3-Aryl-5-furylpyrazolines and their biological activities

Article abstract of DOI:10.1002/hc.10159

Aryl-furyl substituted pyrazolines 2a-c and 4a-c were prepared by the reaction of α,βunsaturated carbonyl compounds with hydrazine or phenyl hydrazine. N-chloroacetyl derivatives 3a-c were obtained by the N-acetylation of 2a-c. The antibacterial activities of synthesized pyrazolines were examined by employing the disk-diffusion technique. All synthesized compounds showed antibacterial effects in 1200 μg concentration.

Full text of DOI:10.1002/hc.10159

Heteroatom Chemistry
Volume 14, Number 4, 2003
3-Aryl-5-furylpyrazolines and Their
Biological Activities
A. Cetin,1 A. Cansiz,1 and M. Digrak2
1Department of Chemistry, Faculty of Sciences and Art, University of Firat, 23169 Elazig, Turkey
2Department of Biology, Faculty of Sciences and Art, University of Sutcu Imam, K. Maras, Turkey
Received 16 December 2002; revised 6 February 2003
N-Acetylation of 2a–c was achieved with chloro-
ABSTRACT: Aryl-furyl substituted pyrazolines 2a–c
acetylchloride in the presence of triethylamine to
and 4a–c were prepared by the reaction of α,β-
give 3a–c (Scheme 1) [8].
unsaturated carbonyl compounds with hydrazine or
phenyl hydrazine. N-chloroacetyl derivatives 3a–c
were obtained by the N-acetylation of 2a–c. The an-
tibacterial activities of synthesized pyrazolines were ex-
RESULT AND DISCUSSION
amined by employing the disk-diffusion technique. All
synthesized compounds showed antibacterial effects
Data of the prepared pyrazoline derivatives are given
in Table 1. IR and H NMR spectral data of pre-
1
ꢀ
C
in 1200 µg concentration.
2003 Wiley Periodicals,
pared chalcones and pyrazoline derivatives are given
in Table 2. All newly synthesized compounds ana-
lyzed satisfactorily for nitrogen and structures were
confirmed on the basis of their IR and 1H NMR spec-
tral data. IR spectra of these compounds showed
moderately strong band around 1495–1499, 1390–
1121, and 1255–1251 cm−1 characteristic for the
C N, C N, and N N groups. In the 1H NMR spectra
the characteristic signal due to CH CH2 N protons
appeared at δ 3.4–3.6. The NH and aromatic protons
appeared as a multiplet at δ 6.1–8. The signal due to
furyl N CH CH2 protons appeared δ 6.2–7.
Inc. Heteroatom Chem 14:345–347, 2003; Published on-
line in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/hc.10159
INTRODUCTION
Pyrazoline derivatives constitute an interesting class
of organic compounds with diverse chemical and
pharmacological applications [1–3]. Pyrazolines can
be synthesized from ꢀ,ꢁ-unsaturated carbonyl com-
pounds and hydrazines. They are reported to be po-
tential extractants and powerful drugs [4].
ꢀ,ꢁ-Unsaturated ketones 1a–c were obtained
by Claisen–Schmidt reactions of furfural and p-
substituted acetophenones [5,6]. On heating 1a–c
with hydrazine hydrate the corresponding pyra-
zolines 2a–c were obtained in good yield [7].
Antimicrobial Activity
The pyrazolines 2–4 were screened for their in vitro
antimicrobial activity against some bacteria em-
ploying the disk-diffusion technique. The test or-
ganism employed were Salmonella thypimurium TA
100 hi, Kluyveromyces fragilis, Serratia marcescens
NRRL 3284, Pseudomonas aeruginosa ATCC 27853,
Rhodotorula rubrum, Aoremonas hydrophila ATCC
7966, Enterococcus faecalis ATCC 15753, Corynebac-
terium xerosis UC 9165, Micrococcus luteus LA 2971,
Bacillus megaterium DSM 32, Listeria monocytogenes
Correspondence to: Ahmet Cetin; e-mail: acetin@firat.edu.tr,
acetin74@hotmail.com.
Contract grant sponsor: FUNAF, Elazig, Turkey.
Contract grant number: 326.
2003 Wiley Periodicals, Inc.
c
ꢀ
345

