Studies on arylfuran derivatives Part X. Synthesis and antibacterial properties of arylfuryl-Δ2-pyrazolines

Article abstract of DOI:10.1016/S0014-827X(00)00030-6

Arylfurylpropenones 3 were synthesized by Claisen-Schmidt condensation of arylfurfurals 1 with various substituted acetophenones 2. Cyclocondensation of these arylfurylpropenones 3 with hydrazine hydrate and phenylhydrazine furnished 1H-pyrazolines 4 and N-phenylpyrazolines 6, respectively. In order to study the structure-activity relationships, pyrazolines 4 were converted into their N-acetyl derivatives 5. The antibacterial properties of the new pyrazoline derivatives were studied. (C) 2000 Elsevier Science S.A.

Full text of DOI:10.1016/S0014-827X(00)00030-6

www.elsevier.nl/locate/farmac
Il Farmaco 55 (2000) 256–263
Studies on arylfuran derivativesꢀ
Part X. Synthesis and antibacterial properties of
arylfuryl-D2-pyrazolines
B. Shivarama Holla *, P.M. Akberali 1, M.K. Shivananda
Department of Chemistry, Mangalore Uni6ersity, Mangalagangotri 574 199, India
Received 20 May 1999; accepted 16 February 2000
Abstract
Arylfurylpropenones 3 were synthesized by Claisen–Schmidt condensation of arylfurfurals 1 with various substituted acetophe-
nones 2. Cyclocondensation of these arylfurylpropenones 3 with hydrazine hydrate and phenylhydrazine furnished 1H-pyrazolines
4 and N-phenylpyrazolines 6, respectively. In order to study the structure–activity relationships, pyrazolines 4 were converted into
their N-acetyl derivatives 5. The antibacterial properties of the new pyrazoline derivatives were studied. © 2000 Elsevier Science
S.A. All rights reserved.
Keywords: Arylfurylpropenones; Arylfurylpyrazolines; Antibacterial activity
continuation of our work on the synthesis of N-bridged
heterocycles [12–15], we decided to undertake the syn-
thesis of pyrazolines carrying an arylfuran substituent
and to study their antibacterial activity.
With a view to study the structure–activity relation-
ships, it was decided to introduce substitution at posi-
1. Introduction
Heterocyclic analogues of chalcones were prepared
for biological studies [1–4]. Several 1,3,5-trisubstituted
pyrazolines are reported to possess moderate antibacte-
rial and antifungal activity [5]. Besides, a number of
nitrofurylpyrazoline derivatives were found to possess
antibacterial activity [6]. Some of them also find appli-
cation as food preservatives, especially in preserving
fish sausages. However, the use of nitrofurylpyrazolines
as food preservatives has recently been discouraged
owing to their toxicity [7]. One of the methods em-
ployed to reduce toxicity of nitrofuran drugs is to
introduce arylfurans instead of nitrofurans [8]. Also, it
is worthwhile to note that arylfuran-2-carboxaldehyde
derivatives are found to exhibit antibacterial activity
[9–11]. Keeping these observations in view and in
tion
1 of the 3-aryl-5-(5-aryl-2-furyl)-4,5-dihydro-
1H-pyrazoles (4). For the present study, two series of
compounds viz., 1-acetyl-3-aryl-5-(5-aryl-2-furyl)-4,5-
dihydropyrazoles (5) and 1-phenyl-3-aryl-5-(5-aryl-2-
furyl)-4,5-dihydropyrazoles (6) were synthesized.
2. Chemistry
1-Aryl-3-(5-aryl-2-furyl)-2-propen-1-ones (3) were
prepared by condensing 5-aryl-2-furalaldehydes (1)
(R=NO2, Cl, Br) with substituted acetophenones 2 in
the presence of sodium hydroxide (Scheme 1). Com-
pounds 3a–o were treated with hydrazine hydrate to
ꢀ Presented at the National Seminar on Recent Trends in Organic
Synthesis held at Kakatiya University, Warangal during February
18–19, 1997.
