Comparative study of microwave assisted and conventional synthesis of furfuraldehyde based hydrazone derivatives and their metal complexes with biological evaluation

Article abstract of DOI:10.14233/ajchem.2017.20232

A series of acyl hydrazone derivatives were synthesized by the condensation of different hydrazides (benzohydrazide, isoniazid, nicotinic acid hydrazide and salicylhydrazide) and 5-(4′-nitrophenyl) furan-2-carbaldehyde. These hydrazones were subjected for metal complexation to yield copper(II) and nickel(II) complexes using conventional and microwave irradiation method. The microwave method was found to be successful with nearly the same or higher yields and shorter reaction time. The synthesized compounds were characterized by EIMS, CHN analysis, FTIR and NMR spectroscopy. All the synthesized compounds were screened for their antibacterial and antioxidant activities.

Full text of DOI:10.14233/ajchem.2017.20232

Asian Journal of Chemistry; Vol. 29, No. 2 (2017), 431-436
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2017.20232
Comparative Study of Microwave Assisted and Conventional Synthesis of Furfuraldehyde
Based Hydrazone Derivatives and their Metal Complexes with Biological Evaluation
1
1
1
2
MUSSARAT JABEEN , KARAMAT MEHMOOD , MISBAHUL AIN KHAN , MUHAMMAD NASRULLAH ,
3,*
4
1
TAHIR MAQBOOL , FARHAT JABEEN and MISBAH AFZAL
1Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
2Department of Chemistry, University of Sargodha, Women Campus, Faisalabad 38000, Pakistan
3Department of Chemistry, Government College University, Faisalabad 38000, Pakistan
4Government Degree College (Women), Yazman 63210, Pakistan
*Corresponding author: E-mail: tahirmakbool@gmail.com; chemiub14@gmail.com
Received: 8 August 2016;
Accepted: 20 September 2016;
Published online: 30 November 2016;
AJC-18175
A series of acyl hydrazone derivatives were synthesized by the condensation of different hydrazides (benzohydrazide, isoniazid, nicotinic
acid hydrazide and salicylhydrazide) and 5-(4'-nitrophenyl) furan-2-carbaldehyde. These hydrazones were subjected for metal complexation
to yield copper(II) and nickel(II) complexes using conventional and microwave irradiation method. The microwave method was found to
be successful with nearly the same or higher yields and shorter reaction time. The synthesized compounds were characterized by EIMS,
CHN analysis, FTIR and NMR spectroscopy.All the synthesized compounds were screened for their antibacterial and antioxidant activities.
Keywords: Furfuraldehyde, Benzohydrazide, Isoniazid, Nicotinic acid hydrazide, Salicylhydrazide, Antibacterial, Antioxidant.
synthesis of hydrazones and their metal complexes by
microwave methods have been comparatively less [25]. So
the new and efficient methodology for synthesis of furfural-
dehyde based hydrazone derivatives and their metal complexes
by both conventional and microwave irradiation technique is
of great interest. We hereby report the synthesis, spectral
investigations, antibacterial and antioxident activities of N’-
[{5-(4-nitrophenyl)furan-2-yl}methylene]benzohydrazide
(L1), N’-[{5-(4-nitrophenyl)furan-2-yl}methylene]isonicotino-
hydrazide (L2), N’-[{5-(4-nitrophenyl)furan-2-yl}methylene]-
nicotinohydrazide (L3) and 2-hydroxy-N’-[{5-(4-nitrophenyl)-
furan-2-yl}-methylene]benzohydrazide (L4) and their comp-
lexes with copper(II) and nickel(II).
INTRODUCTION
Hydrazones and their derivatives are attractive targets for
researchers due to their versatility [1], distinctive structural
features and a wide range of pharmacological and biological
applications such as antimicrobial, analgesic, anticonvulsant
[2], anti-inflammatory, antituberculosis [3], antitumor, anti-
HIV [4,5], antimalarial [6], antiviral, antifungal [7], antioxidant
and vasodilator activities [8-11]. These are important precursors
for drug design to treat the genetic disorders like thalassemia
[12,13]. Hydrazone derivatives also act as herbicides, insec-
ticides, nematocides, rodenticides and plant growth regulators
[14]. These play an important role as ligands in coordination
chemistry by forming stable complexes with most transition
metal ions [15]. Some hydrazone metal complexes have not
only shown significant antibacterial, antioxidant and antitumor
activities [16] but also act as enzyme inhibitors [17] and corro-
sion inhibitors [18]. Also, the metal complexes of hydrazones
have potential applications such as catalysts, luminescent probes
and membrane sensors [19].
