Synthesis and characterization of a new 4-pyridone derivative and its complexation of iron(III)

Article abstract of DOI:10.1016/j.molstruc.2011.01.051

A new complexing and extracting agent, 3-hydroxy-2-methyl-1-(p-aminophenyl) -4-pyridone (HZ), was synthesized and its X-ray crystal structure was determined. The protonation constants of free HZ as well as stability constants of ferric mono-, bis- and tri

Full text of DOI:10.1016/j.molstruc.2011.01.051

Journal of Molecular Structure 990 (2011) 237–243
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Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Synthesis and characterization of a new 4-pyridone derivative
and its complexation of iron(III)
⇑
⇑
ˇ
-
´
´
ˇ
´
Astrid Gojmerac Ivšic , Vladislav Tomišic , Zeljka Car, Biserka Prugovecki, Srdanka Tomic
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia
a r t i c l e i n f o
a b s t r a c t
Article history:
A new complexing and extracting agent, 3-hydroxy-2-methyl-1-(p-aminophenyl)-4-pyridone (HZ), was
synthesized and its X-ray crystal structure was determined. The protonation constants of free HZ as well
as stability constants of ferric mono-, bis- and tris(HZ) complexes in the aqueous solution
(Ic = 0.1 mol dmꢀ3 (NaCl), t = 25 °C) were determined using spectrophotometry and potentiometry. Distri-
bution of HZ between the chloroform and aqueous phase was explored spectrophotometrically. The
ligand investigated was shown to be a promising reagent for the extraction of iron(III) from aqueous solu-
tion to organic phase.
Received 15 November 2010
Received in revised form 24 January 2011
Accepted 24 January 2011
Available online 28 January 2011
Keywords:
4-Pyridone derivative
X-ray structure
Protonation constants
Iron(III)
Ó 2011 Elsevier B.V. All rights reserved.
Stability constants
Extraction
1. Introduction
molecule can influence not only the protolytic properties of the
compound, but also its behaviour as a ligand in complexation reac-
4-Pyridone derivatives are excellent complexing agents and
therefore can be used for extraction and spectrophotometric deter-
mination of metal ions [1,2]. There has been a significant interest in
these compounds as sequestering agents for various metal ions. A
particular attention has been focused on their affinities towards
Al(III) and Fe(III) as hydroxypyridones have been shown to be
promising ligands for aluminium and iron chelation therapies
[3–9]. Furthermore, some pyridone derivatives are inhibitors of
bacterial enzymes and are potential antibacterial agents used for
bacterial infections [10,11].
tions with metal ions. Taking that into consideration, we have
investigated in detail the structural properties of the new type of
pyridone reagent, as well as its coordination reactions with Fe(III)
in an aqueous solution. Preliminary investigations of the Fe(III)
extraction with HZ in chloroform were also carried out.
2. Experimental
2.1. Synthesis of 3-hydroxy-2-methyl-1-(p-aminophenyl)-4-pyridone
(HZ)
Numerous spectrophotometric methods, especially the more
sensitive ones, are based on the formation of complexes between
the chelating reagents and metal ions. So far we have shown that
pyridone derivatives could be used for separation and spectropho-
tometric determination of different metals, even those with very
similar chemical properties. The analytical application of a few 3-
hydroxy-4-pyridones has been outlined in the previous papers
[12–17].
In the work presented in this paper we have prepared another
4-pyridone derivative, 3-hydroxy-2-methyl-1-(p-aminophenyl)-4-
pyridone (HZ), and explored its complexing abilities. Introduction
of the amino group into the para position of the 4-pyridone
Starting compounds, p-phenylenediamine and 3-hydroxy-2-
methyl-4-pyrone (maltol, Sigma Aldrich) were purchased and used
as received. All organic solvents were purified using standard pro-
cedures. Column chromatography was performed on Merck silica
gel 60 (size 70–230 mesh ASTM) and TLC monitoring on Fluka sil-
ica gel (60 F 254) plates (0.25 mm). Visualization was effected by
the use of UV light at 254 nm. NMR spectra were recorded using
Bruker Avance (300 MHz) spectrometer. Melting point was deter-
mined with a Büchi B-40 apparatus. Elemental analysis was per-
-
´
formed in the Microanalytical laboratory at the Ruder Boškovic
Institute, Zagreb, Croatia.
