Synthesis and biological evaluation of some novel 1, 3, 5-trisubstituted pyrazolines

Article abstract of DOI:10.1155/2010/415723

A new series of chalcones (3a-j) were synthesized by condensation of simple aldehydes with substituted acetophenones in presence of alkali. The resulted chalcones upon cyclization in presence of glacial acetic acid with isoniazid (INH) will yields the title compounds (4a-j). The newly synthesized compounds were assigned on the basis of IR, ¹H NMR, and Mass spectral data. All the final compounds were evaluated for their in vitro antimicrobial activity.

Full text of DOI:10.1155/2010/415723

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(1), 295-298
http://www.e-journals.net
Synthesis and Biological Evaluation of Some
Novel 1, 3, 5-Trisubstituted Pyrazolines
B. C. REVANASIDDAPPA§*, R. NAGENDRA RAO,
E. V. S. SUBRAHMANYAM§ and D. SATYANARAYANA§
§Department of Pharmaceutical Chemistry,
NGSM Institute of Pharmaceutical Sciences,
Paneer, Deralakatee-574160, Mangalore, Karnataka, India.
Department of Pharmaceutical Chemistry,
S C S College of Pharmacy, Harapanahalli, Karnataka- 583 131, India.
evergreen_revan@rediffmail.com
Received 12 July 2009; Accepted 27 August 2009
Abstract:
A new series of chalcones (3a-j) were synthesized by
condensation of simple aldehydes with substituted acetophenones in
presence of alkali. The resulted chalcones upon cyclization in presence of
glacial acetic acid with isoniazid (INH) will yields the title compounds
(4a-j). The newly synthesized compounds were assigned on the basis of IR,
1H NMR, and Mass spectral data. All the final compounds were evaluated
for their in vitro antimicrobial activity.
Keywords: Pyrazolines, Chalcones, Antimicrobial activity.
Introduction
Nitrogen heterocyclic compounds like pyrazolines have received considerable attention in
recent years due to their varied biological and pharmacological activities. Pyrazoline
derivatives are well known for their anti-inflammatory1, antiviral2, herbicidal3,
antimicrobial4, antifungal5, anti-inflammatory6 activities etc. Many class of
chemotherapeutic agents containing pyrazoline nucleus are in clinical use such as orisul
(bacterostatic), antipyrine (antipyretic), butazolidine (anti-inflammatory).
Based on the above biological activities exhibited by the pyrazoline compounds, we report
here, the synthesis and biological evaluation of some novel pyrazoline derivatives. Chalcones
(3a-j) were prepared from substituted aldehydes and ketones, in presence of alkali NaOH and
alcohol as solvent medium. The later compounds (3a-j) were converted into the title compounds
(4a-j) by reacting with isoniazid (INH) in glacial acetic acid medium. The structures of the
newly synthesized compounds were established on the basis of IR,1H NMR, and mass spectral
data. All the compounds were evaluated for their antibacterial and antifungal activities. The
reaction sequence leading to the formation of the title compounds has been outlined in Scheme 1.

296
B. C. REVANASIDDAPPA et al.
40% NaOH
Alcohol
(3a-j)
(4a-j)
Scheme 1
Experimental
Melting points were determined in open capillary tubes and are uncorrected (Table 1). TLC
(acetone: ethyl acetate 1:9) was used for monitoring the reaction and to check the purity. IR
spectra were recorded on Shimadzu Perkin-Elmer 8201 FT-IR. The PMR spectra were
recorded on BRUKER AVANCE II 400 NMR SPECTROMETER. Chemical shift values
are reported as values in ppm relative to TMS (δ=0) as internal standard. The FAB mass
spectra were recorded on JEOL SX- 102/DA-6000 Mass spectrometer using Argon/Xenon
(6Kv, 10Ma) as the FAB gas operating at 70Ev. Elemental analyses were performed for C, N
and were within 0.4% of theoretical values.
Table 1. Physical data of pyrazolines (4a-j).
Comp
4a
4b
4c
R-CHO
2-Furfural
p- CH3
R1-COCH3
p-Cl
m.p, 0 C
161-163
120-122
110-112
130-132
103-105
147-149
198-200
119-121
172-174
188-190
%, Yield
58
59
p-OH
p-Cl
p-Cl
C6H5
p-OCH3
2-Thiophene
m-NO2
62
68
59
68
p-OH
p-OH
p-NO2
C6H5
4d
4e
4f
67
57
4g
4h
4i
m-NO2
p-(CH3)2-N
p-OCH3
p-OH
p-Br
p-Cl
54
67
4j