EXPERIMENTAL
All the chemicals and solvents were purchased from
Merck/Aldrich and used as such. Melting points were recorded
on a GallenKamp apparatus and are uncorrected. The progress
of the reaction and the purity of the target compounds were
monitored by TLC using aluminium sheets coated with silica
gel 60 F254. FTIR spectra were recorded on Vector 22 FTIR
Microwave-assisted synthesis has a broad range of appli-
cations in both organic and coordination chemistry [20]. It is
being used for carrying out chemical transformation which
are eco-friendly, low cost and offer high yields together with
simplicity in processing and handling [21-24]. Reports on the
1
spectrophotometer. H NMR and 13C NMR spectra were
recorded on Bruker AV 400 and AV 300 spectrophotometer
respectively. Elemental analysis for C, H, N, Cl and metal were

432 Jabeen et al.
Asian J. Chem.
O
C
O2N
carried out by Thermo Scientific FLASH 2000 elemental
analyzer. Mass spectra were recorded on MAT 312 mass spec-
trometer. For microwave mediated reactions microwave oven
with Model No. DW-631 was used.
H
O
CHO
C
O
H2N
EtOH/HCl O2N
MW
N
N
H
R
(L1-L4)
C
R
O
R= C6H5, 4-C5H5N, 3-C5H5N,C6H5O
Synthesis of ligands
Scheme-I
Conventional method: 5-(4'-Nitrophenyl)furan-2-
carbaldehyde was synthesized according to the reported method
[26]. Similarly hydrazides (benzohydrazide, isoniazid, nicotinic
acid hydrazide and salicylhydrazide) was synthesized by both
conventional method and microwave irradiation method as
reported in literature [27,28]. Equimolar amounts of 5-(4'-
nitrophenyl)furan-2-carbaldehyde (10 mmol) and hydrazide
(10 mmol) were dissolved in ethanol with few drops of concen-
trated hydrochloric acid as a catalyst and heated under reflux
for 3-5 h. The completion of reaction was checked by TLC in
a mixture of n-hexane:ethyl acetate (2:1). The mixture was
cooled, filtered and recrystallized from a mixture of ethanol
and ethyl acetate (5:1) to yield target hydrazone ligands (L1-L4)
as coloured compounds (Scheme-I). Physical and spectral data
of ligands is summarized in Tables 1 and 2.
salicylhydrazide) (10 mmol) in ethanol (2 mL) and two drops
of concentrated hydrochloric acid was subjected to microwave
irradiation 600 W for 2-3 min. The solid product obtained
was checked for completion of the reaction by TLC with a
solvent system n-hexane: ethyl acetate (2:1). The resulting
compounds L1-L4 were recrystallized from ethanol and ethyl
acetate (5:1).
Synthesis of metal complexes
Conventional method: A solution of metal(II) chlorides
(10 mmol) in ethanol (10 mL) was added to a warm solution
of ligand (L1-L4) (10 mmol or 20 mmol) in ethanol and DMF
(3:2) (50 mL). The mixture was heated under reflux for 0.5-5
h. The reaction was monitored by TLC with solvent system n-
hexane:ethyl acetate (1:1). The precipitates thus formed after
cooling to room temperature were filtered and washed
successively with DMF and ethanol mixture (1:2) to get the
Microwave irradiation method:A mixture of 5-(4-nitro-
phenyl)furan-2-carbaldehyde (10 mmol) and hydrazide
(benzohydrazide, isoniazid, nicotinic acid hydrazide and
TABLE-1
PHYSICAL DATA FOR LIGANDS
Time
MW
Yield (%)
Elemental analysis (%): Calcd. (Found)
m.p.
(°C)
Ligands
Colour
m.w.