* Corresponding author. Tel.: +91-824-742262; fax: +91-824-
742367.
E-mail address: root@mnglr.ernet.in (B. Shivarama Holla).
1 Present address: Plama Laboratories Ltd., 120 A/B Industrial
Area, Baikampady, New Mangalore 575 011, India.
obtain
3-aryl-5-(5-aryl-2-furyl)-4,5-dihydropyrazoles
(4a–o). This reaction probably involved the intermedi-
ate formation of hydrazones and subsequent addition
of NH on the carbonꢀcarbon double bond of the
propenone moiety. Pyrazolines 4a–e, h–o were further
subjected to acetylation in the presence of acetic anhy-
0014-827X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0014-827X(00)00030-6

B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
257
shown in Scheme 3.
dride to afford 1-acetyl-3-aryl-5-(5-aryl-2-furyl)-4,5-di-
The formation of the derivatives 6, instead of their
regioisomers 7, is favoured because hydrazines attack
preferentially on the carbonyl group of a,b-unsaturated
ketones, rather than the double bond, so that hydra-
zones formation is favoured.
hydropyrazoles (5a–e and h–o). 1-Phenyl-3-aryl-5-(5-
aryl-2-furyl)-4,5-dihydro-pyrazoles
(6a–p)
were
prepared by refluxing the propenones 3 with phenylhy-
drazine in ethanol containing glacial acetic acid.
Condensation of 3 with phenylhydrazine can lead to
two different pyrazolines 6 or 7, as shown in Scheme 2.
According to Baldwin’s rules [16], the formation of
N-phenylpyrazolines 7 involving a 5-exo-Trig. ring clo-
sure is preferred over the formation of N-phenylpyrazo-
lines 6 involving a 5-endo-Trig. ring closure. However,
in the present investigation, as the reaction is catalyzed
by glacial acetic acid, N-phenylpyrazolines 6 are
formed and their formation can be rationalized as
The physicochemical data (yield, melting point and
molecular formula) for compounds 3–6 are given in
1
Tables 1–4. Selected data (MS, IR, UV and H NMR)
are reported in Section 3. X-ray crystallographic analy-
sis of compound 4b unambiguously revealed the forma-
tion of the pyrazoline ring [17].
1
In the 270 MHz H NMR spectrum of compound
4m, the pyrazoline NH proton resonated at l 10.2. The
Scheme 1.

258
B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
Scheme 2.
The fragment ion peaks at m/z 355 and 357 could arise
by the loss of CH3CHO from the molecular ion. The
fragmentation pattern is shown in Scheme 4.
CH2 protons of the pyrazoline ring resonated as a pair
of doublets of doublets at l 3.1–3.4. The CH proton
appeared as a doublet of doublets at l 4.9 due to
vicinal coupling with the two magnetically non-equiva-
lent protons of the methylene group at position 4 of the
pyrazoline ring (J=9.9 and J=12.5 Hz). The aryl-
methyl proton signal appeared at l 2.5 as a singlet.
The mass spectrum of the compound 4c showed a
molecular ion peak at m/z 363 as base peak corre-
sponding to the molecular formula C20H17N3O4 consis-
tent with its structure. A M+ꢀNꢀNH peak was
observed at m/z 334.
The mass spectrum of compound 5o showed a molec-
ular ion peak at m/z 398 corresponding to the molecu-
lar formula C21H16Cl2N2O2. The M+2 peak was
observed at m/z 400. The base peak in this case was
seen at m/z 43 corresponding to the CH3ꢀCꢁO moiety.
3. Experimental
Melting points were determined by the capillary
method and are uncorrected. Elemental analyses were
carried out on Carlo Erba 1108 elemental analyzer and
the results were within +0.4% of the theoretical values.
