a,b-un-
saturated ketones with hydrazines in yields varying from
83-95%.4,7
EXPERIMENTAL SECTION
All melting points were uncorrected and determined in
open capillaries. IR spectra were recorded on a Bruker spec-
1
The structures of all compounds were confirmed by IR,
trophotometer using KBr disc. H NMR spectra (CDCl3)
* Corresponding author. Tel: +972-2-6758700; fax: +972-2-6757076; e-mail: bhusare71@yahoo.com

776 J. Chin. Chem. Soc., Vol. 51, No. 4, 2004
Shinde et al.
Scheme I
OMe
R1
OH
R3
R1
R2
+
R2
H
a
Ha
Hb
Hx
O
O
OMe
1
2
N
N
H
OH
OMe
4a-d
b
R1
R2
OH
R3
R1
R2
R3
c
Ha
Hb
Hx
O
3a-d
OMe
N
N
OH
R3
5a-d
Reagents: a) EtOH/NaOH; b) EtOH/NH2NH2; c) EtOH,AcOH/Ph-NH-NH2
Table 1. Diameter of the inhibition zone (mm)
Compounds
R1
R2
R3
E. coli
S. typhi S. dysentrae
4a
4b
4c
4d
5a
5b
5c
5d
H
H
OH
OH
H
H
OH
OH
OH
OH
H
I
Br
I
Br
I
Br
I
Br
18
08
15
06
19
08
17
11
18
04
18
07
17
04
16
10
16
06
14
09
16
05
18
06
H
OH
OH
H
H
were recorded on Bruker 300 MHz instruments with TMS as
an internal standard.
3-methoxy-4-hydroxy-5-iodo or bromobenzaldehydes (2)
according to Claisen-Schmidt condensation.9-11
General procedure of preparation of 1,3-diphenyl
propen-1-ones (3a-d)
General procedure of preparation of 3,5-diphenyl-2-
pyrazolines (4a-d)
1,3-Diphenyl-2-propen-1-one derivatives were synthe-
sized by condensing appropriate acetophenone (1) with
To a solution of 0.01 mol of the appropriate (3a-d) de-
rivative in 15 mL of ethanol, 0.02 mol hydrazine hydrate

3,5-Diphenyl and 1,3,5-Triphenyl-2-pyrazolines
J. Chin. Chem. Soc., Vol. 51, No. 4, 2004 777
(80%) was added and the reaction mixture was refluxed for 4
h and left overnight. The reaction mixture was cooled to -10
°C and the solid mass separated out was filtered, washed with
cold ethanol and purified from ethanol.
with cold water and purified by ethanol.
1-Phenyl-3-(2-hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-
iodophenyl)-2-pyrazoline (5a)
Yield 94%, mp 127-129 °C; IR (cm-1) 1630, 1505,
1
3-(2-Hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-iodo-
phenyl)-2-pyrazoline (4a)
1234, 1155, 1045. H NMR (CDCl3) d: 3.25 (1H, dd, Ha),
3.98 (1H, dd, Hb), 3.80 (3H, s, OCH3), 5.70 (1H, dd, Hx),
6.80-7.85 (11H, m, Ar-H), (Jab =18.20, Jax = 6.60, Jbx = 11.50
Hz). Anal. Calcd for C22H19N2O3I: C, 54.34; H, 3.94; N, 5.76.
Found: C, 54.26; H, 3.75; N, 5.53.
Yield 88%, mp 107-110 °C; IR (cm-1) 1628, 1525,
1
1240, 1158, 1065. H NMR (CDCl3) d: 3.15 (1H, dd, Ha),
3.92 (1H, dd, Hb), 3.78 (3H, s, OCH3), 5.45 (1H, dd, Hx),
6.78-7.88 (6H, m, Ar-H), (Jab = 18.30, Jax = 6.68, Jbx = 11.48
Hz). Anal. Calcd for C16H15N2O3I: C, 46.85; H, 3.69; N, 6.83.
Found: C, 46.66; H, 3.59; N, 6.73.