346 Cetin, Cansiz, and Digrak
Elemental analyzes were performed at Firat Uni-
versity with a Perkin-Elmer 240-B elemental ana-
lyzer. Starting chemicals were obtained from Fluka
or Aldrich.
O
O
C
NaOH, ethanol
O
CH CH3
X
O
C
CH=CH
X
O
Synthesis of 3-Aryl-5-(2-furyl)-2-pyrazolines
(2a–c)
X= -H, -CH3, -OCH31a c
R
A solution of the respective 0.02 mol furfural p-
substituted acetophenone 1a–c and 0.02 mol hy-
drazine hydrate in 30 ml ethanol was refluxed for
3 h. The reaction mixture was cooled and kept at 0◦C
overnight. The resulting solid was crystallized from
ethanol–hexane (3:1).
N
N
H2N-NH2 H2O
1a c
X
ethanol
O
R= H
2a c
O
C
CH2 CI
Cl
3a c
4a c
R=CICH2CO
R=C6H5
H2N NH C6H5
ethanol
Synthesis of 3-Aryl-1-chloroacetyl-5-(2-furyl)-
2-pyrazolines (3a–c)
SCHEME 1
A mixture 0.02 mol pyrazoline 2a–c, 0.02 mol
chloroacetyl chloride, and triethylamine in 40 ml dry
benzene was left at room temperature overnight. The
reaction mixture was evaporated to dryness by suc-
tion and the remaining solid product was recrystal-
lized from an appropriate solvent.
Scoot A, Proteus vulgaris FMC 1, Mycobacterium
smegmatis CCM 2067, Bacillus subtilis IMG 22,
Staphylococcus aureus Cowan 1, and Escherichia coli
DM. The diameters of zones of inhibition were mea-
sured at 300, 600, and 1200 ꢂg concentration. Al-
though antibacterial effects of all synthesized com-
pounds were generally found to be very low in lower
concentrations, they showed better antibacterial ef-
fect in 1200 ꢂg concentration.
Synthesis of 3-Aryl-5-(2-furyl)-1-phenyl-
2-pyrazolines (4a–c)
A solution of 0.02 mol 1a–c and 0.02 mol phenyl
hydrazine in 50 ml ethanol was refluxed for 8 h.
The reaction mixture was cooled and kept at 0◦C
overnight. The resulting solid was crystallised from
glacial acetic acid.
EXPERIMENTAL
General Data
Preparation of Microorganism Culture
Melting points were determined in open capillary
tubes on digital Gallenkamp melting point apparatus
and are uncorrected. The IR spectra were recorded
KBr with a Mattson 1000 FT-IR spectrometer. The 1H
NMR spectra were run on Varian EM-360, 60 MHz
spectrometers using TMS as internal reference.
All the chemical samples and the standard antibi-
otics, in amount of 300, 600, and 1200 ꢂg, were in-
jected into empty sterilized antibiotic discs having
a dimeter of 6 mm (Schleicher & Schu¨ll No: 2668,
Germany). The discs injected only with chloroform
were used as control. All the bacteria mentioned
above were incubated at 30 0.1◦C for 24 h by inoc-
ulation into Nutrient Broth (Difco) and the yeasts
studied were incubated in Sabourand Dextrose
Broth (Difco) for 24 h. Mueller Hinton Agar (oxoid)
and Sabourand Dextrose Agar sterilized in separate
flasks and cooled to 45–50◦C were distributed to ster-
ilized petri dishes having a diameter of 9 cm, by using
15-ml pipettes. Cultures (1 ml) of bacteria (105 bacte-
ria per ml) and yeast (104 yeast cell per ml) prepared
as mentoined above were incubated for 24 h after the
food medium in the petri dishes had been distributed
homogenously. Dishes injected with extracts were
TABLE 1 Data of Pyrazolines 2–4
Yield (%)
mp (◦C)
2a
2b
2c
3a
3b
3c
4a
4b
4c
65
50
70
70
68–70
75
60
65
68
105
104
125
32
34
38
122
112
133
Yellowish brown
Yellowish brown
Yellow
Brown
Brown
Dark brown
Light yellow
Yellow
Light yellow