The UV spectra were recorded in dimethylformamide
on a Beckman model-24 UV spectrophotometer. The
IR spectra were recorded in Nujol mull on a Perkin–
1
Elmer model 529. H NMR spectra were recorded on a
Bruker WH-270 pulsed FT NMR spectrometer or on a
Perkin–Elmer R-32 (90 MHz) spectrometer using

B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
259
Table 1
DMSO-d6 as solvent and tetramethylsilane as internal
standard. Chemical shift values are given in (ppm) and
coupling constants (J) in hertz. Mass spectra of some
selected compounds were recorded on a JEOL JMS-D
300 mass spectrometer operating at 70 eV.
Physicochemical data of 1-aryl-3-(5-aryl-2-furyl)-2-propen-1-ones
(3a–p) a
Comp. M.p. (°C)
Yield (%)
Recrystalliza- Molecular
tion solvent formula
3a b
3b
3c
3d
3e
170
168
180
212
130–131
114–115
162–163
137
159
193
93
95
89
92
84
80
88
96
88
98
93
C
C
C
C
C
B
C
C
C
C
C
C19H13NO4
C20H15NO4
C20H15NO5
C19H12ClNO4
C19H13NO4
C20H15NO5
C19H12ClNO4
C19H13BrO2
C20H15BrO2
C20H15BrO3
C19H12BrClO2
3.1. General procedure for the synthesis of
1-aryl-3-(5-aryl-2-furyl)-2-propen-1-ones (3a–p)
The suitably substituted acetophenones 2 (10 mmol)
were dissolved in ethanol. Then, a solution of sodium
hydroxide (5 ml, 30%) and suitable arylfurfuraldehydes
1 (10 mmol) in dimethylformamide(10 ml) was added to
the resulting solution with continuous stirring. The
clear solution so obtained was stirred for 4 h at room
temperature and then allowed to stand overnight. The
3f
3g
3h b
3i
3j
3k
155
3l b
3m
3n
3o
3p
131
160
175
141
97
94
95
75
67
C
C
C
C
A
C19H13ClO2
C20H15ClO2
C20H15ClO3
C19H12Cl2O2
C19H13ClO2
96–98
a Recrystallization solvent: (A) EtOH; (B) 1,4-dioxan; (C) EtOH+
DMF.
b See Ref. [19]
solid separated was filtered off, dried and recrystallized
as indicated in Table 1, which also reports the yields,
melting points and molecular formula.
Selected spectral data of this class of compounds are
reported below.
3a: MS, m/z 319 [M+], 273 [M+−NO2]. IR (KBr)
(cm−1), 1649 (CꢁO str.), 1585 (CꢁC str.), 1572 (NO2
asym.), 1338 (NO2 sym.).
3b: Mass, m/z 333 [M+, 80%] UV, umax 270 nm
(m=950) and 400 nm (m=4000). IR (KBr) (cm−1),
1
1668 (CꢁO str.), 1590 (CꢁC str.). H NMR (90 MHz),
l 2.3 (s, 3H, Me), 6.8 (s, 1H, furan 3H, J=3 Hz),
7.1–7.9 (m, 7H, ethylenic, furan 4H and aromatic
Table 2
Physicochemical data of 3-aryl-(5-aryl-2-furyl)-2-pyrazolines (4a–o)
Comp.
M.p. (°C)
Yield (%)
Molecular formula
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
145
180
171
140
110–112
144–145
116–118
115
135
145
90
87
88
91
80
81
60
96
81
88
95
87
89
90
87
C19H15N3O3
C20H17N3O3
C20H17N3O4
C19H14ClN3O3
C19H15N3O3
C20H17N3O4
C19H14ClN3O3
C19H15BrN2O
C20H17BrN2O
C20H17BrN2O2
C19H14BrClN2O
C19H15ClN2O
C19H15ClN2O
C19H15ClN2O2
C19H15ClN2O
112
125
134
126
114
Scheme 3.

260
B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
Table 3
3n: UV, umax 315 nm (m=845) and 400 nm (m=4000).
IR (cm−1), 1647 (CꢁO str.), 1608 (CꢁC str.).