Synthesis and Biological Evaluation
297
General procedure for the synthesis of chalcones (3a-j)
To a solution of substituted aldehydes (0.01 mol) and ketones (0.01 mol) in ethanol (25 mL),
a solution of NaOH (6 mL, 40%) was added. The reaction mixture was stirred at room temp
for a period of 24 h, diluted with water (100 mL) and acidified with dil. HCl. The product
obtained was filtered, washed with water and recrystallized from ethanol.
General procedure for the synthesis of 1, 3, 5-trisubstituted pyrazolines (4a-j)
A solution of chalcone (0.01 mol) and INH (0.01 mol) in glacial acetic acid (25 mL) was
refluxed for about 36-48 h. Excess of solvent was removed under reduced pressure and the
reaction mixture was poured into ice cold water. The product which was obtained is filtered,
washed with water and recrystallized from ethanol.
4d: FTIR (KBr) (cm-1): 3410 (OH), 3332 (NH), 1642 (C=O), 1513(C=N), 1489 (C=C).
1H NMR (CDCl3) : δ 2.40 (3H, s, OCH3), 3.24-3.30 (1H, dd, Ha), 3.82-3.90(1H,dd, Hb),
5.74-5.78 (1H, dd, Hx),7.33-8.03 (13H, m, Ar-H), 8.79(1H, s,OH). Mass (m/z): Molecular
ion peak at 373.
4e: FTIR (KBr) (cm-1) : 3415(OH), 3396(NH), 1679 (C=O), 1585(C=N), 1486 (C=C).
1H NMR (CDCl3) : δ 3.23-3.29 (1H, dd,Ha), 3.78-3.86(1H,dd, Hb), 5.72-5.80 (1H, dd, Hx),
7.24-8.00 (12H, m, Ar-H), 8.76( 1H, s,OH). Mass(m/z): Molecular ion peak at 343.
4f: FTIR (KBr) (cm-1): 3334(NH), 1646 (C=O), 1587(C=N), 1494 (C=C). 1514 (NO2 asym),
1
1330 (NO2 sym) H NMR (CDCl3):δ 3.22-3.28 (1H, dd, Ha), 3.54-3.61(1H, dd, Hb),5.16-5.20
(1H, dd, Hx), 6.87 -7.27(10H,m,Ar-H). Mass (m/z): Molecular ion peak at 378.
Antimicrobial activity
Antimicrobial screening was conducted using cup-plate method7 at a conc of 100 µg/mL. All
the compounds were assessed for their in vitro antimicrobial activity against different strains
of bacteria such as P.aeruginosa, E.coli (gram negative), B.subtilis, S.aureus (gram-positive)
and fungi like A.niger, C.albicans. Solvent DMF was used as solvent control. Standard
drugs like streptomycin and griseofulvin were used for comparison purpose. After 24 h of
incubation at 37 oC, the zones of inhibition were measured in mm. The biological data of the
compound is given in Table 2.
Table 2. Antimicrobial activity of compounds (4a-j).
Diameter of zone of inhibition (mm) at 10 µg/mL concentration
A.niger
Comp
S.aureus B.subtilis E.coli P.aeruginosa C.albicans
4a
4b
4c
4d
4e
4f
13
12
14
13
12
12
10
12
13
14
24
-
12
13
14
15
14
16
15
13
13
14
21
-
11
14
15
14
15
13
14
15
16
14
22
-
14
14
12
13
14
16
14
15
14
13
22
-
14
15
16
14
13
15
13
14
15
15
-
15
14
16
15
13
14
16
15
14
15
-
4g
4h
4i
4j
Streptomycin
Griseofulvin
Control(DMF)
23
-
22
-
-
-
-
-

298
B. C. REVANASIDDAPPA et al.
Conclusion
All the newly synthesized pyrazoline compounds were screened for their antimicrobial activity.
DMF is used as control and Streptomycin and Griseofulvin were used as standard drugs against
bacteria and fungi organisms respectively. Among all the tested compounds 4f, 4i displayed
maximum activity against all the four pathogenic organisms. In the antifungal activity, compounds
4c, 4j displayed maximum activity against both the fungi. From the results it is evident that most
of the compounds are moderately active against both bacteria and fungi organisms.
Acknowledgements
The authors are thankful to NITTE Education Trust for providing the necessary facilities to
carry out this work. The authors are also grateful to the Directors, RSIC, Chandigarh and
CDRI, Lucknow for providing IR, NMR, Mass and Elemental spectra respectively.
References
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Drabu S, Rana A and Harish K, Indian J Heterocycl Chem., 2007, 16, 399-400.
Hussain M I and Shukla S, Indian J Chem., 1986, 25B, 983-986.
Verma B L and Singhal M, Indian J Heterocycl Chem., 2007, 14, 343-346.
Karthikeyan M S, Holla B S and Suchetha N, Eur J Med Chem., 2007, 42, 30-36.
Shekarchia M, Pirali-Hamedania B L, Navidpourb N, Adiba and Shafieeb A, J
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Joshi H S, Popat K H and Nimavt K S, Indian J Heterocycl Chem., 2003, 12, 225-228.
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