1-Phenyl-3-(2-hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-
bromophenyl)-2-pyrazoline (5b)
Yield 86%, mp 113-115 °C; IR (cm-1) 1633, 1510, 1235,
1158, 1045. 1H NMR (CDCl3) d: 3.18 (1H, dd, Ha), 4.05 (1H,
dd, Hb), 3.85 (3H, s, OCH3), 5.68 (1H, dd, Hx), 6.85-7.78
(11H, m, Ar-H), (Jab =18.28, Jax = 6.76, Jbx = 11.40 Hz). Anal.
Calcd for C22H19N2O3Br: C, 60.15; H, 4.36; N, 6.38. Found:
C, 59.83; H, 4.13; N, 6.22.
3-(2-Hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-bromo-
phenyl)-2-pyrazoline (4b)
Yield 92%, mp 82-85 °C; IR (cm-1) 1630, 1520, 1235,
1160, 1062. 1H NMR (CDCl3) d: 3.19 (1H, dd, Ha), 3.95 (1H,
dd, Hb), 3.80 (3H, s, OCH3), 5.62 (1H, dd, Hx), 6.72-7.58
(6H, m, Ar-H), (Jab =18.35, Jax = 6.92, Jbx = 11.55 Hz). Anal.
Calcd for C16H15N2O3Br: C, 52.91; H, 4.16; N, 7.71. Found:
C, 52.76; H, 4.05; N, 7.54.
1-Phenyl-3-(4-hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-
iodophenyl)-2-pyrazoline (5c)
Yield 95%, mp 95-98 °C; IR (cm-1) 1631, 1503, 1230,
1150, 1038. 1H NMR (CDCl3) d: 3.17 (1H, dd, Ha), 3.95 (1H,
dd, Hb), 3.83 (3H, s, OCH3), 5.60 (1H, dd, Hx), 6.85-7.85
(11H, m, Ar-H), (Jab =18.30, Jax = 6.85, Jbx = 11.63 Hz). Anal.
Calcd for C22H19N2O3I: C, 54.34; H, 3.94; N, 5.76. Found: C,
54.18; H, 3.83; N, 5.65.
3-(4-Hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-iodo-
phenyl)-2-pyrazoline (4c)
Yield 83%, mp 79-82 °C; IR (cm-1) 1625, 1500, 1235,
1155, 1045. 1H NMR (CDCl3) d: 3.30 (1H, dd, Ha), 3.98 (1H,
dd, Hb), 3.79 (3H, S, OCH3), 5.63 (1H, dd, Hx), 6.75-7.77
(6H, m, Ar-H), (Jab =18.10, Jax = 6.40, Jbx = 11.35 Hz). Anal.
Calcd for C16H15N2O3I: C, 46.85; H, 3.69; N, 6.83. Found: C,
46.71; H, 3.47; N, 6.74.
1-Phenyl-3-(4-hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-
bromophenyl)-2-pyrazoline (5d)
Yield 88%, mp 143-145 °C; IR (cm-1) 1628, 1508,
1
3-(4-Hydroxyphenyl)-5-(3-methoxy-4-hydroxy-5-bromo-
phenyl)-2-pyrazoline (4d)
1230, 1140, 1047. H NMR (CDCl3) d: 3.28 (1H, dd, Ha),
3.97 (1H, dd, Hb), 3.87 (3H, s, OCH3), 5.50 (1H, dd, Hx),
6.75-7.85 (11H, m, Ar-H), (Jab =18.45, Jax = 6.68, Jbx = 11.58
Hz). Anal. Calcd for C22H19N2O3Br: C, 60.15; H, 4.36; N,
6.38. Found: C, 59.86; H, 4.17; N, 6.43.
Yield 86%, mp 93-95 °C; IR (cm-1) 1632, 1515, 1233,
1148, 1065. 1H NMR (CDCl3) d: 3.23 (1H, dd, Ha), 4.02 (1H,
dd, Hb), 3.81 (3H, s, OCH3), 5.62 (1H, dd, Hx), 6.73-7.78
(6H, m, Ar-H), (Jab =18.25, Jax = 6.70, Jbx = 11.85 Hz). Anal.
Calcd for C16H15N2O3Br: C, 52.91; H, 4.16; N, 7.71. Found:
C, 52.72; H, 4.39; N, 7.54.
Received August 7, 2003.
General procedure of preparation of 1,3,5-triphenyl-2-
pyrazolines (5a-d)
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