CM
(h)
CM
MW
C
H
N
(min)
2.10
3.00
3.00
3.40
L1
L2
L3
L4
1.5
3.0
3.0
4.0
62.10
66.90
60.71
66.10
85.37
80.95
77.68
88.30
Golden yellow
Dark yellow
Yellow
243
225-226
245
335
336
336
351
64.47 (64.4)
60.71 (60.63)
60.7 (60.6)
3.91 (3.88)
3.60 (3.38)
3.60 (3.38)
3.73 (3.57)
12.53 (12.50)
16.66 (16.37)
16.66 (16.58)
11.96 (11.74)
Bright yellow
236-238
61.54 (61.7)
CM = (a) Conventional method; MW = Microwave irradiation method
TABLE-2
FTIR, 1H NMR AND 13C NMR DATA FOR LIGANDS
1H NMR δ (ppm) (DMSO)
13C NMR δ (ppm) (DMSO)
Ligands
FTIR (cm-1)
11.98 (1H, s, N-H), 8.43 (1H, s, C-H=N), 8.34-
3268.3(m) (N-H), 1650.3(sh) (C=O), 1514.3(sh) 8.32 (2H, d, J = 8 Hz, H-3,5), 8.07-8.05 (2H, d,
112.42 (C-2 furan), 116.16 (C-3
furan), 124.52, 124.60, 127.69,
128.49, 131.83, 133.26, 135.17,
136.97 (CH=N), 146.33, 151.01 (C-1
& 1333.5(sh) (Asym and sym -NO2),
1603.5(m) (C=N), 1281.7(sh) (C-O-C),
1146.1(m) (C-N), 1030.6(m) (N-N)
J = 8 Hz, H-2',6'), 7.93-7.91 (2H, d, J = 8 Hz,
H-2,4), 7.61-7.60 (1H, d, J = 4Hz, H-2 furan),
7.567-7.527 (3H, m, Ar), 7.17-7.16 (1H, d, J = 4 furan), 151.74 (C-NO2), 152.41 (C-4
L1
Hz, H-1 furan)
furan), 163.14 (C=O)
12.2 (1H, s, N-H), 8.82-8.81 (2H, d, J = 4 Hz,
H-3', 5’), 8.44 (1H, s, C-H=N), 8.36-8.34 (2H, d, furan), 121.46, 124.52, 124.71,
J = 8 Hz, H-3,5), 8.07-8.06 (2H, d, J = 4 Hz, H- 135.08, 138.08 (CH=N) 140.27,
2',6'), 7.85-7.83 (2H, d, J = 8 Hz, H-2,4), 7.53-
7.52 (1H, d, J = 4 Hz, H-2 furan), 7.23-7.22
(1H, d, J = 4 Hz, H-1 furan)
112.43 (C-2 furan), 116.92 (C-3
3219.0(m) (N-H), 1664.9(sh) (C=O),
1512.9(sh) & 1330.7(sh) (Asym and sym -
NO2), 1602.7(m) (C=N), 1416.9(s) (C=N of
pyridine), 1286.5(sh) (C-O-C), 1147.9(m) (C-
N), 1027.3(s) (N-N)
L2
L3
L4
146.42 (C-1 furan), 150.36, 150.64
(C-NO2), 152.71 (C-4 furan), 161.62
(C=O)
12.12 (1H, s, N-H), 9.08 (1H, s, CH=N pyridine
3182.4(s) (N-H), 1651.5(sh) (C=O), 1512.4(sh) ring, H-1'), 8.79-8.77 (1H, d, J = 8 Hz, H-5'
pyridine ring), 8.41 (1H, s, C-H=N), 8.35-8.33
(3H, d, J = 8 Hz, H-3, 5, 3'), 8.08-8.06 (2H, d, J
pyridine ring), 1295.5(sh) (C-O-C), 1157.5(m) = 8 Hz, H-2,6), 7.62-7.59 (1H, d of d, H-4'
112.40 (C-2 furan), 116.61 (C-3
furan), 123.60, 124.49, 124.65,
135.10 (CH=N), 135.40, 137.52,
146.36 (C-1 furan), 148.51, 150.73
(C-NO2), 152.34 (CH=N pyridine),
152.58 (C-4 furan), 161.67 (C=O)
& 1333.6(sh) (Asym and sym -NO2),
1598.3(m) (C=N), 1424.2(s) (C=N of
(C-N), 1030.8(m) (N-N)
pyridine ring), 7.515-7.505 (1H, d, J = 4 Hz, H-
2 furan), 7.22-7.21 (1H, d, J = 4 Hz, H-1 furan)
11.95 (1H, s, N-H), 11.77 (1H, s, O-H), 8.44
3428.3(b) (O-H), 3241.7(sh) (N-H), 1627.6(sh) (1H, s, C-H), 8.356-8.338 (2H, d, J = 7.2 Hz, H- furan), 116.69, 117.24, 118.95,
112.45 (C-2 furan), 116.13(C-3
(C=O), 1505.5(sh) & 1339.2(sh) (Asym and
sym -NO2), 1600.9(s) (C=N), 1226.6(sh) (C-
O-C), 1144.1(m) (C-N), 1029.8(s) (N-N)
3, 5), 8.081-8.063 (2H, d, J = 7.2 Hz, H-2,6),
7.887-7.875 (1H, d, J = 4.8 Hz, H-2 furan),
7.51-7.48 (2H, m, Ar), 7.2-7.188 (1H, d, J = 4.8 furan), 150.79(C-NO2), 152.59 (C-4
Hz, H-1 furan), 7.01-6.98 (2H, m, Ar) furan), 158.81 (C-OH), 164.66 (C=O)
124.54, 124.66, 128.62, 133.82,
135.13(CH=N), 137.66, 146.38 (C-1

Vol. 29, No. 2 (2017)
Comparative Synthesis of Furfuraldehyde Based Hydrazone Derivatives and their Metal Complexes 433
TABLE-3
PHYSICO-CHEMICAL DATA OF COMPLEXES
Time
Yield (%)
Elemental analysis (%): Calcd. (Found)
m.p.
