Synthesis and characterizations of (3E,8E)-3,9-dimethyl-6,6-diphenyl-5,7dioxa-4,8-diazaundeca-3,8-diene-2,10-dione dioxime, and its copper(II),

nickel(II) and cobalt(II) complexes

SerdarKarabocek*, Nevin, Karabocek, Cagla Akkol, Uur Kazanc

Department of Chemistry, Karadeniz Technical University, 61080 Trabzon, Turkey

Abstract: A new dioxime ligand and its copper(II), nickel(II), cobalt(II) were synthesized and
characterized by spectral methods. Elemental analyses and spectroscopic data of the ligands
and its copper (II), nickel(II) and cobalt(II) complexes are consistent with the formation of the
ligand and its metal complexes. In addition to the free ligand and copper(II), nickel(II) and
cobalt(II) complexes (3-6) were evaluated for biochemical properties

Keywords: copper(II), nickel(II), cobalt(II) complexes, dioxime.

* Adress correspondence to Serdar Karabocek, Department of Chemistry, Karadeniz

Technical University, 61080 Trabzon, Turkey. E-mail: serdar@ktu.edu.tr

INTRODUCTION
The dioximes are the most widely used ligands in the coordination chemistry. [1-4] They
are now being as widely used mono-, di-, and poly nuclear transition metal complexes. This
ligand groups and their metal complexes play a key role of the coordination chemistry.

[5-8]

There is considerable interest in the chemistry of transition metal complexes due to the
biochemical activity and industrial uses.

[9,10]

Oximes metal complexes have been synthesized

and stimulated much interest for their noteworthy contributions in single molecule-based
magnetism,
hydrolysis.

[11]

[12]

catalysis of many reactions like reduction, oxidation, epoxidation and

This is due to the fact that dioximes offer opportunities for tuning the metal

centred electronic factor, catalyst, and different chemical applications,

[13]

for the purpose of

carrying a radionuclide into a target cell, [14] in magnetic resonance imaging reagents. [15, 16] The
coordination number usually varies from four to six depending upon the donor site geometry
around the metal and above all the steric constraints imposed by the ligand itself.
This article describes the synthesis and characterization of a new oxime ligand and its
copper(II), nickel(II) and cobalt(II) complexes. The properties of the complexes were
investigated by magnetic, physical, and spectral methods. Furthermore, the free ligand and
copper(II), nickel(II) and cobalt(II) complexes (4-6) were evaluated for biochemical
properties

EXPERIMENTAL
General
1

H-NMR and 13C-NMR spectra were recorded on a Varian Gemini 200 spectrometer

with CDCl3 and DMSO-d6 as solvents. Chemical shifts () are reported in ppm relative to
tetramethylsilane using the solvent signal as internal reference. Elemental analyses (C, H, and
N) were performed on a Costech 4010 CHNS Elemental analyzer and metal contents were

estimated spectrophotometrically.

[17]

Infrared (IR) spectra were recorded on an ATI Unicam

Matson 1000 Model FTIR spectrophotometer and UV-Vis spectra on an ATI Unicam UV2
Model UV-Vis spectrophotometer. Mass spectra (ESI) were recorded on a Micromass Quanto
LC-MS/MS spectrophotometer. All chemicals were of the highest quality available, obtained
from local suppliers, and used as received. The test microorganisms; E. coli RSKK 340, S.
aureus RSKK 96090, A. niger Z10, T. harzianum, (Rifai) were obtained from the Refik
Saydam National Public Health Agency-Turkey.
(3E,8E)-3,9-dimethyl-6,6-diphenyl-5,7-dioxa-4,8-diazaundeca-3,8-diene-2,10-dione, (2)
A solution

of

2,3-butanedione

monoxime

(2.1

g,

20

mmol)

and

1,1'-

(dichloromethanediyl)dibenzene (2.37 g, 10 mmol) in 1:1 EtOH/H 2O (25 mL) was added a

