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IJPRD, 2014; Vol 6(10):December-2014 (096 - 103)
International Standard Serial Number 0974 – 9446
-------------------------------------------------------------------------------------------------------------------------------------------------SYNTHESIS AND BIOLOGICAL ACTIVITY OF HYDRAZIDE–HYDRAZONES AND THEIR CORRESPONDING 3ACETYL-2,5-DISUBSTITUTED-2,3-DIHYDRO- 1,3,4-OXADIAZOLES.
Amit Aher*1 and Dr. Shobha Borhade1
1
Hikal LTD., Pune
ABSTRACT
Hydrazone derivatives have attracted a great deal of interest in
synthetic chemistry and considerable research on them in
relation to their synthetic utility has been accomplished furoyl
hydrazone was synthesized from 2-furoyl hydrazide and 3-(4’-(4”fluorophenyl)-2’-cyclopropylquinolin-3hl) propenaldehyde. The
structure of synthesized compound was confirmed by 1H-NMR
and Mass spectroscopy.
Keywords- Furoyl hydrazione, Propenaldehyde, NMR, Mass
Correspondence Author
Amit Aher
Hikal LTD., Pune Maharashtra
Email: [email protected]
INTRODUCTION
Heterocycles are present in a wide variety of drugs,
most
vitamins,
many
natural
products,
biomolecules, and biologically active compounds,
including antitumor, antibiotic, antiinflammatory,
antidepressant,
antimalarial,
anti-HIV,
antimicrobial, antibacterial, antifungal, antiviral,
antidiabetic, herbicidal, fungicidal, and insecticidal
agents. Also, they have been frequently found as a
key structural unit in synthetic pharmaceuticals
and agrochemicals.
Hydrazone derivatives have attracted a great deal
of interest in synthetic chemistry and considerable
research on them in relation to their synthetic
utility has been accomplished. Hydrazones are
extensively studied as reactants or re-action
intermediates since they can readily undergo
various ring closure reactions [1]. Hydrazone group
plays an important role for the antimicrobial
activity [2-6].Various important properties of
hydrazones, along with their applications in
medicine and analytical chemistry [7] .The
structural motif present in heterocyclic hydrazones
is a remarkable tool for the development of
multifunctional organic receptors that find
application in chemical environmental and
biological sciences [8]. Heterocyclic hydrazones
constitute an important class of active drugs that
attracted the attention of medical chemists due to
their wide ranging pharmacological properties like
antifungal [9] antibacterial [10] and anticonvulsant
compounds [11]. N-substituted hydrazones of
aldehydes are of interest because of their
biological and pharmacological activities [12–16].
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International Journal of Pharmaceutical Research & Development
Five member heterocyclic compounds show
various type of biological activities among than
2,5disubstituted 1,3,4-oxadiazole are associated
with diverse biological activities [17].Various
biological activities like antimicrobial, antitubercular, antiinflammatory, Anticonvulsant [18],
Hypnotic [19], Anesthetic activity [20]. 1,3,4oxadiazoles showed antibacterial properties[21].
3.43 ml (107.24 mmol ) of anhydrous hydrazine and
1.21 g (15.32 mmol ) of pyridine was added in
round bottom flask. The reaction mixture was
cooled ice with stirring. 2.0 g (15.32 mmol) of 2furoyl chloride dissolved in 20 ml tetrahydrofuran
added slowly. After addition reaction mixture was
refluxed about 2 hour gives 2-furoyl hydrazide
Synthesis of N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide (5).
0.5 g (1.57 mmol ) 3-(4’-(4”-fluorophenyl)-2’cyclopropylquinolin-3hl) propenaldehyde followed
by 10 ml (20 Vol) ethanol and 0.2 g (1.57 mmol) 2furoyl hydrazide. 0.5 ml (1 vol) acetic acid was
added in reaction mixture. Reaction mass was
refluxed for 3 hour. Clear solution was formed.
Reaction mass was cooled at room temperature.
