Synthesis, characterization, and biological activities of 3,5-dibenzyloxybenzoyl hydrazone and its complexes with some transition metals

Article abstract of DOI:10.1081/SIM-120021650

A new chelating ligand, 3,5-dibenzyloxybenzoyl-2,4-dihydroxybenzaldehyde hydrazone (H₂L), and its five transition metal complexes, M(HL)(OAc) [M = Co(II), Ni(II), Cu(II), Zn(II), Mn(II)], have been prepared and characterized on the basis of elemental analyses, magnetic moment, molar conductivity, IR, ¹H NMR and electronic spectra. Structures of the prepared complexes are suggested. The antibacterial activities of the prepared compounds were tested, and the results are discussed.

Full text of DOI:10.1081/SIM-120021650

Synthesis and Reactivity in Inorganic and Metal-Organic
Chemistry
ISSN: 0094-5714 (Print) 1532-2440 (Online) Journal homepage: http://www.tandfonline.com/loi/lsrt19
Synthesis, Characterization, and Biological
Activities of 3,5‐Dibenzyloxybenzoyl Hydrazone
and Its Complexes with Some Transition Metals
Ling Zhang , Ning Tang , Jin‐Cai Wu , Min‐Yu Tan , Qin Wang & Yin Han
To cite this article: Ling Zhang , Ning Tang , Jin‐Cai Wu , Min‐Yu Tan , Qin Wang & Yin Han
(2003) Synthesis, Characterization, and Biological Activities of 3,5‐Dibenzyloxybenzoyl
Hydrazone and Its Complexes with Some Transition Metals, Synthesis and Reactivity in
Inorganic and Metal-Organic Chemistry, 33:5, 847-856, DOI: 10.1081/SIM-120021650
To link to this article: http://dx.doi.org/10.1081/SIM-120021650
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Date: 29 February 2016, At: 22:33

SYNTHESIS AND REACTIVITY IN INORGANIC AND METAL-ORGANIC CHEMISTRY
Vol. 33, No. 5, pp. 847–856, 2003
Synthesis, Characterization, and Biological
Activities of 3,5-Dibenzyloxybenzoyl
Hydrazone and Its Complexes with
Some Transition Metals
1
1
Ling Zhang,1 Ning Tang,1, Jin-Cai Wu, Min-Yu Tan,
*
Qin Wang,2 and Yin Han2
2
1Department of Chemistry, and Department of Biology,
Lanzhou University, Lanzhou, P.R. China
ABSTRACT
A new chelating ligand, 3,5-dibenzyloxybenzoyl-2,4-dihydroxybenzal-
dehyde hydrazone (H2L), and its five transition metal complexes,
M(HL)(OAc) [M = Co(II), Ni(II), Cu(II), Zn(II), Mn(II)], have been
prepared and characterized on the basis of elemental analyses, magnetic
moment, molar conductivity, IR, 1H NMR and electronic spectra.
Structures of the prepared complexes are suggested. The antibac-
terial activities of the prepared compounds were tested, and the results
are discussed.
*
Correspondence: Ning Tang, Department of Chemistry, Lanzhou University,
Lanzhou, 730000, P.R. China; E-mails: zhanglinglzu@163.com, tangn@lzu.edu.cn.
847
DOI: 10.1081/SIM-120021650
0094-5714 (Print); 1532-2440 (Online)
www.dekker.com
Copyright D 2003 by Marcel Dekker, Inc.