Physicochemical data of 1-acetyl-3-aryl-(5-aryl-2-furyl)-2-pyrazolines
(5a–e and h–o)
3.2. General procedure for the synthesis of
3-aryl-5-(5-aryl-2-furyl)-2-pyrazolines (4a–o)
Comp.
M.p. (°C)
Yield (%)
Molecular formula
21H17N3O4
C22H19N3O4
C22H19N3O5
5a
5b
5c
5d
5e
5h
5I
5j
5k
5l
5m
5n
5o
190
184
191
255
115–117
151
152
139
150
131
168
118
177
85
89
86
86
89
88
91
82
95
91
82
86
88
C
To a solution of 1-aryl-3-(5-aryl-2-furyl)-2-propen-1-
ones (3a–o) (10 mmol) in ethanol (10 ml), hydrazine
hydrate (90%, 5 ml) was added dropwise. The reaction
mixture was heated under reflux for 4 h and then
cooled and poured onto crushed ice. The resulting
3-aryl-5-(5-aryl-2-furyl)-2-pyrazolines (4a–o) were col-
lected by filtration and recrystallized from a mixture of
dimethylformamide and ethanol. Physicochemical data
of this class of compounds are given in Table 2. Se-
lected spectral data are reported below.
C21H16ClN3O4
C21H17N3O4
C21H17BrN2O2
C22H19BrN2O2
C22H19BrN2O2
C21H16BrClN2O2
C21H17ClN2O2
C22H19ClN2O2
C22H19ClN2O3
C21H16Cl2N2O2
4b: UV, umax 370 nm (m=1531), 270 nm (m=1138)
and 290 nm (m=1131).
4c: Mass, m/z 363 [M+, 100%], 334 [M+−N2H,
13%], 214 (p-nitrophenylfuronitrile, 80%), 133 (p-
methoxybenzonitrile, 21%), 348 [M+−Me, 6%], 334
[M+−Et, 4%], 333 [M+−NO, 11%], 305 [M+−NO
and CO, 17%].
protons), 8.0–8.2 (d, 2H, p-nitrophenyl, J=8 Hz),
8.3–8.5 (d, 2H, p-nitrophenyl, J=8 Hz).
3c: Mass, m/z 349 [M+, 100%]. IR (cm−1), 1656
(CꢁO str.), 1599 (CꢁC str.), 1558 and 1331 (NO2 asym.
and sym.).
3d: Mass, m/z 353 [M+], 307 [M+−NO2]. IR
(cm−1), 1556(CꢁO str.), 1599 (CꢁC str.)
4e: Mass, m/z 333 [M+, 95.6%], 304 [M+−N2H,
12.8%], 214 (m-nitrophenylfuronitrile, 37%), 103 (ben-
zonitrile, 13.6%), 303 [M+−NO, 9.7%], 275 [M+−
3f: Mass, m/z 349 [M+, 100%]. IR (cm−1), 1655
(CꢁO str.), 1598 (CꢁC str.). 1H NMR (400 MHz,
DMSO-d6); l 3.89 (s, 3H, OCH3), 7.12 (d, 2H, ArꢀH,
J=8.79 Hz), 7.24 (d, 1H, furyl proton, J=3.91 Hz),
7.48 (d, 1H, furyl proton, J=3.4 Hz), 7.58 (d, 1H,
ethylenic, J=15.4 Hz), 7.78–7.81 (d, 1H, ethylenic,
J=15.63 Hz), 8.16 (d, 2H, ArꢀH, J=8.79 Hz), 8.37–
8.39 (m, 4H, m-nitrophenyl).
1
NO and CO, 6%]. H NMR (270 MHz, DMSO-d6); l
2.9–3.5 (d, d, 2H, pyrazoline CH2), 3.7 (s, 3H, OCH3),
4.7–4.9 (d, d, 1H, pyrazoline CH), 6.4–8.2 (m, aro-
matic and furyl protons), 10.3 (s, 1H, NH).