solution of KOH (1.12 g, 20 mmol) in EtOH (10 mL) at 0oC over ca. 30 min. After stirring for
24 h at room temperature, the reaction mixture was decanted and the soft waxy substance
washed with 1:1 EtOH/H2O mixture. The crude product was recrystallized from EtOH as a
white microcrystalline white solid. Yield: 2.7 g (73%), m.p.: 47oC, Ms: (ESI) m/z = 366.15
M+. Elemental Anal. Calcd (C21H22N2O4) (%): C, 68.8; H, 6.1; N, 7.7. Found: C, 68.7; H, 6.2;
N, 7.6.
(3E,8E)-3,9-dimethyl-6,6-diphenyl-5,7-dioxa-4,8-diazaundeca-3,8-diene-2,10-dione
dioxime, (3, DPTMD)
A solution of compound 2 (3.66 g, 10 mmol) and HONH2.HCl (9.87 g, 142 mmol) in
pyridine (50 mL) was stirred at room temperature for 24 h and the mixture was then poured
into ice cold H2O (200 mL). The resulting precipitate was collected, washed successively with
ice cold H2O and Et2O, and dried in vacuum over P2O5. Recrystallization from 1:1 EtOH (30
cm3) gave (H2L) as a colorless microcrystalline solid. Yield: 2.5 g (63%), m.p.: 120oC,
Ms: (ESI) m/z = 396,15 M+. Elemental Anal. Calcd (C21H24N4O4) (%): C, 63.6; H, 6.1; N,
14.1. Found: C, 63.5; H, 6.0; N, 14.2.

The product is a white, air-stable, crystalline solid, unsoluble in water, soluble in

methanol, acetonitrile, ethanole and strong acids (with protonation), Infrared spectra has been
measured by using a potassium bromide disc. IR (, cm1) 3225 (OH), 1596 (C=N). 1HNMR (ppm in CDCl3 relative to TMS): at 1.85 singlet (2 CH 3); at 2.19 singlet (2 CH3); at
7.25-7.54 multiplet (2C6H5-) at 9.0 br. singlet (2 C=NOH).
Preparation of copper(II), nickel(II) and cobalt(II) complexes
Cu(II), Ni(II) and Co(II) complexes (4-6) have been synthesized by the same method.
A solution of MCl2.XH2O (1 mmol) in (CH3)2CO (25 mL) was added to the ligand (1 mmol)
solution in (CH3)2CO (10 mL), and the mixture was boiled under reflux with stirring for 3 h.
Then, hot water was added a few dropwise to the mixture and solution was left to crystallize.
After the all of solid products were filtered off, washed with H 2O, EtOH, Et2O respectively
and dried over P2O5. M.p. 300 oC < for the all of metal complexes.
For (C21H23CuN2O4Cl), (4), elementel analysis (%): calculated: C, 51.0; H, 4.7; N,
11.3; Cu, 12.9; found: C, 50.4; H, 4.4; N, 10.8; Cu, 13.3. MS (ESI): m/z = 459.4 [M+1]+.
Yield, a blue solid 55%. For (C21H23NiN4O4Cl), (5), elementel analysis (%): calculated: C,
51.5; H, 4.7; N, 11.4; Ni, 12.0; found: C, 52.0; H, 4.4; N, 10.9; Ni, 11.7. MS (ESI): m/z =
453.5 [M]+. Yield, red solid 60 %. For (C21H23CoN4O4Cl), (6), elementel analysis (%):
calculated: (%): C, 51.5; H, 4.7; N, 11.4; Co, 12.0; found: C, 51.2; H, 4.2; N, 10.9; Co, 12.6.
MS (ESI): m/z = 454 M+. Yield, a brown solid 70%.

Antimicrobial Activity
The free ligand and its metal complexes, the metal salts, and the control (DMSO ) was
tested in vitro against gram-positive bacteria (Staphylococcus aureus), and gram-negative
bacteria (Escherichia coli) by paper disc method.

[18]

The free ligand and its metal complexes

(0.5 and 1 mgL1) in different concentrations DMSO. The results were compared with
ciprofloxin. [19]
The cultures of fungi were purified by single-spore isolation technique. The glucose
nitrate (GN) medium was used for growth of fungi. The mycelia biomass was then dried along
with filter paper in an oven at 655 oC to constant weight, cooled, and finally weighed. The
MDW was obtained by subtracting the weight of mycelium-free filter paper from final dry
weight.

[20]

The percentage error was found to be 0.01. The percent decrease in MDW to the

test compound in each case was calculated and tabulated in terms of average percentage
inhibition. The results indicate that the free ligand and its Cu (II), Ni (II), and Co (II)
complexes arrested the growth of fungi.
RESULS AND DISCUSSION
A new dioxime was synthesized and characterized by elemental analysis, 1H-NMR,
13

C-NMR, IR and mass spectral data (Scheme 1). Then the metal complexes of a new ligands

have been prepared and characterized by elemental analysis, magnetic moment, Uv-Vis, and
mass spectral data. In the proposed structure of this ligand N4 donor units available for the
complexation of transition metal ions.