3-Hydroxy-2-methyl-4-pyrone (5 g, 39.6 mmol) and p-phenyl-
enediamine (8.5 g, 79.3 mmol) were mixed with water (15 ml)
and stirred at 100 °C for 5 days under reflux. The reaction was
monitored by TLC (5:2 ethyl acetate/methanol). The mixture was
⇑
Corresponding authors. Tel.: +385 1 46 06 190/136; fax: +385 1 46 06 131.
E-mail addresses: agi@chem.pmf.hr (A. Gojmerac Ivšic´), vtomisic@chem.pmf.hr
(V. Tomišic´).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.01.051

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A. Gojmerac Ivšic et al. / Journal of Molecular Structure 990 (2011) 237–243
238
then evaporated and column chromatography on silica gel (5:2
ethyl acetate/methanol) gave HZ (3.6 g, 42%). The crude product
was recrystallized from ethyl acetate. Colour: pale brown; mp:
202 °C; 1H NMR (CD3OD) d = 2.11 (3H, s), 6.44 (1H, d, J = 7.19 Hz),
6.78 (2H, m), 7.03 (2H, m), 7.53 (1H, d, J = 7.19 Hz); 13C NMR
(CD3OD) d = 13.78, 112.37, 115.98, 128.34, 132.73, 133.97,
139.89, 146.70, 150.88, 171.18. Elemental analysis: N 13.00%, C
66.60%, H 5.29%, calculated: C12H12N2O2, N 12.96%, C 66.68%, H
5.60%.
1 ꢂ 10ꢀ2 mol dmꢀ3) was prepared by dissolving the required mass
of FeCl3 in 0.1 mol dmꢀ3 HCl. The iron solution was standardized
by titration with 0.05 mol dmꢀ3 EDTA at pH 2.5 [24]. To prevent
the formation of iron(III) hydrolysis species in water, working
samples of lower concentrations of iron(III) were prepared daily
by diluting aliquots of the stock solutions with water. All the
reagents used were of analytical purity. Deionized water was used
to prepare all aqueous solutions.
O
2.2. Single crystal X-ray diffraction of 3-hydroxy-2-methyl-1-(p-
aminophenyl)-4-pyridone ethyl acetate solvate
OH
O
O
NH2
OH
The single crystal X-ray diffraction data of HZꢁEtOAc (EtOAc =
H2O
N
ethyl acetate) were collected by
x-scans on an Oxford Diffraction
+
5 days,100 oC
42%
Xcalibur
3 CCD diffractometer with graphite-monochromated
Mo K radiation. Data reduction was performed using the CrysAlis
a
software package [18]. Solution, refinement and analysis of the
structure was done using the programs integrated in the WinGX
system [19]. The structure was solved by the direct method using
SHELXS [20]. The refinement procedure was performed by the full-
matrix least-squares method based on F2 against all reflections
using SHELXL97 [21]. The non-hydrogen atoms were refined aniso-
tropically. All hydrogen atoms were located in the difference Fou-
rier maps and refined isotropically. Geometrical calculations were
done using PLATON [22]. Drawings of the structures were prepared
using PLATON and MERCURY [23] programs. The crystallographic
data are summarized in Table 1.
NH2
NH2
Scheme 1. Synthesis of HZ.
2.3. Reagents and apparatus for spectrophotometric measurements
Solutions of HZ were prepared by dissolving weight amount of
the compound in the appropriate solvent. Its stock solution in 96%
(v/v) ethanol was used for the spectrophotometric measurements
in a water–ethanol mixture. Stock solution of the Fe(III) ion (about
Table 1
Crystallographic data for compound HZꢁEtOAc.
Compound
HZꢁEtOAc
Chemical formula
Mr
C
12H12N2O2ꢁC4H8O2
304.34
Crystal colour, habit
Crystal size (mm3)
Crystal system
Space group
Unit cell parameters
a (Å)
Colourless, plate
0.56 ꢂ 0.30 ꢂ 0.15
Monoclinic
C2/c
12.4976(3)
16.0974(4)
15.6544(4)
90
b (Å)
c (Å)
a
(°)
b (°)
99.873(3)
90
3102.69(14)
8
c
(°)
V (Å3)
Z
Fig. 1. An ORTEP drawing of HZꢁEtOAc with displacement ellipsoids drawn at the
Dcalc (g cmꢀ3
)
1.303
50% probability level.