3-Aryl-5-furylpyrazolines and Their Biological Activites 347
1H NMR Spectra δ (DMSO)
TABLE 2 IR and 1H NMR Spectral Data of 1–4
cm−1
IR Spectra (µ
)
max
1a
1b
1c
3150, 3030, 1664, 1600, 1580, 1555, 1450, 1256,
1016, 750, 700
3120, 3030, 2960, 1850, 1660, 1600, 1580, 1555,
1450, 1256, 1016
3125, 3020, 2962, 2840, 1659, 1600, 1580, 1553,
1450, 1260, 1173, 1017
6.2 (d, 1H, ar. CH C), 6.5 (d, 1H, C CH CO), 7.2–7.5 (m, 6H,
3H furyl CH, 3H ar. C H), 7.8 (m, 2H, ar. CH).
2.2 (s, 3H, CH3), 6.2 (d, 1H, ar. CH C), 6.5 (d, 1H, C CH CO),
7–7.8 (m, 7H, 3H furyl CH, 4H ar. CH).
3.8 (s, 3H, OCH3), 6.3 (d,1H, ar. CH C), 6.5 (d, 1H, C CH CO),
6.8–6.9 (d, 2H, furyl H3 H4), 7.3 (m, 5H, 1H furyl H2 ve 4H
ar. CH)
2a
2b
3332, 3150, 3020, 2960, 2836, 1673, 1600, 1513,
1410,1255, 1175, 1017
3329, 3150, 3020, 2960, 2836, 1673, 1600, 1251,
1174, 1029, 1015
3.6 (d, 2H, CH2), 5.2 (t, 1H, CH), 6.2 (d, 1H, NH), 6.8 (s, 2H,
furyl H3, H4), 7–8 ( m, 6H, 5H ar. CH ve 1H furyl H2).
2.8 (s, 3H, CH3), 3.6 (d, 2H, CH2), 5.3 (t, 1H, CH), 6.1 (d,
1H, NH), 6.8 (m, 2H, furyl H3 H4), 7.4–8 (m, 5H, 4H ar. CH
ve 1H furyl H2).
2c
3a
3333, 3120, 2837, 1672, 1661, 1256, 1030, 1015
3.4 (s, 2H, CH2), 4.1 (s, 3H, OCH3), 4.8 (m, 1H, CH), 6.6 (d,
1H, NH), 7–8.3 (m, 7H, 3H furyl CH, 4H ar. CH).
2.2 (s, 2H, CO CH2 CI), 3.6–3.8 (d, 2H, CH2), 5.3 (t, 1H,
CH), 6.3 (d, 2H, furyl H3, H4), 7–8.2 (m, 6H, 5H ar. CH, 1H
furyl H2).
3160, 3090, 2840, 1680, 1609, 1520, 1251, 1044,
765
3b
3115, 3000, 2960, 2866, 1682, 1613, 1435, 1013,
1025, 760
2.2 (s, 2H, CO CH2 CI), 2.8 (s, 3H, CH3), 3.7 (d, 2H, CH2),
5.3 (m, 1H, CH), 6.5 (m, 2H, furyl H3, H4), 7.2–8.2 (m, 5H,
4H ar. CH, furyl H2).
3c
4a
4b
4c
3100, 3020, 2955, 2840, 1677, 1601, 1512, 1450,
1258, 1020, 752
3125, 3020, 2920, 1597, 1495, 1450, 1393, 1251,
1121
3150, 3020, 2920, 1597, 1498, 1390, 1324, 1251,
1121
3117, 3020, 2922, 2837, 1609, 1499, 1391, 1280,
1254, 1180, 1122
2.6 (s, 2H, CO CH2 CI), 3.4 (m, 2H, CH2), 4.1 (s, 3H, OCH3),
4.8 (s, 1H, CH), 7.3–8.4 (7H, 3H furyl CH ve 4H ar. CH).
5 (d, 2H, CH2), 5.3 (t, 1H, CH), 6.2 (m, 2H, furyl H3 H4),
7–7.8 (m, 11H, 10H ar. CH ve 1H furyl-H2).
2 (s, 3H, CH3), 3.5 (d, 2H, CH2), 5 (m, 1H, CH), 6.2 (m, 2H,
furyl H3 H4), 6.5–7.5 (m, 10H, 9H ar. CH ve 1H furyl-H2).
3.6 (d, 2H, CH2), 4.1 (s, 3H, OCH3) 5.5 (m, 1H, CH), 7.1–8
(m, 12H, 9H, ar. CH ve 3H, furyl-CH).
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Turkey, 2000.
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