Ice was added slowly in reaction mass, solid
precipitated out. Crystalline product was
recrystallized
MATERIALS AND METHODS
Synthesis of 2-Furoyl Chloride (2)
3.0 g (26.76 mmol) of 2-furoic acid was added in 30
ml dichloromethane and solution was stirred at
room temperature for 10 minutes followed by 2.34
ml (32.04 mmol, 1.2 eq.) of thionyl chloride and
mixture was refluxed for 1 hour. The reaction mass
was cooled at room temperature. The solvent was
distilled off under reduced pressure to give 2furoyl chloride
Synthesis of 2-Furoyl Hydrazide (3)
Reaction
OH
Thionyl Chloride,
DCM
Cl
O
O
130.53
1
126.12
2
F
H
N
O
3
N
Acetic Acid/
Acetic Anhydride
3
N
O
F
F
NH2
O
Ethanol
Reflux
NH2
O
O
112.09
H
H
N
NH2-NH2
O
O
O
ISSN: 0974 – 9446
N
O
H
N
O
O
O
N
N
317.37
425.47
466.52
4
5
6
Characterisation of Compounds
NMR spectra
NMR spectra of synthesized compound has been
taken . Instrument used BRUKER AC 400F NMR
spectrophotometer 33 HZ with CDCl3 solvent. The
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International Journal of Pharmaceutical Research & Development
NMR spectra of 2-furoyl chloride, 2-Furoyl
Hydrazide and N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-
ISSN: 0974 – 9446
2’-cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide as shown in Fig 1-3.
Fig 1 : 1H NMR of 2-Furoyl Hydrazide
Fig 2 : 1H NMR of N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’-cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide in CDCl3
Fig 3 : 1H NMR of N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’-cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide in D2O
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International Journal of Pharmaceutical Research & Development
HPLC Chromatographic analysis
HPLC was applied for testing the presence of
number of organic compounds available for
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compound 5. One of the components with 96.78 %
& 3.958 retention time may have detected Table 1.
Fig 4.
Fig 4. HPLC Chromatogram of N’
N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’- cyclopropylquinolin-2cyclopropylquinolin
Propenyllidene)]
Propenyllidene)]-2-furoyl Hydrazide
Method
Column : Sunfire C-18,
18, 50 x 4.6 mm, 3.5 u
M.P.A. : 10 mM Ammonium Acetate
M.P.B. : Acetonitrile
Gradient : (% B/T) : 50/0, 50/0.5, 75/4, 95/8.5,
95/9.5,
50/9.8,
50/10
@
0.8
ml/min
Column Temp : 30 C
RESULTS AND DISCUSSION
2-furoyl
furoyl chloride (2) gives 80 % yield is about 2.8
gm. 2-furoyl
furoyl hydrazide (3) gives 74 % yield and N’
N’Available online on www.ijprd.com
[(1E,
2E)-3--(4’-(4”-fluorophenyl)-2’cyclopropylquinolin-2-Propenyllidene)]
Propenyllidene)]-2-furoyl
hydrazide (5) gives 60% ( 0.43 gm ) yield.For 22
furoyl hydrazide (3)1H NMR: 4.05(s, 2H), 6.52 (1H),
7.15(1H), 7.45(1H), 7.63(s, 1H) and for N’-[(1E,
N’
2E)3-(4’-(4”-fluorophenyl)-2’-cyclopropylquinolin
cyclopropylquinolin-2Propenyllidene)]-2-furoyl
furoyl Hydrazide (5) 1H NMR:1.08(m, 2H), 1.40(m, 2H), 2.44(m, 1H), 6.56(s, 1H),
6.87(s, 1H), 7.26(4H), 7.33(3H), 7.47(s, 1H), 7.64(t,
1H), 7.81(s, 1H), 8.97 (d, 1H), 9.24 (s, 1H), Mass
m/z 426 (M+).
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International Journal of Pharmaceutical Research & Development
Table 1. Peak Table
Retention time
Area
3.525
5479
3.602
6417
3.958
7745830
4.839
443
5.124
262548
6.238
720
6.856
4046
7.939
645
8.487
2666
8028785
Peak
1
2
3
4
5
6
7
8
9
10
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Area %
0.068
0.080
96.476
0.006
3.270
0.009
0.050
0.008
0.033
100.00
Fig 5 :MS spectrum
Fig 6 : Mass spectra of 2-Furoyl Hydrazide
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International Journal of Pharmaceutical Research & Development
ISSN: 0974 – 9446
Fig 7 : Mass spectra of N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’-cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide in CDCl3
Fig 8: Mass spectra of N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’-cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide in D2O
Fig 9 : Mass spectra of N’-[(1E, 2E)-3-(4’-(4”-fluorophenyl)-2’-cyclopropylquinolin-2-Propenyllidene)]-2-furoyl
Hydrazide
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International Journal of Pharmaceutical Research & Development
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