Temperature (K)
Wavelength (Å)
l
293
0.71073
0.094
(mm–1
)
Table 2
Selected bond distances and bond angles (Å, °) for
HZꢁEtOAc.
F(0 0 0)
1296
2716
2185
279
0.0328
0.0869
1.05
ꢀ0.17, 0.23
Number of unique data
Number of data [Fo P 4
Number of parameters
r
(Fo)]
O1–C3
1.3593(15)
1.2719(16)
1.4516(16)
1.3800(18)
1.4951(19)
121.53(10)
118.26(11)
121.65(12)
118.74(11)
118.13(12)
O2–C4
N1–C7
R1a, [Fo P 4
r
(Fo)]
b
wR2
N2–C10
C2–C13
Goodness of fit on F2, Sc
Min. and max. electron density (e Åꢀ3
)
C2–N1–C7
O1–C3–C2
O2–C4–C3
N1–C2–C13
C9–C10–C11
P
P
P
a
R = ||Fo| ꢀ |Fc||/ |Fo|.
wR ¼
h
i
1=2
P
P
2
2
ðF2o ꢀ F2c Þ = wðF2oÞ
.
b
h
i
1=2
2
wðF2o ꢀ Fc2Þ =ðNobs ꢀ Nparam
Þ
.
c
S ¼

´
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A. Gojmerac Ivšic et al. / Journal of Molecular Structure 990 (2011) 237–243
Fig. 2. Packing arrangement of HZꢁEtOAc molecules displayed in the unit cell showing a double layer network of hydrogen bonds.
Table 3
pH = 5.75
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
(a)
Geometry of intra- and intermolecular hydrogen bonds (Å, °) for HZꢁEtOAc.
D–Hꢁ ꢁ ꢁA
D–H (Å)
Hꢁ ꢁ ꢁA (Å)
2.471(19)
1.76(2)
2.108(18)
2.159(17)
2.415(17)
2.520(15)
2.585(14)
Dꢁ ꢁ ꢁA (Å)
D–Hꢁ ꢁ ꢁA(°)
O1–H1ꢁ ꢁ ꢁO2
O1–H1ꢁ ꢁ ꢁO2i
N2–H9ꢁ ꢁ ꢁO2ii
N2–H9ꢁ ꢁ ꢁO3ii
C13–H2ꢁ ꢁ ꢁO1
C9–H6ꢁ ꢁ ꢁO1iii
C6–H20ꢁ ꢁ ꢁN2iv
0.90(2)
0.90(2)
2.7747(14)
2.6255(13)
2.9759(17)
3.0172(17)
2.8131(18)
3.2459(16)
3.3529(17)
100.1(14)
159.4(18)
163.0(16)
169.0(15)
103.7(11)
132.6(12)
139.8(11)
pH = 11.68
0.895(18)
0.870(17)
0.979(17)
0.958(15)
0.934(14)
pH = 10.12
A
i
1 ꢀ x, y, ꢀ1/2 ꢀ z.
ii
iii
iv
ꢀ1/2 + x, 1/2 ꢀ y, 1/2 + z.
x, ꢀy, 1/2 + z.
pH = 1.54
1ꢀx, y, 1/2 ꢀ z.
For spectrophotometric measurements the solutions of Fe(III)-
HZ complexes in the aqueous phase were prepared as follows: to
a known volume of the working iron solution a given amount of
HZ solution and 96% (v/v) ethanol were added. pH of the solution
was adjusted by addition of an appropriate amount of universal
buffer solution, and the volume was made up to 5 cm3. Absorbance
measurements were made in a wavelength range between 800 and
400 nm on a Varian Cary 3 spectrophotometer with 1.0-cm quartz
cells. Acidity was measured with Radiometer PHM 85 Precision pH
meter provided with a combined glass-Ag/AgCl electrode. The pH
meter was calibrated by standard buffer solutions. A Griffin flask
shaker with a time switch served for extraction.