NMR Spectra
The 1H-NMR spectra data were given in the experimental section. In the proton NMR
spectrum of the dioxime (DPTMD) was seen at 1.85 singlet (6H, -CH 3); at 2.19 singlet (6H,
-CH3); at 7.25-7.54 multiplet (10H, -C6H5-) at 9.0 br. singlet (2H, C=NOH) (in CDCl3). The
eleven resonance signals were observed in the 13C-NMR spectra of dioxime ligand, which was
also consistent with the formula for the dioxime ligand (DPTMD) (Scheme 1). The signals

have been seen in the singlet at = 9.0 ppm for the =N-OH hydrogen, disappears on
deuterium exchange.
Mass Spectra
The mass spectra of the dioxime and its Cu(II), Ni(II), and Co(II) complexes were
recorded in DMSO solution. In the mass spectra (ESI) was seen the molecular ion at m/z =
396.25 M+ for the free ligans (DPTMD). This result were indicated formation of ligands. The
molecular ion peaks appeared (m/z, ESI) at 459.4[M+1]+, 453.5 and 525.32 [M+] for the CuDPTMD, Ni-DPTMD and Co-DPTMD respectively. The mass spectra showed the formation
of the ligand and its metal complexes.

IR Spectra
Characteristic IR bands of the free ligand and its metal complexes(in cm -1) were given
in Table 1. In general, metal complexes also suggest that a similar structure, exhibits very
comparable IR bands. The strong band at 3240 and 1588 cm -1 might be assigned to (O-H)
and (C=N) vibration for the dioxime ligand (DPTMD) respectively.

[2, 21]

After the complex

formation (4-6) the vibrational bands were shifted to a higher and lower frequency ca. 10-40
cm-1. In the IR spectrum of free ligand was observed at 3240 cm -1 OH vibrational band but
could not be observed in the metal complexes. Instead, a weak vibration band is observed ca.
at 1700 cm-1, and this is due to O-H.O bridge.

[1, 3]

The significant shifts in (C=N) upon

complexation support the concept of coordination of ligand the dioxime ligand (DPTMD)
C=N nitrogen atoms (Fig 1).

Magnetic properties and Electronic Absorption Spectra

Electronic spectra of the Cu(II), Ni(II), and Co(II) complexes were recorded in DMF
(max nm) The experimental values of magnetic moment and electronic spectra are given in

Table 2 and 3. The band around ca. at 320-420 nm was due to the n * transition of the
nonbonding electron present on the nitrogen or oxygen atom of the ligand. The band around
ca. at 260-300 nm was due to the * transition. In the complexes (4-6), d-d transitions
were observed at ca. 525570 nm (Table 2). The energy of the d-d transition suggested a
distorted square planar geometry. [2, 22]
Electronic spectral data of the copper complex coupled with detected magnetic
moment ca. 1.77 B.M. suggest octahedral geometry.

[23, 24]

These electronic transitions along

with magnetic moment ca. 2.80 B.M. suggest octahedral or square planar geometry for Ni(II)
complex. [24, 25] The magnetic moment of cobalt(II) complex ca. 3.90 B.M (Table 3) indicate a
high-spin square planar complex.

[25, 26]

These data support the proposed geometry for the

Cu(II), Ni(II), and Co(II) complexes.

Antimicrobial Activity
The oxime ligand and its metal complexes were tested to antimicrobial activity against one
gram-positive bacterium (S. Aureus), gram-negative bacterium (Escherichia coli), and fungi
A. Niger and Trichoderma. The free ligand and its metal complexes exhibit antibacterial
activity against both strains. Cu (II), Ni (II), and Co (II) complexes exhibit higher activity
than the free ligand. The ciprofloxin was chosen as the standard for comparison antibacterial
inhibitions. The free ligand and its metal complexes showed lower activity than standard (table

4). The metal salts did not show antimicrobial activity. [27, 28] While biological activity does not
show metal salts, metal complexes show activity is consistent with the literature.

[29]

The

antibacterial inhibition of metal complexes has been found to concentration dependent and
was found to increase with increasing concentration. The Cu (II) complex exhibits higher
activity against each class of organism. The literature supports to the nature of this case.