4g: Mass, m/z 367/369 [M+, 100%/34.3%], 338 [M+
−N2H, 6.4%], 214 (m-nitrophenylfuronitrile, 37.1%),
137/139 (p-chlorobenzonitrile, 10.4%/21.1%), 337 [M+
−NO, 4.4%], 309 [M+−NO and CO, 5.4%]. 1H NMR
(90 MHz, DMSO-d6); l 8.45 (s, 1H, NH), 7.5 (d, 2H,
p-chlorophenyl, J=8.3 Hz), 7.7 (d, 2H, p-
chlorophenyl, J=8.3 Hz), 8.1 (m, 4H, m-nitrophenyl),
7.2 (d, 1H, furyl proton, J=3.42 Hz), 6.57 (d, 1H,
furyl, J=3.42 Hz), 4.95–5.03 (d, d, 1H, CH), 3.2–3.3
(d, d, 2H, CH2).
3k: IR (cm−1), 1647 (CꢁO str.), 1590(CꢁC str.).
3l: IR (cm−1), 1657 (CꢁO str.), 1587(CꢁC str.).
Table 4
Physicochemical data of 1-phenyl-3-aryl-(5-aryl-2-furyl)-2-pyrazolines
(6a–p)
Comp.
M.p. (°C)
Yield (%)
Molecular formula
C25H20N3O3
C26H22N3O3
C26H22N3O4
C25H19ClN3O3
C25H20N3O3
C26H22N3O4
C25H19ClN3O3
C25H20BrN2O
C26H22BrN2O
C26H22BrN2O2
C25H19BrClN2O
C25H20ClN2O
C26H22ClN2O
C26H22ClN2O2
C25H19Cl2N2O
C25H19ClN2O
4i: m/z 380/382 [M+/M+2, 100%/99%], 351 [M+−
N−NH, 14.2%], 247/249 (p-bromophenylfuronitrile,
54.2%/8.5%), 117 (p-tolylcyanide, 19.9%). IR (cm−1),
3230 (pyrazoline NH), 1600 (ring CꢁN), 1480 (ring
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
155
173
159
185
80
86
84
80
88
98
89
82
86
85
88
83
84
80
81
80
1
NꢀN) H NMR (270 MHz, DMSO-d6); l 2.2 (s, 3H,
130
CH3), 3.0–3.5 (d, d, 2H, pyrazoline CH2), 4.7–4.9 (d,
d, 1H, pyrazoline CH), 6.3–8.2 (m, aromatic and furyl
protons), 10.3 (s, 1H, NH).
145–150
160–165
140
179
168
143
139
175
170
4j: IR (cm−1), 3346 (pyrazoline NH), 1611 (CꢁN
1
str.), 1518 (NꢀN str.). H NMR (90 MHz); l 3.1–3.6
(d, d, 2H, CH2), 3.8 (s, 3H, OCH3), 4.7–4.9 (d, d, 1H,
CH), 10.3 (s, 1H, pyrazoline NH).
4m: 3300 (pyrazoline NH), 1590 (ring CꢁN), 1480
1
(ring NꢀN). H NMR (270 MHz); l 2.5(s, 3H, CH3),
162
120–121
3.1–3.4 (d, d, 2H, CH2), 4.9 (d, d, 1H, CH), 10.2 (s,
1H, NH), 6.4 (d, 1H, furyl proton, J=3.3 Hz), 6.9 (d,

B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
261
Scheme 4.
1H, furyl proton, J=3.3 Hz), 7.2, 7.5 (d, d, 4H, p-tolyl,
J=8.6 Hz), 7.5, 7.7 (d, d, 4H, p-chlorophenyl, J=8.3
Hz).