(°C)
Comp.
Colour
m.w.
MW
(min)
1
CM (h)
0.5
CM
MW
83
C
H
N
M
L1-Cu
L1-Ni
L2-Cu
L2-Ni
L3-Cu
L3-Ni
L4-Cu
L4-Ni
76
62
67
62
78
54
77
65
Dark
green
Crimson
red
Black
Brick red
Rust
241
732.16
727.3
59.06
(59.01)
59.45
(59.49)
47.01
(48.00)
47.55
(47.64)
47.01
(47.06)
3.30
(3.36)
3.33
(3.35)
2.55
(2.62)
2.58
(2.41)
2.55
(2.54)
2.58
11.48
(11.43)
11.56
(11.52)
12.90
(13.09)
13.05
(13.03)
12.90
(12.99)
13.05
8.68
(8.60)
8.07
4.5
0.5
2
2
74
81
77
83
68
82
73
Above
330
268
(8.01)
14.63
(14.65)
13.67
(13.65)
14.63
(14.53)
13.67
(13.60)
8.32
1
434.29
429.44
434.29
429.44
764.16
759.3
1.50
1.30
2.50
1
266-269
168-170
265-267
245
0.5
3
Cherry
47.01
(47.60)
56.58
(2.69)
3.17
(13.03)
11.00
1
Yellowish
brown
Orange
red
(56.67)
56.94
(3.06)
3.19
(10.99)
11.07
(8.31)
7.73
3.5
2.10
233-234
(57.18)
(3.29)
(10.94)
(7.67)
CM = (a) Conventional method; MW = Microwave irradiation method; *Decompose
H
C
target complexes (Scheme-II). The physical and spectral data
of complexes is tabulated in Tables 3 and 4.
O
H
C
O2N
N
N
N
H
N
EtOH/DMF
MW
C
O
O
(L1-L4)
C
TABLE-4
NO2
R
O
R
=
L1=C6H5,
FTIR (cm–1) DATA OF THE METAL COMPLEXES
FTIR (cm–1)
L2= 4-C5H5N,
L3= 3-C5H5N,
L4= C6H5O
M
Compd.