848
Zhang et al.
INTRODUCTION
Acid hydrazides and their corresponding condensation products,
acylhydrazones, have attracted much attention over the past years in synthetic
chemistry and inorganic chemistry due to their diverse biological activities
and various chelating forms.[1,2] Especially, isonicotinhydrazide and its N-
isopropyl acylhydrazone have been used as effective drugs in curing human
tuberculosis in the past few years.[3] Metal complexes of acylhydrazones,
particularly the copper(II) complexes of 2-pyridine- carboxylaldehyde-2’-
pyridylhydrazone and salicylaldehyde benzoylhydrazone show antitumour
activity.[4] It is assumed that their mode of biological action is attributed to the
formation of stable chelates with transition metals present in the cell. Such a
process inhibits many vital enzymatic reactions catalyzed by these transition
metal ions.[5] Due to the biological importance and strong ability to form
stable chelates with metal ions of acylhydrazones, we synthesized a new
ligand, 3,5-dibenzyloxybenzyol-2,4-dihydroxybenzaldehyde hydrazone
(H2L), and prepared its complexes with cobalt(II), nickel(II), copper(II),
zinc(II) and manganese(II). All of the compounds synthesized were tested for
their antibacterial activities against E. coli, B. subtilis and S. aureus. The test
results were also evaluated. The structure of the ligand is shown in Figure 1.
EXPERIMENTAL
Materials
All chemicals used in this work were of analytical reagent grade. 2,4-
Dihydroxybenzaldehyde was recrystallized with ethanol before used. 3,5-
Dibenzyloxybenzoic hydrazide was prepared according to the literature.[6,7]
Measurements
The melting points of the compounds were determined on an X-4
microscopic melting point apparatus (made in China) and are uncorrected.
Figure 1. Structure of the ligand.

3,5-Dibenzyloxybenzoyl Hydrazone Complexes
849
Elemental analyses were carried out on a Vario EL elemental analyzer. IR
spectra were obtained in KBr discs on a Nicolet FT-IR 5DX spectrometer
1
in the 4000–400 cm–1 region. H NMR spectra (DMSO-d6) were recorded
on a Bruker AC-80A instrument with TMS as an internal standard. Mass
spectra were performed on a VG-7070E spectrometer (made in USA, EI at
70 eV). All conductivity measurements were performed in DMF with a
DDS-11A conductometer (made in Shanghai, China) at 25 °C. Magnetic
susceptibility measurements at room temperature (13 °C) were carried out
by using a Gouy balance with (NH4)2Fe(SO4)2 as calibrant. The electronic
spectra of the complexes (DMF solution) were abtained using an Unicam
UV-340 spectrometer.
Preparation of the Ligand (H2L)
To an ethanol solution (25 mL) of 3,5-dibenzyloxybenzoic hydrazide
(1.74 g, 5 mmol), an ethanol solution (15 mL) of 2,4-dihydroxybenzal-
dehyde (0.69 g, 5 mmol) was added with stirring at room temperature.
Then the mixture was refluxed in an oil bath for 8 h. After cooling to room
temperature, the precipitated solid was filtered, washed with ethanol and
recrystallized from absolute ethanol to give the ligand (H2L) in a yield of
1
86 % (2.01 g); m. p. 218–219 °C. H NMR (DMSO-d6, 80 MHz) d: 11.80
(1H, s, OH (B)), 11.41 (1H, s, OH (A)), 9.95 (1H, s, NH), 8.50 (1H, s,
CH), 7.43 (10H, m, ArH), 7.12 (3H, m, ArH), 6.90 (3H, m, ArH), 5.16
(4H, s, OCH2). MS (70 eV) m/z (%): 468 (M + , 31), 333 (35), 317 (100),
91 (56).
Preparation of the Complexes
A solution of M(OAc)2ꢀ4H2O (0.2 mmol) [M= Co(II), Ni(II), Cu(II),
Zn(II), Mn(II)] in anhydrous ethyl alcohol (5 mL) was added dropwise with
stirring to a solution of the ligand (0.0936 g, 0.2 mmol) in anhydrous ethyl
alcohol (15 mL). The reaction mixture was refluxed in an oil bath for 4–5
h, then cooled and filtered. The filter cake was washed three times with
anhydrous ethyl alcohol and one time with anhydrous diethyl ether, and
finally dried in vacuo.
Testing of the Antibacterial Activity
All of the compounds synthesized were tested for their antibacterial
activities employing the cup-plate method[8] at a concentration of 50 mg/mL
against E. coli, B. subtilis and S. aureus in the nutrient agar media. The
zone of the growth inhibition of the bacteria, produced by the diffusion of
the compounds from the cup into the surrounding medium, was measured