[30]

The free ligand and its metal complexes show more activity against gramnegative E. Coli

than against gram-positive S. Aureus. The metal complex biological activities follow the order
CuL >CoL >NiL, which is exactly same as the order of stability constants of these
complexes. The Cu (II) complex is more active than the free ligand against A. Niger, but free
ligand is more active against Trichoderma.
CONCLUSIONS
In this study, a new dioxime ligand and its copper(II), nickel(II), cobalt(II) were synthesized
and characterized by spectral methods. Elemental analyses and spectroscopic data of the
ligands and its copper (II), nickel(II) and cobalt(II) complexes are consistent with the
formation of the ligand and its metal complexes. In addition to the free ligand and metal
complexes were evaluated for biochemical properties. The all metal complexes were found to
be paramagnetic. The metal ions were complexed with nitrogen atoms(N 4) of dioxime ligand.
The environment of metal ions was proposed as distorted tetragonal geometry.
Acknowledgement
This work was supported by Karadeniz Technical University Research Fund, and its project
code is 2005,111.02.2.

TABLE 1
Characteristic IR bands of the free ligand(DPTMD) and its metal complexes (in cm-1)
Compound
DPTMD
Cu-DPTMD
Ni-DPTMD
Co-DPTMD

(-O-H)
3240
3225
3207
3215

(O-HN)
1800
1790
1795

(C=N)
1588
1596
1570
-

TABLE 2
Electronic spectral data for the ligands and its metal complexes, (max in nm)
Compound

n
d-d band
DPTMD
270
310
Cu-DPTMD
272
420
570
Ni-DPTMD
275
380
540
Co-DPTMD
270
365
525
a
b
Per metal atom at 297 K(B.M.). UV/Vis spectra were taken in DMF.

TABLE 3
Physical data of the ligands and its metal complexes.
Comp.

Empirical formula

Color

Yield

MS(m/z)

aef

DPTMD

C21H24N4O4

white

63

396

Cu-DPTMD C21H24CuN2O4Cl

blue

55

529

1.77

Ni-DPTMD C21H24NiN4O4Cl

red

60

524

2.80

Co-DPTMD C21H24CoN4O4Cl

brown

70

525

3.90

TABLE 4
Antibacterial activities and antifungal activity weight (mg) (% inhibition) of the oxime ligand
and its metal complexes
Antibacterial activity (mg mL1)
E. coli
S. Aureus

Antifungal activity (mg mL1)

A. niger
Trichoderma

Conc.

0.5

0.5

0.5

0.5

Control(DMSO)

Ciprofloxin

40

45

42

44

74

72

65

60

DPTMD

12

12

11

18

75(20)

70(25)

50(20)

30(60)

Cu-DPTMD

20

28

15

26

65(35)

40(60)

35(50)

25(75)

Ni-DPTMD

15

22

12

20

60(40)

25(75)

35(65)

30(60)

Co-DPTMD

12

20

12

15

55(25)

30(70)

30(60)

25(65)

REFERENCES
1. Karabocek, S.; Bayraktar, U.; Karabocek, N.; Sahin, Z.S.; Isik, S.; Muhsir, S. J. Coord.
Chem. 2012, 65, 1118-1129.

2. Karabocek, N.; Armutcu, M.; Karabocek, S.; Tanak, H.; Isik, S.; Baskan, O. Synth. React.
Inorg. Met.-Org. Nano-Met. Chem. 2011, 41, 1249-1256.
3. Karabocek, N:; Kucukdumlu, A.; Senses, E.; Karabocek, S.; Ozcimder, R. Synth. React.
Inorg. Met.-Org. Nano-Met. Chem. 2011, 41, 1095-1101.
4. Karabocek, S.; Karabocek, N.; Armutcu, A. Transition Met. Chem. 2006, 31, 459-464
5. Celik, C.; Tumer, M.; Serin, S. Synth. React. Inorg. Met.-Org. Chem. 2002, 32, 1839-1854.
6. Rasool, R.; Hasnain, S.; Nishat, N.;Desig. Monom. Poly. 2014,17, 217-226.
7. Elbohy, S.A.H.; Int. J. Electrochem. Science2013, 8, 12387-12401.
8. Sumrra, Sajjad H.;Chohan, Zahid H.J. Enz.Inhibit. Med. Chem. 2013, 28, 1291-1299.
9. Ramesh, R.; Sivagamasundari, M. Synth. React. Inorg. Met.-Org. Chem. 2003, 33, 899910.
10. Maurya, R.C.; Verma, R.; Singh, T. Synth. React. Inorg. Met.-Org. Chem. 2003, 33, 309325.
11. Rodriquez de Barbarin, C.O.; Bailey, N.A.; Fenton, D.E.; He, Q.Y. J. Chem. Soc., Dalton
Trans.