L1-Cu
1514.9(sh) & 1336.5(sh) (Asym and sym -NO2), 1611.2(s)
(C=N-N=C), 1281.1(s) (C-O-C), 1107.9(s) (C-O), 1022.8(m)
(N-N), 580.6(s) (M-N), 459.1(s) (M-O)
NO2
O
O
C
N
N
C
H
1500.7(sh) & 1326.8(sh) (Asym and sym -NO2), 1597.0(m)
(C=N-N=C), 1271.0(m) (C-O-C), 1102.9(m) (C-O), 1022.4(m)
(N-N), 564.7(s) (M-N), 496.8(s) (M-O)
(L1)
L1-Ni
L2-Cu
H
C
1512.7(sh) & 1333.0(sh) (Asym and sym -NO2), 1600.3(m)
(C=N-N=C), 1423.8(s) (C=N of pyridine), 1281.8(s) (C-O-
C), 1105.2(m) (C-O), 1021.8(m) (N-N), 546.9(s) (M-N), 494.9(s)
(M-O)
NO2
N
N
N
C
O
O
O
OH
CH
M
HC
HO
C
O
Cl
N
N
N
N
M
(L2)
1510.8(sh) & 1333.1(sh) (Asym and sym -NO2), 1598.7(m)
(C=N-N=C), 1421.0(s) (C=N of pyridine), 1275.4(s) (C-O-
C), 1106.1(m) (C-O), 1021.0(m) (N-N), 562.2(s) (M-N), 454.9(s)
(M-O)
O
C
L2-Ni
L3-Cu
O
NO2
H
C
1599.8(sh) (C=N-N=C), 1514.4(sh) & 1338.5(sh) (Asym and
sym -NO2), 1420.2(s) (C=N of pyridine), 1283.1(s) (C-O-C),
1107.7(m) (C-O), 1017.4(s) (N-N), 548.3(s) (M-N), 485.7(s)
(M-O)
O2N
N
N
C
(L4)
N
O
O
M
M
= Cu(II), Ni(II)
(L3)
Cl
1598.8(s) (C=N-N=C), 1513.7(sh) & 1333.3(sh) (Asym and
sym -NO2), 1421.3(s) (C=N of pyridine ring), 1278.5(s) (C-
O-C), 1106.2(s) (C-O), 1023.0(m) (N-N), 457.4(s) (M-O)
L3-Ni
L4-Cu
L4-Ni
NO2
3251.0(b) (O-H), 1514.7(sh) & 1331.1(sh) (Asym and sym -
NO2), 1597.7(m) (C=N-N=C), 1253.0(s) (C-O-C), 1103.4(s)
(C-O), 1035.9(m) (N-N), 533.2(s) (M-N), 485.1(S) (M-O)
Scheme-II
Antibacterial activity: The antibacterial activity of all
3443.2(b) (O-H), 1514.4(sh) & 1333.5(sh) (Asym and sym -
NO2), 1596.7(m) (C=N-N=C), 1258.7(s) (C-O-C), 1100.5(s)
(C-O), 1048.8(s) (N-N), 492.0(s) (M-O)
the synthesized compounds was studied systematically against
nine different bacterial strains including both the gram positive
and gram negative bacteria by using disc diffusion method.
The organisms were sub-cultured on nutrient broth Agar
medium, incubated at 37 °C for 24 h and stored at 4 °C in the
refrigerator to maintain stock culture. Petri plates were
prepared with 20 mL of sterile Nutrient broth Agar medium
and allowed to solidify. 100 µL of the cultures were spread on
the top of the solidified media by spread-plate method and
allowed to dry for 10 min. The tests were conducted at concen-
trations 500 µg/disc respectively of the synthetic derivatives.
Microwave irradiation method:A mixture of corresponding
metal(II) chlorides (10 mmol) and (10 mmol or 20 mmol) of ligands
(L1-L4)inethanol(1mL)andDMF(1mL)wassubjectedtomicro-
wave irradiation at 600 W for 1-4 min. The solid product obtained
was checked for completion of the reaction by TLC in a mixture of
n-hexane:ethyl acetate (1:1). The resulting metal complexes were
washed several times with DMF and ethanol mixture with 1:2. The
physicalandspectraldataofcomplexesistabulatedinTables3and 4.

434 Jabeen et al.
Asian J. Chem.
TABLE-5
ANTIBACTERIAL ACTIVITY FOR LIGANDS (L1-L4) AND ITS METAL COMPLEXES
Zone of inhibition in diameter (mm)
Compd.
Gram-positive
Gram-negative
S. typhi Shigella
S. aureus
Bas.
8
–
–
–
Asch.
Pseudomonas
B.b
–
–
–
–
E. coli
Salmonella
L1
L1-Cu
L1-Ni
L2
–
–
–
–
–
–
–
–
–
–
–
–
8
9
–
–
–
–
–
10
–
–
–
–
–
9
–
L2-Cu
L2-Ni
L3
–
–
–
–
–
–
–
–
–
–
–
9
–
–
–
–
–
–
–
–
–
13
10
–
–
–
–
L3-Cu
L3-Ni
L4
–
–
–
–
–
–
–
–
–
12
–
–
–
–
–
–
9
–
8
13
–
–
–
–
–
–
–
L4-Cu
L4-Ni
Standard
9
8
11
–
–
11
–
–
12
10
–
16
–
–
24
–
–
10
–
–
25
–
–
27
–
–
17
The loaded discs were placed on the surface of the medium
and left for 0.5 h at room temperature for compound diffusion.