850
Zhang et al.
after 24 h. Chloromycetin (a trademark used for an antibiotic preparation of
chloramphenicol) was used as a standard.
RESULTS AND DISCUSSION
The elemental analyses and some physical properties of the ligand and
its complexes are given in Table 1. The analytical results show that the
ligand coordinates to the central metal ions in the keto form of the
hydrazone group, and the composition of its complexes corresponds to
M(HL)(OAc) [M = Co(II), Ni(II), Cu(II), Zn(II), Mn(II)]. The formation of
the complexes may be expressed by the following equation:
H2L þ MðOAcÞ2ꢀ4H2O ! MðHLÞðOAcÞ þ HOAc þ 4H2O
The ligand is soluble in common organic solvents, such as ethanol,
methanol, acetone and chloroform, while the complexes are insoluble in
water and common organic solvents and only soluble in DMF and DMSO.
The low molar conductance (3.2–7.3 O–1 cm2 mol–1) of the complexes
suggests that they are non-electrolytes in DMF solution.[9]
IR Spectra
The spectral data of the compounds and their tentative assignments are
shown in Table 2. It can be seen that the characteristic absorption peaks in
the IR spectra of all complexes are similar, which indicates that the
complexes have similar structures. The bonding of the ligand to the metal
ions was investigated by comparing the infrared spectra of the free ligand
with its metal complexes. The following conclusions in this regard may
be drawn.
(i) The spectra of the ligand exhibit a shoulder band at 3195 cm–1 of
the n(NH/OH) vibration, though in its complexes it became a
single band and shifted to lower frequency by 11–28 cm–1. This
indicates that the phenol OH (A) group takes part in the
coordination through deprotonation and breaks up the hydrogen
bond between the OH (A) and NH groups.
(ii) The IR spectra of the complexes show that the n(C =O) band at
1630 cm–1 in the spectra of the ligand made a distinct shift
towards lower frequency by 52–59 cm–1. This suggests the
bonding of the ligand through the carbonyl oxygen in the keto
form of the hydrazone group.[10]

3,5-Dibenzyloxybenzoyl Hydrazone Complexes
851

852
Zhang et al.
Table 2. IR spectra data of the ligand (H2L) and its complexes (cm–1).a
n
N
N
n
nas
ns
Compound
H2L
(NH/OH) (C=O) (C=N) (N–N) (CH3COO–) (CH3COO–)
3196 w, 1630 s 1586 s 971 m
sh
Co(HL)(OAc)
Ni(HL)(OAc)
Cu(HL)(OAc)
Zn(HL)(OAc)
3183 w
3168 w
3179 w
3185 w
1578 s 1537 s 985 m
1575 s 1534 s 985 m
1578 s 1548 s 987 m
1577 s 1541 s 985 m
1571 s 1530 s 985 m
1603 w
1603 w
1610 w
1608 w
1612 w
1380 m
1390 m
1394 m
1391 m
1392 m
Mn(HL)(OAc) 3179 w
aw = weak, s = strong, m = medium, sh = shoulder.
(iii) The IR spectra of all complexes indicate that the n(C=N) band in
the spectra of the ligand at 1586 cm–1 due to the azomethine
linkage were shifted towards lower frequency by 38–56 cm–1,
indicating that the ligand coordinates to the metal ions via the
azomethine nitrogen.[11]
(iv) Bonding through the azomethine nitrogen[12] is also indicated from
the shift of n(N–N) to higher frequencies by 14–16 cm–1.
(v) The appearance of two new absorptions at ꢁ 1608 and ꢁ 1390
cm–1 in the spectra of the complexes corresponding to nas(COO–)
and ns(COO–) indicates that the acetate group is coordinated to
the metal ions in the unidentate form.[13]
1H NMR Spectra
The ligand (H2L) exhibits signals at (d, ppm) 5.16 (s, OCH2), 6.31–
7.42 (m, ArH), 8.50 (s, CH), 9.95 (s, NH), 11.41 (s, OH (A)), 11.80 (s,
OH (B)), while in the complex Zn(HL)(OAc) signals are at (d, ppm) 1.89
(s, CH3COO–), 5.13 (s, OCH2), 6.30–7.42 (m, ArH), 8.41 (s, CH), 9.23
(s, NH), 11.89 (s, OH (B)). The disappearance of the signal at 11.41 (s,
OH (A)) in the complex proves that the phenol oxygen coordinates to the
metal ion through deprotonation. The downfield shift of the NH signal
suggests bonding of the ligand through the carbonyl oxygen and the
azomethine nitrogen in the keto form of the hydrazone group. The ap-
pearance of a signal at 1.89 (s, 3H) attributed to the acetate group proves
that the acetate ion is coordinated to the metal ions through the carboxylic