260
280
300
320
340
λ
/ nm
(b) 0.8
0.7
0.6
0.5
0.4
Spectrophotometric–potentiometric titrations of the free HZ li-
gand and ferric HZ complexes were carried out by means of a Var-
A
0.3
ian Cary
5 spectrometer equipped with a fibre-optic probe
(Hellma) of 1 cm path length. In both cases the titrand solution
(V0 = 50.0 cm3) was placed in the thermostated vessel (t =
(25.0 0.1) °C) and acidified by the addition of standardized HCl
solution to the pH slightly below 2. The solution was then titrated
by standardized NaOH, and the absorption spectra were recorded
after the pH was stabilized. The ionic strength of both titrans and
titrand was set to 0.1 mol dmꢀ3 by the addition of NaCl. The pH
values of the reaction mixtures were measured with a combined
glass-Ag/AgCl electrode (Metrohm) and a Metrohm 827 pH lab
pH meter. The electrode was calibrated by six standard buffers
(Kemika) in the pH range 2–12. The pH-dependent spectral data
were processed using the pHab program [25].
0.2
0.1
0.0
2
4
6
8
10
12
pH
Fig. 3. (a) UV spectra of aqueous HZ solutions recorded as a function of pH.
c(HZ) = 4.9 ꢂ 10ꢀ5 mol dmꢀ3; Ic = 0.1 mol dmꢀ3 (NaCl); l = 1 cm; t = (25.0 0.1) °C.
Spectra are corrected for dilution. (b) Dependence of absorbance at 313 nm on pH.
j experimental; ––– calculated.
Iron concentrations in the aqueous phase after extraction were
determined after suitable dilution by flame atomic absorption
using a Unicam 919 AA spectrometer. Iron concentrations in the
organic phase were calculated from the difference in the iron con-
centrations in the aqueous phase before and after extraction.

´
A. Gojmerac Ivšic et al. / Journal of Molecular Structure 990 (2011) 237–243
240
Table 4
atom at C2 or C6) influences the nucleophilic attack step and
therefore the whole conversion reaction [27]. Therefore, electron-
withdrawing groups enhance the reactivity of the ring while
electron-donating groups, such as a methyl group, have the oppo-
site effect. This explains a rather moderate yield of this reaction.
Successive protonation constants of free HZ and global stability constants of ferric HZ
complexes in aqueous solution; t = (25.0 0.1) °C; Ic = 0.1 mol dmꢀ3 (NaCl).
Equilibriuma
Log b
3r
LogKHi ꢃ 3
r
H+ + Zꢀ ¢ HZ
9.75 0.01
5.60 0.03
2.96 0.01
H+ + HZ ¢ H2Z+
H+ + H2Z+ ¢ H3Z2+
Fe3+ + H+ + Zꢀ ¢ FeHZ3+
Fe3+ + H+ + 2Zꢀ ¢ FeHZ2
3.2. Single crystal X-ray diffraction of HZꢁEtOAc
19.53 0.08
33.2 0.1
37.1 0.1
34.8 0.1
2+
Fe3+ + 2H+ + 2Zꢀ ¢ FeH2Z2
Fe3+ + 3Zꢀ ¢ FeZ3
3+
The asymmetric unit consists of one HZ molecule and one ethyl
acetate solvent molecule (C12H12N2O2ꢁC4H8O2), Fig. 1. Relevant
geometric parameters are listed in Table 2. The geometry of the
pyridine skeleton is in good agreement with the values observed
for N-benzyl-substituted and N-aryl-substituted analogues [28–
31]. Different substituents in the para position of the disubstituted
benzene molecule induce different deformation in the angular
geometry of the benzene ring resulting in deviation of the endocy-
a
Z denotes fully deprotonated HZ.
Z−
HZ
H3Z2+
100
H2Z+
clic bond angle (r) from the ideal value of 120°. Such deformation
80
60
40
20
0
has been discussed by Domenicano et al. [32]. It was of interest to
make an analysis using the latest structural data from the Cam-
bridge Structural Database [33]. An analysis gave a mean value of
r
of 118.62(3)° for 1111 fragments with the electron-donating
–NH2 substituent, 117.97(1)° for 9874 fragments with the –CH3
substituent, and 119.75(1)° for 4331 fragments with the –OCH3
substituent. The
r angle, C9–C10–C11, in the present structure
amounts to 118.13(24)° which is close to the found mean value.