4n: l 3.7 (s, 3H, OCH3), 2.8–3.6 (d, d, 2H, CH2),
4.7–4.9 (d, d, 1H, CH), 10.3 (s, 1H, NH), 6.2 (d, 1H,
furyl proton, J=3.3 Hz), 6.4 (d, 1H, furyl proton,
J=3.3 Hz), 6.9, 7.2 (d, d, 4H, aromatic, J=8.6 Hz),
7.4, 7.6 (d, d, 4H, p-chlorophenyl, J=8.6 Hz).
refluxed for 3 h. The reaction mixture was cooled and
poured onto crushed ice to decompose the excess acetic
anhydride. The solid material so obtained was collected
by filtration and recrystallized from a mixture of
dimethylformamide and ethanol. Physicochemical data
of these N-acetylpyrazolines are given in Table 3. Se-
lected spectral data are reported below.
5b: Mass, m/z 389 [M+, 100%], 346 [M+−Ac,
72.7%], 330 (346-Me, 72.7%), 318 [M+−43−N2,
63.6%], 117 (p-tolylcyanide, 7.2%), 214 (p-nitrophenyl-
furonitrile, 15.1%), 43 (Ac, 90%). UV, umax 370 nm
(m=2956), 300 nm (m=2275). IR (cm−1), 1668 (CꢁO
str.), 1600 (CꢁN str.), 1506 and 1332 (NO2 asym. and
3.3. General procedure for the synthesis of
1-acetyl-3-aryl-5-(5-aryl-2-furyl)-2-pyrazolines (5a–e,
h–o)
1
sym.), 1510 (NꢀN str.). H NMR (90 MHz); l 3.1–3.9
A solution of 3-aryl-5-(5-aryl-2-furyl)-2-pyrazolines
(4a–e, h–o) (10 mmol) in acetic anhydride (10 ml) was
(d, d, 2H, CH2), 5.5–5.7 (d, d, 1H, CH), 2.4 (s, 3H,
CH3CO), 2.2 (s, 3H, CH3).

262
B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
5c: UV, umax 300 nm (m=2982), 380 nm (m=2015).
6b: Mass; 6b, m/z 423 [M+, 75%], 91 (C6H5N+,
10%), 332 [M+−91, 20%]; 1H NMR (90 MHz), l
3.1–3.9 (d, d, 2H, CH2), 5.25 (d, d, 1H, CH), 6.2–7.9
(m, 11H, aromatic and furylprotons), 8.1 (d, 2H, p-ni-
trophenyl, J=8 Hz), 8.3 (d, 2H, p-nitrophenyl, J=8
Hz), 2.2 (s, 3H, tolyl-CH3).
IR (cm−1), 1668 (CꢁO str.), 1600 (CꢁN str.), 2854
(OCH3 str.), 1515 and 1338 (NO2 asym. and sym. str.),
1500 (NꢀN str.).
5i: UV umax 300 nm (m=3500).5j: UV, umax 300 nm
(m=3500). IR (cm−1), 1670 (CꢁO), 1600 (CꢁN), 1500
1
(NꢀN str.), 2852 (OCH3 str.). H NMR; l 2.4 (s, 3H,
6h: Mass, m/z 442/444 [M+/M+2, 15%], 91
1
CH3CO), 3.7 (s, 3H, OCH3), 3.1–3.6 (d, d, 2H, CH2),
5.5–5.7 (d, d, 1H, CH), 6.3 (d, 1H, furyl protons,
J=3.3 Hz), 6.4 (d, 1H, furyl protons, J=3.3 Hz),
6.7–7.6 (m, aromatic protons).
(C6H5N+, 100%), 350 [M+−91, 20%]. H NMR (90
MHz); l 3.1 (d, d, 1H, CH2, J=11 Hz), 3.8 (d, d, 1H,
CH2, J=11 Hz), 5.25 (d, d, 1H, CH, J=6 Hz), 6.1 (d,
1H, furan 3H, J=3 Hz), 6.4 (d, 1H, furan 4H, J=3
Hz), 6.6–7.7 (m, aromatic protons).