Negative control was prepared by using respective solvent
(DMSO).Ampicillin (50 µg/mL) was used as positive control.
The plates were incubated for 24 h at 37 °C. The zone of inhibi-
tion was recorded in millimetres [29,30] (Table-5).
Free radical scavenging activity: From the stock solution
50 µL of synthesized compounds as well as standard compound
(ascorbic acid) were taken and the volume was made uniformly
to 150 µL using methanol. Each of the samples was then further
diluted with methanol up to 3 mL and to each 150 µL DPPH
(4.3 mg DPPH/3.3 mL) was added. Absorbance was taken
after 15 min at 517 nm using methanol as blank and 3 mL
methanol with 150 µL DPPH as control [31,32].
Total antioxidant capacity: From the stock solution 50 µL
of synthesized compound solution in DMSO as well as standard
was combined with 3 mL of reagent solution (0.6 M sulphuric
acid, 28 mM sodium phosphate and 4 mM ammonium
molybdate). The solutions were incubated at 95 °C for 90 min.
and cooled to room temperature. The absorbance of the solutions
measured at 695 nm against blank and standard (ascorbic acid).
A typical blank solution contained 3mL of the reagent solution
and the appropriate volume of DMSO and it was incubated under
the same condition as the rest of samples [33-35].
FTIR, EIMS and CHN). The elemental analysis and FTIR of
complexes possess 1:2 stoichiometry in case of L1 and L4
while 1:1 stoichiometry in case of L2 and L3 with coordinated
water molecules.
All the synthesized hydrazone ligands exhibit keto-enol
tautomerism [13]. In solid state these ligands exist in keto form
while when reacted with metal(II) ions, the ligands get depro-
tonated from amide moiety. Suggested tridentate, monobasic
(mono-negative) hydrazone ligands and the metal(II) complexes
are formed.
EIMS, 1H NMR and 13C NMR of the hydrazone ligands:
Hydrazone ligands usually exist in keto-enol tautomeric form
(Scheme-III). The presence of keto form of ligands were
indicated by 1H NMR spectroscopy since the enolic OH signal
of enolic forms of ligands were not observed but amide NH
signal of keto forms appeared around 11.98-12.2 ppm. Further-
more one singlet of C-H=N appeared around 8.44-8.41 ppm
which indicated ketonic form of ligands. The other obtained
values for 1H NMR chemical shifts of these compounds (Table-2)
also support the structures of the ligands. Similarly in 13C NMR
spectra of ligands signals of (-C=O) appears at δ 161-164 ppm
and signals of HC=N appears at δ135-138 ppm which confirms
the ketonic forms of ligands. The signals for (C-NO2) appear
around δ 150-151 ppm while others signals observed (Table-2).
Nitric oxide scavenging assay: From the stock solution
50 µL of each of the compound as well as ascorbic acid
(standard compound) were mixed with 150 µL with methanol.
2 mL of sodium nitroprusside 10 mM in phosphate buffer
solution was added in each of the compound solution. The
solutions were incubated at room temperature for 2.5 h and
5 mL of griess reagent (1 % sulphanilamide, 0.1 % naphthyl-
ethylenediamine dichloride and 3 % phosphoric acid) was
added including control. The absorbance of chromophore
formed was measured at 546 nm on UV-visible spectrometer.
Ascorbic acid was used as positive control [36,37].
O
C
O
C
R
R
N
HN
-H+
N
N
C
C
H
H
O
O
+H+
O2N
Scheme-III: Tautomeric forms of hydrazone ligands
O2N
Mass spectra of ligands confirms the structures of target
compounds by showing not only the molecular ion peaks at
335 (L1), 336 (L2), 336 (L3) and 351 (L4) but also fragmen-
tation peaks like L1 (335 [M+], 214 [M+- C6H4NO2], 105
[PhCO], 77 [C6H5]), L2 (336 [M+], 306 [M+-NO], 214 [M+-
C6H4NO2], 106 [M+-C11H8N3O3], 78 [M+-C12H8N3O4]), L3 (336
[M+], 306 [M+-NO], 214 [M+-C6H4NO2], 106 [M+-C11H8N3O3],
RESULTS AND DISCUSSION
All the synthesized compounds are coloured, solid and
stable. Ligands are soluble more or less in organic solvents
while complexes are only soluble in DMSO. The ligands
confirmed by the spectroscopic data (1H NMR, 13C NMR,

Vol. 29, No. 2 (2017)
Comparative Synthesis of Furfuraldehyde Based Hydrazone Derivatives and their Metal Complexes 435
TABLE-6
78 [M+-C12H8N3O4] and L4 (351 [M+], 306 [M+- NO2], 121[M+-
C11H8N3O3], 93 [C6H5O], 77 [C6H5]).