A similar value of 118.19(19)° was found in a structurally related
compound with the –NH2 substituent [30]. In the structure of HZ
the dihedral angle between the benzene and pyridinone rings is
76.74(6)°. An intramolecular hydrogen bond O1–H1ꢁ ꢁ ꢁO2 of
2.7752(12) Å is found. In the crystal structure the molecules are
linked by a pair of O–Hꢁ ꢁ ꢁO hydrogen bonds O1ꢁ ꢁ ꢁO2[1ꢀx, y, ꢀ1/
2 ꢀ z] of 2.6255(13) Å forming a dimer. This type of dimeric struc-
ture is also found in anhydrous and in hydrous 3-hydroxypyridin-
4-one [28–31]. In addition, the molecules are linked by N–Hꢁ ꢁ ꢁO
intermolecular hydrogen bonds N2–Hꢁ ꢁ ꢁO2[1ꢀx, y, 1/2 ꢀ z] of
2.9759(17) Å and intermolecular hydrogen bonds involving the
ethyl acetate molecule N2–Hꢁ ꢁ ꢁO3[ꢀ1/2 + x, 1/2 ꢀ y, 1/2 + z] of
3.0172(17) Å (Fig. 2). Weak C–Hꢁ ꢁ ꢁO and C–Hꢁ ꢁ ꢁN hydrogen bonds
are also found (Table 3).
2
4
6
8
10
12
pH
Fig. 4. Distribution diagram of the protonation species of HZ. c(HZ) =
4.9 ꢂ 10ꢀ5 mol dmꢀ3
; Z
Ic = 0.1 mol dmꢀ3 (NaCl); solvent: water; t = 25.0 °C.
denotes fully deprotonated HZ.
3. Results and discussion
3.1. Synthesis of HZ
The compound was prepared in a one-step synthesis from com-
mercially available maltol and p-phenylenediamine as shown in
Scheme 1. The mechanism of this reaction is already established
and proceeds through the nucleophilic attack by a primary amine,
followed by a pyrone ring opening, elimination of water and ring
closure to give 4-pyridone [26]. Any factor that effects the electron
density on the pyrone ring (especially next to the in-ring oxygen
3.3. Acido-basic properties of HZ in aqueous solution
The pH dependence of the UV absorption spectra of compound
HZ is shown in Fig. 3a. By processing these data using pHab pro-
gram three protonation constants were determined (Table 4). A
rather good agreement between experimental and calculated
absorbances at 313 nm can be seen in Fig. 3b.
1.3
pH=1
pH=2.5
pH=5
λ= 560 nm
λ= 508 nm
λ= 472 nm
1.1
Fe(III) : HZ= 1:1
Fe(III) : HZ= 1:2
Fe(III) : HZ= 1:3
0.9
0.7
0.5
0.3
0.1
0.1
0.3
0.5
0.7
0.9
0.1
0.3
0.5
0.7
0.9
0.1
0.3
0.5
0.7
0.9
[Fe(III)]
[Fe(III)] + [HZ]
Fig. 5. Determination of the complex composition by Job’s method of continuous variation. c(Fe(III)) + c(HZ) = d 5 ꢂ 10ꢀ4 mol dmꢀ3; N 1 ꢂ 10ꢀ3 mol dmꢀ3
.

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A. Gojmerac Ivšic et al. / Journal of Molecular Structure 990 (2011) 237–243
FeHZ22+
pH = 6.52
(a)
100
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
FeH2Z23+
FeHZ3+
80
FeZ3
60
40
20
0
A
pH = 1.84
400
500
600
700
800
2
3
4
5
6
λ
/ nm
pH
0.60
0.55
0.50
0.45
0.40
0.35
Fig. 8. Distribution diagram of ferric HZ complexes. c(HZ) = 4.0 ꢂ 10ꢀ4 mol dmꢀ3
;
(b)
c(Fe(III)) = 1.32 ꢂ 10ꢀ4 mol dmꢀ3
;
Ic = 0.1 mol dmꢀ3 (NaCl); solvent: water;
t = 25.0 °C. Z denotes fully deprotonated HZ.
Table 5
The distribution of HZ between chloroform and aqueous phase of different contenta.
Composition of aqueous phase
D
(1) H2O; (2) 0.1 M NaCl; (3) 0.1 M NaClO4; (4) 1 M NaCl; (5) 1 M
NaClO4
100
A
(6) 0.09 M NaCl + 0.01 M HCl; (7) 0.09 M NaClO4 + 0.01 M HClO4; (8)
0.01 M HCl; (9) 0.01 M HClO4
10.1
(10) 0.9 M NaCl + 0.1 M HCl; (11) 0.9 M NaClO4 + 0.1 M HClO4
(12) 0.1 M HCl; (13) 0.1 M HClO4
2.8
1.9
a
The results are presented as mean values. The relative error is maximum 5%.