5n: Mass, m/z 398 [M+, 100%], 400 [M+2], 355/357
1
[M+−CH3CHO], 43 (Ac). H NMR (270 MHz), 2.2
(s, 3H, CH3), 2.4 (s, 3H, CH3CO), 3.5 (d, d, 1H, CH2),
3.9 (d, d, 1H, CH2), 5.6–5.8 (d, d, 1H, CH), 6.4 (d, 1H,
furyl proton, J=3.3 Hz), 6.9 (d, 1H, furyl proton,
J=3.3 Hz), 7.3 (d, 2H, p-tolyl, J=8.6 Hz), 7.5 (d, 2H,
p-tolyl, J=8.6 Hz), 7.6 (d, 2H, p-chlorophenyl, J=8.6
Hz), 7.8 (d, 2H, p-chlorophenyl, J=8.6 Hz).
5o: IR (cm−1), 1650 (CꢁO str.), 1600 (CꢁN str.),
1510 (NꢀN str.).
4. Antibacterial activity
Some selected arylfurylpyrazolines (4), N-acetylpyra-
zolines (5) and N-phenylpyrazolines (6) were screened
for their in vitro antibacterial activity against E. coli, S.
aureus, B. subtilis and P. aeruginosa. Their minimum
inhibitory concentrations (MIC values) were deter-
mined by serial dilution method [18]. Nitrofurazone
(Furacin) was used as the standard drug for compari-
son. The results of such studies are reported in Table 5.
The screening data indicate that compounds 4–6c,
4–6j and 4–6n carrying p-nitro, p-bromo and p-
chlorophenylfuryl groups, respectively, showed a simi-
lar degree of antibacterial activities against E. coli and
S. aureus compared with the standard drug. The an-
tibacterial activity of the remaining compounds were
not encouraging, although most compounds manifested
moderate antibacterial activity. Thus, it was concluded
that some of the compounds of the series proved to be
promising antibacterial agents and hence deserve fur-
ther pharmacological investigation.
3.4. General procedure for the synthesis of
1-phenyl-3-aryl-5-(5-aryl-2-furyl)-2-pyrazolines (6a–p)
To a solution of 1-aryl-3-(5-aryl-2-furyl)-2-propen-1-
ones (3a–p) (10 mmol) in ethanol (10 ml), phenylhy-
drazine (1 ml) was added. The reaction mixture was
then treated with glacial acetic acid (5 ml). The result-
ing mixture was heated under reflux for 6 h on a water
bath. The precipitated solid was filtered and recrystal-
lized from
a mixture of dimethylformamide and
ethanol. Physicochemical data of this class of com-
pounds are given in Table 4. Selected spectral data are
reported below.
Acknowledgements
Table 5
Antibacterial activity of arylfurylpyrazolines 4–6
The authors are thankful to Head, RSIC, CDRI
Lucknow, Head, RSIC, IIT Madras and Director, SIF,
IISc, Bangalore for providing microanalysis, IR, NMR
and mass spectral data. Two of the authors (P.M.A.
and M.K.S.) are grateful to UGC and CSIR, New
Delhi, respectively, for the award of research fellow-
ships to them.
Comp.
Minimum inhibitory concentration (mg/ml)
E. coli
S. aureus
B. subtilis
P. aeruginosa
4c
4e
4f
4g
4j
4n
5c
5e
5n
6c
6j
6n
4.2
12.5
6.0
12.5
5.0
5.0
4.4
6.0
4.4
3.3
4.0
4.5
6.0
9.2
25.0
25.0
25.0
11.4
10.7
9.3
12.5
9.0
7.7
9.4
6.0
6.0
12.5
12.8
14.0
9.7
6.0
9.3
7.8
9.3
12.5
12.5
12.5
12.6
13.1
8.9
6.0
9.2
7.5
References
[1] D.N. Dhar, The Chemistry of Chalcones and Related Com-
pounds, Wiley, New York, 1981.
[2] K.B. Raut, S.H. Wender, J. Org. Chem. 25 (1960) 50.
[3] Z.S. Ariyan, H.J. Suschitzky, J. Chem. Soc. (1961) 2242.