1997, 161-166.

12. Khan, M.M.T.; Halligudi S.B.; Shukla, S.; Shaikh, Z.A. J. Mol. Catal.1990, 57, 301-305.
13. Kimura, E.; Kodama, Y.; Koike, T.; Shiro, M. J. Am. Chem. Soc.,1995, 117, 8304-8311.
14. Parker, D. Chem. Soc. Rev.,1990, 19, 271-291.
15. Dischino, D.D.; Delaney, E.J.;Emswiler, J.E.;Gaughan, G.T.; Prasad, J.S.; Srivastava,
S.K.; TweedleM.F. Inorg. Chem., 1991, 30, 1265-1269.
16. Fenton, D.E. Chem. Soc. Rev. 1999, 28, 159-168.
17. Vogel, A.I. Textbook of Quantitative Inorganic Analysis, fourth ed, Longman,
London, UK, 1978.
18. Munde, A.S.; Jagdale, A.N.; Jadhav, S.M.; Chondhekar, T.K. J. Kor. Chem. Soc., 2009,

53, 407-414.
19. Ahmad, I.; Mehmood, Z.; Mohammed, F. J. Ethnopharmacol., 1998, 62, 183-193.
20. Woods, G.L.; Brown-Elliott, B.A.; Desmond, E.P.; Hall, G.S.; Heifets, L.; Pfyffer, G.E.;
Ridderhof, J.C.; Wallace, R.J.; Warren, N.C.; Witebsky, F.G. Approved Standard. NCCLS
document M24-A, 2003.
21. Karabocek, S.; Bayraktar, U.; Karabocek, N.;Sahin, Z. S.;Isik, S.; Muhsir, S.J. Coord.
Chem.2012, 65, 1118-1129.
22. Mashaly, M.M.; Abd-Elwahab, Z.H.; Faheim, A.A. Synth. React. Inorg. Met.-Org. Chem.
2004, 34, 233-268.
23. Canbolat, E.; Yazci, A.; Kaya, M. J. Coord. Chem. 2007, 60, 473-480.
24. Eichhorn, G.L.; Bailar, J.C. J. Am. Chem. Soc. 1953, 75, 2905-2907.
25. Lever, A.B.P. Inorganic Electronic Spectroscopy; Elsevier: Amsterdam, 1968, pp. 275361.
26. Cotton, F.A.; Wilkinson, G. Advenced Inorganic Chemistry, 5thed.; Willey: new York,
1988.
27. Efthimiadou, B.K.; Psomas, G.; Sankis, Y.; Katsaros, N. J. Inorg. Biochem., 2007, 101,
525-535.
28. El-Dissouky, A.; Al-Fulaji, O.; Awad, M.K.; Rizk, S. J. Coord. Chem., 2010, 63, 330-345.

29. Thangadurai, T.D.; Natarajan, K. Synth. React. Inorg. Met.-Org. Nano-Met. Chem., 2001,
31, 549-567.
30. Raman, N.; Johnson Raja, S.; Sakthivel, A. J. Coord. Chem., 2009, 62, 691-709.

KOH

Cl
+ 2 HON

O
NH2OH.HCl

EtOH/H2O

Cl

(1)

(2)

SCH. 1. Step synthesis of dioxime ligands.

Figure legends
FIG.1. Proposed structure of the metal complexes
FIG. 2. The 1H-NMR spectra of DPTMD (in CDCl3)
FIG. 3. Mass spectra of DPTMD

N OH

N OH

Py

(3)

FIG. 4. Mass spectra of Cu-DPTMD

FG. 5. Mass spectra of Ni-DPTMD
FIG. 6. Mass spectra of Co-DPTMD

N O
M

H Cl
N O

M = Cu(II) (4), Ni(II) (5), Co(II) (6)

FIG.1. Proposed structure of the metal complexes

FIG. 2. The 1H-NMR spectra of DPTMD

FIG. 3. Mass spectra of DPTMD

FIG. 4. Mass spectra of Cu-DPTMD

FIG. 5. Mass spectra of Ni-DPTMD

FIG. 6. Mass spectra of Co-DPTMD