3.02) [34] and 3-hydroxy-2-methyl-1-(p-methylphenyl)-4-pyri-
done (9.56 and 3.16) [35], the first ðlog KH1 ¼ 9:75Þ and the third
ðlog KH3 ¼ 2:96Þ protonation constants of HZ can be easily assigned
to the protonation of hydroxyl oxygen and pyridone nitrogen,
respectively. Therefore, the remaining constant, log KH2 ¼ 5:60, cor-
responds to the protonation of the amino group on the phenyl ring
of HZ. Distribution diagram calculated for the experimental condi-
tions used is presented in Fig. 4.
2
3
4
5
6
7
pH
Fig. 6. (a) Vis spectra of ferric HZ complexes recorded as
a
function of pH.
c(HZ) = 4.0 ꢂ 10ꢀ4 mol dmꢀ3
;
c(Fe(III)) = 1.32 ꢂ 10ꢀ4 mol dmꢀ3
;
Ic = 0.1 mol dmꢀ3
(NaCl); solvent: water; l = 1 cm; t = (25.0 0.1) °C. Spectra are corrected for
dilution. (b) Dependence of absorbance at 550 nm on pH. j experimental; –––
calculated.
7
3.4. Iron(III) complexation studies
FeZ3
FeHZ22+
FeH2Z23+
6
The chelating ability of HZ towards the Fe(III) ion was estimated
by UV–Vis spectrophotometric measurements. When a solution of
the reagent in ethanol was gradually added to a moderately acidic
solution of FeCl3, a violet colour appeared, which changed to or-
ange-red and finally to orange-yellow. These observations indi-
cated that in the water–ethanol solution iron(III) and HZ formed
different complexes depending on the Fe(III):HZ concentration ra-
tio. The colour changes were also found to be pH dependent.
With the aim of determining the composition of the complexes
in the aqueous solution at different pH values, series of isomolar
solutions containing FeCl3 and HZ were prepared and their absor-
bances were measured at 472, 508 and 560 nm. The results ob-
tained by the Job’s method of continuous variation, indicated the
existence of three complexes. At pH = 1 only a violet complex with
the molar ratio of Fe(III) to HZ 1:1 was formed. Spectrophotometric
measurements at pH = 2.5 and 5.0 indicated that the complexes
with the Fe(III):HZ stoichiometries 1:2 and 1:3 prevailed in the
solution, respectively (Fig. 5).
5
4
FeHZ3+
3
ε
2
1
0
400
500
600
700
800
λ
/ nm
Fig. 7. Calculated electronic spectra of ferric HZ complexes.
deprotonated HZ.
Z
denotes fully
The protonation constants can be attributed by comparison
with analogous compounds. By taking into account the log KH
values of 3-hydroxy-2-methyl-1-phenyl-4-pyridone (9.56 and
3.4.1. Stability constants of ferric HZ complexes
The visible absorption spectra recorded in the spectrophoto-
metric-potentiometric titration of aqueous solution of ferric HZ

´
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A. Gojmerac Ivšic et al. / Journal of Molecular Structure 990 (2011) 237–243
(a)
(b)
-3
c
(HZ)=2x10-3 mol dm
0.9
0.7
0.5
0.3
0.1
-
4
c
(Fe(III))=1.3x10 mol dm-3
0.7
0.5
0.3
0.1
-3
c
(HZ)=5x10-4 mol dm
-
4
c(Fe(III))=1x10 mol dm-3
-3
c
(HZ)=2x10-4 mol dm
400 500
3.0 4.0 5.0 6.0 7.0 8.0 9.0
600
pH
Wavelength / nm
Fig. 9. (a) Dependence of the absorbance of extracted Fe(III)–HZ complex on pH in the aqueous phase. c(HZ) = 1 ꢂ 10ꢀ3 mol dmꢀ3; (b) absorption spectrum of extracted
Fe(III)–HZ complex in chloroform at various HZ concentrations. c(Fe(III)) = 1 ꢂ 10ꢀ4 mol dmꢀ3
.
complexes are shown in Fig. 6a. In the pH range between ꢄ6.5 and
ꢄ5.2 the spectra exhibited bathochromic and hypochromic shifts,
accompanied by the occurrence of a well defined isosbestic point
at 488 nm. That clearly indicated the existence of an equilibrium
between two spectrally distinct species. Another isosbestic point
appeared at 520 nm in the 5.3–3.1 pH range. Below pH = 3.1 fur-
ther decrease of absorbance and bathochromic shift were ob-
served. It should be noted that above pH ꢄ 7 a slight and slow
precipitation (presumably of the uncharged ferric tris(HZ) com-
plex) occurred which made spectrophotometric observations unre-
liable. The spectral data were analyzed by the pHab program.