In FTIR spectra of the carbonyl (C=O) group is justified
by an absorption bands around 1664-1627 cm-1, (C-N) by an
absorption bands around 1157-1144 cm-1. Amide (N-H) stret-
ching bands of these ligands observed at 3200-3100 cm-1 suggest
that the ligands are in keto form.
The IR spectra of complexes show significant differences
from free ligands like absence of N-H, C=O and C-N absorp-
tion bands and appearance of absorption bands of (C=N-N=C)
around 1611-1596 cm-1. The structures of complexes are further
confirmed by the bands approximately 850-848 cm-1 of 1,4-di-
substituted benzene in all ligands as well as metal complexes.
The lower frequency region of the spectra of complexes furnishes
some vital information regarding the mode of coordination of
the ligand with the metal ion. The bands are in the region 580-
533 cm-1 assignable for M-N and at 496-454 cm-1 for M-O.
ANTIOXIDENT ACTIVITIES FOR LIGANDS
AND THE METAL COMPLEXES
Antioxidant (percentage scavenging)
Compd.
Free radical
scavenging
Total antioxidant
capacity
Nitric oxide
scavenging
L1
L1-Cu
L1-Ni
L2
L2-Cu
L2-Ni
L3
L3-Cu
L3-Ni
L4
15.06
30.80
10
32.40
44.25
75.14
25.09
65.27
66.90
6.04
64.11
42.28
12.54
77.35
66.31
–
27.94
26.76
3.52
22.29
31.38
1.03
27.13
31.61
4.14
13.56
1.03
20.57
–
16.58
46.34
11.49
21.15
24.15
24.80
45.95
17.75
1.04
L4-Cu
L4-Ni
Control
Ascrobic acid
–
78.16
96.05
84.33
Biological evaluation
Antibacterial activity: The synthesized compounds were
evaluated for antibacterial activity at the concentration of 500
µg/mL by using disc diffusion assay where ampicillin was
used as standard (Table-5). It is clear that some compounds
showed significant antibacterial activity. In case of L1 and its
complexes, the free ligand show moderate activities against
Bacillus subtilis and Salmonella while copper complexation
caused the activity to increase in case of Salmonella but show
no activity against Bacillus subtilis, similarly nickel comp-
lexation caused the activity to increase in case of Shigella but
inactive against all other strains. In case of L2 and its comp-
lexes, L2 showed moderate activity against E. coli while its
metal complexes show some good activity against the same
strain while inactive against other strains. L3 ligand is active
against Pseudomonas and E. coli, copper complex showed
increase in activity against Pseudomonas while nickel complex
show increase in activity against S. typhi and Shigella. Hydrazone
ligand L4 is inactive against all strains and its complexes are
only active against Pseudomonas and S. aureus.
Antioxidant activity: Table-6 shows the percentage of
DPPH radical scavenged by standard that is ascorbic acid and
metal complexes of hydrazones. It is evident from the data
that L1-Cu, L2-Cu and L3-Cu possess hydrazone donating
capabilities and free radical scavenging ability and can act as
moderate antioxidants.
From all the tested compounds, L4 and L2-Cu exhibited
moderate NO radical scavenging activity (45.95 and 46.34 %,
respectively). Hence these may act as moderate NO radical
scavengers.
83 % in less than 1 h (CM) and in 1 min to 1.30 min (MW).
These hydrazone ligands bind with metal ions in tridentate,
mono basic manner, with ONO donor sites. The compounds
were evaluated for antibacterial activities using disk diffusion
method against nine bacterial strains and antioxidant activities.
As a result of these studies, among the target compounds some
compounds show moderate antibacterial activities while most
are inactive. In case of antioxidant activities, L2-Cu showed
maximum DPPH activity and NO scavenging, while L4-Cu
exhibited maximum total antioxidant activity.
ACKNOWLEDGEMENTS
The authors acknowledge the financial support by HEC
Pakistan in the form of indigenous Ph.D. fellowship and IRSIP
grant.
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