3,5-Dibenzyloxybenzoyl Hydrazone Complexes
853
1
oxygen. Thus, the H NMR studies reinforce the conclusions drawn from
the IR spectra.
Magnetic Studies and Electronic Spectra
Based on the fact that the magnetic susceptibility measurements and
electronic absorption spectra[14] are good diagnostics of the stereochemistry
of the metal complexes, the magnetic moments of the complexes at room
temperature and the electronic spectra in DMF solution were measured. The
data and their tentative assignments of some complexes are shown in
Table 3.
Zn(HL)(OAc) is diamagnetic as expected for a d10 metal ion in a tet-
rahedral geometry. The Ni(II) complex is diamagnetic and in its electronic
spectra shows two absorption bands at 24,691 and 26,954 cm–1 attributed to
the b2g ! b1g and a1g !b1g transition, which is compatible with this com-
plex having a square-planar structure.
The magnetic moment of the Cu(II) complex is 1.92 B. M. and it
shows an absorption band at 25,734 cm–1 corresponding to the d–d tran-
2
2
sition T2 ! E, which indicates the tetrahedral geometry of Cu(HL)(OAc).
In the spectra of the Co(II) complex is observed an absorption band at
4
4
25,189 cm–1 attributed to the A2 ! T2 (F) transition and a broad band at
4
4
28,818 cm–1 attributed to the 4A2 ! T1(F) and 4A2 ! T1(P) transitions,
indicating the tetrahedral geometry of the complex. This is also indicated
by its magnetic moment (meff = 3.44 B. M.).
Antibacterial Activity
The antibacterial activity test results of the ligand and its complexes
are shown in Table 4. Preliminary bioassays indicate that most of the
Table 3. Electronic spectra and magnetic moments of the complexes.
Compounds
l
max/cm–1 d–d
Tentative assignments
meff (B. M.)
4
Co(HL)(OAc)
25,189
28,818 (br)
4A2 ! T2 (F)
3.44
4
4A2 ! T1 (F),
4
4A2 ! T1 (P)
Ni(HL)(OAc)
Cu(HL)(OAc)
24,691
26,954
16,750
b2g ! b1g
a1g ! b1g
Diamagnetic
1.92
2
2T2 ! E

854
Zhang et al.
Table 4. Antibacterial activities of the ligand (H2L) and its complexes.
Compd.
S. aureus
B. subtilis
E. coli
H2L
+
+
ꢂ
Co(HL)(OAc)
Ni(HL)(OAc)
Cu(HL)(OAc)
Zn(HL)(OAc)
Mn(HL)(OAc)
DMSO
++
+
++
+
++
ꢂ
++
+
++
+
+
ꢂ
+
ꢂ
++
ꢂ
ꢂ
ꢂ
Chloromycetin
+++
+++
+++
Zone diameter of growth inhibition: < 10 mm (ꢂ), 10–12 mm (+), 13–15 mm (++),
> 16 mm (+++). The diameter of the cup is 8 mm.
compounds were active against these three bacteria, although they did not
reach the effectiveness of the bacterastatic activity of chloromycetin taken
as standard drug at the concentration of 50 mg/mL. It is manifested that the
complexes of copper and nickel were active to all three bacteria, and
showed more significant antibacterial activity than the ligand. It is also
interesting to note that the complex of manganese possesses better activity
against E. coli compared to all the other compounds.
CONCLUSIONS
From the above discussions, the following conclusion may be drawn:
the metal ions are four-coordinated by the ligand with O, O and N donors
from the phenol (OH (A)) via deprotonation, the carbonyl (C=O) and the
azomethine (CH=N) groups, respectively, and by one carboxylic oxygen
Figure 2. Suggested structure of the complexes.

3,5-Dibenzyloxybenzoyl Hydrazone Complexes
855
from the acetate group (CH3COO–) in the unidentate form. The suggested
structure of the complexes is shown in Figure 2.
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Received May 2, 2002
Accepted February 10, 2003
Referee I: W. J. Birdsall
Referee II: L. J. Boucher