Among several chemically reasonable speciations used, the best
fit (Fig. 6b) was obtained by assuming the presence of the follow-
phase. The results showed that pH about 6 is optimal for the
extraction of iron(III) with HZ into chloroform (Fig. 9a). The com-
plex species extracted from the aqueous solution was presumably
the uncharged ferric tris(HZ) complex. The absorption spectra of
Fe(III)–HZ complex extracted in chloroform with various HZ con-
centrations are shown in Fig. 9b. The extraction efficiency at opti-
mal pH for the extraction of iron(III) was found to be about 95%.
4. Conclusion
A new 4-pyridone derivative was prepared and explored as
iron(III) complexing agent. Its X-ray crystal structure was deter-
mined as an ethyl acetate solvate.
ing species in the reaction mixtures FeHZ3+, FeHZ22þ, FeH2Z3þ and
2
The values of protonation constants of free HZ were determined
in aqueous solution (Ic = 0.1 mol dmꢀ3 (NaCl), t = 25 °C). The com-
plexation of iron(III) by this ligand was investigated at different
pH values and various Fe(III):HZ molar ratios. Global stability con-
stants of ferric mono-, bis- and tris(HZ) complexes in aqueous solu-
tion (Ic = 0.1 mol dmꢀ3 (NaCl), t = 25 °C) were determined by
means of the spectrophotometric–potentiometric titration.
The extraction of Fe(III)–HZ complexes from aqueous to organic
phase was preliminary studied. The pH of aqueous phase optimal
for extraction was assessed to be about 6, and the extraction effi-
ciency for iron(III) at this pH was found to be about 95%.
FeZ3 (Z denotes fully deprotonated HZ). The calculated global sta-
bility constants of these complexes are listed in Table 4, and their
charge-transfer absorption spectra are shown in Fig. 7.
In the ferric mono(HZ) complex (FeHZ3+) the proton is most
likely bound to the amino group of the ligand. The same holds
for the ferric bis(HZ) complexes FeHZ22þ and FeH2Z3þ, whereas
2
the coordinated ligands in the FeZ3 complex are fully deproto-
nated. Distribution of the complex species as a function of pH is
given in Fig. 8, and is qualitatively in agreement with the results
obtained by Job’s method (Fig. 5).
3.4.2. Studies of the extraction
Supplementary material
The distribution of HZ between chloroform and aqueous
solutions of different acidity and ionic strength was studied. The
concentration of HZ in the aqueous phase was measured spectro-
photometrically using standard concentration–absorbance curves
established previously. These measurements were made at
288 nm. In the concentration range used the solutions of HZ
obeyed Beer’s law. The aqueous media were saturated with chloro-
form and then equilibrated with an equal volume of solutions of HZ
in chloroform for 1 h. Three different concentrations of HZ were
used and the same results were obtained if the initial concentra-
tion in chloroform was 5 ꢂ 10ꢀ5, 1 ꢂ 10ꢀ4 or 1 ꢂ 10ꢀ3 mol dmꢀ3
(Table 5). The distribution coefficient (D) was also independent
of the mineral acid used in the aqueous phase as well as of the ionic
strength. However, distribution of HZ depended on the acidity of
aqueous phase. The increase of acidity resulted in lower distribu-
tion coefficient (Table 5) due to the formation of protonated
cationic species which were better solvated with water in
comparison to chloroform.
Supplementary crystallographic data sets for the structure of
HZꢁEtOAc are available through the Cambridge Structural Data
base with deposition number 771960. Copies of this information
may be obtained free of charge from the director, CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336 033; e-mail:
deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
Acknowledgements
We wish to thank the Ministry of Science, Education and Sports
of the Republic of Croatia for the support of this work (Projects
119-1191344-3121, 119-1191342-2959, 119-1193079-1084, 119-
1191342-2960).
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