[4] A. Jurasek, V. Knoppava, M. Danderova, J. Kovac, Reinprecht,
Tetrahedron 34 (1978) 1883.
8.7
10.2
12.5
10.2
10.9
12.5
10.1
10.0
12.5
Furacin

B. Shi6arama Holla et al. / Il Farmaco 55 (2000) 256–263
263
amino-4-[5-(p-nitrophenyl)-2-furyl]-thiazoles, J. Indian Chem.
Soc. 68 (1991) 341.
[5] A.M. Fahmy, K.M. Hassan, A.A. Khalaf, R.A. Ahmed,
Synthesis of Some New b-lactams, 4-Thiazolidinones and Pyra-
zolines, Indian J. Chem. 26B (1987) 884; Chem. Abstr. 109
(1988) 92871.
[6] N. Hiroshi, S. Akira, I. Masumi, Acetylpyrazolines, Japan
(Kokai), 139 (1970) 7012; Chem. Abstr. 73 (1970) 25457z.
[7] S. Arain, T. Matsuda, Bull. Jpn. Soc. Sci. Fisheries 32 (1966)
655.
[8] A. Krutosikova, R. Frimm, J. Kovac, L. Ebringer, Substituted-
5-(5-phenyl-2-furfurylidene)rhodanines, Czech., 145 (1972) 021;
Chem. Abstr. 78 (1973) 29758z.
[9] T.I. Vozyakova, A.F. Oleinik, K.Y. Novitskii, V. Nauchn, Study
in the Arylfuran Series, Konf. Khim. Teknol. Furanovykh
Soedin. (1978) 100; Chem. Abstr. 92 (1980) 180897.
[10] A.F. Oleinik, K.Y. Novitskii, V. Nauchn, Study in the Arylfuran
Series, Konf. Khim. Teknol. Furanovykh Soedin. (1978) 37;
Chem. Abstr. 92 (1980) 180892.
[13] B.S. Holla, M.K. Shivananda, P.M. Akberali, S. Baliga, S.
Safeer, Studies on arylfuran derivatives. Part VI. Synthesis,
characterization and antibacterial properties of 6-(5-aryl-2-furyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 6-(5-nitro-2-furyl)-
1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles, Farmaco 51 (1996) 785.
[14] B.S. Holla, K.V. Udupa, Synthesis, spectral studies and biologi-
cal activities of some N-bridged heterocycles derived from 3-aryl-
aminomethyl-4-amino-5-mercapto-1,2,4-triazoles, Farmaco 47
(1992) 305.
[15] B.S. Holla, B. Kalluraya, K.R. Sridhar, E. Drake, L.M. Thomas,
K.K. Bhandary, M.J. Levine, Synthesis, structural characteriza-
tion, crystallographic analysis and antibacterial properties of
some nitrofuryl triazolo[3,4-b]-1,3,4-thiadiazines, Eur. J. Med.
Chem. 29 (1994) 301.
[16] J.E. Baldwin, Chem. Commun. (1976) 734.
[17] B.S. Holla, P.M. Akberali (unpublished results).
[18] E.J. Stokes, G.L. Ridgway, Clinical Bacteriology, fifth ed., Ed-
ward Arnold, 1980, p. 226.
[19] R. Frimm, J. Kovac, E. Zavodska, Furan derivatives-VII. a,b-
Unsaturated furan ketones, Zb. Pr. Chem. Fak. SVST. (1967)
41; Chem. Abstr. 69 (1968) 106364m.
[11] B.S. Holla, P.M. Akberali, Studies on Arylfuran Heterocycles.
Part 1. Synthesis of 6-(5-aryl-2-furyl)-1,2,4-triazolo[3,4-b]-1,3,4-
thiadiazoles, J. Indian Chem. Soc. 68 (1991) 171.
[12] B.S. Holla, P.M. Akberali, Studies on arylfuran heterocycles.
Part 2. Synthesis and antibacterial activity of 2-amino/2-aryl-
.